ISPE Good Practice Guide - HVAC
Short Description
Download ISPE Good Practice Guide - HVAC...
Description
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
1 2 3 4 5 6 7
ISPE GOOD PRACTICE GUIDE
8 9
HVAC
10 11 12 13
DRAFT FOR REVIEW
14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
35 36 37 38 39 40 41 42 43 44
© 2008 ISPE. ALL RIGHTS RESERVED.
1
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94
JULY 2008
TABLE OF CONTENTS 1
2
3
4
5
6
7
INTRODUCTION ...................................................... 5 1.1 BACKGROUND .................................................... 5 1.2 SCOPE OF THIS GUIDE ........................................... 5 1.3 OBJECTIVES OF THIS GUIDE ...................................... 6 1.4 DEFINITIONS ................................................... 6 1.5 REFERENCES .................................................... 6 FUNDAMENTALS OF HVAC .............................................. 9 2.1 INTRODUCTION .................................................. 9 2.2 WHAT IS HVAC? ................................................. 9 2.3 AIRFLOW FUNDAMENTALS ......................................... 13 2.4 PSYCHROMETRICS ............................................... 19 2.5 EQUIPMENT .................................................... 21 2.6 HVAC SYSTEM CONFIGURATION .................................... 23 2.7 HVAC CONTROLS AND MONITORING ................................. 39 2.8 SYSTEM ECONOMICS ............................................. 51 2.9 SUSTAINABILITY (TO BE WRITTEN LATER) ........................ 58 THE DESIGN PROCESS ............................................... 59 3.1 INTRODUCTION ................................................. 59 3.2 DEVELOPING THE USER REQUIREMENTS SPECIFICATION (URS) ......... 61 3.3 HVAC SYSTEM RISK ASSESSMENT .................................. 69 HVAC APPLICATIONS BY PROCESS AND CLASSIFICATION .................. 73 4.1 INTRODUCTION ................................................. 73 4.2 SYSTEM APPLICATIONS .......................................... 73 4.3 ROOM LEVEL EXAMPLES .......................................... 78 4.4 ACTIVE PHARMACEUTICAL INGREDIENTS (API) - (WET END) .......... 83 4.5 ACTIVE PHARMACEUTICAL INGREDIENTS (API) - (DRY END) .......... 84 4.6 BIOLOGICS .................................................... 85 4.7 ORAL SOLID DOSAGE (NON-POTENT COMPOUNDING) ................... 86 4.8 ORAL SOLID DOSAGE (POTENT COMPOUNDING) ....................... 89 4.9 ASEPTIC PROCESSING FACILITY .................................. 91 4.10 PACKAGING/LABELING ........................................... 94 4.11 LABS ......................................................... 95 4.12 SAMPLING/DISPENSING .......................................... 99 4.13 ADMINISTRATIVE AND GENERAL BUILDING ......................... 100 4.14 WAREHOUSE ................................................... 101 4.15 PROCESS EQUIPMENT CONSIDERATIONS ............................ 102 DESIGN QUALIFICATION / DESIGN REVIEW (DQ/DR) .................... 106 5.1 DESIGN REVIEW/ DESIGN VERIFICATION/DESIGN QUALIFICATION ..... 106 5.2 INTRODUCTION ................................................ 108 EQUIPMENT FUNCTION, INSTALLATION, AND OPERATION ................. 117 6.1 EQUIPMENT FUNCTION AND MANUFACTURE .......................... 117 6.2 EQUIPMENT INSTALLATION AND STARTUP .......................... 147 6.3 EQUIPMENT OPERATION AND MAINTENANCE ......................... 156 VERIFICATION AND TESTING ........................................ 165 7.1 INTRODUCTION ................................................ 165 7.2 PHILOSOPHY .................................................. 165 7.3 PRINCIPLES .................................................. 166 7.4 REGULATORY EXPECTATIONS ..................................... 167 2
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129
JULY 2008
7.5 KEY CONCEPTS OF VERIFICATION ................................ 7.6 DESIGN, SPECIFICATION, VERIFICATION, AND ACCEPTANCE PROCESS . 7.7 SUPPORTING PROCESSES ........................................ 8 DOCUMENTATION REQUIREMENTS ...................................... 8.1 INTRODUCTION ................................................ 8.2 ENGINEERING DOCUMENT LIFECYCLE .............................. 8.3 DOCUMENTS FOR MAINTENANCE AND OPERATIONS (NON-GMP) .......... 8.4 MASTER/RECORD DOCUMENTS ..................................... 8.5 GMP HVAC DOCUMENTS .......................................... 9 PSYCHROMETRICS .................................................. 9.1 DRY-BULB TEMPERATURE ........................................ 9.2 WET-BULB TEMPERATURE ........................................ 9.3 DEW-POINT TEMPERATURE ....................................... 9.4 BAROMETRIC OR TOTAL PRESSURE ................................ 9.5 SPECIFIC ENTHALPY ........................................... 9.6 SPECIFIC VOLUME ............................................. 9.7 EIGHT FUNDAMENTAL VECTORS ................................... 10 COMMISSIONING AND QIUALIFICATION PROCESS ...................... 10.1 COMMISSIONING AND QUALIFICATION ............................. 10.2 IMPACT RELATIONSHIPS ........................................ 10.3 RISK ASSESSMENT MATRIX ...................................... 11 MISCELLANEOUS HVAC INFORMATION ................................ 11.1 GLOSSARY OF TERMS ........................................... 11.2 EQUATIONS USED IN HVAC AND THEIR DERIVATION ................. 12 REFERENCES .................................................... 12.1 SUMMARY OF USEFUL CLEANROOM EQUATIONS ....................... 12.2 PRESSURE CONTROL WHEN AIRLOCKS ARE NOT POSSIBLE ............. 12.3 HEPA FILTERS FOR HOT ZONES (DEPYROGENATION) ................. 12.4 USEFUL REFERENCE MATERIALS .................................. 12.5 HVAC EXAMPLES AND WORKBOOK (???) ............................ 12.6 EXAMPLE DOCUMENTS ...........................................
3
167 169 170 172 172 172 173 173 174 176 176 176 177 179 179 180 183 185 185 186 187 188 188 188 195 195 196 196 196 196 196
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182
1
INTRODUCTION
1.1
BACKGROUND
JULY 2008
The heating, ventilating, and air conditioning (HVAC) system is one of the more critical systems affecting the ability of a pharmaceutical facility to meet its key objectives. HVAC systems which are properly designed, built, operated, and maintained can help ensure the quality of product manufactured in that facility, improve reliability, and reduce both first cost and ongoing operating costs of the facility. The design of HVAC systems for the pharmaceutical industry requires special considerations beyond those for most other industries, particularly in regards to cleanroom applications. Each of the previously published ISPE Baseline® Guides for facilities (Active Pharmaceutical Ingredients, Oral Solid Dosage, Sterile Products Manufacture, Biopharmaceuticals, etc.) have included some discussion of the considerations for HVAC systems for facilities of that type. This Good Practice Guide is intended to supplement those sections with more detailed information and recommended practices for implementation of HVAC systems in pharmaceutical facilities.
1.2
SCOPE OF THIS GUIDE
The Guide provides supporting information facility types covered by Baseline Guides.
and
HVAC
practices
for
The Guide provides an overview of the basic principles of HVAC only to the extent required to facilitate a common understanding and consistent nomenclature. This guide addresses facility lifecycle.
HVAC
requirements
in
the
following
areas
of
Establishing User Requirements Design Construction Commissioning / Qualification Operation / Maintenance Redeployment for other use Decommissioning
The guide does NOT serve as a handbook for HVAC design (e.g. it does not discuss the details of sizing and selection of equipment. It does go into boring detail on the physics of air and humidity.) The guide clarifies HVAC issues critical to the Safety, Identity, Strength, Purity and Quality (SISPQ) for the production of bulk and finished pharmaceuticals and biopharmaceuticals, and it considers the requirements for HVAC control and monitoring systems. This guide addresses how to implement the recommendations in the Baseline guides to meet FDA and EMEA regulatory expectations for HVAC 5
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235
JULY 2008
design. This guide references but does NOT reiterate the issues or content from the Baseline guides. The appropriate Baseline Guide should be consulted for regulatory expectations. The guide discusses the impact of external conditions on HVAC design. This guide attempts to give information in I/P and SI units. The user of this guide should apply good engineering practice in assessing which of the recommended practices is most applicable to a situation.
1.3
OBJECTIVES OF THIS GUIDE
Provide the Pharmaceutical Engineering Community with common language and understanding of critical HVAC issues. Provide issues.
guidance
on
accepted
industry
practices
to
address
Provide a single common resource for HVAC information included in appendices of the various Baseline© guides. Target a global audience, with particular European (EMEA) regulated facilities.
1.4
focus
on
US
these
currently (FDA)
and
DEFINITIONS
This GPG uses terms as defined in the ISPE Glossary of Pharmaceutical Engineering Terminology and will not repeat these definitions here. Only new terms or terms specific to the content of this GPG are defined in the Glossary.
1.5
REFERENCES
a. ISO Standards for Cleanrooms and Associated Controlled Environments
ISO 14644-1 Classification of air cleanliness ISO 14644-2 Specifications for testing and monitoring to prove continued compliance with ISO 14644-1 ISO 14644-3 Test methods ISO 14644-4 Design, construction and start-up ISO 14644-5 Operations ISO 14644-6 Vocabulary ISO 14644-7 Separative devices (clean air hoods, glove boxes, isolators, and mini-environments) ISO 14644-8 Classification of airborne molecular contamination ISO 14698-1 Biocontamination control, Part 1: General principles and methods ISO 14698-2 Biocontamination control‘ Part 2: Evaluation and interpretation of biocontamination data. 6
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287
JULY 2008
b. IEST Recommended Practices
RP-CC034.2- HEPA and ULPA Filter Leak Tests RP-CC006.3- Testing Cleanrooms RP-CC012.1- Considerations in Cleanroom Design
c. ISPE Baseline Guides
Vol. Vol. Vol. Vol. Vol. Vol.
123456-
Active Pharmaceutical Ingredients Oral Solid Dosage Forms Sterile Manufacturing Facilities Water and Steam Systems Commissioning and Qualification Biopharmaceuticals
d. ASHRAE- specific ASHRAE documents which are used in this GPG:
ASHRAE standard 62.1 - Ventilation for Acceptable Indoor Air Quality ASHRAE standard 90.1 - Energy Standard for Buildings Except Low-Rise Residential Buildings ASHRAE standard 110 - Method of Testing Performance of Laboratory Fume Hoods ASHRAE Handbooks - Fundamentals; Applications; Systems & Equipment
e. ASTM Standard E2500-07 - Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment f. US FDA Guidance for Industry ―Sterile Drug Products Produced by Aseptic Processing- Current Good Manufacturing Practice‖ (2004) g. EudraLex Volume 4 ―EU Guidelines to Good Manufacturing Practice‖
‗Medicinal Products for Human and Veterinary Use‘ Annex 1: Manufacture of Sterile Medicinal Products Annex 2: Manufacture of Biological Medicinal Products for Human Use
h. The Good Automated Manufacturing Practice (GAMP) Guide Validation of Automated Systems in Pharmaceutical Manufacture i. WHO document document.
on
HVAC-
proposed
draft,
does
not
apply
to
for this
j. CFR Title 21 Food & Drugs
Part 11: Electronic records Part 210: Current good manufacturing practice in manufacturing, processing, packing or holding of drugs; general Part 211: Current good manufacturing practice for finished pharmaceuticals
7
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 288 289 290 291 292 293 294 295
JULY 2008
k. FDA Guidance for Industry/ICH Guidelines
Q7A: Good manufacturing practice guidance for active pharmaceutical ingredients Q8: Pharmaceutical Development Q9: Quality Risk Management Q10: Quality Systems
8
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348
2
FUNDAMENTALS OF HVAC
2.1
INTRODUCTION
JULY 2008
Most people live in homes with equipment incorporated into the building to keep them comfortable. They have windows to allow natural ventilation and heating and cooling systems to maintain desired temperatures. We have the same goal in our pharmaceutical manufacturing workplace – to make people comfortable, but we also have the more exacting requirement to control the impact of the environment on the finished product (i.e., product SISPQ). This guide introduces the fundamentals of the HVAC systems that control the GMP workplace environment. Only three room environment variables may have an effect on product and processes (at the ―critical locations‖):
Air temperature at the critical location may affect product or product contact surfaces Relative humidity of the air at the critical location may affect product moisture content, or may affect product contact surfaces (via corrosion, etc.) Airborne contamination at the critical location (may affect product purity or product contact surfaces)
Some variables, such as local contaminants, depend on other HVAC variables such as room pressure, air changes, airflow volume, airflow direction and velocity, and air filter efficiency.
2.2
WHAT IS HVAC?
HVAC (Heating, Ventilation and Air Conditioning) is the generic name given to a system that provides the conditioning of the environment through the control of Temperature, Relative Humidity, Air Movement and air quality - including fresh air, airborne particles, and vapors. HVAC systems can increase or decrease temperature, increase or reduce the moisture or humidity in the air, decrease the level of particulate or gaseous contaminants in the air. These abilities are employed for comfort and to protect people and product. 2.2.1 People Comfort The first role of HVAC systems is to make people comfortable. We notice the HVAC system‘s performance when we are uncomfortable, but what conditions are actually required to make people comfortable? Four criteria are commonly considered for people comfort:
Temperature Humidity Air quality (contaminants, both particles and odors)
9
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366
JULY 2008
Air movement (airflow direction and speed to control ―drafts‖)
2.2.1.1 Temperature and Humidity The following drawing shows two boxes which define "comfort" conditions (Temperature and Humidity) that Americans find comfortable in winter and summer (from the ASHRAE Handbook). This standard varies across the world - for example, in parts the tropics people prefer an office at 75 degrees F (24 degrees C) to one at 72 F (22°C). It should also be noted that these are general guidelines, as many things affect these conditions apart from individual preferences - the type and consistency of work being performed, for example. This is apparent in the office workplace, with the different levels of clothing people wear, some people dressed more heavily than others in order to be comfortable
367
10
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385
386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412
JULY 2008
Figure 2-1 Standard Effective Temperature and ASHRAE Comfort Zones courtesy of ______________________ 2.2.1.2 Air Movement Some people prefer a light sensation of air movement and some prefer still air, so a typical design figure of 0.1 m/s (3 ft/sec) is used in an office environment. Greater air velocities are usually needed for product protection. 2.2.1.3 Air Quality People need fresh air to dilute exhaled carbon dioxide and other environmental contaminants. The amount of fresh air required depends on the activity; the table below shows typical oxygen use for different levels of activity. Level of exertion
Oxygen consumed L/min
Light work
LT 0.5
Moderate work
0.5 to 1.0
Heavy work
1.0 to 1.5
Very heavy work
1.5 to 2.0
Extremely heavy work
GT 2.0
Table2-1 Oxygen Consumption by activity Level The amount of fresh air required to dilute environmental contaminants is a minimum of 15 to 20 cubic feet per minute (cfm) or 24 to 32 cubic meters per hour per person . 2.2.2 Product and Process Considerations Product may be sensitive to temperature and humidity and to airborne contamination - from outside sources or cross-contamination between products. Process operators may need protection from exposure to hazardous or potent materials It is usually possible to find the product‘s environmental requirements, as they will be listed in the NDA when they are considered critical. The impact of conditions outside these ranges will depend on the duration of exposure – prolonged exposure time may reduce the efficacy of the product. Control of airborne cross contamination and contamination are always major issues. These requirements are often interlinked with temperature and humidity – consider the effect of temperature for example; Comfortable people work more efficiently – they are more productive, and make fewer mistakes. They also produce fewer environmental contaminants: A typical person will give off 100,000
11
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467
JULY 2008
particles a minute doing relatively sedentary work (particles sized 0.3 micron and larger – a human hair is approximately 100 micron in diameter). A worker who is hot and uncomfortable may shed several million particles per minute in this size range, including more bacteria. Environmental conditions inside a building can influence the product in other ways – higher temperatures and humidity tend to increase microbial growth rates, particularly with regard to mold. If building conditions are significantly different from those outside and the fabric of the building does not have sufficient integrity, condensation in interstitial spaces can occur and can lead to microbial contamination problems and deterioration of the building. Operator protection also depends on air flow direction both within and between rooms. Airflow can entrain particles of product, product in other rooms, or other hazardous materials harmful to operators. Though differential pressure is commonly used as a control of contamination between two rooms, it is the airflow generated by the differential pressure that contains the product 2.2.3 How does the HVAC system control these parameters? 2.2.3.1 Temperature and Humidity The HVAC system controls the temperature and humidity in the room using the mechanism of supplying the room with air at a condition that, when mixed with the room air, will yield the desired temperature and humidity. The heat gains and losses to and from the space are through the usual mechanisms of heat transfer - Radiant, conductive and convective heat transfer. These may be due to solar gain, external temperature outside the facility, and internal heat gains due to the process, equipment, people and lighting. The changes in humidity are due to the process, people and the environment. Moisture migration into the controlled space from surrounding areas is governed by the difference in vapor pressure, as defined by Dalton‘s law, and can sometimes migrate against an air pressure differential 2.2.3.2 Air velocity In a working environment, air velocity is not as critical in terms of human comfort as it is in an office environment. Velocity is critical to proper mixing of air within the room and transport of airborne particulates. 2.2.3.3 Particulate/fume and vapor control The control of the particulate levels in the room, and in some cases vapors/fumes, may be by dilution and displacement, controlling the particulate levels in the supply air through filtration, and vapor/fume 12
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522
JULY 2008
level by the use of exhaust and replacement (makeup) fresh air where necessary. 2.2.4 What can‘t the HVAC System do? HVAC systems are not a substitute for good process, facilities and equipment design and good operating procedures. HVAC can not clean surfaces that are already contaminated, and as a practical matter, it cannot control processes that generate an excess of contaminants or compensate for improperly designed or maintained facilities. HVAC, while a common suspect area for investigation, is rarely the cause - or the solution - for persistent contamination problems.
2.3
AIRFLOW FUNDAMENTALS
2.3.1 Introduction As was discussed in section 2.1, HVAC can contribute to the control of temperature, humidity, and particulates within a space. In order to understand what equipment is needed to achieve this at the HVAC system level, we must first define what the air is intended to do at the room level. Both the quality (temperature, humidity, filtration) and quantity of air introduced into a room affect its ability to maintain environmental conditions. This explores the effects of physical layout (geometry), air velocity and air volume in assuring effective ventilation. 2.3.2 Ventilation Fundamentals Ventilation is the movement and replacement of air for the purpose of maintaining a desired environmental quality within a space. Ventilation is responsible for the transport of airborne particles, the movement of masses of hot or cold air, the removal of airborne contaminants (e.g., vapors and fumes) and the supply of ―fresh‖ O2 rich air. Although the layman may be conscious of the term ―air change rates‖ (more properly called ―ventilation rate‖), successful pharmaceutical HVAC design can be attributed to proper filtration and attention to the physical geometry of airflow in a space. The layout of inlets and outlets with relation to the sources of contamination/heat and accommodation for expected obstructions are key to controlling contamination and yielding effective HVAC design. The relationship between these factors is expressed in the ―effective ventilation rate‖ for a space. This measure expresses the efficiency of the HVAC system at removing contaminants expressed as a % of the theoretical performance of perfect dilution. When comparing the effective ventilation rates of various designs, it becomes clear that good layout and filtration can produce desired airborne particulate levels and recovery rates at lower than expected air change rates. 2.3.3 Contamination Control The primary factor that separates pharmaceutical HVAC from comfort HVAC is the need to control contamination. This stems from the need to 13
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577
JULY 2008
assure the ―…purity, identity and quality…‖ of the product (21CFR211). Pharmaceutical HVAC is one tool in preventing unwanted environmental contaminants from adversely affecting a product and to prevent products from contaminating one another. It can also assist in limiting operator exposure to potent pharmaceutical compounds, ingredients or reagent vapors. Contamination control is generally achieved by filtering the incoming air, to assure that it does not carry particulates, and then introducing the air to the work space at sufficient velocity and volume to transport unwanted particulate out of the work zone. The orientation of these airflows can aligned so as to protect product or personnel by sweeping across one or the other (or both) on its way from the supply terminal to the extract point. Local supply or extraction can also assist in contamination control by creating a local environment that excludes or removes particulate. Pharmaceutical HVAC can help control contaminants within a space, but these facilities must be designed with several additional features that contribute to this mission of limiting the migration of contaminants. 2.3.4 Airlocks In order to minimize the amount of air that is needed to maintain particle transport velocities (typically over 100fpm times 21 square feet of open door area equals 2100 cfm) it is desirable that the doors of a contamination controlled space remain closed. One way to do this is to provide airlocks or ―ante rooms‖. These rooms control traffic into and out of a space through a series of interlocked doors to assure that a door to the space is always closed. Airlocks serve other purposes as well:
they maintain some differential pressure between the two areas they serve, such that the DP can not drop to zero they provide a location for gowning/de-gowning prior to entering/exiting a classified space they provide a location for sanitizing / decontamination of incoming or outgoing materials and equipment they can be designed with a small volume and high air change rate to allow them to recover quickly and function to minimize the particulate introduced to a classified space by door openings. they provide can provide a high or low pressure buffer to control the ingress and egress of contaminants.
2.3.5 Classified Space A key measurement of room environmental conditions for pharmaceutical operations is the concentration of total airborne particulate and/or microbial contamination within the space; this is referred to as the ―classification‖ of the space. Several systems have been promulgated for the classification of space; however there is not consensus between international regulators on a single best standard for classification. To bridge the gap between the various standards, this guide provides the following reference to be used across facility types requiring air classification, (primarily facilities for sterile/aseptic manufacture and for controlled bioburden processing, such as bulk 14
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 578 579 580 581
JULY 2008
biopharmaceuticals). It should not be used for other facilities, such as bulk chemical intermediates or oral dosage finishing. See the appropriate Baseline Guide for specific air quality information.
15
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 582 REFERENCE ISPE STERILE BASELINE GUIDE
JULY 2008
DESCRIPTION
CLASSIFICATION
ENVIRONMENTAL CLASSIFICATION
GRADE 5
GRADE 7
GRADE 8
Controlled Not Classified with local monitoring
Controlled Not Classified
Descriptive Grade
A (Note1)
B
C
D
Not defined
0.5μ
3 500
3 500
350 000
3 500 000
-
5μ
1
1
2 000
20 000
-
0.5μ
3 500 (Note 3)
350 000
3 500 000
Not stated
-
5μ
1
2 000
20 000
Not stated
-
Maximum permitted number of viable organisms cfu / m3
< 1
< 10
< 100
< 200
-
Maximum particl es permitt ed stated size
ISO 5 Class 100
ISO 7 (Class 10 000)
ISO 8 (Class 100 000)
-
-
Draft 2008 European Commission EU GMP, Annex 1, Volume lV, Manufacture of Sterile Medicinal Products (1997) also PIC/S GMP Annex 1 2002
FDA, October 2004, Guidance for Industry Sterile Drug Products Produced by 583 584 585 586
At Res t (No te 2) In Ope rat ion
In Ope rat ion
Maximum no. particles permitted per m3 ≥ the stated size Maximum no. particles permitted per m3 ≥ the stated size
no. ≥ the
0.5 μ
Table 2-2 Comparison of Classified Spaces
16
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640
JULY 2008
Pharmaceutical HVAC can help control contaminants within a space, but these facilities must be designed with several additional features that contribute to this mission of limiting the migration of contaminants. 2.3.6 Total Airflow Volume and Ventilation Rate Much has been made of the importance of ―air change rate‖ (volume of air/hour ’ room volume) or ―ventilation rate‖, the number of times in an hour that the air volume of a room is replaced. Little is said about the relationship between these rates and the classification of the space, recovery rates and the more important issue of total volume of ventilation. When considering the design of classified first consider the requirement for 20 expressed in the 1987 FDA Sterile Guide. airflow required by the process, many will for ventilation rate by the class of space,
space, designers will often Air Changes/hour (AC/hr), In lieu of calculating the default to ―rules of thumb‖ typically in the ranges:
15-20 AC/hr for Controlled, Not Classified (CNC) spaces 20-40 AC/hr for Grade 8 (EU Grade C) 40-60 AC/hr for Grade 7 (EU Grade B) 300-600 AC/hr for Grade 5 (EU Grade A)
As seen below, these rules of thumb may be overkill, or may prove to be insufficient. The airborne particle levels depend more on a number of factors. 2.3.6.1 Air change or Air Flow? These air change rates often drive decisions regarding room size and airflows, and can have significant cost implications, but do not relate directly to the particle count in the room. Air change rates are related to the room‘s ability to recover from an upset, not the room classification – as is commonly assumed. To explain this difference: Assume a 1 cubic foot volume with a process inside it that generates 10,000 particles per minute. If we purge the volume with 1 cubic foot per minute of clean air, the steady state (equilibrium) airborne particle level will be 10,000 particle per cubic foot (see the Appendix for equations). This 1 CFM creates an air change every minute, or 60 air changes per hour. This value (60/hr) is often assumed to be more than enough to keep a space well below 10,000 particles per cubic foot (PCF). Now put the same process into a 100 cubic foot volume and keep the airflow at 1 cfm, assuming good mixing inside the room. Now the room sees an air change every 100 minutes, or about 0.67 ac/hr. Yet, when we calculate the dilution, the equilibrium airborne particle counts are still 10,000 PCF (10,000 particles per minute divided by 1 cubic foot per minute = 100 particles per cubic foot). If we would supply 1 air change per hour (100 CFM) of clean air, the room airborne counts drop to 100 PCF !!! So it‘s not air changes that determine airborne particle
17
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695
JULY 2008
counts, but three factors (referring to the Appendix): 1. Particles generated inside the space 2. Quantity of dilution air supplied to the space (cubic volume per time) 3. Cleanliness of dilution air (assumed to be negligible in pharma due to HEPA filtration) As is demonstrated elsewhere, a room receiving only 1 air change per hour will take hours to ―recover‖ from in-use to at-rest conditions. With clean air supply of 20 air changes per hour, a 100-fold recovery in particle levels can happen in less than 20 minutes (see the ISPE Sterile Baseline Guide). So when it comes to RECOVERY, air changes ARE important, 20/hr often being the minimum for classified spaces. Although the layman is conscious of the importance of ―air change rate‖ (more properly called ―ventilation rate‖) successful pharmaceutical HVAC design can be attributed to proper filtration and attention to the physical geometry of airflow in a space. 2.3.6.2 Impact of UDF (UFH) hoods on air change rates Later sections will discuss ―mixed flow‖ rooms with clean air supplied at the ceiling through terminal filters as well as clean air being introduced to the room from Unidirectional Flow Hoods (UFH or UDF, once called ―Laminar Flow‖) operating inside the room. Since air leaving the space served by the hood is often orders of magnitude cleaner than the room it leaks into, the relatively clean hood air serves to dilute airborne particles in the room, along with the supply air from the HVAC. In many respects the added flow from the hood not only reduces airborne particles in its path, but can also accelerate the recovery time of the room from in-use to at-rest conditions. The entire flow from the hood will likely not be available to add into air change calculations, however, due to:
Short circuiting of the hood air back to the hood inlet. Only areas near the airflow path will see the added dilution. Hood air is not as clean as HVAC supply air. Even though the hood might be rated as Grade 5 (class 100) the air leaving the work space has collected additional contaminants from equipment and people outside the critical zone.
