February 3, 2017 | Author: Majdi Hasan Ayoub | Category: N/A
Download 2012-10-may-risk-based-approach-c-q.pdf...
5/13/12
ISPE Commissioning and Qualifica9on Guidance An Overview of New Guidance Timothy P. Howard, CPIP, PE Vice President Commissioning Agents, Inc.
Agenda • Brief History Lesson • Science and Risk Based Approach – ICH Q8 / Q9 – ASTM E2500
• New Guidance Documents – ISPE Guidance Document – ISPE Good Prac9ce Guide
1
5/13/12
In the Beginning… A number of seminal documents established the principles of a Risk Based Approach to C&Q: • ISPE Baseline Guide 5 (2001) • “Pharmaceu9cal cGMPs for the 21st Century – A Risk Based Approach” – FDA (2004) • ISPE White Paper – “Risk Based Qualifica9on for the 21st Century” (2005) • ICH Q8 Pharmaceu9cal Development (2005) • ICH Q9 Quality Risk Management (2006) • ASTM E 2500 (2007)
Evolu0on Of Commissioning & Qualifica0on
FDA Guide to Process Validation
EU Annex 15
FDA: Pharmaceutical CGMPs For The 21st Century
ICH Q9
1987 2000 2002 2004 ss2222222222222222201020102010220112010204321093248 ISPE C&Q Baseline 5 Guide
ISPE 21st Century Qualification White Paper
FDA: Quality Systems Approach to Pharmaceutical cGMP Regulations
ICH Q10
2006 2008 2010 0932148 093218420394820934802 93840293842010
ICH Q8
ASTM E250007
ISPE GPG (Draft)
2011
FDA Process Val. Guidanc e
ISPE Guide FSE ICH Q9 ASTM
2
5/13/12
ISPE Baseline Guide – Volume 5 • Defined Commissioning • Introduced System and Component Level Impact Assessments • Systems Based Approach
3
5/13/12
10 Principles for Risk-‐Based Qualifica0on 1. Focus on that which affects product quality 2. 3. 4. 5. 6. 7. 8. 9. 10.
Process User Requirements key to acceptability (IQ/OQ subordinate to PQ) Risk assessments and process knowledge used to iden9fy cri9cal elements Only cri9cal features/func9ons to be qualified All ac9vi9es must contribute value Risk-‐based asset delivery – not “cookbook” requirements Value-‐added documents based on technical merit Use of supplier documenta9on Test planning (and one-‐9me tes9ng) Foster innova9on – all change is not bad
ISPE White Paper “Risk Based Qualification for the 21st Century” March 2005
ICH Q9 – Quality Risk Management • …the protec9on of the pa9ent by managing the risk to quality should be considered of prime importance.” • Risk evaluated based on scien9fic knowledge • Level of effort commensurate with level of risk
4
5/13/12
ICH Q8 – Pharmaceu9cal Development • Cri9cal Quality Agributes – A physical, chemical, biological or microbiological property or characteris9c that should be within an appropriate limit, range, or distribu9on to ensure the desired product quality.
• Cri9cal Process Parameters – A process parameter whose variability has an impact on a cri9cal quality agribute and therefore should be monitored or controlled to ensure the process produces the desired quality.
FDA Quality Systems Guidance • Quality risk management integral to quality systems • Encourage con9nuous improvement • Equipment and facili9es – Use of technical experts – Quality unit review basis for design: process requirements, risk to pa9ent
5
5/13/12
ASTM E2500-‐07 Standard Guide for the Specifica9on, Design and Verifica9on of Pharmaceu9cal and Biopharmaceu9cal Equipment, Systems and Facili9es
ASTM Key Principals • • • • • • •
#1 Risk Based #2 Science Based #3 Cri9cal Quality Agributes (CQA) #4 Quality by Design (QbD) #5 Good Engineering Prac9ces (GEP) #6 Subject Mager Experts (SME) #7 Use of Vendor Documents
6
5/13/12
ASTM Process • • • •
Requirements Defini9on Specifica9on and Design Verifica9on Acceptance and Release
Suppor9ng Ac9vi9es • • • •
Good Engineering Prac9ce Risk Management Design Review Change Management
7
5/13/12
The Specifica9on, Design and Verifica9on Process
Cri9cal Aspects of Mfg Systems • “…typically func9ons, features, abili9es, and performance or characteris9cs necessary for the manufacturing process and systems to ensure consistent product quality and pa9ent safety. “ • They should be iden9fied and documented based on scien9fic product and process understanding. • “…referred to as “cri9cal aspects.” • Verifica9on ac9vi9es should focus on these aspects of manufacturing systems and should be documented.
