Launch of IPEC/PQG Excipient GMPs guide Kevin McGlue, Steve Moss

1. Launch of IPEC/PQG Excipient GMPs guide Kevin McGlue, Steve Moss

2. IPEC/PQG Excipient GMPs guide • The organisations • Background • Key milestones • Joint charter (governance and oversight) • Development process • Major improvements • Benefits to Industry and Regulators • Implementation Strategy

3. IPEC • International Pharmaceutical Excipients Council • Formed in 1991 by manufacturers and end-users of excipients • Three associations covering the US, Europe and Japan • Objective: to contribute to the development and harmonisation of international excipient standards, the introduction of useful new excipients to the marketplace and the development of good manufacturing practice for excipients. • First published GMP Guide for Bulk Pharmaceutical Excipients in 1995, revised in 2001 to align with ISO 9001:2000.

4. PQG • Institute of Quality Assurance, Pharmaceutical Quality Group • Formed in UK in1977 • Key objective: To promote the development of a consistent approach to pharmaceutical quality and good manufacturing practice. • In 1990 published three codes of practice - pharmaceutical raw materials, printed and contact packaging materials. In 1995 revised and integrated these with ISO 9002:1994. • Raw materials code revised and reissued as PS 9100:2002 Pharmaceutical excipients, an application standard and GMP guide for pharmaceutical excipients.

5. Background to the joint guide • Increased focus on Excipient GMPs led to the need for a single international guide • June 2002 • IPEC Europe, IPEC Americas and PQG signed a letter of intent in committing to collaborate on a Baseline GMP guide for excipients • December 2002 • Joint charter issued

6. Joint Charter – Purpose • To produce a joint international GMP guide for excipients, which will build upon and replace the two groups’ existing documents. It will be aligned to ISO 9001:2000 and include a baseline (minimum) GMP for excipients. • During development of the document excipients used in more critical applications will be considered for inclusion in Appendices, as appropriate • The document will also provide the basis for a certification scheme for excipient suppliers separate from the basic GMP guideline.

7. Joint Charter - Boundaries • Includes: • GMP guide for excipients for all pharmaceutical products • GMP guide could be used for certification in subsequent phase • Future inclusions include audit and training guides • Excludes: • Sterile excipients • Active Pharmaceutical Ingredients • Products of biotechnology • Certification process

8. Joint Charter - Structure • Steering Committee (Sponsors): • 2 Members IPEC-Europe • 2 Members IPEC-Americas • 2 Members PQG • Team Members (Core team): • Six members, two from each organisation

9. Joint Charter – Some Stakeholders 1 • Association of the British Pharmaceutical Industry, • CEFIC, • Certification bodies for PQG Scheme, • European Federation of Pharmaceutical Industry Associations, • Excipient suppliers, • European Community DG3, • European Pharmacopoeia, • International Conference on Harmonisation, • IPEC-Europe, IPEC-Americas, • International Pharmaceutical Excipients Auditing Inc (IPEA),

10. Joint Charter – Some Stakeholders 2 • Institute of Quality Assurance • PQG committee, • Pharmaceutical companies, • Pharmaceutical Research and Manufacturers of America (PhRMA), • Regulatory bodies (Food & Drug Administration, Medicines & Healthcare Products Regulatory Authority etc), • United States Pharmacopoeia, • World Health Organisation, • Japanese Pharmaceutical Excipients Council (JPEC) - as an observer

11. Key milestones • Initial meeting • Review process • Draft new guide • Consultations and review • Final review • Publication and launch

12. Initial team meeting 23rd January 2003 • Key principles • Project timescales • ISO 9001 format • Overall document structure • Consultation and review process

13. Initial review process Started March 2003 • Reviewed detail of key source documents • PQG, IPEC, ISO 9001, ICH Q7a • Compared all the clauses in a matrix • Chose the most appropriate guidance appropriate for excipients • Resolved differences • Significant update in line with current thinking • Involved careful consideration and deliberation

14. Drafted NEW guide Q2 2003 to Q1 2004 • Improved assignment to ISO sections • more logical flow and improved readability • Key areas improved with significant rewriting include: • structure & responsibility of quality unit, product release, validation, stability, change control, GMP principles, auditing considerations • “Continuous processing” accounted for throughout • E.g. bulk materials, batch documentation and release

15. Further development of guide Q2 to Q3 2004 • Many multi-day meetings in UK, US, France • Continual adaptation to the prevailing changing environment • Maintained focus on developing voluntary baseline guidance • Potentially with need for additional guidance for specialist applications

16. Consultation and review Q4 2004 to Q3 2005 1. Members comment x2 (some external bodies eg EFPIA via members) • Consolidated comments (100’s!) to produce approved draft for external release 2. External circulation - Key organisations including regulatory authorities, trade organisations and other stakeholders • Consolidated comments 3. Issued to members for final comment • Consolidated comments to produce final draft 4. Comprehensive QC checks x2 teams • Corrected to produce draft for printing

17. Publication & printing Q4 2005 Hardcopy • US English by IPEC Americas • letter and pocket versions • UK English by IPEC Europe • A4 and pocket versions Electronic • A4/letter downloadable from websites

18. Thanks to the GMP/Partners groups and the wider membership of each organisation for help and excellent contributions!

19. Major improvements 1 • Better assignment to ISO sections to give more logical flow and improved readability • Accurate and legible wording • Appropriate guidance for excipients • Key ‘awkward clauses’ addressed e.g. stability, validation, change control • Included continuous processing - particularly the impact on batch definition and records

20. Major improvements 2 • Improved auditing considerations - GMP principles and applications • Harmonized glossary - rationalised to ICH where possible • Consistent use of terminology e.g. document, records; rework, reprocess • Removed ambiguity for international use (e.g. recall/retrieval; batch/lot)

21. Benefits to Industry and Regulators 1. Broadacceptance • Document critically reviewed by all stakeholders to obtain consensus • Well received by excipients industry and by pharmaceutical companies and their industry bodies, regulators EMEA and EC - suggests balance is appropriate • Overall good collaboration between US and Europe resulting in international acceptance

22. Benefits to Industry and Regulators 1. Broadacceptance (cont’d) • Participation and involvement with many good comments from many members, organisations, etc • Working with EC - new guide helping focus discussions and benchmarking appropriate principles which may become law for certain excipients

23. Benefits to Industry and Regulators 2. Ease of application • Builds additional GMP guidance onto the ISO framework • commonly used by the industry already • Practical guidance for excipient manufacturer • balancing pharmaceutical customers' expectations with usual constraints • Clear unambiguous wording

24. Benefits to Industry and Regulators 2. Ease of application(cont’d) • Provides common guide eliminating the need for multiple customers' requirements. • Manufacturer – applies common & appropriate standard, quality systems & controls • User – provides common expectation of what is appropriate for excipient manufacturers, audits • Clearly differentiates guidance for excipients • more than ISO 9001 • more appropriate than ICH Q7a

25. Implementation Strategy • Launch events • IPEC Americas – Orlando, 26th January 2006 • PQG – London, 7th February 2006 • IPEC Europe – Cannes, 9th February 2006

26. Additional copies available now • ipec.org and pqg.org • Order forms for printed copies • Members download free • Please spread the word!