2.3.7 Room Distribution and Quality of incoming air The layout of inlets and outlets with relation to the sources of contamination and accommodation for expected obstructions are key to controlling contamination and yielding effective HVAC design. The relationship between these factors is expressed in the ―effective ventilation rate‖ for a space. This measure recognizes that good layout and filtration can produce desired airborne particulate levels and recovery rates at lower than expected air change rates. Taking the example above, good air mixing (dilution) and faster recovery can be accomplished in a room where clean air supply is distributed over a high percentage of the ceiling and not just from one 18
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750
JULY 2008
air outlet. Although it‘s not necessary to create a ―laminar flow ceiling‖, numerous air outlets equally spaced with equal flow rates can create a ―plug flow‖ for faster recovery (often less than 10 minutes for 20 ac/hr) and also prevent ―hot spots‖ of high particle count in the room. 2.3.8 Airflow Direction and Pressurization Since constructing a space that is totally airtight is not practical is normal construction, other means must be provided to assure that particulate can be prevented from migrating into or out of a space. Assuring that air is always flowing in the desired direction through the cracks in building construction (door gaps, wall penetrations, conduits, etc.) can influence contamination through the transport of airborne particulates. A velocity of 1-200 FPM will contain light powders and bioburden One method to control this direction of airflow is by controlling the relative pressurization of adjacent spaces or the Differential Pressure (DP) between the spaces. A simplified method (neglecting the orifice coefficient for the opening) to calculate the expected velocity of airflow from a given pressure is: V = 4005 (sqrt VP) or VP =(V/4005) (where V is velocity in ft/min, VP is pressure difference in inches w.g., A is area of the opening in square feet, Q is airflow in CFM) – We can breakdown velocity as being volume divided by area, giving V = Q/A, or VP = (CFM/4005A) 2 – Assuming room DP converts fully to Velocity Pressure thru an opening (a conservative assumption), calculating the opening area, such as the crack area around a closed door between rooms, allows calculation of the airflow (CFM) required to create a pressure, or the velocity that results from a known DP. – For A=1 sq foot (0.1 sq.M) opening, 890 CFM (about 1500 CuM/hr or 0.45 CuM/sec) will create 0.05" w.g. (12.5 Pa) differential pressure (V = Q/A = 890 FPM = 4.5 M/s)
2.4
PSYCHROMETRICS
2.4.1 Introduction Psychrometrics is the science that involves the properties of moist air (a mixture of dry air and water vapor) and the process in which the temperature and/or the water vapor content of the mixture are changed. Psychrometrics – ―psychro‖ means moisture and ―metrics‖ means to measure. A psychrometric chart is used to identify conditions of air and to illustrate the process of achieving the desired state of the controlled space. An in-depth knowledge of psychrometrics is impossible 19
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802
JULY 2008
to impart in this document; the reader is referred to other sources such as the ASHRAE Fundamentals Handbook. 2.4.2 Basic Properties of Air 2.4.2.1 Dry air is comprised of 78.1% nitrogen, 21% oxygen, and has trace amounts of ten additional elements totaling 0.9%. The air around us is a mixture of dry air and water vapor. When this moist air reaches a level at which it can not hold any more moisture, it is said to be, ―saturated‖. The colder the air, the less moisture which can be held in the air while warmer air can hold larger quantities of moisture in the air. 2.4.2.2 The moisture in dry air (its specific humidity) is measured in grains of moisture per pound of air (7,000 grains equal 1 pound). Air at 75°F and 60% RH has a specific humidity of 78 grains of water per pound (7000 grains) of dry air. Therefore, one pound of this air contains 77 grains of water and 6923 grains of dry air. 2.4.2.3 A psychrometric chart provides an overview of thermodynamic properties of air-water mixtures, and shows the relationships of air at different conditions. If any two properties of the air mixture are known, the chart allows an engineer to determine all its other properties. Air-water vapor mixtures have interrelated psychrometric properties that can be plotted on a psychrometric chart. (See Appendix for psychrometric chart discussion). 2.4.2.4 Sensible heat causes a change in the temperature of a substance. Sensible heat can be ―sensed‖ or felt and quantified by measurement with a dry bulb thermometer. Addition or removal of sensible heat will cause the measured temperature to rise or fall. Sensible heat shows on the psychrometric chart as a horizontal line; there is no resulting change in the amount of water vapor in the air. 2.4.2.5 Latent Heat comes from the Latin word meaning ―hidden‖. Changes in latent heat are neither ―sensed‖ or felt; however they will cause a change of state in the substance. Latent heat is the heat required to evaporate the moisture which the air contains. For example, if sufficient latent heat is added to water in the liquid state, it will change state into a vapor or steam. The change of state from a liquid to steam is called the ―latent heat of vaporization‖ and from a steam to a liquid is called ―the latent heat of condensation‖. The change of state from a liquid to a solid is called ―the latent heat of fusion‖ and from a solid to liquid the ―latent heat of melting‖. Latent heat appears on the psychrometric chart as a vertical line. 2.4.3 Psychrometric Properties of Air See the Appendix for a discussion of the terms used in Psychrometrics and for an explanation of the Psychrometric Chart.
20
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Measurable Psychrometric Properties Dry-bulb temperature
tDB
Calculable Psychrometric Properties Specific enthalpy
h
Wet-bulb temperature
tWB
Specific volume
v
Dew-point temperature
tDP
Humidity ratio
Relative humidity
803 804 805 806 807 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825 826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849
RH PBAR Barometric pressure Table 2-3 Psychrometric Terminology
2.5
Water vapor pressure
W p WV
EQUIPMENT
2.5.1 Introduction Each piece of HVAC equipment helps contribute to sustaining the user requirements for room environmental conditions. HVAC equipment serving GMP areas are intended to work in conjunction with associated controls and sequences of operation systems to:
Maintain room temperature Maintain room pressurization and differential pressure cascades Provide make up air for ventilation and room pressurization Condition the air stream to remove and/or add moisture content of the air Minimize airborne contamination to the condition space Provide required air change rates to maintain room cleanliness classification when required
The following major components of an HVAC system for GMP spaces are discussed in more depth in Chapter 6. 2.5.2 Air Handling Unit (Ahu) An equipment package that includes a fan or blower, heating and/or cooling coils, air filtration, etc. for providing heating, ventilation, and air conditioning (HVAC) to a building. 2.5.3 Fan An electrically driven air moving device used to supply, return or exhaust/extract air to or from a room through ductwork to generate air in sufficient amounts to provide ventilation, heating, cooling or to overcome air pressure losses. 2.5.4 Fume Exhaust/Extraction System A system made up of ductwork, fans and possibly filters that discharges unwanted air outside into the atmosphere to a safe distance from buildings and people. 2.5.5 Heating Coil A heat transfer device consisting of a coil of piping which increases the sensible heat into an air stream, using steam or hot water or 21
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 850 851 852 853 854 855 856 857 858 859 860 861 862 863 864 865 866 867 868 869 870 871 872 873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 897 898 899 900 901 902 903 904
JULY 2008
glycol as the heating medium. And electric air-heating element can also be called a ―heating coil‖. 2.5.6 Cooling Coil A heat transfer device consisting of a coil of piping, which reduces the sensible heat and possibly latent heat (via condensation of water vapor) from the airstream using chilled liquid or refrigeration as the cooling medium. 2.5.7 Humidifier A device to increase the humidity within a controlled space by means of the discharge of water vapor into the supply air stream or directly into the room. 2.5.8 Dehumidifier A special humidity.
device
that
removes
water
vapor
from
the
air
to
reduce
2.5.9 Air Filtration Devices to remove particulate material from an airstream by means of various media types. 2.5.10
Ductwork
A network of air conduits distributed throughout a building, connected to a fan to supply, return or exhaust/extract air to or from zones in a building. 2.5.11
Damper And Louver
2.5.11.1 Found in ductwork, a damper consists of a movable plate(or numerous plates), plunger, or bladder that opens and closes to regulate airflow. Dampers are used to regulate airflow to certain rooms. 2.5.11.2 A louver is an assembly of sloping vanes intended to permit air to pass through and to inhibit transfer of water droplets from outdoors into air systems. A louver may also be found in return air ductwork at room interfaces. 2.5.12
Diffuser And Register
Air distribution outlet or grille designed to introduce air to a space using direct airflow in desired patterns. Air diffusers are usually located to distribute the air as uniformly as possible through out a space. 2.5.13
Ultraviolet (UV) Light
A UV light uses microorganisms.
precise
ultraviolet
22
light
wavelength
to
destroy
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Air Handler
X
X
X
Fan Fume Systems
Heating Coil Cooling Coil
Airflow
X
X
X
X
Exhaust/Extract
Air Quality
Static Room Pressure
Humidification
Cooling
Heating
Equipment
Dehumidification
905
X
X
X
X X
X
Air Filter
X
Humidifier
X
Dehumidifier
X
Ductwork
X
X
Damper & Louver
X
X
Diffuser & Register
X
UV Light 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928 929
X
TABLE 2-4 System components and their primary function relating to environmental parameters
2.6
HVAC SYSTEM CONFIGURATION
2.6.1 Introduction This section gives a brief overview of the key factors to consider, the options available to an HVAC system designer, and the factors influencing the decision to choose a particular system type. This section should be read in conjunction with section APPLICATIONS BY PROCESS AND CLASSIFICATION‖.
4
―HVAC
One question to answer is ‗how many Air Handling Units should be used‘? It is common practice to divide a manufacturing area into zones, and use a separate Air Handling Unit per zone – a zone in general Building Services design would be an area with similar heat gains and losses, a similar approach is used within the pharmaceutical industry – and is usually considered as an area with one type of manufacturing process or area classification, e.g. a tablet compression suite or all Grade 7 areas, as the area requirements will be similar. Other factors that are 23
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954
JULY 2008
considered when dividing a facility into zones include:
Use of multiple units improves reliability of the area – it would be unusual for all of the units to fail. The use of multiple smaller units might make air balancing easier The use of multiple smaller units means that the main distribution ducts are smaller, making then easier to route in small ceiling voids. It is easier to make modifications to parts of the facility in future and upgrade a small unit than change a large single unit Use of multiple units allows for easier separation of areas within a multi-product concurrent manufacturing plant.
The decisions regarding AHU system zoning are very important as a factor in subsequent facility commissioning, qualification and related documentation. 2.6.2 Basic System Types There are three basic categories of HVAC system; 2.6.2.1 Once through - uses treated outside air to provide the design internal conditions, this air is then extracted from the space and discarded.
Outdoor air
Supply air
Air Handler Unit
(AHU)
Exhaust
Infiltration
Room
Exfiltration 955 956 957 958 959 960 961 962 963
Figure 2-2 Once-through HVAC Advantages of this system:
This system provides an abundance of O2 rich fresh air to dilute contaminants The system can handle hazardous materials, though the extracted air 24
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987
JULY 2008
may need treatment before it is discarded. Lower risk of cross contamination of products from another room via HVAC Exhaust fan may be located remote from the AHU making duct routing simpler As there are less concerns about the ductwork noise in the extract ductwork, it can usually be sized for a high velocity, making it easier to route as high velocity = smaller diameter
Disadvantages of this system:
More expensive to operate than an equivalent recirculating system, especially when cooling and heating. Filter loading very high = frequent replacement Potential need for exhaust air treatment (scrubbers, dust collectors, filters) Room conditions more difficult to maintain
2.6.2.2 Recirculating systems - This category is much more common – the room supply air is made up of a percentage of treated outside air mixed with some of the air extracted from the space. A percentage of the air is either discarded or lost through leakage to adjacent areas, due to local area pressurization.
Makeup (Fresh) air
Supply air
Air Handler Unit (AHU)
Possible extract
Room
Return air
Exfiltration 988 989 990 991 992 993 994 995 996 997
Infiltration Figure 2-3 Recirculated HVAC Advantages of this system:
Usually less air filter loading = lower filter maintenance and lower cost opportunity for higher grade air filtration Lower energy cost than once through Less challenge to HVAC means that it is simpler to obtain better 25
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015
JULY 2008
control of parameters (T, RH, etc) Disadvantages of this system:
Return air ductwork routing to air handler may complicate above ceiling Chance of cross contamination via HVAC = Requires adequate supply air filtration (and sometimes return air filtration to prevent contamination of the air handler) Chance of recirculation of odors and vapors and of inadequate fresh air supply
2.6.2.3 Exhaust (Extract) system – sometimes a stand-alone system that removes airborne contaminants, either solid particles or gasses/vapors. It may be interlinked to a once-through or recirculated air supply system. Used alone, the extract/exhaust system will create a negative differential pressure in the room or enclosure it serves
Air cleaner Fan Infiltration duct leakage
Stack (follow 1.3x rule of thumb if "foul air"… see ASHRAE)
Exfiltration duct leakage
Ductwork "Space" with airborne contaminants 1016 1017 1018 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 1031 1032 1033
Space may be a room, a glovebox or an exhaust hood Figure 2-4 Exhaust System Advantages of this system:
Simple to operate. Makeup air is pulled from surrounding spaces.
Disadvantages of this system:
If used to capture large quantities of contaminants, such as from open processes, a large energy cost will be associated with conditioned air being thrown away (see once-through system above).
2.6.2.1 Use of Air Handling Units in parallel or series It is possible to put units in series, for example if a higher air pressure is required to offset the pressure drop through HEPA filters 26
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088
JULY 2008
in one area served by an HVAC system. The use of parallel units is common practice where large areas are being conditioned, for example warehouses and large research laboratories, where this approach may make it possible to maintain acceptable conditions in the area should one unit fail. When configuring units in parallel, care must be taken to assure that the fans can be isolated and started independently. Automatic isolation dampers and variable fan drives assist in managing these factors. 2.6.2.2 Configurations and combinations The basic components and concepts outlined above can be assembled in an infinite variety of ways. Shown below are a few examples of design concepts commonly used. (Note: Add some combinations.) 2.6.3
basic
block
diagram
schematics
to
illustrate
these
Air Handling Unit Configurations
There are two basic types of AHU configuration – blow through or draw through. The term describes the relationship of the fan to the coils in the air handling unit. The two approaches have distinctive characteristics; 2.6.3.1 Blow through units Air is drawn into the unit, typically through a set of pre-filters used to reduce the dirt load on the (usually more expensive) final filters, and to prevent build up of dirt onto the heating and cooling coils, which would quickly reduce their efficiency. One advantage of this type of unit is that it allows the AHU discharge temperature to be at the cooling coil discharge air temperature, because the fan heat is removed in the cooling coil. This is particularly useful when heat loads are particularly high and supply air temperature must be as cold as possible. It is not advisable to follow a blow through unit immediately with a set of HEPA filters unless special precautions are included to prevent moisture carryover from the cooling coil. Another advantage is that if the drain trap on the cooling coil runs dry, then air will blow out through the trap – wasting a small amount of treated air. The disadvantage - the unit typically needs to be longer to allow a diffuser to be installed after the fan to ensure that the airflow is spread over the entire coil area, and not concentrated on the middle, which would cause a drop in system performance. 2.6.3.2 Draw through units These units are typically arranged with the pre-filters and coils before the fan. The advantage of this is that the unit is often smaller, and the motor and fan provide a small amount of reheat (usually 1-2 degrees F) to the air coming off the cooling coil. This 27
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105
JULY 2008
lowers the RH of the air and prevents the problems with wetting final AHU HEPA filter banks. One precaution with draw through units is that if the drain trap is dry, then untreated air can be drawn into the unit through the trap, with only the final filter to protect the conditioned environment. The design must include provisions for maintaining a wetted drain trap, which can be several inches in height. 2.6.3.3 Air Handling Unit Design variations A design variation worth considering is the use of a face and bypass damper – the concept is shown below – a portion of the air passing through the AHU is redirected through a treatment stage, with the volume altered to vary the condition of the resulting output air. This is a useful concept to use to gain improved accuracy, particularly if the treatment process is not easily controllable – e.g. chemical desiccant dehumidification.
Dehumidifier
_
1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122 1123 1124
Figure 2-5 Face and bypass control with a packaged dehumidifier and cooling coil (-) A similar concept is often employed in the first mixing box of the AHU when enthalpy control is used – in all cases careful sizing of the dampers, to ensure adequate velocity for control, is necessary to obtain proper operation of these systems, maintaining constant system volume as the proportions of the air streams are varied. 2.6.3.4 Air Handling Unit Components Numerous design options are possible within the 2 basic types. Here will establish a lexicon of design components, or modules, that can be assembled into an AHU design and discuss the motivations that drive the selection of each. To illustrate the possible options, the following demonstration uses a draw-through, Recirculating AHU:
28
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
Mixing Box
1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168
Energy Recovery Coil
JULY 2008
Humidifier
Dehumidifier
Reheating Coil
Supply Fan
Figure 2-6 Air Handler Unit Components Return Fan Most recirculating air systems will utilize a return fan. This fan allows return pressure and flow to be managed independently from the supply. This is particularly important if the downstream system has volume control boxes on both the supply and return. It also allows the return air to be diverted to exhaust when outside air conditions are closer to desired discharge conditions than return air. This function is referred to as an ―economizer‖ and is generally employed in offices or other spaces that are not pressure controlled. Mixing Box This pieced of equipment is also common in recirculating air systems. The return air can be directed to exhaust or to recirculate, it is then mixed with outside air for pressurization and/or ventilation. The resulting air stream is referred to as ―mixed air‖. In very cold environments the mixed air may be subjected to a turbulence inducing device to assure thorough mixing and avoid stratification. Prefilter or Prefilter and Intermediate Filter Filters are typically provided upstream of coils in an air handler to protect the coils from fouling with dirt or debris. The system typically employs a low efficiency ―dust stop‖ (MERV 7) filter followed by a medium or high efficiency intermediate filter (MERV 7-14). Energy Recovery Coil Once through air systems, or other systems with high amounts of exhaust may employ an energy recovery coil to return a portion of the energy employed in conditioning the exhausted air to the incoming air. These coils are typically upstream of all other coils and may be placed upstream of the filters if used to melt snow in cold climates. These systems may also employ a bypass damper to decrease pressure drop across the coil when energy recovery is not advantageous. Preheat Coil Once through air systems, or other systems with high amounts of outside 29
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223
JULY 2008
air in cold climates may employ a preheat coil to condition the incoming or mixed air. These coils are always upstream of cooling coils, to protect them from freezing and may be placed upstream of the filters if used to melt snow in cold climates. These coils do not typically impose a large pressure drop, so a bypass damper is not common. Humidifier Once through air systems, or other systems with high amounts of outside air in cold climates may employ a humidifier to inject water vapor to condition the incoming or mixed air. These devices are typically downstream of the heating coil and may even be mounted in ductwork where turbulence and high velocity promote absorption of water vapor. When employed in an AHU, mounting upstream of cooling coils provides a natural baffle to prevent carryover of liquid water droplets. Cooling Coil Cooling to maintain environmental conditions is common, if not always required in Pharmaceutical applications. These coils can eliminate both sensible and latent heat and can be upstream or downstream of the fan. If latent cooling is expected drainage of these coils is a key design issue and mist eliminators may be employed to eliminate carryover of liquid water droplets that condense on the coil. These coils do impose a large pressure drop so a bypass damper can be employed, but can pose a risk of unconditioned air leakage and non-attainment of humidity goals. Dehumidifier Dehumidifiers employ a chemical desiccant to remove moisture from the supply air stream when humidity below 30-40% is required. The dehumidifier is often located downstream of the cooling coil as they work most efficiently when airstream relative humidity is high (but within desired limits). However care must be taken to assure that excessive relative humidity or liquid water droplets do not damage the dehumidifier. The choice of desiccant may vary, depending on the application but all desiccants are regenerated using heat; therefore, air leaving the dehumidifier is both dryer and hotter than upon entering. Recool Coil These coils are only commonly installed downstream of dehumidifiers to eliminate sensible heat from the supply air. They are also employed downstream of cooling coils to provide additional latent heat removal. In this second application they operate below chilled water temperature and are typically filled with refrigerant or a low temperature brine of water and glycol (ethylene or propylene). If latent cooling is expected drainage of these coils is a key design issue and mist eliminators may be employed to eliminate carryover of liquid water droplets that condense on the coil. These coils do not typically impose a large pressure drop so a bypass damper would be unusual.
30
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257
JULY 2008
Reheat Coil Systems that require over-cooling to achieve humidity control (in lieu of dehumidification) may also employ a preheat coil to condition the air leaving the cooling coil. These coils are always downstream of cooling coils, to increase the discharge temperature of the air handler and avoid condensation in the ductwork or overcooling of the space. Supply Fan All air systems will utilize a supply fan. This fan provides the motive force for distribution of air throughout the air handling system. Final Filter Filters may be provided as the last treatment step in an air handler. These filters provide assurance of air quality (with reference to particulate) downstream of all air handling operations and are particularly valuable in protecting terminal filters from fouling with dirt or debris and in providing filtration for classified spaces. This is of particular interest in systems that employ fan drive belts which shed particulate into the airstream. Systems typically employs a high efficiency filter in this location (MER V 14+). 2.6.4 AIRLOCK STRATEGIES 2.6.4.1 PRESSURIZATION Airlocks are usually interposed between areas if airflow between the spaces needs to be controlled when they are entered or exited. Airlocks may also serve as material transfer / decontamination rooms, and gown or degown rooms. Three types of airlock pressure arrangements are indicated below:
Airlock
1258 1259 1260 1261 1262 1263 1264
"Cascade"
Airlock
"Bubble"
Airlock
"Sink"
Figure 2-7 Airlock configurations The ―cascade‖ pressurization scheme should be used when there are area cleanliness classification requirements but no containment issues, or where there are containment issues but no cleanliness classification 31
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292
JULY 2008
requirements. (i.e., cascade outward from the room for aseptic operations, but cascade into the room for hazardous compounds.) Doors are usually interlocked to allow only one to be open at a time. The normal differential from one air class to the next (ACROSS the airlock) is 10-15 Pa (0.04 to 0.06‖ w.g.). The pressure INSIDE the airlock is somewhere between the two classes, depending on which door is open. It is not necessary to have 10-15 Pa between a room and its airlock (see ―Not required‖ in the drawing below). If there are requirements for both area cleanliness classification and product containment, then the use of pressure sinks and bubbles may be necessary. Pressure bubbles are usually used for ‗clean‘ operations (i.e., such as gowning or material entry airlock) and pressure sinks are usually used for ‗dirty‘ operations‘ (i.e., de-gowning material decontamination/exit airlock). Normal design pressure differential between classifications should be 0.06― w.g. (15 Pa) with the doors closed. Pressure differential will drop momentarily while one door is opened, but will not drop to zero (as it would with no airlock or if all airlock doors were opened). In no case should pressure differential reverse. For unclassified areas the minimum suggested pressure differential is 0.02‖ w.g. (5 Pa), being the minimum reliably detectable by current pressure sensor technologies. The pressure differential is measured across the airlock, not across each door.
Airlock
0.06" w.g.
Airlock
0.06" w.g.
Acceptable
0.06" w.g. Not Required
"Cascade" Pressure Relationships 1293 1294 1295 1296 1297 1298 1299 1300 1301 1302 1303
Figure 2-8 Example of Cascade Pressure Relationships When using the ―bubble‖ pressurization scheme, the normal design pressure target, with doors closed, between classifications should be 0.06‖ w.g. (15 Pa). There may be different pressure drops across each door due to building tolerances, or adjacent room conditions, this is not considered a problem. If protecting non-sterile processing (areas not classified) a lower pressure is acceptable, but should be measurable. The pressure of the very clean airlock ‗bubble‘ is usually 32
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1304 1305 1306 1307 1308 1309
JULY 2008
designed to be about 0.02 to 0.03 in. w.g (about 5-8 Pa) above the higher of the two room pressures. The positive pressure airlock provides a robust means of segregating areas using positive airflow.
Bubble Airlock @ 0.09" w.g.
Unclassified Space @ 0" w.g.
0.09" w.g.
Clean-Contained Space @ 0.06" w.g.
0.03" w.g.
0.06" w.g. across GMP boundary
1310 1311 1312 1313 1314 1315 1316 1317 1318 1319 1320
"Bubble" Pressure Relationships Figure 2-9 Example of “Bubble” pressure relationships Similarly, with the ―sink‖ pressurization scheme, the normal design pressure between classifications should be 0.04 to 0.06‖ w.g. (10-15 Pa) with doors closed. As with the ―bubble‖ there may be different pressure drops across each door. The pressure of the contaminated airlock ‗sink‘ is usually designed to be about 0.02 to 0.03 in. w.g (58 Pa) below the lesser of the two room pressures.
Unclassified Space @ 0" w.g.
Bubble Airlock @ (-) 0.03" w.g.
0.03" w.g.
Clean-Contained Space @ 0.06" w.g.
0.09" w.g.
0.06" w.g. across GMP boundary
1321 1322 1323 1324 1325 1326 1327
"Sink" Pressure Relationships Figure 2-10 Pressure “sink” relationships It is often necessary to have pressure differentials at boundaries within the same air class area for operational reasons. The minimum operational differential between areas of the same classification 33
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1328 1329 1330 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 1381 1382
JULY 2008
(where required) is suggested to be 0.02― w.g. (5 Pa), with a design target of 0.04‖ (10Pa) suggested. It is also sometimes necessary to have directional air flows for operational reasons without a measurable pressure differential, such as may be found in non-classified areas, such as oral dosage manufacture. Pressure may be maintained across doors between air classes when no airlocks are present. However, without the added protection provided by the airlock, significant airflow volumes and pressure actuated dampers are required. (See the Appendix) This scheme should be adopted only when airlocks are not possible. The airflow leakage rate should be calculated for each room. This calculation must be based on the design pressure differential established in the project documents and not on some rule of thumb method, e.g., percentage of supply air. Door seals are the primary path of room air leakage. Therefore, doors and doorframes are crucial components of the facility construction, as more leakage air must be designed into the system for doors with poor seals. The HVAC design engineer should consult with the facility architect to assure specifications are adequate for pressurization requirements. Door frames may include continuous seals which would reduce leakage required to maintain the desired pressure, as well as provide isolation in case of airflow failure. Doors may be provided with a provision for operable floor sweeps which drop down as the door closes, but these may present cleaning problems. Where double doors are used in the facility, gasketed astragals are required. Door grilles should be avoided unless part of a pressure scheme without airlocks (as discussed in the Appendix). Figure 14, Chapter 27 of the 2005 ASHRAE HandbookFundamentals should be used in calculating the air leakage rate of doors. Common practice is to design for a 0.10‖ average crack between the door and frame on sides, top, and bottom. Note that corrections are to be applied for design pressure differentials using the formula contained in Figure 14. A similar leakage calculation is discussed in the article, Airlocks for Biopharmaceutical Plants, del Valle, Pharmaceutical Engineering , Volume 21, Number 2, March/April 2001 Material transfer openings are another key room air leakage path. To calculate leakage through these and other fixed openings use the formula, Q = A x 4005sqrt (VP)
(―Sqrt‖ = square root)
Q = airflow (CFM) A = area of opening (sq. ft.) VP = velocity pressure— the velocity pressure at the opening (in. w.g.) is roughly the same as the differential pressure across the opening, (or the, room differential pressure), This method provides a conservative leakage number. In most cases, a slightly smaller leakage airflow will produce the desired pressure differential for a given leakage path. Because of this, during commissioning there may be more return air leaving the room than
34
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1383 1384 1385 1386 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410
JULY 2008
designed, so return air dampers should have some extra capacity. In some cases the calculated room leakage may exceed the minimum air change rate for small rooms such as airlocks. In these instances the total supply air to the space must match the calculated leakage. However, provisions should be made in the design for some return air from the space in case the actual leakage is less than calculated. A good rule-of-thumb is to size the return for half the supply air flow into the room. In applying this approach, care should be taken in sizing any volume control (damper or CV box) on the return air side to ensure that the actual flow rate is with the operable range of the control device. For this reason it is a good engineering practice to put a tighter specification on the supply air volume, being more critical to maintain the room conditions, and a larger design range on the return, which will be whatever value is needed to maintain desired differential pressures. Two methods of measurement are commonly applied to monitor room pressure relationships; room-to-room and common reference point. While both have been used successfully, the preferred is the common reference point method in order to minimize compounded error. Here, one port of the differential pressure transmitter (usually, but not always, the ―High‖ side) is piped to the room being monitored and the other side (usually, but not always, the ―Low‖ side) is piped to a common reference in the interstitial space. Interstitial Space- common reference H
Space A
1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 1421
PDT
L
H
Space B
PDT
L
H
Space C
PDT
L
Space A
H
PDT
L
Space B
Common Reference Monitoring
Room-to-Room Monitoring
Figure 2-11 Differential Pressure Sensor Locations The common reference point should not be outdoors, as the effect of wind direction may give unstable readings. Where room to room monitoring is used it is a good practice to confirm through the system balancing that net airflow into the facility is greater than the extract/exhaust. All signals are sent to the control system where differentials are 35
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476
JULY 2008
calculated by means of an algorithm. In the event that the reference (interstitial) space is partitioned by fire walls or other means, it may be necessary to provide multiple common reference points by building ―zone‖. In this case the pressure relationship across a ―zone‖ will need to be room-to-room or the use of two differential pressure transmitters, one to each reference point, will be required. For information monitoring.
on
monitoring
system
see
section
2.7
Control
and
dilution
and
2.6.5 Ventilation/supply strategies 2.6.5.1 Room Air Distribution: There are two basic types of displacement air distribution.
room
air
distribution:
In a dilution design, room air is mixed continuously with supply air to help achieve uniform air temperatures within the space. In areas where temperature uniformity is the only factor, aspirating-type diffusers are used to allow turbulent mixing of room air with supply air. From a particulates perspective, dilution also mixes ―less clean‖ room air with the clean supply air. Aspirating-type diffusers are not acceptable in any of the clean classified rooms. Even though non-aspirating diffusers do not eliminate turbulent air patterns in the room, using non-aspirating diffusers in clean rooms reduces the mixing effect. The particulate level in the room can be reduced with dilution by increasing the air-change rate of clean air supply. Dilution distribution with non-aspirating diffusers (typically perforated face plate over the terminal HEPA media) is acceptable to clean classified areas up to ISPE-7. In a displacement design, room particulates are displaced by clean terminal HEPA filtered unidirectional air. This design requires continuous HEPA coverage at the ceiling and properly sized and located low level return or exhaust grills. ISPE-Grade 5 should use displacement air distribution (typically a unidirectional flow hood – UFH). 2.6.5.2 Room Air Distribution options Conventional air distribution techniques are generally acceptable for administrative, warehouse, and unclassified spaces. Large warehouse spaces, however, may see hot and cold spots with poor air distribution. GMP spaces and cleanrooms require more stringent methods. Supply air should be introduced at the ceiling level and return/exhaust air should be extracted near the floor. The use of non-aspirating diffusers on the face on terminal HEPA filters may improve airflow patterns. Within mixed airflow rooms, airflow patterns should be from clean side of the space to the less clean. For example, within a space that contains an ISO 5 micro-environment/zone with an ISO 7 background, airflow should always be from the cleaner zone into the less clean background area.
