Changes to EU Guide to Good Manufacturing Practice (GMP)

Presented by Trevor Schoerie

10 August 2015

141010_POUT

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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

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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

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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

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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

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ASEAN Nations & PIC/S members

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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.

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“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

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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

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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

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1 Trillion $USD market

Source: IMS Health Market Prognosis, September 2012

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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

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More changes PIC/S PE 009-11

Effective on 1st March 2014

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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)

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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

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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

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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

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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

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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

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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

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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?

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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)

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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

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EU GMP Guide Annex 15 “Qualification & Validation

Design Space

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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

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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

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Thank you for your time.

Trevor Schoerie

trevor.schoerie@pharmout.net

www.pharmout.net

Managing Director

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