8
5/13/12
New ISPE Guidance Documents ISPE GUIDE: • SCIENCE AND RISK-‐BASED APPROACH FOR THE DELIVERY OF FACILITIES, SYSTEMS, EQUIPMENT (FSE)
ISPE GOOD PRACTICE GUIDE: • APPLIED RISK MANAGEMENT FOR COMMISSIONING AND QUALIFICATION (GPG)
ASTM E2500-‐07 Implementa9on Guidance Wrigen by ISPE C&Q COP Working Group
9
5/13/12
FSE-‐ Ra9onale for the New ISPE GUIDE Presents a structured lifecycle approach to the delivery of facili9es, systems and equipment which support these regulatory ini9a9ves Designed to improve the way in which the industry delivers regulated manufacturing capacity – Improve the ability to meet documented process requirements – Control risks within the manufacturing process – Produce high quality products which consistently meet product user requirements. The GUIDE describes the Principles required when applying a science and risk based program.
Qualifica0on
“Tradi0onal” vs. Risk Based Approach (RBA) Tradi0onal Approach (Product) User Requirements not Formally Documented Protocols Developed from “Templates” IQ/OQ Protocols “Preapproved” Commissioning not Leveraged Engineering and “Valida9on” Personnel Omen Dis9nct Emphasis on Documents – Not System Performance
RBA Based on ASTM E 2500 Process Requirements Documented, Approved Risk Assessments Determine Cri9cal Aspects of Design Engineering Tes9ng (“Commissioning”) Verifica9on All Documents with Technical Merit Used as Evidence of Fitness for Use Emphasis on Mee9ng Process Requirements
10
5/13/12
Baseline Guide 5 vs. FSE Guide Engineering Change Management QA Change Control
BG 5 Guidance
Design Development Enhanced Design Review
Commissioning
PQ
Process Valida9on
IQ & OQ
Engineering Change Management
New Risk-‐based Approach
QA Change Control
Design Development Design Review
Verifica9on Tes9ng
PT
Process Valida9on
Performance Tes9ng
FSE GUIDE Overview Chapters Titles 1 Introduc9on 2 Overview Of The Lifecycle 3 Requirements 4 Specifica9on & Design 5 Verifica9on, Acceptance and Release 6 Con9nual Improvement 7 Quality Risk Management 8 Good Engineering Prac9ce 9 Design Review 10 Change Management 11-‐15 Appendices 16 Appendix 6 Glossary and Acronyms 17 Appendix 7 References Note : Automa9on dealt with throughout each chapter
11
5/13/12
Scope
• New commercial manufacturing and modifica9on to exis9ng regulated mfg facili9es • Planning, specifica9on, design, and delivery (harmonized) with GAMP 5 • Addresses the verifica9on (or qualifica9on) por9on of the valida9on life cycle on which process valida9on is built
Purpose
Scien9fic product and process knowledge
Documented specifica9on, design, and verifica9on of equipment/ systems/u9li9es
Fit for intended use, and minimize risk to pa9ent safety and product quality
12
5/13/12
Benefits
Encourage the industry and individual organiza9ons to reassess the terminology, prac9ces, and roles and responsibili9es involved in delivering new manufacturing capacity to focus on the criteria required to establish “suitability for intended use.”
Key Concepts
Science Based Quality Risk Management – Describes the importance of a QRM program – Documented risk assessments focused on risk to pa9ent – Focus on iden9fying , assessing and controlling risk
Product and Process Understanding
– Resul9ng from scien9fic inves9ga9on – Enhanced con9nually during ongoing opera9ons – Begins with knowing the product CQAs and associated CPPs
Focus on Achieving Fitness for Intended Use
– Verifica9on ac9vi9es focused on confirming that CAs of equipment/ systems and associated meet acceptance criteria – Verifica9on inspec9ons and tests are not limited to CAs
13
5/13/12
Key Concepts (cont.)