36
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
ISO Class 5
1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501
ISO Class 7
Mixed Airflow GMP Space Figure 2-12 Mixed Airflow Space Some process operations, i.e., centrifugation, are inherently particle generating. Airflow patterns within the spaces that contain these processes should take this into account by locating returns/exhausts at floor level near the particle generating operation. Airlocks and gown rooms are usually divided, often by a physical line on the floor, into clean and ―dirty‖ zones in accordance with the flow of personnel, material, and equipment. Within such spaces, the air pattern should from the clean to the ―dirty‖ side of the airlock. Therefore, HEPA supplies should be located on the clean side and low wall returns should be located on the opposite side of the room. Low wall returns should be located no more than 12‖ above the floor. Returns should be generously sized with a maximum grille face velocity of no more that 400 FPM. Ductwork should be sized for a maximum pressure drop or 0.1‖ per 100‘ or a maximum velocity of 850 FPM, whichever is more restrictive. The heel of the connecting elbow should have a minimum 6‖ radius to facilitate cleaning. The elbow and connecting ductwork, up to an elevation of 5 feet above the floor, should be Type 304 or 304L stainless steel.
37
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
1'-0" maximum
6" Radius
Typical Low Wall Return 1502 1503 1504 1505 1506 1507 1508 1509 1510 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521
Figure 2-13 Typical Low Wall Return Return air ducts located in stud wall spaces need not be insulated within the walls. Insulation shall terminate at the top of the wall. The mechanical engineer should consult with the facility Architect to assure that, where needed, wall cavities are adequate to contain low wall returns. 2.6.6 EXTRACT (EXHAUST AND / OR RETURN) STRATEGIES Why we use low level or high level extract, the area affected by an extract point – do we want to cover dust extract systems at all here?? 2.6.7 DISTRIBUTION Design concepts for ductwork distribution systems – equal velocity, static regain etc are covered in the ASHRAE Handbooks. Such calculations should be performed by only qualified HVAC professionals, 38
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562
1563 1564 1565
JULY 2008
who should be familiar with ASHRAE.
2.7
HVAC CONTROLS AND MONITORING
2.7.1 Introduction This section will give a brief overview of the options available for controlling and monitoring HVAC systems and the environments that they provide, providing guidance on the points to consider when designing a new system or reviewing an existing installation. An important early decision is to decide if the control system will also be the quality ―system of record‖ providing the alarms and recording that the environment is being maintained within the specified limits, or if there will be an independent system to do this, with the HVAC control system providing only ―engineering‖ information and alarms. 2.7.2 Controls There are many types of equipment that can be used to control an HVAC system, each with advantages and disadvantages, three of the more common variations are described below; 2.7.2.1 Basic control system A basic system may use packaged controllers (Packaged ―PID‖ units) for each of the controlled variables. There may be independent control units – e.g. temperature, humidity, or a single combined unit, with the sensors and controlled items – dampers, valves etc connected to the controller. The controller may also have the capability of providing alarms. This option provides a low purchase and installation cost, control panels in a large installation can be standardized and complete panels held as spares. However there is no ability to monitor the system performance, or analyze trends or component performance with this system, hence it is rarely used. A picture of a typical control unit is shown below.
Figure 2-14 Typical Single Loop Control (Courtesy of __________) 39
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1566 1567 1568 1569 1570 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 1601 1602 1603 1604 1605 1606 1607
JULY 2008
2.7.2.2 Building Management System (BMS) The most common solution found in the industry is the BMS or BAS (Building Automation System) system. This is a proprietary packaged system typically comprising of a number of local independent control panels, field panels or outstations with the software / control logic installed – the panel may control one or several HVAC or other building systems. This panel is then connected by a network cable to one or several ―supervisors‖ – computer terminals which allows a user to see the input and output signals, set up the system to record, and allow the user to review plant performance data and trends, change set points and have alarms reported / printed in a central location. This type of system is more expensive, but brings additional capability allowing system performance to be monitored remotely, with adjustments made to set points from a central location if required - a hierarchy of alarms can also be easily set up. The large scale use of these systems has reduced the cost significantly. Figure 2-15 – (to be added) 2.7.2.3 Fieldbus Systems The ―next generation‖ BMS uses ―intelligent‖ sensors connected via a network cable to the control system.
and
valves
There are a number of industry standard communication protocols which mean that the owner is not tied to a single supplier, e.g. Hart or Foundation Fieldbus. The software is held within the control system which communicates with the devices; the device can self diagnose faults, automated components can also self calibrate to the control signals. This type of system is the most expensive to install, but should be more reliable, and simple to maintain as they are self checking. The cost typically limits the use of this type of system to process operations at present, but this may change as the costs reduce.
40
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
1608 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624 1625 1626 1627 1628 1629 1630 1631 1632 1633 1634 1635 1636 1637 1638 1639 1640 1641 1642 1643 1644
JULY 2008
Figure 2-16 Field Bus system (courtesy of _________) 2.7.3 Actuation methods There are two common means of actuating components – electrical and pneumatic. 2.7.3.1 Electrical/Electronic The actuator will use a low voltage control signal, to control an electric motor, the units can be on off, or proportional These systems are used where the speed of actuation can be slower, typical times for a valve to go from fully open to fully closed are in the range of 1-2 minutes. Installation is simple, as all signals are by cable – e.g. control signal, power supply, and any feedback, such as valve position, or open/closed signals. The actuators can be supplied as fail open, fail closed, or with a manual override facility. 2.7.3.2 Pneumatic The control signal is used to vary the output pressure from a pneumatic controller, which is fed to a pneumatic actuator on the controlled component. The system requires the use of an I/P (control signal to pneumatic) converter, with an instrument quality air supply, then local tubing to the actuator. In order to get the best response time the converter should be as close as possible to the actuator. Fully pneumatic controls are available but seldom used with large installations and BMS.
41
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1645 1646 1647 1648 1649 1650 1651 1652 1653 1654
1655 1656 1657 1658 1659 1660 1661 1662 1663 1664 1665 1666 1667 1668 1669 1670 1671 1672 1673 1674 1675 1676 1677 1678 1679 1680 1681 1682 1683 1684
JULY 2008
The units use air pressure one way, with an opposing spring to return the controlled item to the fail position. The system is naturally proportional control – i.e. the controlled item position is proportional to the control signal. These units typically have a faster response time than an electric or electronic unit. The pneumatic system is also ideal for hazardous areas requiring intrinsically safe installations.
Figure 2-17
I/P transmitter
For HVAC applications response time is not usually critical, as the response time of the overall system is slow, e.g. if the full equipment heat load is added instantaneously, the room temperature will rise slowly, not instantaneously, similarly the rate of change of external conditions is typically slow. 2.7.4 Instrumentation It is important to consider the requirements for the instrumentation to be used, in order to select the most cost effective type, and to define the appropriate calibration/verification regime. There is a lot of difference between domestic and commercial building type sensors and industrial type units, the latter being in general more reliable, and certainly more robust – for this reason on this grade of instrument should be considered. For some instruments accuracy and repeatability are important, e.g. measuring room temperature, for others accuracy is not important, but repeatability is, e.g. measuring a system flow rate in order to maintain constant flow through the control of a variable speed fan. Thus three point calibration verification may be justifiable.
may
be
required,
The parameters usually requiring monitoring include:
42
or
single
point
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1685 1686 1687 1688 1689 1690 1691 1692 1693 1694 1695 1696 1697 1698 1699 1700 1701 1702 1703 1704 1705 1706 1707 1708 1709 1710 1711 1712 1713 1714 1715 1716 1717 1718 1719 1720 1721 1722 1723 1724 1725 1726 1727 1728 1729 1730 1731 1732 1733 1734 1735 1736 1737 1738 1739
JULY 2008
2.7.4.1 Airflow Measurement of airflow is typically done to allow control of airflow in a system. For classified spaces, airflow should be kept constant to assure that particle counts, recovery, and room pressure are in control. This may be done using a flow grid – The Grid consists of a row of tubes with closed ends, some of the tubes are perforated with small holes facing upstream sensing total pressure, while others have holes facing downstream to sense throat sub-static pressure the tubes are connected by manifolds with the distribution designed to compensate for non uniform flow profile in the duct . The difference in pressure signal between the two sets of tubes is proportional to the square of the mean velocity in the airway. By connecting the output tubes to a suitable instrument, the pressure difference and hence the volume flow rate can be easily measured. In order to get an accurate reading the installation should have straight duct runs equivalent 2-3 times the duct diameter upstream and downstream of the flow grid. A similar grid system uses hot wire anemometer elements. Because flow sensing is not dependent on the square root of pressure, better accuracy at low flows is possible. Another system gaining popularity is the fan venturi meter, either retrofitted to or an integral part of the system fan inlet (evase) – with the advantage of established accuracy. Its performance is independent of the ductwork design - hence is a useful commissioning aid. The wiring is all local to the fan/AHU, simplifying installation. It should be noted that the usual function of the grid is not to get an accurate reading, but to maintain a preset reading determined during system commissioning, whether actual flow or not. Due to the square law operating principle, differential pressure flow measurements have a limited turndown capability. For specialized applications such as the monitoring of unidirectional air flow protection devices (laminar flow hoods) hot wire anemometers are used. Vane anemometers are commonly used for commissioning as they tend to have an averaging affect over the fan area compared to the spot reading from the hot wire unit. 2.7.4.2 Flow control The most common form of flow control is the damper – these can be manually adjusted, or actuated, use a single blade, or be multi blade parallel or opposed blade These items are fairly basic, and the relationship between air flow and position is non linear improved control is available using devices such as a ―pneumatic‖ damper – this uses a bladder inflated with low pressure compressed air to open aerodynamically shaped blades. These provide more linear control with better pressure recovery and turndown.
43
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
1740
1741 1742 1743 1744 1745 1746 1747 1748 1749 1750 1751 1752 1753 1754 1755 1756 1757 1758 1759 1760 1761 1762 1763 1764 1765
Figure 2-18 Pneumatic (“Bladder”) dampers Another device that may be used to provide better control is a variable orifice, such as the item shown below: Figure 2-19 Variable Orifice (Venturi) Damper GRAPHIC MISSING 2.7.4.3 Control Valves The correct selection of fluid (liquids or steam) control valve is critical for good system performance, together with tuning of the control loop. There are two types of control valve; the three port valve, which can be used as a mixing or diverting valve to supply the controlled equipment, or the two port valve, which directly controls flow to the equipment. The three port valve was once the industry standard , however the use of two port valves with variable flow rate systems is becoming far more common, as a well designed system is as effective, and has a lower capital and operating cost.
44
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1766 1767 1768 1769 1770 1771 1772 1773 1774 1775 1776 1777
1778 1779 1780 1781 1782 1783 1784 1785 1786 1787 1788 1789 1790 1791 1792 1793 1794 1795 1796 1797 1798 1799 1800
JULY 2008
Correct valve selection is important for the correct operation of a system, a brief over view of the process follows, but for readers who require more information references are given in the references section. Valve characteristic The valve characteristic is the ratio of flow through the valve to the valve lift (opening) at a constant differential pressure. There are three main types of valve characteristic:
Figure 2-20 Valve Characteristics (Courtesy of _____________) These are shown graphically as in a globe valve;
The fast opening valve is typically used for on / off control. The Linear valve has a flow rate directly proportional to the amount it is open, and is commonly used for diverting applications in HVAC supplying water to heating or cooling coils.. The equal percentage valve is more commonly used in two port applications.
The characteristic should be chosen with respect to the application of the valve. The installed characteristic is the relationship between the flow and valve lift in the system where it is installed. Where the pressure drop across the valve decreases with increasing flow the EP valve will produce a more desirable linear characteristic. Simple Flow coefficient calculation or Cv for liquids Cv= design flowrate (gpm) Allowable pressure drop1)
x
sqrt
1
(Specific
Gravity
of
the
fluid/
Calculation should be based on the allowable pressure drop to determine the CV needed. Selected valve should have that CV at 90% opening or less.
45
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1801 1802 1803 1804 1805 1806 1807 1808 1809 1810 1811 1812 1813 1814 1815 1816 1817 1818 1819 1820 1821 1822 1823 1824 1825 1826 1827 1828 1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843 1844 1845 1846 1847 1848 1849
JULY 2008
Select a valve where the required Cv is in the 10-80% range of the stroke – use of a valve that is too small (typically less than half the line size) or too large (line size or greater) would be wrong – the valve will not have the ability to control the flow accurately, i.e. not have adequate authority. If the valve normal operating condition results in operation in a near closed condition control can be erratic, particularly if installed where flow tends to close the valve. Valve Authority This is defined as the percentage of total system pressure drop assigned to the valve, i.e. in a circulation system the pump will deliver some head to overcome pipe and heat exchanger losses and some to overcome valve resistance. If the latter is small in comparison to the former the valve will have less ability to control effectively. Differential Pressure There are pressure:
three
applications
for
the
measurement
of
differential
The use of a differential pressure monitor to interpret the readings from a flow measuring device. The use of a pressure switch to detect: Flow failure of a fan (not usually necessary if the system has flow monitoring) Detection of high pressure across a filter or filter set, to provide an indication that the filters require changing. The detection of low differential pressure between rooms to provide an indication of the incorrect airflow direction (non sterile areas), or failure of a design differential pressure (sterile areas).
2.7.4.4 Differential Pressure sensing/Indication There are a number of options here; One of the most basic instruments is the Magnehelic gauge, a robust device based on the measurement of the deflection of a metal diaphragm which provides a visual indication of differential pressure. This device is also available with a switch output, or a variable output. An alternative is a simple device using a colored ball mounted in an inclined tube, as shown below – this type of unit operates from first principles, so does not require calibration, the disadvantage is that there is airflow through the unit, so it requires routine cleaning.
46
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
1850 1851 1852 1853 1854 1855 1856 1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 1867 1868 1869 1870 1871 1872 1873 1874 1875 1876 1877 1878 1879 1880 1881 1882 1883 1884 1885 1886 1887 1888 1889
JULY 2008
Figure 2-21 Visual DP indicator (courtesy of _____) Where greater sensitivity is required, or a control function based on a differential pressure an electronic pressure transducer can be used – these are available with or without indicator LEDs to allow an operator to see if conditions are acceptable or not. The most sophisticated DP sensors are pressure diaphragms with an accuracy of +/- 0.005‖ (0.25 Pa). Output is commonly 4-20 mA. When specifying these units be careful to consider the operating pressure range, and ensure that the device is robust enough to handle the occasional pressure spike. 2.7.4.5 Temperature sensor The almost universal industrial sensor used to monitor temperature is the resistance thermometer (RTD). Liquid and gas expansion systems are used for self acting controllers and switches. 100 Ohm RTDs with a 38.5 Ohm fundamental interval are the industry standard and are available with different accuracy standards, some as accurate as ________. Some HVAC systems may utilize 1000 Ohm sensors of a lower accuracy. 2.7.4.6 Humidity sensor It is far more common to monitor relative humidity, though there are applications where it may be advantageous to monitor absolute humidity, for example in a system used to supply multiple areas, each equipped with a local branch re-heater, so that the moisture reading is independent of the temperature (in the example given the supply temperature would be reset to minimize the use of the re-heaters, thus each change in supply temperature would require the supply RH to be reset, whereas the humidity would be constant). The sensors used industrially to monitor relative humidity now are generally units which measure the change in capacitance between two plates due to the variation in humidity. Accuracy is in the range of __________.
47
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1890 1891 1892 1893 1894 1895 1896 1897 1898 1899 1900 1901 1902 1903 1904 1905 1906 1907 1908 1909 1910 1911 1912 1913 1914 1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 1925 1926 1927 1928 1929 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942
JULY 2008
2.7.5 Environmental Monitoring 2.7.4.1 It is a regulatory requirement to monitor critical process parameters. These vary depending on the product, but commonly include;
Temperature Humidity Air flow direction / area differential pressure (as it is difficult to monitor air flow, differential pressure is the parameter typically monitored) And may include particle monitoring for classified areas or for airborne hazardous particles for worker protection
Viable particles (CFU - Colony Forming Units) for classified spaces It is now common practice in the industry to validate the monitoring system (sensors, transmitters, indicators, recorders, alarms) for those parameters defined as critical (usually in the process monitoring computer system), and use GEP to ensure the development and maintenance of a robust control system (via the HVAC control system). This approach provides the quality organization with a record of the conditions from a validated system, without the need for cumbersome quality change control process on the control system (an engineering change control system is still required, which typically is less cumbersome, and less extensive in its scope – e.g. may not include all set points). 2.7.5.1 With any monitoring system the main factors to consider are:
Accuracy & repeatability required Long term stability & failure modes Sensor location / locations Alarm requirements Record requirements
2.7.5.2 Accuracy required The accuracy of the monitoring system should be subtracted from the defined limits, in order to ensure that the product requirements are met – thus it is cost effective to use a reliable high accuracy sensor, allowing the maximum latitude for the control system. For example if the conditions are 18 – 25 degrees C, and the system has an accuracy of ± 0.5 degrees, the space can be within the limits 18.5 – 24.4 degrees C; if the monitoring an accuracy of ± 2 degrees C, then the conditions need to be between 20 and 23 degrees C. 2.7.5.3 Long term stability and failure modes 2.7.5.4 Sensor location / locations
48
monitoring maintained sensor has maintained
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1943 1944 1945 1946 1947 1948 1949 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997
JULY 2008
This is an area of great discussion, let us consider temperature and humidity (typically Relative Humidity – the most important thing to remember is that conditions are very rarely uniform throughout a room – see fundamentals of HVAC systems. The traditional location for the monitoring sensor was in the common return air duct – this is still a good location, giving an average of the conditions in the space, assuming that the supply diffusers are doing a good job of mixing the supply with the room air. It may be necessary to study the relationship between worst conditions in the room and the mixed condition in the return duct.
case
If there are any significant heat or humidity gains then the local conditions near the source will be different. When considering sensor locations also consider the process as seen by the product – for example consider a typical tablet compression room; The raw material sits in a hopper typically near a supply register, so that the area is flushed with clean air, it is then fed into the dies, where it is compressed – the process generating a significant amount of heat – the compressed tablet is then released into a de-duster/metal detector, into a collection bin, where it is cooling and exposed to the room conditions – due to the localized heat, the local RH will be lower. As the equipment generates a significant amount of heat the air change rate is high – typically around 20 times per hour, to keep the supply air temperature differential reasonable – circa 0.5 degrees. The most critical area is the feed hopper, which is covered by the supply air – thus in this instance it could be argued that this would be the location to monitor. There are also a number of options to consider for Differential Pressure, it is common practice to measure across the doors of the airlock, though the requirement it maintain the difference between the rooms, as it is usually desirable to maintain a positive pressure in the manufacturing area where there is any risk of ingress of outside air, hence some may prefer to monitor the room pressure compared to an external reference point. 2.7.5.5 Alarm requirements It is important to consider the desired response to an alarm state. Many alarms will provide early warning to the facility engineering staff of an unusual state requiring some attention or adjustment, but not indicating any transgression of required operating conditions. Other alarms often for the same variable at a worse condition may indicate that operating conditions have exceeded the specified states and production need to take action with the process to ensure product quality is not compromised. These alarms need to be relayed to the appropriate business unit.
49
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051
JULY 2008
The regulatory requirement is for a local alarm, notifying the operator when the conditions are outside the defined limits. This may be by an audible and or visual indication – e.g. a horn and flashing light mounted in a common area of the production suite, where it can be seen or heard from the whole suite. It is a good practice to set this action alarm at the extreme conditions, and have an engineering ―alert‖ alarm at conditions just outside the normal operating range, to alert the engineering staff of a potentially unusual condition as soon as possible, so that action may be taken to prevent an action alarm. This engineering alarm may come from the validated monitoring system, or the GEP control system. 2.7.5.6 Record requirements Every company has its own standards – it may be acceptable to just have a record of any alarms during manufacturing – or lack thereof! – recorded on the batch record sheet. It may be preferred to have an actual record. With current data logging systems this may be in the form of a continuous chart, or a daily printout of min, max average, Standard Deviation. 2.7.6 Equipment monitoring There are a number of consider a fan motor:
ways
that
HVAC
equipment
can
be
monitored;
The control contactor can be wired so that an alarm is given if the unit goes into overload. The motor current can be monitored The motor temperature can be monitored Vibration or acoustic output may be monitored. The airflow from the fan can be monitored using an in duct device, or a in fan device
The unit which measures the flow is the unit which will detect all of the fan failure modes, the others have potential limitations, depending on the fan drive arrangement, this measurement is also likely to be the most sensitive. With the new generation of accelerometers it is cost effective to monitor the performance of rotating equipment to ensure early detection of system wear (due to vibration). The sensors can be wired to a BMS, or be wireless, transmitting data to a base station for monitoring. 2.7.5.1 Other equipment parameters may also be monitored, primarily as part of GEP to ensure lowest life cycle cost: Fan speed (or current draw, to indicate added pressure drop due to
50
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2052 2053 2054 2055 2056 2057 2058 2059 2060 2061 2062 2063 2064 2065 2066 2067 2068 2069 2070 2071 2072 2073 2074 2075 2076 2077 2078 2079 2080 2081 2082 2083 2084 2085 2086 2087 2088 2089 2090 2091 2092 2093 2094 2095 2096 2097 2098 2099 2100 2101 2102 2103 2104 2105 2106
JULY 2008
filter loading) Supply duct pressure Damper actuator positions (to predict need for re-balancing of the HVAC) Filter pressure drop (where filters tend to load quickly) Cooling coil leaving temperature Other HVAC parameters, to aid in predicting maintenance and in troubleshooting performance problems 2.7.5.2 Sensor mounting considerations The things to consider when selecting where to mount a sensor are: The instrument needs to be mounted so that it is easy to calibrate. The instrument specification and mounting need to consider any local cleaning required It is best to keep pneumatic control lines as short as possible.
2.8
SYSTEM ECONOMICS
2.8.1 Introduction The pharmaceutical industry is unusual in that the potential impact of an HVAC system failure could be financially very significant, for example causing loss of a batch of product, or the loss of control of the conditions in a research laboratory, potentially invalidating the results of a long term test. Thus the risk assessment of a system‘s failure must encompass the product quality issues as well as the potential business issues. The benefit of providing a clear definition of the potential impact of system failure is that it can influence and justify the allowable budget for the system. If the cost and likelihood of failure is high, duplication of systems/equipment may be viable. But a better recourse is to redesign the system or process to reduce the risk. The potential impact of redundancy will not only influence the HVAC system design and maintenance but also the design requirements for the supporting utilities – for example, there may be no sense having duplex air conditioning systems if there is only one chiller and one circulating pump for the chilled water supply to the HVAC cooling coil. There is another ―softer‖ consideration – appearance. The industry is open for audit, typically by internal as well as external agencies, and there is a strong desire to maintain the appearance of the facility. Thus the cost of the equipment installed may be higher than in equivalent plant in other industries. These requirements present Engineers with a unique set of challenges which vary from system to system. The engineer needs to review the risk and potential impact of system failure considering all of the potential modes of failure, for example;
Airflow failure 51
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2107 2108 2109 2110 2111 2112 2113 2114 2115 2116 2117 2118 2119 2120 2121 2122 2123 2124 2125 2126 2127 2128 2129 2130 2131 2132 2133 2134 2135 2136 2137 2138 2139 2140 2141 2142 2143 2144 2145 2146 2147 2148 2149 2150 2151 2152 2153 2154 2155 2156 2157 2158 2159 2160
JULY 2008
Filter failure (loss of control contamination) Failure of temperature control Failure of humidity control
of
airborne
particles
or
cross-
This risk analysis assessing the potential impact of system failure can significantly influence the HVAC system design, and maintenance, as well as the design of the supporting utilities. The scope of the analysis may include business as well as quality aspects – simplistically put if the system fails, and the qualified (verified) monitoring system advises quality that the area is not within specifications, there is no patient risk, but the coat to the business could be considerable. These considerations are on top of the conventional considerations balancing capital and operating costs.
economical
The user requirements have serious implications on the design, and need to be carefully considered and defined, they should include the following:
Internal conditions - How much variation is acceptable, - a wider operating range will mean a lower cost system, both to install and operate. Many believe that if they specify closer operating ranges, they will get a ―better‖ i.e. more robust system, this is not necessarily the case, in order to maintain closer tolerances the plant may be selected with greater capacity and faster responding sensors, and actuators, which are more sensitive and require careful tuning, and maintenance. Having specified these closer tolerances the system must be commissioned to operate to meet these specifications. The capital and operating costs of this more complex system are likely to be higher. External conditions - If the facility is to kept operable 365 days a year then the plant needs to be sized to handle the peak external design conditions. If it is acceptable to have a a few percent downtime during peak seasons, then the HVAC system and supporting utilities can be downsized to suit, or a system of load shedding incorporated into the design of the support utilities, with the HVAC system components being sized to suit the extremes.
