annex 1 revision · annex 1 update –2. pqs reinforce the existing requirements of eu gmp eu...
TRANSCRIPT
Annex 1 Revision
Greg McGurk, GMP Manager (acting)
GMP Conference
7 February 2017
Dublin
History
First issued in 1989
Number of revisions since then 1996, 2003, 2005,
2007 and 2009, but not full revisions
2012 first proposal to revise
Proposal Re-issued in 2014
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Rationale for Revision
Needed “Tidying up”
Introducing principles of Quality Risk Management
New technologies:
• Reinforcing the need of manufacturers to keep up with current technologies
• Single use closed systems
• Disposable systems
• Innovative technologies
• Some ambiguities
Micro data averages
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Annex 1 update
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Section Number General overview
1.Scope Additional areas (other than sterile medicinal products) where the general
principles of the annex can be applied
2.Principles General principles as applied to the manufacture of medicinal products. Includes
requirements for Contamination Control Strategy
3. Pharmaceutical
Quality System (PQS)
Highlights the specific requirements of the PQS when applied to sterile medicinal
products
4. Personnel Guidance on the requirements for specific training, knowledge and skills. Also
gives guidance to the qualification of personnel
5. Premises General guidance regarding the specific needs for premises design and also
guidance on the qualification of premises including the use of barrier technology
6. Equipment General guidance on the design and operation of equipment
7. Utilities Guidance with regards to the special requirements of utilities such as water, air
and vacuum
Annex 1 update
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Section Number General overview
7. Utilities Guidance with regards to the special requirements of utilities such as water, air
and vacuum
8. Production and
specific technologies
Discusses the approaches to be taken with regards to aseptic and terminal
sterilisation processes. Also discusses different technologies such as single use,
lyophilisation and BFS / FFS where specific requirements may be required.
Discusses approaches to sterilization of products, equipment and packaging
components
9. Viable and non viable
environmental and
process monitoring
This section differs from guidance given in section 5 in that the guidance here
applies to ongoing routine monitoring with regards to the setting of alert limits
and reviewing trend data
The section also gives guidance on the requirements of Aseptic Process
Simulation
10. Quality control Give guidance on some of the specific Quality Control requirements relating to
sterile medicinal products
11. Glossary Explanation of specific terminology
Annex 1 updates – 1. Scope
• New section to link to other annexes and chapters
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Annex 1 update – 2. PQS
Reinforce the existing requirements of EU GMP
EU Directive 2003/94 Article 5
EU Directive 2001/83 Article 23
Chapter 3
Chapter 5 (5.10)
QRM application, alternative at least as good as the stated objective
RCA & Product Impact Assessment
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Annex 1 update – 5. Personnel
Goggles (face coverings)
Training/knowledge
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Annex 1 update – 6. Premises 7. Equipment
Design
QRM application
Again reinforcing the need to keep the operators away from the product using current technology
Restricted Access Barrier Technology
Isolators
Cleanroom qualification: ISO 14644; 5.0 µm
Disinfection – Efficacy
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Annex 1 update – 8. Utilities
General services such as compressed air
WFI by RO - Possibility that this could then be moved to a separate section of the
GMPs
Biofilms
Cooling systems
Steam
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Annex 1 update – 9. Production and Specific technologies
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Blow Fill Seal
Form Fill Seal
Sterilisation Process & Controls
Aseptic Preparation
Finishing
Filtration – Pre-Use Post Sterilisation Integrity Test
Lyophilisation
Closed Systems
Single Use Technology
Annex 1 update – 10. Environmental Monitoring
Keep all monitoring in one place
To include Non Viable Particulates
To include all viable monitoring except the sterility test
To include process simulations
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Annex 1 update – 10. Environmental Monitoring
Reinforce the development of the “system” by risk assessment – process inputs, processes, operations / activities
Setting of appropriate operational limits
Emphasis on determination of adverse trends and evaluation of trend data
5.0 µm particles
Remove reference to averaged values for results
Rapid microbial methods
Aseptic Process Simulations – Zero growth, CAPA strategy
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Annex 1 update
• 11. Quality Control
• 12. Glossary
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Annex 1 update - Progress
Public Consultation phase – Estimated – Q2 2017
IWG & PICs review – Feb 2017
Container closure integrity & Pre-use post sterilisation integrity
Comments received back
Two rounds of review - circulated to PIC/S and IWG Mid 2016 & November 2016
Subgroups – tasked with drafting various sections
Joint working group between PIC/S and EMA
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Questions