Flexible Approaches to SpecificaSon and VerificaSon
– Several approaches to structure the documents, inspec9ons, and tes9ng ac9vi9es – Demonstra9on of fit for intended use and sufficient to meet regulatory expecta9ons
ClarificaSon of Roles and ResponsibiliSes
– The roles of Quality Unit and SME are described in the context of the scope of ac9vi9es covered by this Guide. – Subject Mager Experts (SMEs) are defined as those individuals with specific exper9se in a par9cular area or field. – The Quality Unit has a key role within the quality management system governing facili9es, systems, and equipment. – In addi9on to ac9ng as a Subject Mager Expert (SME), the Quality Unit is responsible for overseeing quality and compliance
Role of the Quality Unit The Quality Unit is expected to iden9fy, approve, and verify those aspects that are necessary to manufacture a quality product, and to ensure that appropriate procedures are followed to ensure that risks to the pa9ent in the manufacturing systems are adequately controlled The term Quality Unit is used as an encompassing term that includes many quality-‐related roles, including those responsibili9es covered by the role of Qualified Person (as defined in Ar9cle 51 of 387 EU Direc9ve 2001/83/EC)
14
5/13/12
The Risk-‐Based Verifica9on Process
Concerns from Some in Industry • Too Big of a Leap for Us • Too much 9me spent on implemen9ng quality systems with BG5 model • I like the concepts but don’t see how I can fully implement this model • My facility is all legacy systems
15
5/13/12
ISPE Good Prac9ce Guide #10 Applied Risk Management for Commissioning and Qualifica9on
16
5/13/12
Good Prac0ce Guide Structure 1 – Introduc9on 2 – Fundamentals 3 – Cont. Improvement 4 – Suppor9ng Prac9ces 5 – Quality Risk Mgmt 6 – Cost Control and Process Performance 7 – Specialty Applica9ons
Appendices • User Requirements • C&Q Plans • Organiza9onal Maturity • Commissioning • References • Glossary
Select Highlights • • • • •
Sec9on 2.3 – Process Flow Diagram Figure 2.5 – Two Tiered Risk Assessment Table 3.2 – Legacy System Challenges Table 4.1 -‐ QMS Challenge Examples Table 10.1 -‐ Organiza9onal Maturity Model
17
5/13/12
Knowledge Brief (Jan 2010) • Industry is undergoing a sea of change with science and risk based pharmaceu9cal development, valida9on, and manufacturing • Risk Base C&Q an important part of change • Quality Systems must adapt for commercial and compliance reasons • The road for each firm will be different
Timothy P. Howard, CPIP, PE Vice President Commissioning Agents, Inc.
[email protected] 919-‐538-‐3482
18
5/13/12
BACKUP SLIDES – ISPE GUIDE
FSE GUIDE CONTENT
SCIENCE-‐BASED APPROACH
• Scien9fic knowledge should be the basis on which risk assessments performed to support design, development, and verifica9on to ensure that pharmaceu9cal systems are suitable for intended use • Iden9fica9on of the CPPs and CQAs, along with defined appropriate opera9ng limits or acceptance criteria, should be included in the documented product development data, process flow diagram, and product quality strategy • Product and process requirements should be used to define appropriate verifica9on ac9vi9es and acceptance criteria to ensure that manufacturing elements are suitable for their intended use
19
5/13/12
QUALITY RISK MANAGEMENT IN THE LIFE CYCLE
• QRM should underpin the specifica9on, design, and verifica9on process, and be applied appropriately at each stage • Two primary principles of quality risk management are iden9fied in ICH Q9: – the evalua9on of the risk to quality should be based on scien9fic knowledge and ul9mately link to the protec9on of the pa9ent – the level of effort, formality and documenta9on of the quality risk management process should be commensurate with the level of risk
QUALITY BY DESIGN
• Quality should be built into the design throughout the specifica9on, design, and verifica9on process. • Assurance that manufacturing elements are suitable for intended use should not rely solely upon verifica9on amer installa9on. • The process control strategy is essen9al to the overall product quality control strategy: – to mi9gate process risks by design – to control risks via the process control strategy – to detect failure of the process to meet cri9cal to quality aspects by measurement, alarming and ac9on as part of an overall product quality control strategy limits
20
5/13/12
SPECIFICATION AND VERIFICATION • The process of specifica9on, design, and verifica9on of equipment and systems should include the following ac9vi9es: – – – –
requirements defini9on specifica9on and design verifica9on acceptance and release
• GEP, QRM, and design reviews should be applied throughout the process and throughout the lifecycle
GOOD ENGINEERING PRACTICE
• GEP is defined as established engineering methods and standards that are applied throughout the project life cycle and ensure the effec9ve sa9sfac9on of stakeholder requirements • They deliver appropriate, cost-‐effec9ve solu9ons to meet user requirements and compliance with all applicable regula9ons • GEP should be applied to all stages of the specifica9on, design, and verifica9on process • GEP ensures that an engineering project meets the requirements of the user while being cost effec9ve, compliant with regula9ons, and well documented. Established guidance and standards support effec9ve GEP. • For GMP projects, it is cri9cal to the overall project success, that the principles of GEP are applied with the full coopera9on of suppliers, engineering and construc9on companies, and an organiza9on’s own cross-‐func9onal teams.