Other factors will affect the system economics:
Building envelope - A low cost poorly insulated facility will mean a corresponding increase in the operating cost and capital cost of the HVAC system, for a given set of internal conditions. Similarly a review of the facility construction/insulation may be beneficial – for example improving the insulation may allow a warehouse facility to require only a heating system, rather than air conditioning. Internal layout/design - A well developed design will keep the influence of major heat loads outside the conditioned area, or use the other utilities required to minimize the internal loads, for example a dust extract unit can also extract heat from a motor in the room, reducing space heat gains. There may be benefits from grouping the environmentally critical areas within the building,
52
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2161 2162 2163 2164 2165 2166 2167 2168 2169 2170 2171 2172 2173 2174 2175 2176 2177 2178 2179 2180 2181 2182 2183 2184 2185 2186 2187 2188 2189 2190 2191 2192 2193 2194 2195 2196 2197 2198 2199 2200 2201 2202 2203 2204 2205 2206 2207 2208 2209 2210 2211 2212
JULY 2008
keeping them away from the external walls, to reduce the external load variations. 2.8.2 Life Cycle Cost Analysis Typical method – Evaluate payback against incremental cost of options e.g. design types – for dehumidification chemical dehumidification vs. chilled water or DX systems optimizing air distribution, use of Computational Fluid Dynamics (computer airflow modeling), allowing larger room supply air temperature differences, humidification using local electric boilers, water spray injection (ultrasonic or air blown.) Ductwork design based on static regain, requiring minimum balancing. Typical HVAC Economic Issues:
Availability Sizing Volume vs. temperature to achieve ―Q‖ Waterside vs. Airside energy reductions Energy Recovery
TABLE 2-5 WHAT IS IT?
Table to go in!!
When reviewing potential solutions, the life cycle cost should be analyzed – the analysis will encompass the following aspects, considering capital cost and lifetime operating costs. 2.8.2.1 First Cost vs. life cycle cost There is a balance between first cost and operating cost, as well as considering the factors described in this section, the designer must consider:
The system design life Labor costs and trends Energy costs and trends
The maximum capital spend that will make the project financially viable 2.8.2.2 The system design life If the facility has a short life, then it may be possible to save money on the equipment, and not invest in plant of the quality that would be optimum for a facility with a long predicted operating life. Maintenance costs (as discussed below) extend over the entire facility life, becoming more cost-significant as the facility life increases. 2.8.2.3 Labor costs and trends The decision to invest in performance monitoring and, for centralized lubrication systems will similarly be influenced anticipated facility life and the cost of labor.
53
example by the
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2213 2214 2215 2216 2217 2218 2219 2220 2221 2222 2223 2224 2225 2226 2227 2228 2229 2230 2231 2232 2233 2234 2235 2236 2237 2238 2239 2240 2241 2242 2243 2244 2245 2246 2247 2248 2249 2250 2251 2252 2253 2254 2255 2256 2257 2258 2259 2260 2261 2262 2263 2264 2265 2266
JULY 2008
2.8.2.4 Energy costs and trends The cost of energy must be considered not only from the system design concepts, but the perspective of component selection, for example:
AHU housing – low cost units may be made of pre-finished steel, and have minimal insulation. The unit may suffer from high air leakage, causing increased operating costs, and sweating, causing external corrosion and a shorter working life. Fan – the fan may be direct drive, with a variable frequency supply to vary the fan speed to maintain a constant supply volume. It may use a high efficiency flat belt drive instead of the traditional Vbelts to improve energy efficiency. Filter selection – the optimum selection of pre-filtration systems will balance labor cost, filter cost, the contaminants in the local environment, the capacity of the filter, energy costs and the cost of cleaning the AHU during changing of the filter – this may be the conventional panel / bag, or may be a bag / bag filter combination. Chillers cooled using cooling tower water rather than air cooled condensers. Chilled water cooling vs. direct expansion
Energy Recovery The potential risk of cross contamination means that some of the simpler means of heat recovery, such as the rotating wheel are not acceptable, however other systems such as heat pipes, and run around coils are and should be reviewed to see if there is a payback. Similarly systems which use the measurement of enthalpy to vat the amount of fresh air may be economic, though the design and sizing of the dampers needs to be more carefully considered for an application where it is important to maintain system volumes, and room pressure differentials. 2.8.2.5 Consumables Costs The life and cost of each consumable component must be considered filters are an obvious example – the optimum selection of prefiltration systems will balance labor cost (for the actual replacement and the cleaning required when a filter is removed prior to installing the new filter), filter cost, the contaminants in the local environment, the capacity of the filter, rate of change of pressure drop, energy costs in order to recommend an optimum selection – this may be the conventional panel / bag arrangement or may show a bag / bag filter combination to be more cost effective. Another example would be the drive belt – V-belts have a significantly shorter life than a flat belt, but cost less. They are not as energy efficient as a flat belt though, thus the savings in maintaining a stock of spare belts, energy savings, and saving in labor costs to replace the belts, and re-tension them may make them cheaper over the plant operating life.
54
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2267 2268 2269 2270 2271 2272 2273 2274 2275 2276 2277 2278 2279 2280 2281 2282 2283 2284 2285 2286 2287 2288 2289 2290 2291 2292 2293 2294 2295 2296 2297 2298 2299 2300 2301 2302 2303 2304 2305 2306 2307 2308 2309 2310 2311 2312 2313 2314 2315 2316 2317 2318 2319 2320 2321
JULY 2008
2.8.2.6 Impact of system failure If the cost and likelihood of failure is very high, and product value and risk are also high, duplication of systems/equipment may be advisable. The potential impact of system failure will not only potentially influence the HVAC system design and maintenance but affect design of the supporting utilities. 2.8.2.7 Appearance is another factor many believe influences plant room, system and equipment design and specification. The industry is open for audit, typically by internal as well as external agencies, and there is a strong desire to maintain the appearance of the facility – in addition to complying with the GMP requirements, ensuring that not only the equipment but the plant room area and is easily cleanable. 2.8.2.7 Reliability / Maintenance Costs The life cycle cost maintenance aspects.
analysis
must
also
consider
reliability
/
Consider the lowest cost material used for a cooling coil, aluminum fins on copper tube. In a poor environment there will be corrosion on the fin material, reducing the efficiency of the unit, with the fins eventually corroding to the extent that the unit will not perform adequately. There are options for the specification of this item, each increasing the first cost, but increasing the operating life: Copper tube with polyester coated aluminum fins or Copper tube with electro tinned copper fins A fan specification with a long design bearing life will allow for extended operating periods without maintenance. Grouped lubrication points will minimize costs, and allow lubrication when the plant is in operation. The cost of routinely calibrating instrumentation should not be overlooked – it may be cost effective to have one calibrated differential pressure switch across a bank of filters, with uncalibrated ―engineering information‖ pressure gauges across each filter. 2.8.2.9 As well as the obvious factors there are other ―political‖ factors to consider to vary the ratio of direct (capital) vs. indirect (operating) cost;
There may be grants available to assist with capital costs There may be incentives to make the system more energy efficient
2.8.3 User Requirements Specification As a project is considered justifiable, before the design details are developed the quality critical environmental requirements must be 55
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2322 2323 2324 2325 2326 2327 2328 2329 2330 2331 2332 2333 2334 2335 2336 2337 2338 2339 2340 2341 2342 2343 2344 2345 2346 2347 2348 2349 2350 2351 2352 2353 2354 2355 2356 2357 2358 2359 2360 2361 2362 2363 2364 2365 2366 2367 2368 2369 2370 2371 2372 2373 2374 2375
JULY 2008
defined by the user, typically in a User Requirement Specification – this may include;
Temperature for product and for workers Humidity for product and for workers Air flow directions / differential pressures for contamination control Area classification (particles – viable and non-viable (classified spaces) Clean up times from in-sue to at-rest (classified spaces)
The user requirements can have a significant influence on system cost, and need to be carefully considered and defined. For example: 2.8.3.1 Air Change rates There is a common misconception within the Pharmaceutical Industry of a regulatory requirement of a minimum air change rate for an area – typically held to be 20. This is generally not true, especially for non-classified areas. In the European regulations there is a requirement for a ―clean up‖ time of 15 to 20 minutes in a sterile product processing facility – calculating this based on a clean air supply to a room, completely uniform mixing from class 10,000 to class 100 gives 14 minutes recovery time – in practice neither of these assumptions are realistic. However, the 2004 FDA ―Guidance for Industry for Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice‖ gives the following guidance: For Class 100,000 (ISO 8) supporting rooms, airflow sufficient to achieve at least 20 air changes per hour is typically acceptable. Significantly higher air change rates are normally needed for Class 10,000 and Class 100 areas. Some companies specify their own arbitrary air change rates – this is not a good practice; the designer should take responsibility for defining this based on a number of factors. There may be a benefit in assuming air change rates to use as a basis for establishing an initial project concept cost used to determine the viability of a project. In order to define the actual air change rate required the designer must consider the following interrelated factors:
Heat gain to the conditioned space due to external influences – e.g. solar gain Heat gain to the space due to internal influences – e.g. equipment Moisture gain to the conditioned space due to external influences – e.g. external humidity Moisture gain to the space due to internal influences – e.g. occupants The number and location of the occupants in the space 56
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2376 2377 2378 2379 2380 2381 2382 2383 2384 2385 2386 2387 2388 2389 2390 2391 2392 2393 2394 2395 2396 2397 2398 2399 2400 2401 2402 2403 2404 2405 2406 2407 2408 2409 2410 2411 2412 2413 2414 2415 2416 2417 2418 2419 2420 2421 2422 2423 2424 2425 2426 2427 2428
JULY 2008
The tasks the occupants are doing The clothing (gowning level) of the occupants The process The cleanliness of the supply air The means and efficiency of coverage of distributing the supply air The means and location of extracting the air from the conditioned space Where the control and monitoring sensors are located The locations where the specified conditions are critical – e.g. in a tablet compression room the process will add a considerable amount of heat to the product – the critical area is likely to be where the raw material is exposed. The cost of putting in a system capable of higher air change rates than those actually required is significant both in terms of the capital and system operating costs. As discussed earlier, a process that generates low volumes of particles, in a large room, may need fewer air changes to maintain desirable particle levels.
2.8.4 Life Time Operating Costs These are the total costs of building and operating the installation, including design, purchasing, installing, commissioning, operating and maintaining (including labor, energy and spare parts) the system during the working life of the asset, and its dismantling. Cleaning and disposal cost. Refer to 2.8.2, and 2.8.4 for the factors affecting this. 2.8.5 Comparing Options Most companies have internal accounting systems that will facilitate the evaluation of different design concepts, evaluating payback against the cost of the different design options, (investment analysis) considering the design life of the facility e.g. chemical dehumidification vs. chilled water or DX systems, humidification using suitably treated plant steam, local electric boilers, water spray injection (ultrasonic or air blown), or clean steam, water cooled vs. air cooled chillers. Some of the areas to consider are provided below:
Energy sources Airflow management – through the use of flow measurement and fan speed control Energy efficient ductwork design based on low velocity static regain, requiring minimum balancing Night setback of temperature and or humidity, reduction in airflow if no production Fume hood velocity control and fume hood diversity Minimizing the use of local heating/cooling batteries Energy recovery systems – air to air or air to fluid to air (e.g. rotary wheels, heat pipes, run around coils). Recovery and use of cooling coil condensate Reuse of cooling tower blow down water 57
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2429 2430 2431 2432
2.9
JULY 2008
Use of non storage water heater (calorifier)
SUSTAINABILITY
(TO BE WRITTEN LATER)
58
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2433 2434 2435 2436 2437 2438 2439 2440 2441 2442 2443 2444 2445 2446 2447 2448 2449 2450 2451 2452 2453 2454 2455 2456 2457 2458 2459 2460 2461 2462 2463 2464 2465 2466 2467 2468 2469 2470 2471 2472 2473 2474 2475 2476 2477 2478 2479 2480 2481 2482 2483 2484 2485 2486 2487
3
THE DESIGN PROCESS
3.1
INTRODUCTION
JULY 2008
The HVAC engineer is responsible for the development of a GMP compliant design for that particular application which also meets other key customer requirements such as reliability, maintainability, sustainability, flexibility, and safety and which complies with local codes and standards. In the pharmaceutical industry, the role of the HVAC design engineer requires not only an understanding of both basic and advanced HVAC system design, but also a thorough understanding of the most current requirements of the regulatory authorities which will govern that particular facility‘s operations. This includes cGMPs of the countries where the facility‘s product will be sold as well as where the facility is located. To be successful in delivering such a design, the HVAC engineer must also understand how those systems integrate into and are affected by other aspects of the facility design and operation. People, equipment and material flow patterns, architectural layout, finishes and tightness of room construction, air locks, spatial requirements for HVAC equipment an d ductwork, intake locations and exhaust locations are all examples of where the HVAC engineer must coordinate the HVAC design with other disciplines for a successful project. 3.1.1 System Design Process The engineer responsible for HVAC system design follows a process that includes first defining and documenting the key requirements of the end user (process and quality criteria, maintainability, etc.). This will require collaboration with the user and the quality unit in determining which are the critical operating parameters and thus the environmental requirements which must be provided by the facility design, including the HVAC systems. This defining of user requirements is the most critical step in the design process and has the greatest impact on the size and complexity of the facility, and ultimately the cost to construct, commission, qualify, operate and maintain it. Even small incremental increases in the level of cleanliness and the amount of classified space can result in relatively large increases in the initial cost of the facility and ongoing operating costs. It is important to clearly establish the required levels of cleanliness for any particulate, biological and/or chemical contamination for the processes, equipment and personnel in the facility. The HVAC engineer plays a key role throughout the design process in helping the project team understand the implications of excessive requirements on the cost of the project and the ongoing operating costs of the facility. Once user requirements are established, the HVAC engineer must use his knowledge of HVAC systems to work with other disciplines to develop a functional (or schematic) design. This includes a risk assessment of alternative engineering solutions that can meet the user requirements. The risk assessment can be combined with an economic analysis to arrive at a facility and HVAC system which will have the lowest total cost of ownership. In addition to the cGMP related user requirements, the following are some additional issues that the HVAC engineer and the project team need to address in order to develop the functional design 59
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2488 2489 2490 2491 2492 2493 2494 2495 2496 2497 2498 2499 2500 2501 2502 2503 2504 2505 2506 2507 2508 2509 2510 2511 2512 2513 2514 2515 2516 2517 2518 2519 2520 2521 2522 2523 2524 2525 2526 2527 2528 2529 2530 2531 2532 2533 2534 2535 2536 2537 2538 2539 2540 2541
JULY 2008
for the facility:
Flow patterns of people, product, equipment and other materials Potential sources and risks of contamination Hierarchy of cleanliness classification to control contamination risks Procedures to control contamination (i.e., cleaning, sanitization) Requirements for redundancy of equipment and/or systems Requirements for flexibility of the facility and/or systems Economics of facility first cost and operational costs
In developing the functional design, the HVAC engineer must also consider the design in light of the need to construct, commission, qualify, operate and maintain the facility and its HVAC systems. At certain points in the design process, often at the end of functional design and before detailed design begins, the HVAC engineer will be involved in a formal design review/design qualification which is intended to verify that the project as designed will deliver a facility, including an HVAC system, which will meet the user requirements. After detailed design is completed, the HVAC engineer will often remain involved in the project by helping to resolve construction questions from the field and performing on-site construction reviews. He/she may also be involved in activities related to the receipt and installation of equipment and systems intended to verify that they were delivered and installed in a manner consistent with the design. The HVAC engineer is also often involved in the commissioning and qualification of the HVAC systems to verify that they perform as designed. This could include involvement in developing the Commissioning and Qualification (C&Q) protocols and/or executing the C&Q verification activities. The HVAC engineer is often involved in Factory Acceptance Testing (FAT) and/or Site Acceptance Testing (SAT) of major HVAC equipment and systems. The engineer is well advised to include planning for C&Q activities on the project during the design phase. Multiple past projects have proven that failure to consider C&Q requirements during the design phase may have a negative impact to the project in scope, cost and schedule. 3.1.2 Regulatory Considerations To be an effective member of the design team, the HVAC engineer needs an understanding of the regulatory requirements which will govern the facility and its processes. This requires an understanding of the cGMPs where the facility is located and those where the facility‘s products will be marketed, and the implications on the design of the facility and its HVAC systems. ISPE‘s Baseline Guide series provides practical advice for understanding and meeting regulatory requirements for various types of facilities (Parenteral, OSD, API, etc.) and their systems (maintenance, water & steam systems, etc.) and should be consulted in conjunction with this Good Practice Guide. These regulatory requirements identified in the Baseline Guides from such governing bodies as the FDA, EMEA, USP, ASTM, ICH, ISO, WHO, etc. will impact the project design at the HVAC system design level in such
60
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2542 2543 2544 2545 2546 2547 2548 2549 2550 2551 2552 2553 2554 2555 2556 2557 2558 2559 2560 2561 2562 2563 2564 2565 2566 2567 2568 2569 2570 2571 2572 2573 2574 2575 2576 2577 2578 2579 2580 2581 2582 2583 2584 2585 2586 2587 2588 2589 2590 2591 2592 2593 2594 2595
JULY 2008
areas as:
pressure differentials temperatures air change rates specific alert and alarm ranges facility layout (cleanliness classification hierarchy airlock strategy, etc) monitoring and control platforms (BMS, DCS, PLC, etc.) Commissioning & Qualification
strategy,
In addition to the cGMP quality regulatory requirements, the HVAC engineer must also be knowledgeable about other compliance related codes and standards which apply to the design of facilities and HVAC systems where the facility is located. These include applicable local building, mechanical, electrical, fire and energy codes. Other compliance related requirements will usually apply which govern employee health & safety and process safety. The owner‘s insurance representative may also have additional requirements for their clients beyond those of the local codes.
3.2
DEVELOPING THE USER REQUIREMENTS SPECIFICATION (URS)
3.2.1 Introduction User requirements provide key information that defines the processes, activities, and environments needed for an operating facility. Assembling programming data for a facility early in the design process is critical to the successful operation, not only in terms of production output and efficiency, but also in delivering the asset at the right time to maximize Return On Investment (ROI) and provide the lowest Total Cost of Ownership(TCO). Decisions and commitments made in the early phase of project planning are often too costly to change as the project advances to final design and then to execution phase. Therefore, developing the user requirements that drive HVAC criteria early in the design process is critical in setting the overall HVAC strategy for the facility. HVAC costs, both operating and initial capital costs, can account for a significant portion of a facilities cost. It is important to ensure that user requirements are well understood and properly applied. For HVAC systems in a pharmaceutical environment, user requirements are developed as a result of gathering relevant data with regards to the following: Process – Critical environmental parameters that must be achieved and maintained. Quality – Regulatory guidance and quality principles to guide decision making on HVAC parameters that can have product impact.
61
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2596 2597 2598 2599 2600 2601 2602 2603 2604 2605 2606 2607 2608 2609 2610 2611 2612 2613 2614 2615 2616 2617 2618 2619 2620 2621 2622 2623 2624 2625 2626 2627 2628 2629 2630 2631 2632 2633 2634 2635 2636 2637 2638 2639 2640 2641 2642 2643 2644 2645
JULY 2008
Operations – Proper environment for the working conditions that impact the HVAC design. Maintenance – Provide input on critical aspects of the HVAC design that would ensure a low TCO User requirements have often been associated with qualification, that is, critical HVAC parameters (e.g., temperature, humidity, differential pressure, air quality) are segregated from non critical HVAC parameters. Critical HVAC parameters are part of direct impact systems while non-critical HVAC parameters are either indirect or no impact systems. In either case, all HVAC systems are commissioned following GEP while direct impact systems are further qualified. User requirements can either be in the form of performance based information that describes an operation and sets expectations or strict criteria where critical HVAC parameters are well defined, e.g., Temperature, Relative Humidity, etc. In the case of performance based information, the HVAC designer would gather relevant information and propose the necessary criteria that would meet the user requirements. It is accepted practice to copy HVAC criteria from one facility to another (similar) facility – as long as the rationale for the original criteria is well understood. For example, determining temperature and relative humidity criteria in an aseptic environment is dependent on, type of process (closed or open, powder or liquid), local regulatory expectations, gowning procedures, environmental monitoring procedures, the level and type of activity in the area, and alert and alarm limits,. The HVAC designer should carefully consider each of these variables when proposing criteria and avoid using "industry norms" or "accepted industry practices" without an understanding of the variables involved. Once user requirements are established, the HVAC designer should begin to consider design strategies and impact. It is desirable to segregate HVAC parameters that are critical and non-critical under different HVAC systems rather than mix critical and non-critical HVAC parameters under the same system. Although there may not be any restrictions from a process viewpoint, segregating HVAC system components between direct and indirect impact adds to the complexity of commissioning and qualification. It could unnecessarily drive up qualification and ongoing maintenance costs. The flow diagrams shown below are a simple model segregating critical HVAC parameters with separate HVAC systems versus combining critical and non-critical HVAC parameters, by virtue of a single HVAC system. Both design approaches would meet user requirements but it illustrates the potential complexity when using a single HVAC system to serve direct and indirect/no-impact areas.
62
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2646 2647 2648 2649 2650 2651 2652 2653
2654 2655 2656 2657 2658 2659 2660 2661 2662 2663 2664 2665 2666 2667 2668
JULY 2008
The impact assessment methodology evaluates the HVAC system at the component level to separate out critical and non-critical components, thus making it possible to have a single HVAC system. Well defined and accepted procedures should be in-place or agreed upon when defining the user requirements that would allow the single HVAC system to have a lower total cost of ownership. If these concepts are not well understood or established procedures or practices do not recognize this methodology, the HVAC design may increase the total cost of ownership.
Figure 3-1 User Requirements drive HVAC critical parameters 3.2.2 References for User Requirements ISPE Baseline Guides provide a framework to understand the different products and processes within pharmaceutical and biopharmaceutical manufacturing facility. The baseline guides that would apply to this section include the following:
Bulk Pharmaceutical Chemicals Oral Solid Dosage Forms Sterile Manufacturing Facilities Biopharmaceuticals Packaging, Labeling & Warehousing Operations (under development)
63
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2669 2670 2671 2672 2673 2674 2675 2676 2677 2678 2679 2680 2681 2682 2683 2684 2685 2686 2687 2688 2689 2690 2691 2692 2693 2694 2695 2696
JULY 2008
Laboratories (draft)
(Include a chart with a timeline and activities to illustrate?.... no) The following section describes HVAC parameters as covered in the Baseline Guides listed above and the importance of each parameter in each type of facility. 3.2.3 HVAC Parameters HVAC parameters that may have impact on product generally include:
Temperature Relative Humidity Airborne contamination (viable and non-viable particles), which is affected by:
Room Relative Pressure Airflow patterns Air Changes Air Filtration
Within the context of the baseline guides listed, some parameters are common to all facility types while other parameters only apply to specific facilities. The following chart depicts at-a-glance the typical HVAC parameters that would generally apply to each facility type. HVAC Parameter
Facility Type Bulk Pharmaceutical Chemicals Oral Solid Dosage Forms Sterile Manufacturing Facilities Biopharmaceuticals Pack., Labeling & Warehousing Laboratories 2697 2698 2699 2700 2701 2702 2703 2704 2705 2706
Relative Humidity
Temperature
Room Relative Pressure
Airborne Particles
Air Changes
Air direction
Table 3-1 Typical HVAC Critical Parameters by facility type Hatched areas represent the HVAC parameter used to set criteria that normally would have product impact or is required for creature comfort. Non-shaded areas are HVAC parameters that do not normally have product impact and are not used to set criteria. However, there may be other requirements such as local codes or regulations that may require certain parameters be considered in the design. For example, room relative pressure may not have product impact in a Bulk Pharmaceutical 64
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2707 2708 2709 2710 2711 2712 2713 2714 2715 2716 2717 2718 2719 2720 2721 2722 2723 2724 2725 2726 2727 2728 2729 2730 2731 2732 2733 2734 2735 2736 2737 2738 2739 2740 2741 2742 2743 2744 2745 2746 2747 2748 2749 2750 2751 2752 2753 2754 2755 2756 2757 2758 2759 2760 2761
JULY 2008
facility, but due to governing codes, the design may implement room pressurization controls in order to sustain certain safety requirements due to the high presence of flammable liquids or vapors. Individual HVAC parameters are discussed in the following section with an emphasis on establishing the minimum requirements to achieve "compliance", the importance of the parameter, the impact on design, and the challenges faced in determining these requirements. 3.2.3.1 Temperature General Temperature requirements will vary depending product impact, and operator comfort. ……………
on
the
application,
This looks to be light… why discuss just temperature? 3.2.4 Critical Parameters Provide typical critical HVAC parameters under a given process or classification; i.e., Product Type, Solvent Issues, Environmental Classification, Open/Closed processes, Terminally Sterilized, Oral Solid Dosage Forms. Discuss assumptions or clarifications The risk assessment process is used to determine which HVAC system components are critical to the SISPQ of the product. These components will require additional attention via qualification and may require higher levels of redundancy to avoid business impact. This logic could be extended to determine which components should be under cGMP change control, with the remainder of the system under GEP change control. There are a number of ways to address this. One suggested method will be provided in the form of a matrix in which the individual components of the HVAC system (preheat coil, fan, temperature sensor, etc.) are listed on one axis and a series of challenge questions which will aid in determining the GMP-critical nature of that component are listed on the other axis. Managing HVAC Parameters (Monitoring) – Accountability for alerts and alarms. Methodology in determining appropriate alarm delays. Guidance on how to monitor - BAS, procedural means or manual monitoring. Determining what should be monitored – every room or select rooms. Table 3-2 (HVAC System Impact Matrix) See
Appendix for graphic
3.2.5 Programming and Layout Considerations The following is a listing of issues and considerations regarding HVAC systems and how they may affect the programming and layout of the facility design. These are areas in which the HVAC engineer and the project programmer must coordinate their knowledge and experience to avoid future problems in the construction, verification, operation and 65
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2762 2763 2764 2765 2766 2767 2768 2769 2770 2771 2772 2773 2774 2775 2776 2777 2778 2779 2780 2781 2782 2783 2784 2785 2786 2787 2788 2789 2790 2791 2792 2793 2794 2795 2796 2797 2798 2799 2800 2801 2802 2803 2804 2805 2806 2807 2808 2809 2810 2811 2812 2813 2814 2815 2816
JULY 2008
maintenance of the facility. The impact of HVAC on programming and layout will vary by the type of facility, generally increasing as the complexity of the facility increases from general administrative office areas to more complex facilities for aseptic and/or potent compound processing. It is important to establish User Requirements before beginning layout and design. It is especially important to identify critical parameters versus controlled parameters, as this is a major factor determining environmental cleanliness classifications. In general, the larger the classified area and the more stringent the environmental cleanliness class the more complex and costly the HVAC system, both first cost and the ongoing operating cost. Determine if there are there special requirements for temperature or RH for specific rooms (freezers, chill rooms, stability storage chambers, R&D suites, etc.). The flow of materials, equipment and people (unidirectional flow; gravity flow, etc.) must be understood by the HVAC engineer in determining area classifications, pressurization strategies, airlock strategies (the use of airlocks to separate areas of different requirements for cleanliness, pressure, temperature, and/or RH) and their classification, HVAC system zoning, etc. Area functionalities and adjacencies (both horizontal and vertical) Determine functional/relational adjacencies (i.e., don‘t put large air compressors adjacent to a laboratory with vibration-sensitive precision analytical equipment.) There may be special considerations in the layout and adjacencies for projects employing prefabricated modular construction. The locations and considerations for HVAC and utilities equipment, ducting/piping routing, supply/exhaust/return diffusers/grilles. Outside air intakes and exhaust stacks must be located to avoid entrainment/re-entrainment of noxious fumes and odors such as lab fume hood exhausts, process vents and diesel fumes from idling trucks near docks and other loading/unloading facilities. Will major equipment be located in basement, penthouse, roof or elsewhere? Building configuration (H x W x L) may affect the location of central services and how they are distributed. Understand the requirements for maintenance, testing, repair and/or replacement. This includes the locations for access doors/panels for HVAC system inspection, testing and maintenance, including HEPA filter scan testing and maintenance. Access to field instruments for calibration, testing, and repair must also be considered. For AHU maintenance, consider how to remove/replace large motors & fans, DH wheels, coils, filters. You not only need access around the AHU for equipment removal, but must consider how large equipment will be removed from the area and replacements moved into the area (clear pathways, hoists/elevators, etc.). Identify the locations and need for access to BMS/EMS data and control, and what local indications and/or control features are needed. What are the maintenance philosophies for the facility (i.e., maintain from inside or outside of room)?
