Changes to EU Guide to Good Manufacturing Practice (GMP)
Presented by Trevor Schoerie
10 August 2015
141010_POUT
Slide 2 © PharmOut 2015
Key Global Regulations
• Every country is governed by their own legislated requirements
• Many countries have adopted global standards to facilitate better export / import opportunities
• Merging regulations
Slide 3 © PharmOut 2015
Key Global Regulations – Examples
Global harmonisation led by EU, Japan and US
• Guidance's are compilations of global regulations (mainly EU, US FDA and other key regulators) and are feeding back into local harmonised regulations
• ICH Q12 “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management” being drafted
• ICH Q7 (API) Working Group drafting a Q&A document. Due in 2015 but review of Q7 likely
• Disagreements between manufacturers and ICH
ICH – International Conferenceon Harmonisation
Slide 4 © PharmOut 2015
Key Global Regulations – Examples
Authority for health within the United Nations system
• First WHO GMP published in 1967
• Main principles and supplementary guidelines
• Guidelines in the form of Technical Reports and Annexes
• Used in over 100 countries
• Revised on an ongoing basis
Very practical and detailed.
WHO – World Health Organisation
Slide 5 © PharmOut 2015
Key Global Regulations – Examples
10 member states (next slide)
• Elimination of technical barriers to trade posed by GMP regulations
• Exchange of information
• Harmonisation of procedures and systems
• Looking towards PIC/S membership for the authorities in all 10 countries (Authorities in Singapore, Malaysia and Indonesia are currently PIC/S members)
ASEAN – Association of South East
Asian Nations
Slide 7 © PharmOut 2015
Key Global Regulations – Examples
Currently 46 authorities have adopted (28 from Europe)
• GMP Guidance’s used as regulatory requirements by EU and Asia-Pacific countries
• Is an informal “Cooperative Arrangement” between GMP regulatory authorities; i.e. not a legal treaty.
PIC/S – Pharmaceutical Inspection Co-op Scheme
No obligation for member authorities to accept inspection reports of other
members.
Slide 8 © PharmOut 2015
“Old" and new structures
Old • Made by Production
and tested Quality Control
• Most important persons?
New• But
• ….. Now released by QA
• ….. QA is the final signature?
• ….. QA processes, CC, Deviations, Complaints, OOT, OOS, etc.
• Hierarchical, strong functional structure
Slide 9 © PharmOut 2015
Key Global Regulations – Examples
Currently national requirements for the 28 member countries of the European Union
• Very similar to PIC/S (some local EU legislative requirements added/clarified)
Applicable to all US states and territories
• Similar concepts to PIC/S but captured in specific legal requirements
EU (Eudralex) – European Union
US FDA Code of Federal Regulations
Slide 10 © PharmOut 2015
1 Trillion $USD market
The U.S., EU5, Japan and China account for just under 70% of total global medicine spending
Source: IMS Health Market Prognosis, September 2012
Slide 12 © PharmOut 2015
Our focus
Countries
• Australian – TGA
• New Zealand – Medsafe
• Both on version 8
Regional Areas / Organisations
• ANZTPA – Australia – New Zealand
• International Conference on Harmonisation - ICH
• ASEAN – to become PIC/S members by 2015
Slide 14 © PharmOut 2015
PIC/S is heavily involved in developing the EU GMPs
The procedure to change GMPs is continuous
• These two groups cooperate closely and work in parallel on the GMP Guidelines. There exists an agreement on the procedure used and the changes are happening almost simultaneously.
Current version v11 – issued 1st - March 2011
• Current ANZ version v8 – PIC/S Guide to Good Manufacturing Practice for Medicinal Products, PE 009-8 – issued 15th January 2009 (6 years)
Slide 15 © PharmOut 2015
Revision Procedure in EU and PIC/SEffort for parallel paths
Initiative to Inspectors WG at
EMA
Concept paper published and commented
Discussion of draft and approval at the IWG at EMA.