21
5/13/12
CONTINUAL IMPROVEMENT • Once the verifica9on process is completed, the system will be subject to the appropriate quality system(s) for ongoing support and con9nual improvement • An evalua9on should be performed periodically or upon specific incidents, such as frequent non-‐conformance of the system or product, to review the performance of the system and its ability to con9nue func9oning as required to meet cri9cal aspects of manufacturing capability. The review should confirm that the system remains suitable for intended use or recommend poten9al improvements • Where system improvements are recommended, this Guide may assist in their appropriate design and implementa9on
CHANGE MANAGEMENT • Change Management prac9ces should be appropriate to the ac9vi9es performed and the stage within the system life cycle • Change Management prac9ces may, generally, be iden9fied as: – engineering change management, based upon GEPs – formal QA change control, using similar GEPs augmented with pre-‐ and post-‐ approvals by the Quality Unit, is required during commercial manufacturing
• Implemen9ng formal QA Change Control, with Quality Unit pre and post approvals, prior to star9ng commercial manufacturing opera9ons is unlikely to provide benefit
22
5/13/12
SUBJECT MATTER EXPERTS • Subject Mager Experts (SMEs) are defined as those individuals with specific exper9se in a par9cular area or field • SMEs should take the lead role in the verifica9on of manufacturing elements • SME responsibili9es include planning and defining verifica9on strategies, defining acceptance criteria, execu9on of verifica9on tests, and reviewing results • SMEs are encouraged to understand, iden9fy, and leverage best prac9ces and processes related to automated equipment system.
SUPPLIER MANAGEMENT • Use of supplier documenta9on, inspec9on results, and test results can help to reduce duplica9on of effort • In the case of supplied equipment or systems with cri9cal aspects, appropriate SMEs should assess the QMS of the supplier to determine whether, and the extent to which, supplier documenta9on, inspec9ons, and test results can be leveraged • The regulated organiza9on should establish a clear approach for ensuring that the fabricated and delivered system or equipment complies with the pre-‐established requirements • The regulated organiza9on should establish how compliance is verified and documented during verifica9on tes9ng and performance tes9ng
23
5/13/12
AUTOMATION
• Automa9on should be an integral part of the verifica9on process for a manufacturing system that takes into account systems, process flows, automa9on and equipment elements of the system, as well as other func9ons such as data flow, alarming, and repor9ng • Once cri9cal aspects of manufacturing, their acceptance criteria, and the verifica9on plan are in place, the development and tes9ng of the automa9on, both in the development environment and the produc9on environment, become engineering ac9vi9es • Verifica9on ac9vi9es may help determine actual opera9ng ranges within which the system is capable (process capabili9es)
Commissioning • “Commissioning is a managed and planned process of bringing a facility or equipment from its installed or constructed state into opera9onal service. This normally involves a process of sevng to work followed by regula9on and adjustment. These ac9vi9es should be based on the principles of GEP. Commissioning ac9vi9es are based on the principles of GEP and it should be a well planned, executed, and documented process • Commissioning is a process executed by engineers, which applies to all aspects of a facility, equipment, and services. The key ac9vi9es are similar regardless of whether commissioning is applied to a new facility or a simple piece of equipment has been constructed and installed; only the complexity is different. Key ac9vi9es include: o o o o
planning schedule inspec9on and tes9ng report
24
5/13/12
“QualificaSon” • The term “qualifica9on” may con9nue to be used • “qualificaSon” should mean that equipment has been found to be suitable for its intended use, based on: – the design criteria (process requirements or equivalent necessary to manufacture a quality product) – demonstra9on of sufficient control of risks to the pa9ent – documenta9on compiled through the verifica9on work performed throughout the delivery process and life cycle
• This does not imply the necessity to conduct addi9onal work in the form of separate DQ, IQ, and OQ protocols – the defini9on of DQ, IQ, and OQ is based on providing “documented verifica9on.” This guide recommends a compliant yet efficient method of producing this verifica9on evidence
Verifica0on • Defined in Verifica9on Plan(s) – – – –
Scope of work Verifica9on strategy Acceptance criteria for cri9cal aspects Documenta9on requirements
• Verifica9on Tes9ng (Phases) – – – – – –
Design Reviews Factory Acceptance Tes9ng (FAT) Site Acceptance Tes9ng (SAT) Installa9on Verifica9on (IV) Func9onal Verifica9on (FV) Performance Tes9ng (PT/PQ)
25
5/13/12
Common GEP Prac9ces • • • •
Good Documenta9on Prac9ces (GDP) Engineering Project Change Management Project Audits Planning Related Ac9vi9es o o o o
• • • • • • •
Project Planning Quality Planning Communica9on Plan Procurement Plan
Design Reviews Management Systems Construc9on Quality Standards Project Site Logis9cs Project Quality Control Non GMP Regula9on Compliance Turnover and Project Closure
26