66
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2817 2818 2819 2820 2821 2822 2823 2824 2825 2826 2827 2828 2829 2830 2831 2832 2833 2834 2835 2836 2837 2838 2839 2840 2841 2842 2843 2844 2845 2846 2847 2848 2849 2850 2851 2852 2853 2854 2855 2856 2857 2858 2859 2860 2861 2862 2863 2864 2865 2866 2867 2868 2869 2870 2871
JULY 2008
What are the materials to be used in the process (i.e., potent, solvents, cytotoxic, sterile) and the approaches & technologies for product containment and for clean/sterile processing. The use of minienvironments (barrier isolators, RABS, biosafety cabinets, etc.) will usually reduce both the required amount and grade of classified space compared to traditional ‗ballroom‘ cleanroom processing. The location of hazardous equipment & ductwork and the need to maintain them may affect the facility layout. Issues related to codes and standards:
What codes and standard apply to this jurisdiction? (ADA, Fire, OSHA, Energy, IMC, etc.) Egress and other safety considerations Must understand risks associated with various layout and programming issues (i.e., area electrical classification, blowout panels, SISPQ risks…) Special considerations with hydrogen operations
The requirements of local codes and standards may need special attention in the design and construction of prefabricated modules. When facility modules are fabricated in a different jurisdiction than the location of the facility, this may become a major problem if not identified early in the design process. Within the room: Consider the locations of people, processes and product with respect to HVAC supplies and exhaust/returns. Consider the equipment heat loads (where is heat generated and how is it cooled or extracted?) Consider the location of utilities connection with respect to the operations to be performed. Room HVAC system must be designed as an integrated system in rooms with fume hoods, BSCs, LEV systems and process equipment HVAC systems. The decision of whether to use a manifold exhaust system versus one fan per hood may affect facility layout. 3.2.6 Architectural Considerations Similar to the previous section, the following is a listing of issues and considerations regarding HVAC and how they may affect the architectural portion of the project and vice versa. All of the previously identified issues for consideration in the programming and layout of the facility (Section 3.2.4) are areas in which the project HVAC engineer and project architect need to coordinate their designs. The following are additional areas in which the HVAC engineer and the project architect must also coordinate their knowledge and experience to avoid future problems in the construction, verification, operation and maintenance of the facility. The materials address.
of
construction
of
the
facility
is
a
major
area
to
Room Finishes: Must be cleanable, resistant to cleaning and sanitization chemicals, suitable for the environment, and be wear/bump resistant. 67
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2872 2873 2874 2875 2876 2877 2878 2879 2880 2881 2882 2883 2884 2885 2886 2887 2888 2889 2890 2891 2892 2893 2894 2895 2896 2897 2898 2899 2900 2901 2902 2903 2904 2905 2906 2907 2908 2909 2910 2911 2912 2913 2914 2915 2916 2917 2918 2919 2920 2921 2922 2923 2924
JULY 2008
Flooring: The same considerations as for Room Finishes. Selection of the flooring material for the application is important, but equally important is verifying the technique and skills of the flooring installer. Often, installing test patches of the materials and the techniques being considered is the best method to evaluate their performance in a specific application.
The construction methodology for the facility is another key area in which the architect and the HVAC design engineer must coordinate their designs.
Room tightness. Use floor to ceiling walls where pressure differential is important. If RH is important, then address reducing moisture migration through unsealed penetrations, door seals, and porous wall materials. Considerations in the door specifications need to address seals, windows, interlocks, construction of the door, actuation and hardware. Consider a commissioning test to verify room tightness (i.e., room leakage test or room integrity test).
The use of prefabricated modular construction techniques might impose additional restrictions on the HVAC design (design might be limited to equipment vendors with which the module contractor has an established relationship; the size of AHUs might be limited to the size of a standard module; etc.)
Impact of HVAC on programming and layout will vary by the type of facility. (some of this is redundant)
Flow of materials, equipment and people (unidirectional flow; gravity flow, etc.) Area functionalities and adjacencies (both horizontal and vertical) Determine functional/relational adjacencies (i.e., don‘t put large air compressors adjacent to a laboratory with vibration-sensitive precision analytical equipment. Locations and considerations for HVAC and utilities equipment, ducting/piping routing, supply/exhaust/return diffusers/grilles. Major equipment in basement, penthouse, roof or ???? Requirements for testing, repair and/or replacement (i.e., HEPA filter scan testing and maintenance) Access doors/panels for HVAC system inspection, testing and maintenance For AHU maintenance- how to remove/replace large motors & fans, DH wheels, coils, filters, Environmental cleanliness classifications Materials to be used in the process: Potent, solvents, cytotoxic, sterile? Determining User Requirements (critical parameters versus controlled parameters) What codes and standard apply? (ADA, Fire, OSHA, ??) Egress and other safety considerations 68
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2925 2926 2927 2928 2929 2930 2931 2932 2933 2934 2935 2936 2937 2938 2939 2940 2941 2942 2943 2944 2945 2946 2947 2948 2949 2950 2951 2952 2953 2954 2955 2956 2957 2958 2959 2960 2961 2962 2963 2964 2965 2966 2967 2968 2969 2970 2971 2972 2973 2974 2975 2976
3.3
JULY 2008
Building configuration (H x W x L) may affect the location of central services and how they are distributed. Approaches and technologies for product containment. Routing of ductwork & utilities Location of Hazardous equipment and ductwork Manifolded exhaust systems versus one fan per hood. In general, the larger the classified area and the higher the environmental cleanliness class, the more complex and costly the HVAC system, both first cost and the ongoing operating cost. Room HVAC system must be designed as an integrated system in rooms with fume hoods, biosafety cabinets (BSCs), LEV systems and process equipment HVAC systems. Must understand risks associated with various layout and programming issues (i.e., area electrical classification, blowout panels, SISPQ risks…) Special considerations with hydrogen operations Location of HVAC inlet air and exhaust stacks Special temperature (or RH) rooms (freezers, chill rooms, stability storage chambers, R&D suites, etc.) Use of airlocks to separate areas of different requirements (cleanliness, pressure, temperature, RH) and their classification Location and need for access to BMS/EMS data and control; what local indications and/or control features are needed Access to field instruments (calibration, testing, and repair) Special considerations for prefabricated modular construction Locations of people, processes and product within the space with respect to HVAC supplies and exhaust/returns Consideration of equipment heat loads (where is heat generated and how is it cooled or extracted?) Location of utilities connection
HVAC SYSTEM RISK ASSESSMENT
3.3.1 Introduction Risk assessment is a process for determining the impact of systems or components on product SISPQ. Risk assessment is performed by organizing or dividing the components into systems and evaluating the impact of those systems/components on Critical Quality Attributes and/or Parameters. As the components included within a system can significantly impact results, the definition of system boundaries is a critical step in a successful risk assessment. The risk assessment process may be used to determine: The testing requirements for the system and associated controls
The level of documentation that is appropriate The components that should be verified (commissioned/qualified) The necessary level of change control to apply for the system components
69
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 2977 2978 2979 2980 2981 2982 2983 2984 2985 2986 2987 2988 2989 2990 2991 2992 2993 2994 2995 2996 2997 2998 2999 3000 3001 3002 3003 3004 3005 3006 3007 3008 3009 3010 3011 3012 3013 3014 3015 3016 3017 3018 3019 3020 3021 3022 3023 3024 3025 3026 3027 3028 3029
JULY 2008
From a patient safety perspective the key data is typically kept in an environmental monitoring file to facilitate quality review: The contents of this file would include as applicable:
Typical HVAC performance parameters that impact CQA/CQP are: HEPA filter test data Air change rates/airflow volumes Area differential pressures Temperature Relative humidity Particle count Typical HVAC-related room performance parameters which CQA/CQP are: Clean up & Room recovery time Total particle count (area classification) Microbial Viable particulate test results – in air Microbial Viable particulate test results – swab tests
impact
The ―package‖ of data produced should be critiqued to ensure that it is adequate to minimize risk to quality. There are a number of approaches to performing a risk assessment; approach is described below:
one
1.0 Define the Critical Quality Attributes/Parameters (CQA/CQP) for the area served by the HVAC system, together with the supporting rationale. Some examples may be:
Humidity is not aqueous liquid.
Temperature is not a critical factor as the product is contained in temperature controlled vessels.
Air quality is considered a critical factor – the room supplied is categorized classified as ISPE Grade 8 because product is exposed
Room pressure differentials are considered a critical factor in order to maintain the room environment, minimizing the risk of contamination/cross contamination, because the room is classified ISPE Grade 8.
a
critical
factor
for
the
product
as
it
is
an
2.0 Define system boundaries for HVAC system:
Systems can be organized by components of like type (i.e., system that is all one type of components, such as only HEPA filters)
Systems can be organized geographically (i.e., at room level)
Systems system)
can
be
organized
by
connected
70
components
(i.e.,
an
AHU
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3030 3031 3032 3033 3034 3035 3036 3037 3038 3039 3040 3041 3042 3043 3044 3045 3046 3047 3048 3049 3050 3051 3052 3053 3054 3055 3056 3057 3058 3059 3060 3061 3062 3063 3064 3065 3066 3067 3068 3069 3070 3071 3072 3073 3074 3075 3076 3077 3078 3079 3080 3081 3082 3083
JULY 2008
Control and monitoring system can be either a separate system, or may be included as part of another system.
3.0 Define how the Critical Quality Attributes/Parameters (CQA/CQP) are monitored. Some examples may be:
Humidity is monitored by an independent SCADA based environmental monitoring system.
Temperature is monitored by an independent SCADA based environmental monitoring system.
Air quality is monitored by a routine test using a particle counter to per ISO CEN 14644 for all particles., and microbial
Microbial monitoring for viable particles is tested
Room pressure differentials are monitored by an independent SCADA based environmental monitoring system
per local SOP.
4.0 Define how the Critical Quality Attributes/Parameters (CQA/CQP) are achieved, and any associated equipment risks of failure and the probability of detection of those failures. Some examples may be:
Humidity control is achieved by either dehumidifying the air through cooling below its dew point to remove moisture, or by adding moisture with a steam humidifier. As humidity is continuously monitored by a verified system it is considered adequate to commission the humidifier/dehumidifier system, and maintain it under engineering change control
Temperature control cooling coils. As verified system it system, and maintain
Air quality is obtained through the final HEPA grade filter which is leak tested annually, with a particle count conducted periodically. As the HEPA filter integrity is not continuously monitored, and is directly responsible for this aspect of the system performance it will be verified and maintained under quality change control.
Room pressure differentials are achieved through the leakage from and to the conditioned space from adjacent areas and via the HVAC system balance. As pressure is continuously monitored by a verified system it is considered adequate to commission the duct/damper system and maintain it under engineering change control.
is obtained through the use of the heating or temperature is continuously monitored by a is considered adequate to commission the heat it under engineering change control.
Based on the above examples, the equipment to be verified and maintained under Quality Change Control is therefore shown is a shaded box in the system drawing shown below: (Note: the editor has issues with the items shown as being under change control. Don‘t be surprised if the drawing below changes in the final 71
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3084 3085 3086 3087 3088
3089 3090 3091 3092 3093 3094 3095 3096 3097
JULY 2008
version, as fans and control valves are usually NOT critical devices. The monitoring systems for airflow, DP, and temperature/RH are. The shading is in the wrong place, and I can‘t change it.)
Figure 3-2 A Typical schematic of critical devices Examples of other methods for performing an HVAC risk assessment, including some typical for risk assessments of HVAC components, are included in the appendix.
72
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3098 3099 3100 3101 3102 3103 3104 3105 3106 3107 3108 3109 3110 3111 3112 3113 3114 3115 3116 3117 3118 3119 3120 3121 3122 3123 3124 3125 3126 3127 3128 3129 3130 3131 3132 3133 3134 3135 3136 3137 3138 3139 3140 3141 3142 3143 3144 3145 3146 3147 3148
JULY 2008
4
HVAC APPLICATIONS BY PROCESS AND CLASSIFICATION
4.1
INTRODUCTION
There are many types of facilities, each with its own type of HVAC system, but design philosophies remain the same. The following are key design steps during the design:
Identify product and process critical HVAC parameters and acceptance criteria. Define the type of facility and the operational requirements of each area within the facility. Define the design criteria for each area within the facility. Identify potential paths of product/process contamination and evaluate risks. Develop a set of HVAC systems that meets the design criteria with an appropriate balance of cost and risk. Provide a means to control the systems so that design criteria are met. Assure that the systems meet the design criteria.
Certain parts of a facility may be subject to regulatory compliance. It is imperative that HVAC systems that affect regulated operations are designed to an end result that repeatedly meets the expectations of the regulatory body. Air handling systems should be designed to achieve physical separation in order to prevent cross contamination. Product separation guidelines should be consulted when determining the boundaries of air handling systems. Separate air handling units are often used to segregate different building functions such as production, production support, warehouse, administration, mechanical areas, etc. Within production areas, further segregation is often advisable for various unit operations, e.g., upstream cell culture vs. downstream purification, pre- vs. post-viral, filling, etc. Manufacturing areas supporting key unit operations require maximum on-stream reliability. The air handling units supporting these areas may be configured for partial operation during routine maintenance operations to support this requirement for areas still in production. Shutdowns for routine maintenance are permissible for certain product forms, with classified spaces requiring continuous service. Therefore, air handling units serving these less rigorous spaces may be designed accordingly.
4.2
SYSTEM APPLICATIONS
Typical AF&ID (air flow and Instrument diagrams) are included in the Appendix and referenced in this section. 4.2.1 ISPE Grade 7 or ISPE Grade 8 5
With local protection or ISPE grade
73
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3149 3150 3151 3152
JULY 2008
Figure 4-1 GRAPHIC
74
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3153 3154
3155 3156 3157 3158
JULY 2008
4.2.2 ISPE Grade CNC (Controlled Not Classified) or unclassified
Figure 4-2 Typical Controlled space AF&ID
75
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3159 3160
3161 3162 3163 3164
JULY 2008
4.2.3 LAB
Figure 4-3 Typical Lab AF&ID
76
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3165 3166
3167 3168 3169 3170
JULY 2008
4.2.4 Warehouse:
Figure 4-4 Typical Warehouse AF&ID
77
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3171 3172
3173 3174 3175 3176 3177 3178 3179
JULY 2008
4.2.5 Administrative:
Figure 4-5 Typical Admin area AF&ID
4.3
ROOM LEVEL EXAMPLES
Facility Type
System Type
Notes
API end
Once Through
If solvents consider erc
-
Wet
Central Station Fixed Balance Central Filtration Draw Through Humidification
System Type
present
-
Economics Airflow Tracking or pressure control are possible Merv 7, 13/14 Unless load requires air near dew point In cold climates for static control
3180 3181 Facility
are
Product and Process Requirements EHS
Notes 78
Economics Economics
EHS
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Type API end
-
Dry
Once Through
If solvents are present - consider erc
Recirc is possible Central Station Fixed Balance
with LEL detection, or if no solvents
Central Filtration Final Filtration HEPA or ULPA Draw Through Humidification Return or Exh Filtration
Airflow Tracking or possible Merv 7, 13/14 for final API containment
steps
pressure
or
control
potent
are
compound
Unless load requires air near dew point In cold climates for static control For potent compounds, cross contamination control or as a dust stop for equip/personnel Grade must be appropriate to paricle size and risk
3182 3183 Facility Type OSD
System Type
Notes
Recirculated
Once through may be used for Multi-product or solvent use
Central Station Distributed units Makeup / Recirc Fixed Balance Central Filtration Draw Through Humidification Return or Exh Filtration
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent Airflow Tracking or possible Merv 7, 13/14
pressure
control
are
Unless load requires air near dew point In cold climates for static control For cross-contamination Control
3184 3185 Facility Type Biologics
System Type
Notes
Recirculated
Once through may be used for Multi-product or solvent use
Central Station Distributed units Makeup / Recirc Fixed Balance
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent Airflow
79
Tracking
or
pressure
control
are
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Central Filtration Final Filtration Draw Through Humidification /Dehumidificat ion Return or Exh Filtration
possible Merv 7, 13/14 May be used if CNC / Grade D / ISO 8 or 9 Unless load requires air near dew point In cold climates for static control / Is common, especially for hygroscopic products. For cross-contamination Control
3186 3187 Facility Type Aseptic Processing
System Type
Notes
Recirculated
Once through may be used for Multi-product or solvent use
Central Station Distributed units Makeup / Recirc Fixed Balance Central Filtration Final Filtration Draw Through Humidification /Dehumidificat ion Return or Filtration
Exh
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent active pressure control is common Merv 7, 13/14 May be used if CNC / Grade D / ISO 8 or 9. Double for A&B (AHU and Terminal) are not uncommon. Unless load requires air near dew point In cold climates for static control / Is common, especially for hygroscopic products and micro control, operator comfort and condensation control For cross-contamination Control
3188 3189 Facility Type Packaging / Labeling
System Type
Notes
Recirculated
Once through may be used for Multi-product or solvent use
Central Station Distributed units Makeup / Recirc Fixed Balance Central Filtration Final Filtration
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent Airflow Tracking or possible Merv 7, 13/14
pressure
control
May be used if CNC / Grade D / ISO 8 or 9
80
are
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Draw Through Humidification Return or Exh Filtration
Unless load requires air near dew point In cold climates for static control For cross-contamination Control
System Type
Notes
3190 3191 Facility Type Labs
Once through may be used for Multi-product or solvent use Central Station Distributed units Makeup / Recirc Fixed Balance Central Filtration Final Filtration Draw Through Humidification Return or Exh Filtration
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent Airflow Tracking or possible Merv 7, 13/14
pressure
control
are
May be used if CNC / Grade D / ISO 8 or 9 Unless load requires air near dew point In cold climates for static control For cross-contamination Control
3192 3193 Facility Type sampling and subdivisio n
System Type
Notes
Recirculated
Once through may be used for Multi-product or solvent use
Central Station Distributed units Makeup / Recirc Fixed Balance Central Filtration Final Filtration Draw Through Humidification Return or Exh Filtration
Distributed units work well for multi-product concurrent Excellent for multi-product concurrent Airflow Tracking or possible Merv 7, 13/14
System Type
control
May be used if CNC / Grade D / ISO 8 or 9 Unless load requires air near dew point In cold climates for static control For cross-contamination Control
3194 3195 Facility Type
pressure
Notes
81
are
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW Pressure Control Volumetric Airflow Control
JULY 2008
Room level active control of maintain pressure differential Room level active control of maintain flow differential
Active Fixed Balance Fixed Balance 3196 3197
82
supply
and/or
exh/return
to
supply
and/or
exh/return
to
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3198 3199 3200 3201 3202
3203 3204 3205 3206 3207 3208 3209 3210 3211 3212 3213 3214 3215 3216 3217 3218 3219 3220 3221 3222 3223
4.4
JULY 2008
ACTIVE PHARMACEUTICAL INGREDIENTS (API) - (WET END)
4.4.1 System Schematic (Sample)
4.4.2 System Design Considerations
Bulk biotech products may require area classification (see the Biopharmaceutical Baseline Guide for requirements) Air systems should be once through where solvents or potent compounds are handled. Air systems may recirculate with the OA necessary to maintain pressure relationships, in support areas, where no solvents or potent compounds are handled. Manufacturing rooms should be fitted with low or combination high/low returns. Manufacturing rooms should be protected from migration of contaminants or solvent vapors via the use of pressure or tracking differentials. Where solvents are handled, closed processing or capture exhaust systems are strongly recommended. Oxygen depletion and LEL monitors may be employed as appropriate to assure that dangerous conditions do not occur, especially when recirculated air is used, in accordance with fire and building codes. 83
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3224 3225 3226 3227 3228 3229 3230 3231 3232 3233 3234 3235 3236 3237 3238 3239 3240 3241 3242 3243 3244 3245
4.5
JULY 2008
Provide LEV for dry product addition; drum handling, manways and spills in wet areas. Provide LEV for containment devices. Provide all spark-proof exhaust equipment serving process areas. Provide explosion proof or intrinsically safe electrical components in the exhaust air stream. Heating coils may not be required for systems in warm climates. Dehumidification and post cooling coils should be considered for low humidity room control or for facilities with limited cooling capacity. Humidification should be considered for cold climates where static control is a concern. Risk assessment should be performed to determine need for fan redundancy (parallel fans or fan walls) If required, Unidirectional flow hoods (UFH) that have recirculation should be supplied with a small percentage of fresh air to offset fan heat.
ACTIVE PHARMACEUTICAL INGREDIENTS (API) - (DRY END)
4.5.1 System Schematic (Sample)
3246 3247 3248
84
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3249 3250 3251 3252 3253 3254 3255 3256 3257 3258 3259 3260 3261 3262 3263 3264 3265 3266 3267 3268 3269 3270 3271 3272 3273 3274 3275 3276 3277 3278 3279 3280 3281 3282 3283 3284 3285 3286 3287 3288 3289 3290 3291 3292 3293 3294 3295 3296
JULY 2008
4.5.2 System Design Considerations
4.6
Oral dosage (―dry‖) product handling areas (i.e. centrifuge, dryer, blender, mill, pack-off rooms) do not require classified cleanrooms; however, they should be designed in a manner consistent with ISPE CNC practices. Areas serving bulk product that will be sterile products (including bulk Biopharm) should meet ISPE Grade 8. This corresponds to: HEPA filtration on the inlet air, low returns with local filtration on the outlet, high-pressure airlock, instrumentation for verification of room conditions. When in doubt, final bulk API areas should meet the requirements for dispensing of API in the finishing facility. Air systems should be once through where solvents or potent compounds are handled. Air systems may recirculate with the minimum Outdoor Air necessary to maintain pressure relationships, in support areas, where no solvents or potent compounds are handled. Manufacturing rooms should be fitted with low or combination high/low returns. Manufacturing rooms should be protected from migration of contaminants or solvent vapors via the use of pressure or tracking differentials. Where solvents are handled, 100% exhaust (once-through) systems are strongly recommended. Oxygen depletion and LEL monitors may be employed as appropriate to assure that dangerous conditions do not occur, especially when using recirculated systems. Such systems should also comply with fire and building codes. Provide LEV for dry product addition; drum handling, manways and spills in wet areas. Provide LEV for any containment devices. Provide spark-proof exhaust equipment serving process areas. Provide explosion proof or intrinsically safe electrical components in the exhaust air stream. Heating coils may not be required for systems in warm climates. Dehumidification and post cooling coils should be considered for low humidity room control or for facilities with limited cooling capacity. Humidification should be considered for cold climates where static control is a concern. Risk assessment should be performed to determine fan redundancy (parallel fans or fan walls) Unidirectional flow modules (LFU) that have recirculation should be supplied with a small percentage of fresh air to offset fan heat.
BIOLOGICS
4.6.1 System Schematic (Sample)
85
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3297 3298 3299 3300 3301 3302 3303 3304 3305 3306 3307 3308
JULY 2008
4.6.2 System Design Considerations See requirements for API above. Also refer to the ISPE Biopharmaceutical Facility Baseline Guide for area classification requirements.
4.7
ORAL SOLID DOSAGE (NON-POTENT COMPOUNDING)
4.7.1 System Schematic (Sample)
86
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3309 3310 3311 3312 3313 3314 3315 3316 3317 3318 3319 3320 3321 3322 3323 3324 3325 3326 3327 3328 3329 3330 3331 3332 3333 3334
JULY 2008
4.7.2 System Design Considerations
Further discussion for Oral Solids Dosage facilities is covered in the ISPE Baseline Guide for OSD. Oral dosage facilities do not require areas with assigned cleanliness classifications. Process and process support areas, however, require critical parameters to be controlled and maintained to protect the product from contamination, whether from another product in a multi-product facility or from external or personnel contamination. Low returns in CNC (w/local monitoring) areas are recommended and should be located behind process equipment where applicable and where clearance is sufficient to allow proper air extraction from the space. CNC (airflow filtration with access control) areas do not require low level returns but can be used if deemed necessary by the design team. AHU filtration – min 30% followed by 85% filtration is recommended. Final filtration - 95% DOP efficiency is recommended in exposed Oral Solid Dose and dry bulk (non-Aseptic) product areas, but terminal HEPA filters may be more practical. Where terminal HEPA filters are employed for cross-contamination control, 95% pre-filtration will maximize terminal filter life. HEPA filtration may be considered to prevent cross-contamination and limit operator exposure in all recirculation systems.
87
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3335 3336 3337 3338 3339 3340 3341 3342 3343 3344 3345 3346 3347 3348 3349 3350 3351 3352 3353 3354 3355 3356 3357 3358 3359 3360 3361 3362 3363 3364 3365 3366 3367 3368 3369 3370 3371 3372 3373 3374 3375 3376 3377 3378 3379 3380 3381 3382 3383 3384 3385 3386
JULY 2008
Non-recirculation systems do not require HEPA filtration for crosscontamination control. All return or exhaust air grilles should be equipped with 30% ―dust stop‖ filters. Recirculation systems may be applied in multi-product areas, where solvents are not present. Recirculation of room air is not recommended when solvents are present. Recirculation of room air is not allowed when solvents may be present above 25% of LEL.. Where solvents are occasional and in small volume, return air duct should be equipped with hydrocarbon sensors to switch the system to 100% outdoor air in the event of a spill. Recirculation of return air from production areas to supply nonproduction areas without treatment is not acceptable. Cleanliness of open processing areas should be maintained via control of airflow between product handling area or airlock and surrounding spaces. Isolation via airflow from a clean airlock (pressure bubble or pressure sink) or corridor into the area of highest contamination is strongly recommended. Where solvents are used, this configuration is required. Monitoring and alarming of direction of airflow (through differential pressure, hotwire velocity sensors, or flow tracking) to surrounding rooms is strongly recommended. Airflow and makeup air delivery should be directed to flow from the operator‘s breathing zone and the room entrance, toward the source of airborne dust. Non-aspirating diffusers are recommended to minimize air disturbances, eddies and re-entrainment of dust. Provide LEV for control of fugitive emissions at open operation or equipment break point. LEV for open operation should be designed and engineered according to ACGIH standards. Recirculation of LEV exhaust within a production room requires HEPA filtration. Consult the ACGIH Ventilation Manual decision analysis and design criteria for guidance on when recirculation is acceptable. Recirculation of LEV exhaust to the AHU is not acceptable. Filtration of LEV through HEPA filters, scrubbers, or other equivalent treatment methods prior to release outdoors is required. For operations that generate or have the potential to generate active dusts or aerosols – LEV must be provided at all emission points. Leak free connections are recommended. A testing and preventative maintenance program will ensure the integrity of HEPA filtration system and LEV performance. Dust collection systems designed to allow removal of contaminated media without contact or exposure with these compounds (e.g. bag in/bag out HEPA filters) should be considered. Heating coils may be required for systems in cold climates with higher percentages of outside air. Dehumidification and post cooling coils should be considered for low humidity room control or for facilities with limited cooling
88
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3387 3388 3389 3390 3391 3392 3393 3394 3395 3396 3397 3398
3399 3400 3401 3402 3403 3404 3405 3406 3407 3408 3409 3410 3411 3412
4.8
JULY 2008
capacity. Humidification should be considered for cold climates where static control is a concern. Risk assessment should be performed to determine the need for fan redundancy (parallel fans or fan walls) Unidirectional flow hoods (UFH) that have recirculation should be supplied with a small percentage of fresh air to offset fan heat.
