Launch of IPEC

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 Explain JPEC Specific regulatory situation in Japan means JPEC support the initiative but can�t participate. They were observers at an initial meeting.Explain JPEC Specific regulatory situation in Japan means JPEC support the initiative but can�t participate. They were observers at an initial meeting.

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. Broad acceptance 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. Broad acceptance (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!