How to Select a Freeze Dryer

VirTis * FTS * Genevac * Hotpack * Hull Helping you make more time for science

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Selecting a Freeze Dryer

The Objective of this Webinar: To provide information to aid in the proper selection of lyophilizer features vs. corresponding project requirement Most selection criteria will be process driven and dependant on application

Important points to consider:

Load size Vials or Bulk Drying Solvents Freeze temp Product Value Validation Containment Issues Sterility or Aseptic Conditions Installation Assitance Training of Staff Facility Layout Available Utilities

Benchtop or Console Flask Dryer – Solvents Present? at least -85C better still -105C or colder depending on vapor pressure chart of solvent – Load Size? Check 24 hour condenser capacity and match to load – Space considerations Lab space some of the most expensive real estate to any company.

Lyophilizers Define type of drying required • R&D • cGMP non Sterile – Active Pharmaceutical Ingredient – Terminally Sterilized – Diagnostic – Non Biological

• Injectible or implantable

Basic Components of a Lyo: White – Vacuum Yellow – Heat Transfer Media Blue – Refrigeration

Product Chamber & Shelves • Calculate required Surface area • Check Interdistance – 4-8mm above partially inserted stopper

• Movable or Fixed shelf – Stoppering – Chamber Access and Cleanability – Loading level

Bulk Surface area requirement Calculation Tray size and # Fill depth Required inter-distance Radiant considerations 10 mm fill 12 mm fill 15 mm fill 20 mm fill

~.89 L/ft sq ~1.06 L/ft sq ~1.33 L/ft sq ~1.77 L/ft sq

1 ft2 = .929,030 m2 Don’t assume more than 21mm unless you know the product will give up it’s water that quickly.

Vial Calculations • For Vial diameters 21mm Vials /ft2 = 92000/ (d (mm))2 # Vials Desires/ Vials /ft2 = required surface area Beware small trays as they can lead to an over estimation of the vial capacity

Vial Calculation Example: • Requirement = 10000 vials @ 20mm vial diameter • 97500 / (20)2 = 243 vials/ft2 • 10000 vials / 243 v/ft2 = ~42 ft2 • Minimum shelf required for this number of vials. • Round up to next available shelf size • 42 ft2 = 7 x 6 ft2 trays • Formula can easily be converted to m2 • 1 ft2 = .929,030 m2

CONDENSER DESIGN SIDERATIONS Always calculate load and compare vs. 24 hour capacity. Consider oversized because freeze drying is not always linear

• • • •

• • • • • •

INTERNAL Cost efficiency Space saving Short vapor path Accessibility

EXTERNAL Barometric control possible (iso valve) Faster turn around Less chance of oil backstreaming Temperatures more uniform Higher ice capacities

REFRIGERATION SYSTEMS • • • • •

• • • • •

Objectives of selecting the correct refrigeration system Contain the solvent on the Condenser, not in the vacuum pump Redundancy (calculate vs product value) Design must remove the heat load Lower temps mean less capacity Consider maintenance intervals and Initial cost vs serviceability and footprint

Single Stage, temperatures to – 55 ºC Two Stage, temperatures to – 75 ºC Auto Cascade, temperatures to – 70 ºC Cascade, temperatures – 85 ºC Liquid Nitrogen to –195 ºC LN2 SUPPLY TANK

GN2 (VENT OR USE) TO VA C PU MP

OutletFlowFront Deflectors Baffle

CONDE NSER (OEM)

Vapor Inlet Rear Baffle

Condensation Plates

GN2 (VENT OR USE) NCO OL HX

HEAT TRANSFER FLUID (FOR SHELVES)

PHASE SEPARATOR

PUMP

FREEZE DRYING CHAMBER (OEM)

The Weakest Link

Wet vs Dry Vacuum pumps initial cost service interval solvent resistance Compound pumps

Solvent in the pump oil causes premature failures and much frustration.

Clean room vs. Non Clean room design

“Pizza” Door – – – -

Autoloading Constant Level loading Containment/Isolator Laminar Flow

Redundant Systems Condenser heat transfer loop N +1 = 1 additional component for all critical systems

Steam in Place (SIP) Injectibles = SIP

Longer Lead Time

ASME Pressure vessel Orbital Welding

$Paperwork$

Clean In Place (CIP) Cytotoxic or Live Product

Multi-products Limited Access The single most commonly underestimated utility in all of Lyo-Land Gallons Per Minute of Water For Injection

Controls Considerations Recipe requirements? How much time do you have to get it right? Process development tools: Smart BE or PVG/CM (See Tech Briefs) Automated Testing Secure Data

Historical Data

21CFR11?

Recipe Screen

Training and proficiency of staff Cost of Deviation control Level of Regulatory Scrutiny

Documentation and Validation PQ

URS

Inverted GAMP 4 Triangle User Requirement Specs Functional and Design Specs Installation Qualification (IQ) Operational Qualification (OQ)

Production or Research oriented? Have a TOC reviewed by your QA Everyone has an opinion

„Factory

OQ

FS DS

IQ Build

and Site Acceptance Testing (FAT/SAT)

„Customized

Workbooks with Material and Welding certifications „Control

System Integration Testing

Summary: Carefully Consider Project Requirements on Front End of Project • • • • • •

Shelves Condenser Cleaning and Sterilization Controls and Instrumentation Installation and Validation Utilities and Layout (Especially Route to Installation Point from Loading Dock