ORAL SOLID DOSAGE (POTENT COMPOUNDING)
4.8.1 System Schematic (Sample)
4.8.2 System Design Considerations Potent OSD facilities should follow the guides above for OSD, with the following exceptions
A minimum, filtration of ASHRAE 85% (MERV 13 or 14) shall be provided to the Supply Air if 100% once-through. Closed containment is the primary means of control for this class of material. If processes are proven closed, recirculated air should include HEPA filtration. Local Exhaust Vents (LEV) should be provided at points in which containment is broken and as needed, in conjunction with other 89
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3413 3414 3415 3416 3417 3418 3419 3420 3421 3422 3423 3424 3425 3426 3427 3428 3429 3430 3431 3432 3433 3434 3435 3436 3437 3438 3439 3440 3441 3442 3443 3444 3445 3446 3447 3448 3449 3450 3451 3452 3453 3454 3455 3456 3457 3458 3459 3460 3461 3462 3463 3464 3465
JULY 2008
technologies. LEV should be used for solvent extraction only where containment is not technically feasible (i.e. maintenance activities, etc.). Where LEV is used with any possibility of duct contamination, HEPA filters should be installed near the room, before the AHU. Isolation via active control of direction of airflow (using differential pressure, hotwire velocity sensor, or flow tracking) into the area of highest contamination from surrounding areas is strongly recommended. Monitoring and alarm of direction of airflow is required. Alarms should be recorded at a manned workstation (control room or maintenance center). Audio and visual alert on loss of airflow containment should be transmitted to the controlled space Room air locks/anterooms are recommended for powder handling areas to provide a barrier that maintains a positive airflow differential with respect to the corridor and the processing room (this may also serve as a gowning area). Airflow into de-gowning areas should be negative with respect to the corridor and processing area to contain particles shed from clothing. A secondary control against the spread of active materials is direction of airflow within the room. Supply air should be directed to flow across the operator‘s breathing zone before crossing the source of dust. Wherever possible, supply air should be directed to flow from a location near the room entrance toward the source of dust and finally out low returns mounted on the far wall. A dedicated HVAC system is recommended for the controlled area. It is strongly recommended that any air leaving the processing room boundary NOT be recirculated. Design main air systems for 100% exhaust, once-through supply. However if air recirculation within the controlled area is required, – employ double HEPA filtration (supply and return) combined with semiannual filter integrity test. Recirculation of air from the controlled space into other areas is not acceptable. Recirculation of local exhaust (LEV) from equipment is not acceptable. Filtration of exhaust from dry product handling areas and LEV through HEPA filters, scrubbers, or other equivalent treatment methods prior to release outdoors is required. It is recommended that exhaust/return filters be located as near to processing area as possible to reduce length of potentially contaminated air ducts. Where containment equipment is provided and PPE is not required, HEPA filters are intended to protect the AHU and facility in case of an accidental release. These should be a room-accessible type – BagIn/Bag-Out is not required, PPE can be used for change-out if needed. Exhaust/Return HEPA filters not located within the room, or where airborne powders are expected, should be safe-change type with BI/BO housing and bubble tight dampers. Terminal HEPA supply filters are required for protection against backflow if product containment should fail during AHU failure. 90
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3466 3467 3468 3469 3470 3471 3472 3473 3474 3475 3476 3477
3478 3479 3480 3481 3482 3483 3484 3485 3486 3487 3488 3489 3490 3491
4.9
JULY 2008
A testing and preventative maintenance program to ensure the integrity of HEPA filtration systems is required, on no less than an annual basis. Filters on processes requiring PPE should be tested more frequently. Appropriate monitoring and interlocking with process equipment should be considered to maintain containment integrity and to control cross contamination and emissions.
ASEPTIC PROCESSING FACILITY
4.9.1 System Schematic (Sample)
4.9.2 System Design Considerations
Considerable background on the design of HVAC systems is covered in the ISPE Baseline Guide for Sterile Manufacturing Facilities. Eliminate contamination introduced through the air conditioning supply system by utilizing properly installed and integrity tested ceiling mounted terminal HEPA filters. Minimize infiltration of contamination from uncontrolled areas by the use of room pressure differentials and airlocks between air classes. Continuous room pressure monitoring with alarms and recording devices that indicate out of spec conditions are recommended. 91
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3492 3493 3494 3495 3496 3497 3498 3499 3500 3501 3502 3503 3504 3505 3506 3507 3508 3509 3510 3511 3512 3513 3514 3515 3516 3517 3518 3519 3520 3521 3522 3523 3524 3525 3526 3527 3528 3529 3530 3531 3532 3533 3534 3535 3536 3537 3538 3539 3540 3541 3542 3543 3544
JULY 2008
Consider automatic pressure controls to keep the spaces within specified pressure limits where process exhausts change, or where door and hatch are frequently opened or door seal integrity varies. Dehumidification and post cooling coils should be considered for low humidity room control. A dedicated air handling system is recommended, serving only the aseptic area and remaining operational for required pressure control when the main building systems are shut down during unoccupied periods. HVAC systems for classified spaces should operate 24hours/day – 7 days/week. Risk assessment should be performed to determine the need for fan redundancy (parallel fans or fan walls) Consider utilizing standby electric power generating systems to maintain fans and design pressure differentials in the event of local power failures. The air handling system should be of the constant volume terminal reheat type utilizing industrial grade equipment. Ductwork should be designed per SMACNA standards but in no case should it be constructed for less than 4" water gauge duct static pressure and seal Class "A". Ductwork should be galvanized steel except where exposed (to a minimum extent) in production areas or subject to moisture, in which case it should be a minimum 304 stainless steel with cleanable finish. Cleaning materials used in the room should be considered. Silencers are not recommended as they can harbor contaminants and viable organisms. The supply fan should be equipped with dampers, vanes or speed controls which can be reset in order to maintain design airflow for the life of the air filters (whose pressure drop increases with time). Air to an aseptic area should be supplied through ceiling mounted terminal HEPA filters. These terminal HEPA filters become part of the aseptic boundary and protect the room from outside contamination. The use of only remote bank mounted HEPA filters in the supply duct is not recommended. Access ports to introduce and monitor PAO (aerosol) challenge materials upstream on the nonaseptic side of the HEPA diffusers are suggested for filter integrity testing. Air supplied through ceiling mounted terminal HEPA filters should be returned at floor level through multiple return duct drops. Return air to the recirculation unit should be filtered through 30% ASHRAE pleated and 85% or 95% ASHRAE bag filters to extend HEPA filter life. Recirculation HEPA/fan units mounted below the ceiling are not recommended as they require service within the aseptic area, do not normally utilize low returns, and lack adequate pre-filtration. The return air openings in the aseptic area should be located near the floor, preferably on at least two (2) walls and along the long dimensions of the room to ensure maximum uniformity of airflow. More return openings are better than too few. Differential air pressure should be employed to minimize infiltration of contaminants from outside the controlled area. The aseptic area should be designed for a positive pressure with all doors closed in relation to less clean adjacent areas outside the 92
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3545 3546 3547 3548 3549 3550 3551 3552 3553 3554 3555 3556 3557 3558 3559 3560 3561 3562 3563 3564 3565 3566 3567 3568 3569 3570 3571 3572 3573 3574 3575 3576 3577 3578 3579 3580 3581 3582 3583 3584 3585 3586 3587 3588 3589 3590 3591 3592 3593 3594 3595 3596 3597 3598
JULY 2008
controlled area (refer to latest issue of Federal Standard 209). Gowning areas should be supplied with air and maintained at a negative pressure relative to the controlled aseptic area and at a positive pressure relative to the outside and uncontrolled areas. Differential pressures are measured ACROSS airlocks (see the ISPE Baseline Guides for Sterile and Biopharm Facilities.) Each area should have an air supply and return with dampers to permit proper balancing. The room layout of the aseptic suite will dictate the pressure relationships to be maintained. The room with exposed product is to be maintained most positive; while ante rooms leading to this room are to be maintained successively less positive down to the zero reference level of uncontrolled areas (the general building). Only high-pressure Grade 7airlocks that have HEPA filtered supply air may have pressures higher than the aseptic filling room. A control range should be established for each room pressure level such that the pressure can float within the range and still satisfy the specified differentials. A remotely operated or automatic damper may be provided in the return air duct from each room as a means of obtaining and setting the established pressure differentials. Simple facilities may be successfully balanced using only manual dampers, especially if terminal HEPA filters do not load quickly. If manual / remotely operated dampers are used, the remote damper controls should be tamper-proof or concealed in a lockable cabinet accessible to authorized personnel only. A differential pressure gauge should be provided for each room adjacent to the remote damper controls. The manual/remote gauges and controls or automatic controls should be mounted in a common panel outside the controlled area. An audible alarm may be provided to indicate loss of area pressure control. This alarm may be manual reset type and equipped with a hard copy printout that indicates the out-of-range alarm. Unidirectional airflow serves as a barrier between product and microbial and particulate contamination generated by the equipment and personnel within the aseptic area. Where possible, terminal HEPA filters should be located directly over the exposed product, components and equipment that are not protected by UFH. When the central system air conditioning air quantity required to maintain room conditions is not sufficient to provide protection over the product, components, and equipment, a supplemental HEPA filtered air recirculating system may be employed. Because all of the cooler central system conditioned air is not supplied over the equipment, it may be distributed to the area in a checkerboard fashion or into the local recirculating fan inlet to maintain room temperature. The engineer should consider the heat generated from the local recirculating system fan motor. This particular oversight is quite common and can lead to serious temperature stratification and overheating in the aseptic area. Airflow patterns within the work space may be uniform with minimum turbulence. Ambient air may not aspirate into the work areas along the perimeter of the unidirectional airflow barrier. The heights and filter area should deliver Class 100 air at a velocity of 90 feet (27.5 meters) per minute, with uniformity within plus or minus 20%, measured at the filter face. Velocity at the work height should also
93
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3599 3600 3601 3602 3603 3604 3605 3606 3607 3608 3609 3610 3611 3612 3613 3614 3615 3616 3617 3618 3619 3620 3621 3622 3623 3624 3625 3626 3627 3628 3629 3630 3631 3632 3633 3634 3635 3636 3637 3638 3639 3640 3641 3642
JULY 2008
be measured. The optimal filter face velocity should be determined during qualification of the UFH using airflow visualization (―smoke testing‖). See the ISPE Sterile Baseline Guide. Room temperatures should be controlled by maintaining constant airflow and modulating a heating coil. Systems in which varying flow is used as a means of controlling room temperatures are unacceptable because of their adverse effects on room pressures. Where low relative humidity is required, special attention may be given to sealing the return duct systems to prevent inward air leakage from uncontrolled areas and resultant high humidity.
4.9.3 Aseptic Potent Compounds:
Processes should be contained in isolators, with dedicated HVAC for the containment enclosure. Where the process leaks into the room, protect the HVAC system and other rooms on the system from hazardous compounds by utilizing nonrecirculating primary air conditioning systems. The exhaust or return air ducts must be fitted with HEPA filters protected from physical damage with a pre-filter or equivalent. These filters should be located within the room where they can be serviced by properly gowned and protected personnel. If filters are located remote from the room where open processing occurs, they should be housed in a high containment bag-in/bag-out filter housing and identified as such. These filters contain the potentially hazardous compounds and minimize particulate "fall back" during fan failure. Gowning areas shall be supplied with air and maintained at a negative pressure relative to the controlled aseptic area and at a positive pressure relative to the uncontrolled areas. The gowning area should be separated from the aseptic filling room by a high pressure airlock. The de-gowning area must be separated from the aseptic filling room by a low pressure airlock. The de-gowning room shall be maintained negative relative to adjacent spaces on the uncontrolled side. Material entering the aseptic filling room must be transferred via a HEPA filtered, high pressure tunnel, box or sterilizer. Material leaving the aseptic filling room must be transferred via a low pressure tunnel or box.
4.10 PACKAGING/LABELING 4.10.1
System Schematic (Sample)
94
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3643 3644 3645 3646 3647 3648 3649 3650 3651 3652 3653 3654 3655 3656 3657 3658 3659 3660 3661 3662
4.10.2
JULY 2008
System Design Considerations
See the PACLAW Baseline Guide for product requirements. Most products require a clean area for packaging, with HVAC meeting CNC. Heating coils may be required for systems in cold climates with higher percentages of outside air. Dehumidification and post cooling coils should be considered for low humidity room control. Humidification should be considered for cold climates where static control is a concern. Return fan and mixing sections may not be required for areas with no pressure requirements, small local exhaust fans may be considered.
4.11 LABS 4.11.1
System Schematic (Sample)
95
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Supply
Exhaust
AMD
AMD
EX2 Hood flow control
Infiltration
LAB
HOOD
Infiltration + Supply = Exhaust NOTE: An arbitrary value for INFILTRATION is chosen, then SUPPLY is adjusted to track exhaust. If supply is insufficient to satisfy room heat load, more exhaust (EX2) may be needed.
3663 3664 3665 3666 3667 3668 3669 3670 3671 3672 3673 3674 3675 3676 3677 3678 3679 3680 3681 3682 3683 3684 3685 3686 3687 3688
AMD=Airflow Monitor
Figure 4-12 Typical Lab HVAC schematic 4.11.2
System Design Considerations
Further information on Labs for Quality Control is included in the ISPE Baseline Guide for Quality Labs. Laboratories using volatile solvents or radioisotopes should be negative (commonly via airflow tracking) relative to corridors, offices and adjacent occupied space. Air from offices or technical spaces adjacent to laboratories should transfer into the laboratory. Classified clean lab spaces should be positive (via airflow tracking) relative to corridors, offices and adjacent occupied space. Provide a high pressure airlock where activities in positively pressurized spaces pose a threat to corridor air quality. Where chemicals or other hazardous materials are handled, air systems should be one hundred percent (100%) exhaust. Recirculation of this laboratory air is not acceptable. Variable Volume Airflow Control Systems are recommended for increased safety through monitoring capabilities and decreased energy usage (using hood diversity and variable flow). Where the minimum ventilation rate (for building or fire code) is greater than the total exhaust from hoods, VAV is NOT recommended. Diffusers should be non-aspirating type selected and located to minimize velocity & turbulence near the hood face; design cross
96
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3689 3690 3691 3692 3693 3694 3695 3696 3697 3698 3699 3700 3701 3702 3703 3704 3705 3706 3707 3708 3709 3710 3711 3712 3713 3714 3715 3716 3717 3718 3719 3720 3721 3722 3723 3724 3725 3726 3727 3728 3729 3730 3731 3732 3733 3734 3735 3736 3737 3738 3739 3740 3741
JULY 2008
drafts should not exceed 30 FPM within 24 inches of the hood opening. 100% outside air handling units are prone to stratification; use variable temperature constant internal flow volume pumped preheat coils or blenders to limit this effect. Provide propylene glycol solution, IFB coils or a reliable, alarmed, pumped chilled water coil to prevent freeze-ups. Silencers can help decrease noise from properly sized exhaust manifold valves. Use packless type for chemical exhaust applications located between the box and hood. Do not oversize VAV boxes. Oversized boxes yield poor airflow control and have a limited range. As a minimum exhaust fans should be AMCA Type B spark resistant construction. Galvanized exhaust ducts, boxes and attenuators should be used except where process or research activity requires special corrosion resistance. Laboratory hood exhaust ducts and accessories which are inaccessible should be stainless steel (304). Laboratory hood exhaust ducts which handle large quantities of acids should be high grade stainless steel, Hastelloy, FRP or other suitable material (stainless steel will corrode rapidly in the presence of high molar concentrations of Hydrochloric Acid). The use of dilution air to maintain stack velocity is not recommended. The exhaust from most chemical laboratories is primarily composed of air. Maintain 10'-0" minimum stack height above building roof; although a stack height equal to 30% of the building height is preferred. If necessary, use variable geometry stacks (not Strobic fans) to maintain velocity at reduced airflows. Locate stacks to avoid re-entrainment of air into HVAC (considering the prevailing winds). VAV systems should be sized with a diversity factor to allow for savings in airflow and first cost of central heating and cooling equipment. A factor of 70% of installed load is common; however, the diversity factor must take in to account the anticipated hood use. If 50% sash height is considered as full flow, do not use a further diversity factor. Hard connect exhaust wherever possible. Provide positionable arms (such as Plymovent or Alsident) for point exhaust sources which do not support hard duct connections. These supplemental point exhausts should be served by an independent exhaust box (where possible) or connected directly to the main (with a volume damper or blast gate). A general room exhaust should only be provided when the hood flows at minimum sash position provides an air change rate less than that required to meet heat loads or the specified minimum air change rate. Air change rate or exhaust quantity will usually dictate the supply air quantity. Exhaust quantities should be reset upward when additional cooling is required. Mount VAV lab controls in accessible panels either flush in alcove outside lab, or in dedicated room. Manifolded exhaust systems are preferred except for perchloric acid hoods. Use of energy conserving enclosures such as glove boxes is
97
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3742 3743 3744 3745 3746 3747 3748 3749 3750 3751 3752 3753 3754 3755 3756 3757 3758 3759 3760 3761 3762 3763 3764 3765 3766 3767 3768 3769 3770 3771 3772 3773 3774 3775 3776 3777 3778 3779 3780 3781 3782 3783 3784 3785 3786 3787 3788 3789 3790 3791 3792 3793 3794
encouraged. Exhaust ductwork does not normally require insulation. Approved exhausted chemical storage cabinets should be provided for solvents and hazardous materials. Recover heat from laboratory utility equipment wherever possible. Provide temperature alarms on refrigerators or freezers. Where critical, connect these to the BAS. Where laboratory offices are on the exterior wall, heating at the perimeter wall is recommended. The use of emergency power for exhaust systems should be considered on a case-by-case basis. In multi-fan manifolded systems the use of emergency power for at least one fan should be considered. Where emergency power is not provided for exhaust fan(s) the hood alarms should be connected to emergency power or furnished with UPS to signal exhaust failure. Supply Air Filtration - 30% ASHRAE and 85% ASHRAE (in series) Exhaust Air Filtration - None (where energy recovery is employed 30% ASHRAE filters are required). Scrubbers may be required for some dedicated hoods.
4.11.3
JULY 2008
Vivarium:
Vivarium facilities should consist of individual suites, each capable of maintaining its own "microenvironment", for the duration of the product study. A system for control of room airflows and relative pressurization should be provided. Actual set points and directions of flow are dependent upon the operating plan of the space and must be determined on a case-by-case basis. Ceiling-mounted non-aspirating diffusers, coupled with a minimum of two (2) low returns on opposite walls with hinged stainless steel grilles fitted with dust stop filters behind the grille, should be employed and should be arranged so as to minimize crosscontamination between subjects and between researchers and subjects. The axis of the non-aspirating diffuser radial fins should be parallel with the wall containing the low exhaust registers. Slope exhaust air grille back box and provide weep holes so that wash down water that might be sprayed into the system will drain back to the room. Humidity control should be provided for each room adjustable to a set point between fifty and sixty percent (50-60%), plus or minus ten percent (+/- 10%) RH of set point. Humidifiers utilizing clean steam should be provided centrally to maintain forty percent (40%) RH with ―trim‖ humidifiers capable of an additional thirty percent (30%) at each room. In colder climates, provide humidifiers in two locations within the AHU to allow the large amount of moisture to be added gradually, i.e., two thirds / one third. Temperature regulation should be provided for each room adjustable to set point using terminal individual reheat. Temperature, humidity and airflow transmitters should be located outside the room, in exhaust ductwork whenever possible. Edstrom and ATC sensors should be located adjacent to one another if possible. HEPA filtration of room supply and exhaust air may be required, 98
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3795 3796 3797 3798 3799 3800 3801 3802 3803 3804 3805 3806 3807 3808 3809 3810 3811 3812 3813 3814 3815 3816 3817 3818 3819 3820 3821 3822 3823 3824 3825 3826 3827 3828
JULY 2008
subject to researcher and CDC/NIH requirements. Air systems should employ one hundred percent (100%) OA supply and one hundred percent (100%) exhaust. Supply systems should employ 95% PAO final filtration (minimum MERV Rating = 15) at the AHU to minimize contamination entering the building. Exhaust systems should employ a minimum of 30% ASHRAE certified filters (minimum MERV Rating = 8) in room with provisions for carbon and HEPA filters to be provided in the future at a central location, if required. Duct construction within rooms should be cleanable and concealed wherever possible. Exposed ductwork should be Type 304 stainless steel with Type 4 finish (Owner approval required). Concealed exhaust ductwork from grille to above the ceiling should be 304 stainless steel. Air systems should have back up capacity to provide required room conditions and air change rates in the event of a power or equipment failure. Back-up refrigeration capacity may also be required and is contingent upon research requirements. (Risk assessment) Room airflow and temperature/RH set points should default to minimum when the room is vacant (no animals in residence), however, room differential flows must remain intact even when a room is unoccupied. Air filtration must be accessible for replacement without shutdown of HVAC. Secondary filters should be installed prior to the reheat coil, to be replaceable with minimum disturbances to the space. If furnished with HEPA filters, provide a means for introducing PAO and performing filter integrity testing on a room-by-room basis.
4.12 SAMPLING/DISPENSING 4.12.1
System Schematic (Sample)
99
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3829 3830 3831 3832 3833 3834 3835 3836 3837 3838 3839 3840 3841 3842 3843 3844 3845 3846 3847 3848 3849 3850 3851 3852 3853
4.12.2
JULY 2008
System Design Considerations
Specific product requirements are in the appropriate Baseline Guide. Once through air may be used for multi-product or solvent use. Heating coils may be required for systems in cold climates with higher percentages of outside air. Dehumidification and post cooling coils should be considered for low humidity room control. Humidification should be considered for cold climates where static discharge control is a concern. Risk assessment should be performed to determine the need for fan redundancy (parallel fans or fan walls) Unidirectional flow modules (LUFH) that have recirculation should be supplied with a small percentage of fresh (or cooled) air to offset fan heat. Return fan and AHU mixing sections may not be required for areas with no pressure requirements, small local exhaust fans may be considered.
4.13 ADMINISTRATIVE AND GENERAL BUILDING 4.13.1
System Schematic (Sample)
100
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3854 3855 3856 3857 3858 3859 3860 3861 3862 3863 3864 3865 3866 3867 3868
4.13.2
JULY 2008
System Design Considerations
Heating coils may be required for systems in cold climates with higher percentages of outside air. Humidification should be considered for cold climates where static control is a concern. Return fan and mixing sections may not be required for areas with no pressure, small local exhaust fans may be considered.
4.14 WAREHOUSE 4.14.1
System Schematic (Sample)
101
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
3869 3870 3871 3872 3873 3874 3875 3876 3877 3878 3879 3880 3881 3882 3883 3884 3885 3886 3887 3888 3889 3890 3891 3892 3893 3894
4.14.2
JULY 2008
System Design Considerations
See the PACLAW Baseline Guide for further information. Many warehouse facilities do not have central air handling, using only unit heaters. Be sure that air outlets do not overheat high stacked material. Heating coils may be required for systems in cold climates with higher percentages of outside air. Humidification should be considered for cold climates where static control is a concern. Return fan and mixing sections may not be required for areas with no pressure, small local exhaust fans may be considered. Mapping of temperature extremes in high bay warehouses is recommended.
4.15 PROCESS EQUIPMENT CONSIDERATIONS In many cases there are specific requirements for equipment, or aspects to consider when looking at the HVAC design for the area containing equipment. 4.15.1
Dust extract systems
Where there is a common dust extract system there are a number of 102
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3895 3896 3897 3898 3899 3900 3901 3902 3903 3904 3905 3906 3907 3908 3909 3910 3911 3912 3913 3914 3915 3916 3917 3918 3919 3920 3921 3922 3923 3924 3925 3926 3927 3928 3929 3930 3931 3932 3933 3934 3935 3936 3937 3938 3939 3940 3941 3942 3943 3944 3945 3946 3947 3948 3949
JULY 2008
aspects to consider in the design:
What happens if the unit fails? Does the unit have a damper that closes, preventing air leaving the system – is the pressure difference between the rooms served by the system adequate to obtain flow – with a consequential risk of cross contamination?
How does the unit clean? Some units are cleaned by a shaker mechanism, others use a pulse of compressed air – during this pulse, which is in the opposite direction to the normal airflow the extract air flow can halt , or even reverse for a short period, - is this acceptable?
It should be noted that one of the advantages of a remote system (be it a common or dedicated system) is that the system heat gain is outside the room, also the extract is often located near an area where the equipment heat gain is high, so those gains are extracted from the room, reducing the load on the area HVAC system.
4.15.2
Granulators/Coaters/Fluid Bed Dryers
These units typically have dedicated air handling systems that are independent of the area HVAC. The design should consider what happens during periods of non use – is there potential for moisture to migrate from the outside environment into the system, if the outside is high humidity. What are the risks of corrosion during use – what ductwork materials should be used? What areas of the duct are pressurized - what is the risk of drawing in untreated air – what is the risk of potentially contaminated (with product) air leaking out? 4.15.3
Glassware depyrogenation tunnels
These units present a challenge to the HVAC system designer, as they are generally located between rooms with different area classifications (grades) and they operate intermittently, yet area pressure differentials are typically help at a consistent level – this usually means some type of active pressure control. (it should be noted that with the increasing use of risk analysis to determine areas of patient/product risk, there may be opportunities to reduce the room differential pressures during periods of no production). As the units are started up, and the temperatures /volumes stabilize there is a dynamic period in terms of changing airflow. 4.15.4
Isolator systems
Barrier-isolator technology may be applied to certain processes where aseptic processing and/or containment of hazardous materials are 103
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 3950 3951 3952 3953 3954 3955 3956 3957 3958 3959 3960 3961 3962 3963 3964 3965 3966 3967 3968 3969 3970 3971 3972 3973 3974 3975 3976 3977 3978 3979 3980 3981 3982 3983 3984 3985 3986 3987 3988 3989 3990 3991 3992 3993 3994 3995 3996 3997 3998 3999 4000 4001 4002 4003 4004
JULY 2008
required. Using Isolator technology for aseptic processing and/or hazardous material will reduce the exposure of operators the operators to disinfection and fogging chemicals that be used in the aseptic processing suite of a conventional
containment of and product to would normally cleanroom.
Isolators should be automatically decontaminated by Vapor Phase Hydrogen Peroxide and then aerated to achieve concentrations of VHP that are less than one part per million. This operation should take place within the isolator so that there is no operator exposure to the VHP. The outside room should be monitored by VHP sensors as a further safety measure. Monitoring for particulate and viable particles should be done within the isolator. The isolator air handling unit obtains supply air from the surrounding room and during different modes of operation returns to either the room or exhausts to the roof. For aseptic processing of non-potent products, intake air during production mode should be taken from the room and returned back to the room, while during aeration mode air should be taken from the room and exhausted through an independent exhaust air system. For potent compounding, intake air during production and aeration should be taken from the room and exhausted through an independent exhaust air system. Air velocity during production is maintained to +/-20% of the average airflow, and is delivered from the HEPA air filter at a rate of 90 fpm (0.45 meters/sec) (measured at 12‖ or 300mm (nominal) below air filter face or air inlet diffuser (CG membrane or equivalent). Reduced air speed may be used during H2O2 bio-decontamination. Fresh air is provided to the inlet of the HEPA filter. Air is recirculated from isolators chamber back to isolators plenum should be ducted by internal double glass windows or doors. A differential pressure device with display and alarming capabilities monitors the differential pressure between the internal zone (filter plenum) and the outside room pressure. The air classification required for the background environment depends on the design of the isolator and the application. Room cooling loads for spaces in which isolators are located must take into account the heat generation by the isolator fan system(s). The most common agent for decontamination of isolators is vaporized hydrogen peroxide (VHP). Consideration should be given to treatment, e.g., catalytic converter, etc., of VHP gas prior to discharging to ambient at the end of the sterilization cycle. Fresh air make-up from the surrounding room should pass through HEPA filters via the isolator. Exhaust air from VHP sterilization should have a scrubber or VHP neutralization. HEPA filters should be readily changeable from outside the Isolators. Each zone will have access ports upstream the HEPA filtration to allow for introduction of DEHStest aerosol for filter integrity testing.