It goes to EU Commission
9 step process: usually takes about 2 years for a document
Slide 16 © PharmOut 2015
Revision Procedure in EU and PIC/SEffort for parallel paths
EU Commission approves and publishes the
draft
Public consultation of draft for 3 to 6
months
Comments are assessed by
Rapporteur and IWG. Possible meetings with
Industry
Slide 17 © PharmOut 2015
Revision Procedure in EU and PIC/SEffort for parallel paths
IWG agrees on new draft
European Commission
performs final legal assessment
European Commission publishes the
new Rule
Slide 18 © PharmOut 2015
Current TGA GMP vs EU GMPParts I and II
ChapterPIC/S Guide to GMP
(v8)EU GMP Guidelines
Degree of change
1 Quality managementPharmaceutical Quality System (Jan 2013)
Major
2 Personnel Personnel (Feb 2014) Major
3 Premises and EquipmentPremise and Equipment (Mar2015)
Major
4 Documentation Documentation (Jan 2011) Major
5 Production Production (Mar 2015) Major
6 Quality control Quality Control (Oct 2014) Major
7 Contract manufacture and analysis
Outsourced activities (Jan 2013)
Minor
8 Complaints and product recall
Complaints and Product Recall (Oct 2014)
Major
9 Self Inspection Self Inspection Same
Part II no clause 2.2
Slide 19 © PharmOut 2015
Current TGA GMP vs EU GMP
Annex PICS Guide to GMP (v8) EU GMP GuidelinesDegree of
change
1 Manufacture of sterile medicinal products
Manufacture of Sterile Medicinal Products (Nov 2008)
Under review now
2 Manufacture of biological medicinal products for human use
Manufacture of Biological active substances and Medicinal Products for Human Use (Jan 2013)
Major
3 Manufacture of radiopharmaceuticals
Manufacture of Radiopharmaceuticals
Major
6 Manufacture of medicinal gases
Manufacture of Medicinal Gases (Feb 2010)
Major
7 Manufacture of herbal medicinal products
Manufacture of Herbal Medicinal Products (Sept 2008)
Major
8 Sampling of starting and packaging materials
Sampling of Starting and Packaging Materials
Same
9 Manufacture of liquids, creams and ointments
Manufacture of Liquids, Creams and Ointments
Same
Slide 20 © PharmOut 2015
Current TGA GMP vs EU GMP
Annex PICS Guide to GMP (v8) EU GMP GuidelinesDegree of
change
10Manufacture of pressurised metered dose aerosol preparations for inhalation
Manufacture of Pressurised Metered Dose Aerosol Preparations for Inhalation
Same
11 Computerised systems Computerised Systems (Jan 2011) Major
12Use of ionising radiation in the
manufacture of medicinal products
Use of Ionising Radiation in the Manufacture of Medicinal Products
Same
13Manufacture of investigational medicinal products
Manufacture of investigational medicinal products (Feb 2010)
Minor
15 Qualification and validationQualification and Validation (in draft)
Major
16Qualified person and batch release
Certification by a Qualified Person and Batch Release (in draft)
Under Review
17 Parametric release Parametric Release Same
19Reference and retention samples
Reference and Retention Samples Same
20 Quality risk management Refer to Q9 in Part III (Jan 2011) Same
Slide 21 © PharmOut 2015
EU GMP Guide Annex 15 “Qualification & Validation”
• Finally Released Annex 15.
• Drivers for the revision:
• ICH Q8, Q9, Q10 and Q11
• Advancements in manufacturing technology
• EMA draft Guide on Process Validation
• Changes to other Chapters, Sections and Annexes
• Catch up with the US FDA?
Slide 22 © PharmOut 2015
EU GMP Guide Annex 15 “Qualification & Validation”
Main Changes:
• Cross-reference made to Annex 11 Computerised systems
• Planning and documentation for Qualification and Validation
• Added information on the qualification stages for equipment, facilities and utilities
• Major revision of the Process and Cleaning Validation sections
• New sections added (next slide)
Slide 23 © PharmOut 2015
EU GMP Guide Annex 15 “Qualification & Validation”
New sections on:
• Ongoing Process Verification during Lifecycle
• Verification of Transportation
• Validation of Packaging
• Qualification of Utilities
• Validation of Test Methods
Slide 25 © PharmOut 2015
Our comments
• V-model versus Verification model (ASTM E2500)
• No reference to the benefits/use of other types of specifications other than URS/FS
• Could also have adopted a lifecycle approach to DQ preceding design reviews
• The definition of “Performance Qualification”is somewhat different within the current PIC/S document PI 006-3 and the US FDA Process Validation Guidance.
• EU PV versus US FDA PV
Slide 26 © PharmOut 2015
Next session….
Soon to be adopted by PIC/S? Version 12
Chapters
• 1: Pharmaceutical Quality Systems
• 2: Personnel
• 6: Quality Control
• 7: Outsourced activities
Recent changes?
• Chapters 3, 5, 6 and 8
Slide 27 © PharmOut 2015
Thank you for your time.
Trevor Schoerie
www.pharmout.net
Managing Director
Slide 28 © PharmOut 2015
This presentation and all associated materials are copyrighted and all rights reserved by PharmOut.
No part of this presentation may be reproduced or transmitted in any form or for any purpose without the express permission of PharmOut in writing. The information contained herein may be changed without prior notice.
Data contained in this presentation serves informational purposes only.
PharmOut does not warrant the accuracy or completeness of the information, text, graphics, links, or other items contained within this presentation. This presentation is provided without a warranty of any kind, either express or implied, including but not limited to the implied warranties of merchantability, fitness for a particular purpose, or non-infringement.
PharmOut shall have no liability for damages of any kind including without limitation direct, special, indirect, or consequential damages that may result from the use of this presentation.
©PharmOut Copyright Notice - 2015All rights reserved