104
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4005 4006 4007 4008 4009 4010 4011 4012 4013 4014
JULY 2008
Filter faces shall be accessible with the fans operational forfilter integrity scanning. The temperature control of all zones is provided by a cooling system of the intake air taken out of the room. A temperature measuring transmitter with display and alarming capabilities will control and monitor temperature.
105
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4015 4016 4017 4018 4019 4020 4021 4022 4023 4024 4025 4026 4027 4028 4029 4030 4031 4032 4033 4034 4035 4036 4037 4038 4039 4040 4041 4042 4043 4044 4045 4046 4047 4048 4049 4050 4051 4052 4053 4054 4055 4056 4057 4058 4059 4060 4061 4062 4063 4064
JULY 2008
5
DESIGN QUALIFICATION / DESIGN REVIEW (DQ/DR)
5.1
DESIGN REVIEW/ DESIGN VERIFICATION/DESIGN QUALIFICATION
There is one important thing to remember about design reviews – it is far easier and cheaper to change a design before it is constructed, than during or after construction. The process of reviewing a design (drawings and specifications) as it develops from concept to issue for construction status has a number of objectives:
To ensure that the design follows the clients preferred custom and practice To ensure that the design will perform to meet client expectations To ensure that the concepts proposed are capable of performing to meet the requirements defined in the User Requirement Specification (URS) in the clients opinion. To ensure that the design minimizes risk to product quality / patient. To ensure that the design is robust and will perform reliably To ensure that the design proposed is cost effective.
For systems able to affect product quality it is common practice to split these design reviews into two categories – (although this is not mandatory): Engineering reviews Quality (or GMP) focused reviews Similarly it is common to perform a final specific ―quality‖ review to confirm that the system (and the specified related conditions for area it serves – Temperature, Humidity, Particle Classification, Differential Pressures etc.) comply with GMP regulations/company standards – this review may be called ―Design Qualification‘, or ―Design Verification‖, allowing the statement to be formally made that –―the design is fit for its intended purpose‖, as well as confirming that the requirements defined in the URS are compliant. It should be noted that there is not a mandatory requirement to perform this review – the process of approving the design to be released for construction or the overall review process may also be considered a verification or qualification of the design, because it confirms that all client comments have been adequately addressed, and the client agrees with releasing the design for use. An overview of a typical diagrammatically below:
design
106
/design
review
process
is
shown
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Project Initiation / & Concept Design
Divide the scope into systems
Yes – then write system URS
Ability to impact product Quality
Design Development
Change control
No – then no specific URS is generally required.
Design Reviews
Approve Design
4065 4066 4067 4068 4069 4070 4071 4072 4073 4074 4075 4076 4077 4078 4079 4080 4081 4082 4083 4084 4085 4086 4087 4088 4089 4090 4091 4092 4093 4094 4095 4096 4097 4098 4099 4100 4101 4102 4103 4104
Issue for Construction Design
Figure 5-1 Diagram of Design Review Process (Arrows missing) An effective design review is dependant on the people conducting it, although most companies are now trying to develop knowledge capture systems such as:
Design review checklists (An example is included as an attachment) Design guides – defining the preferred way of designing a given system
These approaches have a common objective of trying not to be prescriptive, losing the ability to consider novel concepts, ensuring that company experience is captured and considered.
too but
In order to make the process as effective as possible it is important to pre-define the method to be used, and agree the review participants. A preferred approach is to use a multi–disciplinary team to ensure all view points are considered, with Subject Matter Experts in HVAC, Controls and regulatory requirements. For areas where high system reliability is required, e.g. Vivarium, a formal review may be conducted, such as a FMEA, to ensure that the design is adequately robust. A simplified version of this approach may be beneficial even for simple manufacturing facilities considering the impact of system failures on adjacent areas, to ensure that the design is robust. Notes taken from the review will be implemented through drawing/specification changes; if the revision cross references the notes it is not necessary to formally close out all actions in this GEP environment – the SME who will sign off the drawing is expected to check that all necessary changes have been incorporated. In practice where there is a large project there will be multiple reviews at key stages – for example a review at the concept stage to ensure that the client team agrees with the proposals from the A&E design company – these may focus on individual systems, or on overall 107
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4105 4106 4107 4108 4109 4110 4111 4112 4113 4114 4115 4116 4117 4118 4119
JULY 2008
areas of the design, e.g. HVAC controls.. For smaller projects with perhaps only one system, there may be less reviews – the project team should agree the approach to be applied to a specific project.
5.2
INTRODUCTION
As the design is developed interested parties.
it
will
with
input
Typically the process is formalized to make it more efficient. An example of the approach is shown below:
Client URS
Concept design developed by A&E consultant Design revised to suit review comments
Design reviewed
Design revised to suit review comments
Design concept developed to detail level
Detail design reviewed
Completed design
4120 4121 4122 4123
evolve,
Figure 5-2 The Design Process
108
from
all
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4124 4125 4126 4127 4128 4129 4130 4131 4132 4133 4134 4135 4136 4137 4138 4139 4140 4141 4142 4143 4144 4145 4146 4147 4148 4149 4150 4151 4152 4153 4154 4155
JULY 2008
The design review process is intended to ensure that:
original ideas from the design team are captured and reviewed company specific requirements / standards are incorporated in the design (after an evaluation of potential benefits/drawbacks to ensure company requirements are ―best practices‖) the design will perform to meet the requirements defined in the URS the design is robust and will perform reliably
The review may be structured to cover all design aspects, or divided into two:
A GEP review - to ensure that engineering best practices incorporated A cGMP review - to ensure that all compliance requirements adequately addressed by the proposed design.
are are
The cGMP review is typically straight forward and consistent - it is expected that any resultant observations are tracked to ensure that they are addressed, with an audit trail created. The GEP review may be more involved, (a lot of knowledge and experience within a company can be captured and used in the review process) also a formal audit trail is not usually required for GEP observations – typically the reviewer ensures that comments have been addressed, hence there may be a benefit in keeping independent reviews. This suggestion is developed challenges shown below:
into
a
series
of
categorized
Table 5-1 Design concept stage cGMP review Design Challenge Are the units and associated controllers located in a controlled access space? Maintainability
Response
(Consider accessibility to key components of the system, filter maintenance requirements, filter integrity testing (if required), regeneration requirements, emissions, etc.) Review and evaluate the AHU service distribution drawing and consider the following: How many AHU units (zones) are proposed, is the zoning based on the process requirements?(.)
109
Action
design
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Are the airflow directions / differential pressures correct to control product exposure / cross contamination? Are the temperature and humidity design and operating conditions defined? Are any area classifications required / defined? Are the systems once through or recirculating? (Are there provisions to handle solvents, high potent compounds or high particle generating operations, as required by the product/process operations?) Is the control scheme clearly defined, including monitoring and alarm requirements? 4156 4157 4158 4159
Figure 5-2 Detail Design or IFC stage cGMP review Design Challenge Have the peak external design conditions been established from a reliable source, which considers local geographical features/ meteorological factors – lakes, prevailing wind direction etc? Has the user defined availability requirements for the products to allow the design external conditions to be defined? (i.e. the percentage of time that the facility will be able to maintain the manufacturing conditions) Are the internal requirements specified:
Response
Temperature / humidity / airflow direction – area differential pressures/classification. Review location of outside air intake and exhaust. Is the prevailing wind direction defined for the site, with the HVAC inlet and outlet locations defined to demonstrate no risk of recirculation? Is the facility divided into 110
Action
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW Design Challenge manufacturing zones (areas)? What rationale is used to divide the facility into zones? Is the location of the monitoring sensors specified such that they will give representative readings of the space conditions: are they easily accessible for maintenance and calibration activities?
JULY 2008 Response
Action
Response
Action
(For large areas, such as a warehouse multi-point mapping and monitoring may be required, for smaller areas, 1 or 2 points is generally adequate, with the reading demonstrated as representative of the areas where product is susceptible to conditions during qualification using sensors. Consider the size of the room and the location of key process operations (e.g. product exposure) in establishing the location and number of monitored points.) If there area multiple air handling units servicing the manufacturing area, how will failure modes affect the intended operation? Will failure of one unit increase the risk of cross contamination? Is there a site drawing /component numbering system which has been used? Are airflow directions / differential pressures (from clean to less clean) appropriate to provide the minimum risk of product contamination / cross contamination, considering potential system failure modes? 4160 4161 Design Challenge Are there airlocks which separate areas of different classifications, with a target design DP of 15 Pa across the airlock?
111
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW Design Challenge The design airlock classification should be same as the area served when measured at rest.
JULY 2008 Response
Are the airlocks specified with interlocked doors? (It is recommended that the design differential pressure is a minimum of 15 Pa to allow for construction issues.) Does the process require containment; if so is exhaust air filtered using safe change high efficiency filters with suitable re-filters (bag-in, bag-out)? Are there any provisions to handle solvents, high potency drugs, and/or high particle generating materials? If so, are the provisions in line with the area GMP operational requirements? (Airflow should be designed to contain high potency compounds. For biotech facilities design shall conform to the Center for Disease Control biosafety control levels.) Are the air handling systems designed for re-circulation where appropriate, and with suitable return air filtration? What assumptions have been made to specify the position of the temperature sensor to ensure that it is representative of room conditions? What assumptions have been made to specify the position of the humidity sensor to ensure that it is representative of room conditions? Is there a qualified system for manufacturing areas to monitor and maintain records of temperature, humidity, and airflow direction? (Define what will be the system 112
Action
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Design Challenge of record and what will be the system of control.) Is there a locally mounted alarm indicator for any out of limit environmental condition temperature, humidity, airflow direction?
Response
Have alarm limits been defined based on product and process requirements Has the position of inlet/outlet grilles been specified where necessary? (If the area is classified, it is common practice to design with ceiling mounted supply grilles and return air taken at low level in the room? Is the area served a Laboratory, if so what considerations have been made for; fume hoods microenvironments, humidity rooms
e.g.
low
Sensitive scales? Does humidification use plant steam, if so does it use approved additives (21 CFR 173.310) or chemical free steam? (If so it should be injected before the final HEPA filter where one is used.) Is the ductwork specified using an appropriate allowance for leakage – is it shown on the design? Are the AHUs mounted inside, if not what provision is there to protect them and the staff from the weather during maintenance? Does the specification for the AHUs include access panels and test ports to facilitate maintenance, and HEPA filter testing if required? Are AHUs designed for constant volume, and low leakage of conditioned air? 113
Action
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW Design Challenge How does the specification of the AHU ensure that it will not degrade or corrode during its working life, to affect its performance? Are progressive pre-filters specified – what is the basis for their selection? What final stage filters are specified?
JULY 2008 Response
.
Are all classified areas served via 99.97 % efficient HEPA filters? (Note terminal filtration is preferred). (H13 specified for in situ leakage testing, or H 14) Are lockable dampers specified, and is there a requirement to record the as balanced setting in the commissioning records? Confirm that the specification permits no interior lining of ductwork, with any sound attenuators specified using non shedding lining. What Security arrangements are there for controls? What happens in the event of power failure? Is the ductwork made of Galvanized steel, or are there special requirements, for non classified areas does the specification limit the use of flexible ductwork to 4 feet long? Confirm that for classified areas the use of flexible ductwork is not permitted. What are the leakage allowances – are they appropriate? (The use of flexible hosing must be carefully evaluated. Maintenance requirements must be discussed as part of the review process.) 4162 4163 4164 4165
Figure 5-3 Design concept stage GEP review
114
Action
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW Challenge What considerations are made for reliability/robustness? Does the design proposed demonstrate current best practices? How are maintenance / calibration requirements addressed? How are failure modes considered? Are ceiling plenum returns proposed – if so how would the ceiling void be cleaned? 4166 4167 4168 4169
JULY 2008 Response
Action
Figure 5-4 Detail Design or IFC stage GEP review Cleanability Challenge Response What arrangements are made to facilitate cleaning the system internally? How does the design consider the risk of building sickness syndrome? Operability Challenge Response Are airflow directions proposed for any catering areas, to contain odor? Are there arrangements to extract from copier rooms? Is the AHU construction specified to avoid risk of external condensation? If not are the air handling systems designed for re-circulation where appropriate, and with suitable return air filtration? What assumptions have been made to specify the position of the temperature sensor to ensure that it is representative of room conditions ? What assumptions have been made to specify the position of the humidity sensor to ensure that it is representative of room conditions? How does the design allow for future changes in the room layout in terms of sensor locations and zoning? Maintainability Challenge Response Are the site specific requirements defined in terms of preferred suppliers?
115
Action
Action
Resolution
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
Are AHUs located in an area suitable for easy maintenance, suitably protected from the external environment to facilitate maintenance? Does the specification for the AHUs include access panels and test ports to facilitate maintenance? Is the system designed with progressive filtration? How have filter grades been decided – are they a site standard? Are lockable dampers specified, and is there a requirement to record the as balanced setting in the commissioning records? What Security arrangements are there for controls? What happens in the event of power failure? Is the fan drive external or a high efficiency/low loss design e.g. flat belt? What is the bearing design life at the maximum rated fan speed? Constructability Challenge Is the ductwork made of Galvanized steel, how is the internal finish specified, to ensure that the galvanizing is of good quality and finish? Does the ductwork specification limit the use of flexible ductwork to 4 feet long? 4170 4171
116
Response
Resolution
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4172 4173 4174 4175 4176 4177 4178 4179 4180 4181 4182 4183 4184 4185 4186 4187 4188 4189 4190 4191 4192 4193 4194 4195 4196 4197 4198 4199 4200 4201 4202 4203 4204 4205 4206 4207 4208 4209 4210 4211 4212 4213 4214 4215 4216 4217 4218 4219 4220 4221 4222 4223 4224
JULY 2008
6
EQUIPMENT FUNCTION, INSTALLATION, AND OPERATION
6.1
EQUIPMENT FUNCTION AND MANUFACTURE
6.1.1 Introduction The HVAC equipment section is geared around those items that deliver conditioned air to GMP spaces. The design and construction of the equipment is intended to meet safety, product and regulatory requirements while providing environmental comfort and protection to employees. They should have robust capabilities for achieving initial, continuous, and long-term operation, ease of maintenance, and low energy use. HVAC equipment serving GMP areas are intended to work in conjunction with associated controls and sequences of operation systems to:
Maintain room temperature and relative humidity Maintain room pressurization and differential pressure cascades Provide make up (fresh) air for ventilation and room pressurization Minimize airborne contamination delivered to the conditioned space Provide required air flow rates to maintain room cleanliness classification when required
6.1.2 Air Handler Unit (AHU) GMP air-handlers should be constructed to meet the more stringent performance, improved reliability, and maintenance requirements for critical areas being served. Air handler components such as coils, humidifiers, dehumidifiers, dampers, fans, motors, and filters should be designed and constructed so that the system can operate at 115% of anticipated design due to the potential for increased demand or future expansion. 6.1.2.1 Cabinet Construction In geographic regions of moderate to high humidity levels, consideration should be given to have no through metal (a thermal break) on all wall, floor, doorframe, ceiling sections and doors. Potential for exterior condensation is possible if thermal breaks are not properly designed and implemented. AHU designated to operate at locations with high temperature and humidity conditions should have a true thermal break construction. Total air leakage rate shall be no greater than ½% at 150% of the design positive/negative in total pressures or 50 cfm (1.42 m3/min), which ever is greater, or the requirements stated in the EN 1886 standard, for the most sever ―leakage class‖ operation. 6.1.2.2 Panel Insulating Materials It is recommended that roof, floor and ceiling panels be insulated with foam (polyisocyanurate) that is FM approved and meets NFPA fire rating. 117
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4225 4226 4227 4228 4229 4230 4231 4232 4233 4234 4235 4236 4237 4238 4239 4240 4241 4242 4243 4244 4245 4246 4247 4248 4249 4250 4251 4252 4253 4254 4255 4256 4257 4258 4259 4260 4261 4262 4263 4264 4265 4266 4267 4268 4269 4270 4271 4272 4273 4274 4275 4276 4277
JULY 2008
Foam should not be exposed to the air stream nor surrounding area. Where required by special conditions, panels may optionally be insulated with rock wool if the qualified vendor meets all minimum criteria herein. Panels should be constructed to be no less than 2‖ (51mm) thick and that the equipment manufacturer should guarantee that sweating will not occur anywhere on the AHU at the operating environmental conditions, in which the cabinet will be exposed. 6.1.2.3 Panel Lining The interior wall and ceiling panel surfaces and joints should be ripple free, smooth, and continuous, constructed of a material such as aluminum or stainless steel, that can be wiped clean and will not easily rust or corrode. In compartments serving cooling coils or steam humidification injection, it is recommended to line this section with 304L SS. It is unacceptable for exposed insulation or lining be exposed inside an air handling system serving a GMP area due to the potential of providing an area for mold propagation. 6.1.2.4 Panel Joints All interior joints should be sealed with RTV silicon sealant caulk, compliant with appropriate regulations for food grade applications, with all exterior joints sealed with caulking having at least a 25-year life with mold inhibitor. 6.1.2.5 Duct Connections Cabinet duct connections, which are of reduced size, can significantly reduce systems delivery capacity if selected to match ductwork mains. It is recommended that the return and supply duct connections be sized large enough to ensure air velocity is no-greater-than 1,100 fpm. Suitable transitions should then be connected to the main ductwork to ensure smooth and turbulent free transfer of air to duct mains. 6.1.2.6 Removable Wall Panels Removable panels provide a means to remove large components such as fan assemblies and coils that would not fit through the man door. The removable panel allows removal of panel using simple hand tools and avoid cutting or sawing through thermal breaks and cabinet constructed walls making removal and subsequent sealing possible. 6.1.2.7 Flooring Flooring should be of a sufficient thickness to prevent oil caning or deformation when walked upon. Flooring should be of diamond faced aluminum plate with a minimum 3/16‖ (4.76mm) thickness. Floor seams should be fully welded and the perimeter edge should have a minimum 2‖ (51 mm) lip turned up and sealed to the wall for a watertight floor system. Floor should be designed to have a capacity of 100-psf live load, to accommodate a service mechanic working inside unit.
118
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4278 4279 4280 4281 4282 4283 4284 4285 4286 4287 4288 4289 4290 4291 4292 4293 4294 4295 4296 4297 4298 4299 4300 4301 4302 4303 4304 4305 4306 4307 4308 4309 4310 4311 4312 4313 4314 4315 4316 4317 4318 4319 4320 4321 4322 4323 4324 4325 4326 4327 4328 4329 4330 4331
JULY 2008
6.1.2.8 Condensate Pan The cooling coil condensate drain pans (up and downstream) shall be of smooth 304L SS. The pan shall be double or triple sloping as to enhance total drainage. Its length shall extend beyond its downstream face, a minimum of 12‖ (30 cm) or ½ the height of the coil, whichever is greater, and a minimum of 6‖ (15 cm) beyond its upstream face. (Refer to the ASHRAE – Systems & Equipment Handbook, Chapter 21.4.) Stacked cooling coils shall have their own drain pan, with drainage into the lower coil section(s). Its length shall extend beyond its downstream face, a minimum of 12‖ (30 cm) or ½ the height of the coil, whichever is greater, and a minimum of 4‖ (10 cm) beyond its upstream face. Drain pans shall slope a minimum 1:50 towards drain outlet. Connections shall be piped to exterior of unit casing. Condensate drain traps shall be sufficiently designed and constructed so as to not cause puddles (which can lead to biological growth) and air movement into or out of the air handler during operating conditions. 6.1.2.9 Wash Down Capability In certain applications, the interior of the air handler is cleaned and washed down. In these applications, all AHU sections (excluding condensate pans) requiring drainage capability for wash down should have a 2‖ (51mm) minimum diameter opening fully welded around the perimeter. The opening shall be fitted with a secured/removable, flush-mounted, airtight 304 SS cover plate or plug. 6.1.2.10
Roof
Air handling units located outdoors should be provided with roof panels sloped to a centerline peak or to one side as required while maintaining a flat ceiling inside. Entire panel shape should be fully insulated without gaps at the peak. Roof should have a minimum slope of 1:50 for drainage. All exterior AHUs should have perimeter roof gutter with appropriate down spouts and rain guards above all exterior access doors constructed of same materials as casings. 6.1.2.11
Hardware
All hardware (i.e., screws, nuts, washers, etc.) should be 304 SS. Other materials, which oxidize or promote rust, should not be used in the construction of equipment. 6.1.2.12
Doors
Access doors should be installed on all sections of the AHU (i.e., coils, filters, fan, humidifier, etc.), wide enough (minimum width 24‖ (610 mm)) to allow entry by an operator for cleaning and inspection. All coils should have an access door on each side (up/downstream). Access doors shall be arranged to open against the direction of higher relative pressure for safe use and positive air seal. Positive pressure sections of the air handler shall have doors labeled as such. Doors 119
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4332 4333 4334 4335 4336 4337 4338 4339 4340 4341 4342 4343 4344 4345 4346 4347 4348 4349 4350 4351 4352 4353 4354 4355 4356 4357 4358 4359 4360 4361 4362 4363 4364 4365 4366 4367 4368 4369 4370 4371 4372 4373 4374 4375 4376 4377 4378 4379 4380 4381 4382 4383 4384 4385 4386
JULY 2008
should be of a double gasket compression design. All access doors should have an instrument test port to allow temperature and pressure readings to be collected without drilling into cabinet during air balancing commissioning. All doors should have impact, mar-resistant, clear view ports (double pane wire, Mylar-backed glass or polycarbonate (Lexan)), minimum 12‖ x 12‖ (305 mm x 305 mm) or 12‖ (305 mm) diameter. All doors shall have handles located on the inside of the AHU for safety. Interior door handles will prevent someone from being trapped inside of the unit. 6.1.2.13
Mixing Plenum
Mixing plenum is a chamber within an HVAC system where outdoor air is mixed with return air. The mixed air becomes the supply air for the space after passing thru filtration, heating or cooling steps within the air handler. 6.1.2.14
Electrical
All lighting should consist of vapor tight fluorescent fixtures (typically 4 ft (1200 mm)) with two T8 lamps and electronic ballasts. All sections should have at least one fixture. There should be a minimum of two waterproof 6-hour maximum timer light switches per AHU, one per end. Junction boxes should be should be sealed airtight.
weatherproof
and
all
conduit
penetrations
All electrical components, wiring, and terminals shall be tagged. High voltage terminals shall be labeled as such. Internal power cabling shall be shielded. All materials and installation methods shall be in compliance with NFPA and NEC. Sections with fans and moving parts shall have warning signs ―ISOLATE BEFORE ENTRY‖ affixed to doors. AHUs manufactured for Europe should have a CE mark (Conformite Europenne). A CSA (Canadian Standards Association) rating should be placed on all electrical devices. 6.1.3 Fans Fan selection is critical for generating the proper quantity of air (supply, return, exhaust/extract) and required pressure to overcome losses due to dampers, coils, filters, silencers, and ductwork. It is important to consider a number of items when selecting fans so they can operate smoothly over their intended life. This includes, materials of construction (rigidity, weight, corrosion, cleanability) determined for the type of operation (clean/contaminated air, humidity, temperature, severity), bearing, lubrication, direct vs. belt driven, static pressure flow sensing, and safety guards.
120
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4387 4388 4389 4390 4391 4392 4393 4394 4395 4396 4397 4398 4399 4400 4401 4402 4403 4404 4405 4406 4407 4408 4409 4410 4411 4412 4413 4414 4415 4416 4417 4418 4419 4420 4421 4422 4423 4424 4425 4426 4427 4428 4429 4430 4431 4432 4433 4434 4435 4436 4437 4438 4439 4440 4441
JULY 2008
Air handlers are configured as either a draw-thru or blow-thru operation, with the former most typically used. Draw-thru units have the fan located downstream of the pre-filters, coils, and humidifier. Their advantages include a shorter unit length, negative pressure on all access doors except the fan discharge section, and reheating of air leaving the fan section, which will reduce reheat coil requirements. Fan pressure performance and construction are identified as Class I, II, III, or IV by AMCA, based on certain minimum operating criteria. A Class I fan offered by any particular manufacturer has a lower allowable minimum operating range than its Class II counterpart. As a result, a Class I fan with less mechanical design strength and with less expense than a Class II fan. Typically, Class II & III fan performances are sufficient to handle pharmaceutical applications. Fans typically direct driven Exhaust/extract axial or a belt
used for air handlers on the supply side are either a plug/plenum fan or a belt driven centrifugal fan. operations typically use direct or belt driven vane driven centrifugal fan
Plenum fans are limited to approximately 12‖ static pressure and roughly 75,000 cfm of air, while centrifugal fans can produce 20‖ of static pressure and greater than 200,000 cfm of air. Vane axial fans can typically produce up to 10‖ static pressure and 100,000 cfm of air. Plenum fans should be designed for high efficiency, with nonoverloading airfoil aluminum wheels. They should include inlet cones matched to the wheel intake rim to ensure efficient and quiet operation. Vane Axial fans are designed where large volumes of air are required at moderate to high pressures. The tubular design, high efficiency rotor and integral straightening vanes provide high performance using minimal space. These fans are an excellent choice for HVAC systems using variable air volumes, clean rooms, and exhaust/extract. They are most efficient as return to air handlers and for exhaust/extract applications (fume hoods, bio-safety cabinets.) These units should be configured for direct drive though belt driven could be used. Another variation of the direct drive fan configuration is an array of smaller plug fans (commonly called a fan wall) to replace a traditional single large fan. This arrangement reduces the overall footprint of the air handler, allows design flexibility, simplifies maintenance, reduces downtime, reduces low-frequency noise (rumble) within the air handler, and usually saves energy, The use of multiple direct-drive fans operating in parallel improves reliability by providing redundancy. Direct driven fans eliminate belt replacement, shedding and alignment. In addition, there are present, which eliminates lubrication.
guards, and belt no shaft bearings
All belt-driven fans should have their motor and fan belt/sheave assemblies completely enclosed (front and rear) in a rigid, 304 SS or painted steel guard that protects personnel from injury and have an access for measuring tachometer readings. These guards are to be
121
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4442 4443 4444 4445 4446 4447 4448 4449 4450 4451 4452 4453 4454 4455 4456 4457 4458 4459 4460 4461 4462 4463 4464 4465 4466 4467 4468 4469 4470 4471 4472 4473 4474 4475 4476 4477 4478 4479 4480 4481 4482 4483 4484 4485 4486 4487 4488 4489 4490 4491 4492 4493 4494 4495 4496
JULY 2008
removable without the use of any tools but should include a warning label to notify the operator to secure the equipment prior to opening. Motor base shall automatically control belt tension and be of permanently aligned type to allow belt changes without realigning. For multiple belt systems, belts provided should be matched sets. Entire fan assembly shall be centered in the air stream both vertically and horizontally to assure proper airflow. All fan inlets and discharges should have 304 SS operator protective screens. Belt driven fans should be laser aligned to decrease the chance of failure to bearing, shaft and belts and energy consumption. Fan belt tension is extremely important during their entire life. Special attention should be incorporated, especially when installing new Vbelts. Once the new belt(s) have operated for a short time, they most likely will need to be readjusted due to belt wear-in. Improper undertensioning will result in premature failure and increased energy usage. Over-tensioning can reduce bearing life. Synchronous belts reduce energy consumption since they don‘t slip during start-up and operation. All fan housings shall be continuously welded to provide strength and durability for extended service life. They should have a primer with at least one coat of industrial strength or epoxy paint finish to eliminate rusting. For centrifugal fans a drain connection should be included, located at the bottom of the fan housing for draining any fluids that may accumulate. Fan wheels should be of aluminum construction where possible to reduce weight and rusting and be fully welded and non-overloading. All wheels are both statically and dynamically balanced. Fan shafts should be precision ground, polished and sized so that the first critical speed is at least 25% over the maximum operating speed. A shaft seal should be included to reduce leakage and protects the bearings from a contaminated air stream. Fan shaft bearings shall be selected for a minimum average life of ABMA L10 200,000 hours. Automatic bearing lubricators should be installed to increase bearing life and reduce maintenance. This will eliminate the possibility of over/under lubrication, resulting in premature bearing failure. Recommend lubricator installed directly to bearing housing. Lubricators should be sized to supply lubricant for a minimum of 6 months without refill or replacement. The vendor needs to work closely with the lubricator supplier to provide the proper lubricant and device for the intended operation of the air handler. Note: The lubricator should not be mounted or activated until the fan is put into full operation, to eliminate automatic, excessive lubrication and damage. Include removable inlet and outlet fan guards to provide protection for personnel and equipment meeting OSHA standards. Center the fan inlets in both the horizontal and vertical planes within the air handler. For measuring fan airflow without impeding air movement in or near the fan inlet, which would increase system static pressure, it is
122
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4497 4498 4499 4500 4501 4502 4503 4504 4505 4506 4507 4508 4509 4510 4511 4512 4513 4514 4515 4516 4517 4518 4519 4520 4521 4522 4523 4524 4525 4526 4527 4528 4529 4530 4531 4532 4533 4534 4535 4536 4537 4538 4539 4540 4541 4542 4543 4544 4545 4546 4547 4548 4549 4550
JULY 2008
recommended to install, a combination piezometer ring and static pressure tap, integrated into the inlet cone. The inlet cone of the fan is used as the flow nozzle. Vibration shall conform to ANSI/AMCA Standard 204, ―Balance Quality and Vibration Levels for Fans‖ and have a maximum balance and vibration BV4 category. The vibration limits shall be 2.5 mm/s (0.10 ips) for rigid mounted (direct driven) fans and 3.8 mm/s (0.15 ips) for flexibility mounted (belt driven) fans. The balance quality grade for impellers shall be no greater than G2.5 mm/s (0.10 ips), ANSI S 2.19 (ISO 1940) ―Balance Quality for Rigid Bodies‖. Balance readings shall be taken by electronic type equipment in the axial, vertical, and horizontal directions on each of the bearings. Fans and motors should be provided with vibration sensors with signal wiring brought out to a vibration interface enclosure mounted on the outside of the AHU to provide early warning and trending of bearing performance. 6.1.3.1 Motors & Drives All motors that are anticipated to operate at various loads should be inverter duty, rated NEMA premium efficiency and should comply with NEMA MG1, Part 31. A shaft grounding system or isolated bearings should be installed to prevent bearing failures caused by induced electrical current. Motor bearings shall be selected for a minimum average life of ABMA L10 200,000 hours. Automatic bearing lubricators should be installed to increase bearing life and reduce maintenance. This will eliminate the possibility of over/under lubrication, resulting in premature bearing failure. Recommend lubricator installed directly to bearing housing. Lubricators should be sized to supply lubricant for a minimum of 6 months without refill or replacement. The vendor needs to work closely with the lubricator supplier to provide the proper lubricant and device for the intended operation of the air handler. Note: The lubricator should not be mounted or activated until the fan is put into full operation, to eliminate automatic, excessive lubrication and damage. It is recommended to include variable frequency drives (VFD) to control the volume of air delivered to the various spaces. The advantage of the VFD in lieu of variable inlet guide vanes include better volume control, energy usage, less maintenance, soft start of fan motor reducing the in-rush of electrical current and stress on the fan, and positive control feedback to the building automation. Invertors should include line and load reactors to eliminate motor failure. It is recommended fans with belt drives use a synchronous belt with matching sprocket in lieu of V-belts and sheave. The advantages include non-slip operation, longer life, less maintenance, little to no belt shedding, single sync. belt vs. multiple V-belts for same operation and reduced energy consumption. The one disadvantage is that it will possibly produce higher noise levels.
123
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4551 4552 4553 4554 4555 4556 4557 4558 4559 4560 4561 4562 4563 4564 4565 4566 4567 4568 4569 4570 4571 4572 4573 4574 4575 4576 4577 4578 4579 4580 4581 4582 4583 4584 4585 4586 4587 4588 4589 4590 4591 4592 4593 4594 4595 4596 4597 4598 4599 4600 4601 4602 4603 4604 4605
JULY 2008
6.1.4 Fume Exhaust/Extract Systems Laboratory and process fumes shall be directly exhausted to a safe location outside the building. To maximize the intent of exhausting unwanted contaminants, the inlets to the exhaust system should be as close to the point of generation as possible. The exhaust plume height shall be great enough to avoid re-entrainment of exhaust air into air inlets or onto roof and to disperse the exhaust. The effective stack height should be used when analyzing design issues. Wherever an occupational or environmental risk may exist attributed to a HVAC or local exhaust ventilation (LEV) system installation, a building airflow wake simulation shall be performed. This simulation shall to verify the effective mitigation of aerosol contaminant reentrainment to meet current ACGIH TLV® country-specific level, the company OEG for APIs, and/or biohazardous agent safety level. Factors impacting the wake flow requirements include: toxicity of the material, quantities and frequency of generation, inlet and exhaust placement, discharge filtration and velocities, prevailing wind directions and velocities, existence of adjoining buildings or structures, and area topography. Discharge velocities from exhaust stacks should be no less than 3,000 fpm (15.24 m/s). Exhaust from the hoods, BSC, or process equipment can be accomplished by ducting each piece of equipment to a dedicated fan or by manifolding the ducts to a centralized fan system. The manifolded system is preferred due to its 100% redundancy and reduced energy and maintenance costs. However, when only a few hoods exist or hood locations are remote from one another or for specific applications, then individual dedicated fans will probably be more applicable. Fans should be located exterior to the building so as to establish a negative pressure within the entire length of the exhaust ductwork. Where external location is not possible, the ductwork on the discharge of the fan, which will be under positive pressure, shall be welded pipe and pressure tested for zero leakage. Automatic dampers shall be strategically installed so as to not cause exhaust air to be drawn back down into the building or short cycled from an idled companion fan. Care must be taken to address noise sensitive areas and aesthetics in the location of the fans and their operation. This may include acoustical silencer nozzles and roof sound barriers. Two fan types are considered acceptable for this application. These include the preferred mixed-flow impeller (combines the benefits of axial flow and centrifugal flow fans) or the centrifugal fan. Whichever fan application is chosen during project development, it should provide for safe, easy inspection and maintenance of the fan drive components. Fans shall meet AMCA type B or C spark-resistant construction. All metal surfaces shall be coated with an epoxy for protection against weather, UV, and chemical vapors. Fans and accessories shall have internal drain systems to prevent rainwater from entering building duct system.
124
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4606 4607 4608 4609 4610 4611 4612 4613 4614 4615 4616 4617 4618 4619 4620 4621 4622 4623 4624 4625 4626 4627 4628 4629 4630 4631 4632 4633 4634 4635 4636 4637 4638 4639 4640 4641 4642 4643 4644 4645 4646 4647 4648 4649 4650 4651 4652 4653 4654 4655 4656 4657 4658 4659 4660
JULY 2008
The motor, belt drive, and bearings shall all be located outside the contaminated air stream. Replacement of any of these components shall not require removal of the fan from the system or exposing maintenance, service personnel to the potentially contaminated interior of the fan. Electric motors should be TEFC chemical duty, with a 1.15 service factor for continuous duty operation, NEMA Design B with class F insulation, and sealed bearings with a minimum bearing life of L10 100,000 hours. A NEMA 3R non-fused disconnect switch shall be provided, mounted, and wired to the motor. Fans shall be tested under ANSI/ASHRAE 51 or British Standard 848-I. Sound testing shall be in accordance with AMCA 300. Fans shall be UL and CUL listed per UL 705 safety standard or ENEC (European Norms Electrical Certification), or country-specific requirements, and shall meet the criteria of NFPA-45 and ANSI/AIHA Z9.5. 6.1.5 Heating and Cooling Coils Coils should be fully drainable with vent and connections extending external to the AHU or ductwork. All steam coils should be fitted with vacuum breakers. Water system velocities should be kept between 2 and 6 fps (0.61 and 1.83 m/s) to provide for proper turbulence and to minimize erosion. Water velocity through a coil needs to be > 1 ft/sec to ensure heat transfer ability of coil. Should fluid speed reduce toward laminarity, this can result in reduced sensible and latent heat transfer capacity. Coils, which are exposed to salt or corrosive conditions may be beneficial to select a fin material of copper rather than aluminum due to degradation of the aluminum material exposed to corrosive atmospheres. All coil performances should be designed and achieve rating in accordance with ARI Std. 410. Coils sizing, configuration, and installation will have an impact on their performance to meet the delivery of conditioned air. Peak moisture load should be considered for coil design using the climatic data from the ASHRAE Fundamentals Handbook or CIBSE Guide A. Air handler cooling coils should have a maximum average face velocity of 450 fpm (2.29 m/s) to eliminate condensate carry over. Cooling coil face velocities shall be fairly uniform with actual velocity hot spots being no greater than 525 fpm (2.67 m/s). Steam and hot water coils should have a maximum face velocity of 600 fpm (3.0 m/s), to reduce static pressure resulting in a lower (coil to energy) cost ratio, when compared with coils having velocities of 800 fpm (4.06 m/s) and higher. Air handler cooling coil tubing should be of nominal 5/8‖ (15 mm) O.D., 0.035‖ (0.89 mm) thick seamless copper, with aluminum fins of at least 0.0095‖ (0.24 mm) thickness. Coil casings and frames should be 304L SS for better longevity and elimination of rust with a center tube support for coils greater than 48‖ (1.2 m) in width. Cooling coils should be no more than 10 rows deep and 10 fins/inch to enhance cleaning and better heat transfer.
125
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4661 4662 4663 4664 4665 4666 4667 4668 4669 4670 4671 4672 4673 4674 4675 4676 4677 4678 4679 4680 4681 4682 4683 4684 4685 4686 4687 4688 4689 4690 4691 4692 4693 4694 4695 4696 4697 4698 4699 4700 4701 4702 4703 4704 4705 4706 4707 4708 4709 4710 4711 4712 4713 4714 4715
JULY 2008
Air handler heating coil tubing should be of nominal 5/8‖ (15 mm) O.D., 0.035‖ (0.89 mm) thick seamless cupro-nickel for better corrosion resistance, with aluminum fins of at least 0.0095‖ (0.24 mm) thickness. Coil casings and frames should be 304L SS with a center tube support for coils greater than 48‖ (1.2 m) in width. Preheat steam and hot water coils should consist of no less than 2 rows to provide lower downstream face temperature variation. Duct mounted coil tubing should be a minimum nominal 1/2‖ (13 mm) O.D., 0.025‖ (0.64 mm) thick seamless copper, with aluminum fins of at least 0.008‖ (0.20 mm) thickness. Coils should be fully drainable with vent and connections extending external to the AHU or ductwork. Include full port shut-off valves with hose connection with cap and chain. All steam coils should be fitted with vacuum breakers. All coils, which are exposed to salt or corrosive conditions, should have corrosion resistant coating. All cooling coils should be coated to enhance heat transfer and reduce biological growth. All coils shall be fitted onto 304L SS tracks for ease of removal. 6.1.6 Humidifiers Humidifiers should be comprised of steam injection dispersion/sparge tubes and accessories to provide drip-free steam absorption without downstream condensate. When clean steam is required for humidification, sanitary tri-clamp connection control valves and thermostatic steam traps, along with other components made of 316L SS, should be used. Modulating steam control valves should be included to provide accurate control. A wye strainer should be installed upstream of the control valve to provide it from dirt. When located in the air-handling unit, the humidifier section should be located directly upstream of the cooling coil section to ensure efficient absorption of vapor into the air stream. The humidifier condensate drain pans (up and downstream) should be 12 gauge 304L SS, and at least 2‖ (5 cm) deep. Its length should extend beyond its downstream face to the upstream side cooling coil section and a minimum of 6‖ (15 cm) beyond its upstream face. Connections should be piped to exterior of unit casing. When the humidifier is located within ductwork, the ductwork shall be constructed of fully welded 304L SS, 2 ft (0.6 m) upstream and 5 ft (1.5 m) downstream of the humidifier. Humidifier ductwork sections shall be pitched downstream of the humidifier to a drain. 6.1.7 Dehumidification When standard chilled/glycol systems are unable to sufficiently reduce relative humidity levels, several dehumidification systems are available to handle lower relative humidity limits. These include:
126
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4716 4717 4718 4719 4720 4721 4722 4723 4724 4725 4726 4727 4728 4729 4730 4731 4732 4733 4734 4735 4736 4737 4738 4739 4740 4741 4742 4743 4744 4745 4746 4747 4748 4749 4750 4751 4752
4753 4754 4755 4756 4757 4758 4759 4760 4761 4762 4763
JULY 2008
Run-around coil systems Heat pipe systems Dual-path systems Desiccant systems
Because they are capable of delivering air at much lower dew points than coils, desiccant systems have been the most widely used method for dehumidification in the pharmaceutical industry. Proper layout of equipment should include filters upstream of the coils and fans downstream of coils (draw-through mode) to provide a small amount of reheat. Select low face velocity coils to reduce air pressure drop and improve dehumidification performance. When dehumidification is integrated into a cooling system, pay special attention to these issues: Select and size HVAC equipment (coils, fan, pump, damper, etc.) for sensible and latent cooling at peak load conditions. These usually don‘t occur simultaneously. Design for energy efficiency at part-load conditions because peak load usually occurs for only about 2% of the operating time. A run-around coil system is a simple piping loop with an upstream precooling coil and a downstream reheating coil that sandwiches the main cooling coil. The circulating fluid is pumped to transfer heat from the warm mixed air to the off coil cold supply air. The run-around system reduces the cooling load on the main cooling coil; reheat is provided by the heat picked up by the circulating fluid in pre-cooling coil instead of by an external source of expensive energy. The run-around loop requires a fractional horsepower pump and a threeway valve or a variable-speed drive (VSD) for the pump. For bigger systems, an expansion tank with air vent may be needed.
Figure 6-1 Run-around cooling loop Heat pipes increase the effectiveness of air conditioning systems by helping to decrease the total cooling load of the air. The typical design consists of a refrigerant loop with two connected heat exchangers placed upstream (evaporator coil section) and downstream (condenser coil section) from the cooling coil. As the air passes through the first heat exchanger it vaporizes the refrigerant and is pre-cooled. This allows the coil to more effectively cool the air to a 127
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4764 4765 4766 4767 4768 4769 4770 4771 4772
4773 4774 4775 4776 4777 4778 4779 4780 4781 4782 4783 4784 4785 4786 4787 4788 4789 4790 4791 4792 4793 4794 4795 4796
JULY 2008
point below the dew-point temperature and to extract more moisture. The air then passes through the second heat exchanger and is reheated, which liquefies the refrigerant, causing it to flow back to the first heat exchanger. The heat pipe system is hermetically sealed, uses a wicking action, and requires no pump. The increased dehumidification capacity provided by heat pipes allows for a smaller cooling system. However, the addition of heat pipes will increase the pressure drop, and fan power must be adjusted accordingly.
Figure 6-2 Heat Pipe System A dual-path system uses two coils (either chilled water or DX) to separately cool the incoming outside air and return air. The hot and humid outdoor air is cooled by a primary coil to 42°F to 45°F for dehumidification. The secondary coil furnishes the sensible cooling of part of the relatively cool and dry return air. A portion of the return air may bypass the secondary coil and mix with the cooled return air stream. These two air streams are then mixed into supply air with appropriate temperature and humidity. Dual-path systems offer competitive energy efficiency with run-around loop systems, and provide better control of the outside air ventilation rate. Dual-path systems decouple sensible cooling and latent cooling for easy control of the supply air temperature and humidity. Dual-path systems can be installed separately or integrated with additional HVAC/R equipment. The OA cooling coil should be sized for peak latent load, while the RA cooling coil should be sized for peak sensible load. The OA path controls the humidity of the supply air by modulating the chilled water flow, while the RA path controls the supply air temperature by adjusting the bypass damper position.
128
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
4797 4798 4799 4800 4801 4802 4803 4804 4805 4806 4807 4808 4809 4810 4811 4812 4813 4814 4815 4816 4817 4818 4819 4820 4821 4822 4823 4824 4825 4826 4827 4828 4829 4830 4831 4832 4833 4834 4835
JULY 2008
Figure 6-3 Dual Path Cooling Desiccant Systems are applicable and the most prevalent when operations require large dehumidification and low space humidity levels that would be difficult to achieve with cooling-type dehumidification. They can be configured to condition part or all of the incoming air. The main factors, which influence this, include percentage of outside air, outside and space relative humidity levels, and the quantity of air flow for the conditioned spaces. Desiccant materials possess the affinity for water vapor greater than that of air. They can either be solid or liquid as absorbents & adsorbents. Both solid and liquid desiccants are used in cooling systems, but solid desiccants are the most widely used for HVAC operations. Absorbents are generally liquids or solids, which become liquid as they absorb moisture, i.e. they undergo a physical or a chemical change as they collect moisture. Typical absorbents include Lithium Chloride (LiCl) and Sodium Chloride (NaCl). Adsorbents are mostly solids and do not under go any physical or chemical change when they come in contact with moisture. Water is adsorbed or held on the surface of the material and in the pores. Typical adsorbents include Silica Gel, Molecular Sieve and Activation Alumina, with Silica Gel being the most widely used. The choice of desiccant the amount of moisture desiccants may not have airstreams with direct and maintenance costs.
material must be evaluated taking into account to be removed, exposure to open product (some regulatory (FDA and EU) approval when used in contact with consumable items), and operating
The choice of a desiccant system affects the selection and sizing of the cooling coil, because the cooling coil only needs to handle the sensible load of the supply air, which allows for higher chilled water temperature and efficient operation. The sensible cooling load will be
129
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4836 4837 4838 4839 4840 4841 4842 4843 4844 4845 4846 4847 4848 4849 4850 4851 4852 4853 4854 4855 4856 4857 4858 4859 4860 4861 4862 4863 4864 4865 4866 4867 4868 4869 4870 4871 4872 4873 4874 4875 4876 4877 4878 4879 4880 4881 4882 4883 4884 4885 4886 4887 4888 4889 4890
JULY 2008
higher because of the hot dry air leaving from the desiccant wheel (due to heat of adsorption). However, the addition of a desiccant wheel will increase the pressure drop, fan power and maintenance, and an additional motor is required to rotate the wheel. This extra energy usage must be counted accordingly. Desiccant systems should use lowcost surplus heat, waste heat or solar heat for desiccant reactivation. Dampers or VSD for fans should be installed to control airflow through the wheel. Side access for wheel and filter replacement and maintenance should be provided. Energy recovery and direct/indirect evaporative cooling are frequently incorporated in desiccant systems to reduce the cooling and heating energy. Units should be capable of sustained operation without damage to the humidity transfer media. The dehumidifier should be a fully factory assembled package unit, complete with desiccant rotor, desiccant rotor drive assembly, reactivation heat source, filters, motors, fan(s), access panels, volume dampers, dust-tight electrical enclosure, and all component auxiliaries as recommended by the manufacturer for safe, unattended automatic operation. The unit should be fully automated and equipped with differential pressure gauges and temperature transmitters, which measure and display the pressure drop across the desiccant wheel and the reactivation and pre-cooling air discharge temperatures. The unit casing should be fabricated of strain-hardened aluminum for torsional rigidity and corrosion resistance. The casing should be welded, gasketed, and sealed to be air and vapor tight at design pressures and airflows. Air seals and internal partitions should separate the process and reactivation air streams at operating pressure differentials of up to 8‖ w.g. (1.993 kPa). The dehumidifier should have full-face seals on both the process air entering and the process air leaving sides of the wheel. These should seal the entire perimeter of both air streams as they enter and leave the wheel. The seals should have a minimum working life of 25,000 hours of normal operation. The desiccant wheel media shall be adsorbent, bacteriostatic, nontoxic, non-corrosive, and nonflammable, and fabricated entirely of inert, inorganic binders and glass fibers with the desiccant uniformly and permanently dispersed throughout the matrix structure to create a homogenous media. The desiccant wheel should have the capability of delivering nearly 100% of its drying capability for a minimum of 5 years. Desiccant systems are more competitive when a low supply air dew-point temperature is required, latent load fraction is high, low- or no-cost reactivation heat from steam, hot water or waste heat is available, and electricity costs are high when compared to gas costs. There are several circumstances that may favor desiccant systems rather than cooling-based dehumidification systems. These include:
Economic benefit from low humidity High moisture loads with low sensible load Need for more fresh air Exhaust air available for desiccant post cooling 130
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4891 4892 4893 4894
4895 4896 4897 4898 4899 4900 4901 4902 4903 4904 4905 4906 4907 4908 4909 4910 4911 4912 4913 4914 4915 4916 4917 4918 4919 4920 4921 4922 4923 4924 4925 4926 4927 4928
JULY 2008
Low thermal energy cost with high electrical demand Economic benefit to dry duct work Low-cost heat available for desiccant regeneration
Figure 6-4
A package desiccant HVAC system (courtesy of ___________)
6.1.8 Air Filtration Air filtration is one of the important HVAC components that affects the cleanliness of air delivered to the use point. The following is intended to be an overview of various filtration levels. It does not discuss in detail the construction of the filters themselves, since extensive detailed technical information is readily available from filter manufacturers. Air filtration is performed at various locations within the HVAC system to attain the air cleanliness needed to protect the process (room airborne particles), occupants, and the air handling equipment and ductwork. Initial filtration/pre-filtration (Level I & II Filtration) is performed within the air-handling unit where outside and return air streams enter. The efficiency of the filters should be sufficient to keep the internal components (coils, fan) and the AHU itself relatively clean over an extended period of time, so they can perform as intended. Final filtration (Level III Filtration) occurs at the discharge section of the air handling unit after the air stream has been conditioned and is intended to protect the ductwork, terminal filtration (when provided), personnel and the work space from airborne particles that may have been generated by the coils and supply fan. Terminal filtration, which is located at the room perimeter (ceilings and walls) is intended to provide both the cleanest air possible supplied into the room and when required, to capture air particulates generated by the processes served by the air handler and carried through the return ductwork. The cleanliness of the filtered factors including the quantity
air will be influenced by several and quality of the outside air 131
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4929 4930 4931 4932 4933 4934 4935 4936 4937 4938 4939 4940 4941 4942 4943 4944 4945 4946 4947 4948 4949 4950 4951 4952 4953 4954 4955 4956 4957 4958 4959 4960 4961 4962
JULY 2008
introduced into the system for ventilation/pressurization, the ratio of outside air to return air, and any introduction of particles within the air handler and ductwork. All Pre- and Final-filtration grid systems should be of rigid construction, usually aluminum or 304 SS. Consideration should be made to make sure that all the air travels through the filters and does not bypass around the filters or the grid. Filters should be front-loaded to eliminate air bypass. Filter frames should have closed cell rubberized/neoprene-type gaskets only to prevent shedding. A separation of at least 2‖ (51 mm) should exist between the pre and post filters in the pre-filter section to reduce static pressure and increase the performance of the filters. ASHRAE type filters should be designed at a maximum air velocity of 450 fpm (2.3 m/s) when they are located in the air handler filter banks. Many designers choose to lower the design specification by 10 - 20% to provide future capacity. HEPA filter air velocities should be designed at a maximum of 100 fpm (0.51 m/s) when positioned as terminal supply air filters, and 450 fpm (2.3 m/s) when positioned as a terminal return, in an exhaust/extract air filter housing, or in the air handler. Filters should be of standardized sizes so as to limit inventory and simplify ordering and replacements. Filter classifications and ratings- (Editor‘s Note: We have yet to reconcile this table with additional detail to add to clarify the ASHRAE/MERV ratings, but I want to retain the existing details of the EN1822 and IEST ratings. I haven‘t yet been able to get all that on the same chart. attached below is this draft on 27June2008….Don Moore)
132
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4963 4964 4965
JULY 2008
Table 6-1 ASHRAE vs. EU/EN filter ratings ASHRAE Composit Average ASHRAE MERV e Particle 52.2 Size m Efficie % in ncy, Size Range, E1 - E2 Range 1 Range 0.30 - 1.0 1.0 3.0
- E3 2 Range - 3.0 10.0
EU type EN 779 (Note: These comparisons of IEST Type (RP-CC001.4) (approx (approx filter rating systems are only .) .) approximate as the test methods are different. )
- MERV 3 -
n/a
n/a
E3 < 20
1
EU 1
G 1
n/a
n/a
E3 < 20
2
EU 2
G 2
n/a
n/a
E3 < 20
3
EU 2
G 2
n/a
n/a
E3 < 20
4
EU 2
G 2
n/a
n/a
20 ≤ < 35
E3 5
EU 3
G 3
n/a
n/a
35 ≤ < 50
E3 6
EU 4
G 4
n/a
n/a
50 ≤ < 70
E3 7
EU 4
G 4
n/a
n/a
70 ≤ E3
8
EU 5
F 5
n/a
E2 < 50
85 ≤ E3
9
EU 5
F 5
n/a
50 ≤ < 65
E2 85 ≤ E3
10
EU 5
F 5
n/a
65
E2 85 ≤ E3
11
EU 6
F 6
≤
133
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008
< 80 n/a
80 ≤ E2
90 ≤ E3
12
EU 6
F 6
E1 < 75 90 ≤ E2
90 ≤ E3
13
EU 7
F 7
75 ≤ E1 90 ≤ E2 < 85
90 ≤ E3
14
EU 8
F 8
85 ≤ E1 90 ≤ E2 < 95
90 ≤ E3
15
EU 9
F 9
95 ≤ E1 95 ≤ E2
95 ≤ E3
16
EU 9
F 9 EN 1822 (approx .) *
EU 10
H10
HEPA 85%
@MPPS
EU 11
H11
HEPA 95%
@MPPS
EU 12
H12
HEPA 99.5% @MPPS HEPA 99.97% @0.3m**
A, B, E
EU 13
H13
HEPA 99.95% 99.99% @0.3 m**
EU 14
H14
HEPA 99.999% @0.3 m**
U15
HEPA 99.9995% 99.999 @0.1-0.2 m**
@MPPS F
U16
HEPA 99.99995% 99.9999 @0.1-0.2 m**
@MPPS G
U17
ULPA 99.999995 @MPPS
134
@MPPS C 99.995%@MPPS D, K
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW
JULY 2008 * All EN 1822 tests at MPPS
** All tested with thermally Refer to IEST-RPgenerated DOP aerosol (0.3 m CC001.4 for ratings MMD; ie, CMD is near MPPS) perfilter type F, G & K type filters are tested at either 0.1-0.2 or 0.2-0.3 m. K type filters are 99.995%.
4966 4967 4968
135
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4969 4970 4971 4972 4973 4974 4975 4976 4977 4978 4979 4980 4981 4982
JULY 2008
Filters are typically classified by either IEST Recommended Practice RP-CC001, ASHRAE Standard 52.2 or EN 779/1822 (European standards for, respectively, general ventilation filters/HEPA & ULPA filters). Since the different grading systems are based on different challenge materials and sizes and use different measurement methods, comparisons between the different grading systems are not exact. While the following table is an approximate comparison between filters classified by the different systems and is helpful in understanding relative performance of the various filter classes, the specific standard relevant to the requirements for your application must be quoted to avoid confusion.
136
ISPE GOOD PRACTICE GUIDE
HVAC
DRAFT FOR REVIEW 4983 4984
JULY 2008
Table 6-2 ASHRAE vs. IEST and CEN filter ratings
Filter options and comparisons ASHRAE Arrestance weight %
ASHRAE Dust Spot %
(MERV) ASHRAE 52.2
3-10 micron
View more...
Comments
