History ICH Q 9 QUALITY RISK MANAGEMENT Quality

History ICH Q 9 QUALITY RISK MANAGEMENT Quality Risk Management ICH Q 9 History Disclaimer: This presentation includes the authors views on quality risk management theory and practice. The presentation does not represent official guidance or policy of authorities or industry. prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 1

History ICH Q 9 QUALITY RISK MANAGEMENT Purpose of this part is to: · Guide you through the history of the development of the ICH Q 9 document · Highlight some of the decisions and rationales for making them prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 2

History ICH Q 9 QUALITY RISK MANAGEMENT The history of Q 9 document Osaka November 2003 London March 2004 Yokohama Washington June 2004 November 2004 2006 Draft for consultation March 2005 Chicago November 2005 prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance ICH Q 9 2005 July 2006, slide 3

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Milestones November 2003 Osaka March 2004 June 2004 London Washington Sep. 2004 Nov. 2004 Telecon Yokohama Feb. 2005 March 2005 Telecon Steering C. May 2005 Brussels Nov. 2005 Chicago Concept paper ICH Steering Committee agrees to new document Step 1 Scientific discussions within the EWG Step 2 Consensus of the 6 ICH partners and release for pubic consultation within the 3 Regions Step 3 Consolidation of public comments Step 4 Agreement of the 3 ICH regulators and "Signed off" by ICH Steering Committee Not legally binding, unless incorporated in local law 2006 ongoing Step 5 Implementation within the 3 Regions prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 4

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Concept paper Osaka, November 2003 · Technology focus > Increase process capability > Focus on critical control points · Product > Stabilise manufacturing steps (decrease variability) > Guarantee shelf-life · People > Result in a superior performance of the Q-System · Customer > Reduce deviation > Reduce market complaint rate > Reduce technical related adverse events prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 5

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Meeting London, March 2004 · A draft table of contents, flow diagram, definitions were agreed · Assignments to produce first drafts of the full text for each section of the draft table of contents were agreed · Started the dialogue with the ICH Q 8 EWG · Regulatory flexibility > The degree to which the final versions of both Q 9 and Q 8 could refer to 'regulatory relief' was a debate on principles. > Term changed to “regulatory flexibility” or “risk confidence”. prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 6

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Version 1 “Forget it” expressed what the EWG was thinking in terms of creating text on the agreed content prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 7

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Meeting Washington, June 2004 · Good agreement on overall content > No major disagreements between parties > Training and experience needed · The first official draft (No 2) was issued > All accept that wording is not perfect · Reaching ICH Step 2 in November was still the target > Highly dependent on the extent of comments received on draft prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 8

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Telecon September 2004 · Optional nature of ICH Q 9 to be emphasized · All EWG parties want to push ICH Q 9 forward > No support for delaying ICH Q 9 · Appointments for redrafting in six groups > Subgroup decide on details of Chapter 5 / 6 as annex or not > One subgroup to deal with ICH Q 8 relationships · Case studies: > Which ones are appropriate to use in ICH Q 8, Q 9 or Q 10? > Everybody should decide, whether the case studies should be included as an annex in the ICH Q 9 document or used as training material - Decision to be made in Yokohama prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 9

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Meeting November 2004 · Milestone: Draft 4 issued as “pre-step 2” document · Major concerns were addressed and resolved · Primary principle: link back to the potential harm to the patient · Integration of QRM into existing systems & regulatory processes will take time · For more details: Peter Gough and Stephan Roenninger, ICH Q 9 : Quality Risk Management - an update Regulatory Affairs Journal, 16, 2005, 91 -93 prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 10

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Telecon February, 22 2005 · All EWG parties agreed to put Q 9 forward to step 2 · Training slides will be provided > Slides to be discussed after step 4 · Next meeting of the EWG: ICH Meeting, November 2005, Chicago prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 11

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Expert Working Group (EWG) as of ICH Step 2 Mr. David Horowitz Dr. Greg Guyer (Rapporteur) Dr. H. Gregg Claycamp Dr. Georgia Keresty Director, Office of Compliance, CDER Director Scientific Support Staff Ms. Diana Kolaitis Merck &Co, Vice President, MMD QA Centocor, Inc. , Global. Biologics. Supply Vice President, Worldwide Quality District field inspector Dr. Yukio Hiyama Mr. Jon Edward Clarke Ms. Emer Cooke FDA HFD (alternate: Q 8) Head of sector Inspections EMEA Chief, Third Section: Division of Drugs Mr. Ichiro Tsunoi Compliance & Narcotic division Dr. Yoshihiro Matzuda MHLW, Registration Biol. Dr. Mayumi Shikano Dr. Jacques Morenas Expert Working Group ( EWG ) Inspection and Companies Directorate AFSSAPS, FEMEA, PIC/S Mr. David Cockburn(alternate) Principal Scientific Administrator EMEA Review director Office of biologics Dr. Tamiji Nakanishi Reviewer, Office of new drugs I Dr. Yoshihiro Matsuda Reviewer, Office of new drugs I Mr. Etienne Ouimette Compliance and Enforcement Coordination division, Health prod. & Food Branch Inspectorate Health CDN Mr. Peter Gough International Generic Pharmaceutical Alliance F. Hoffmann-La. Roche, CH, Global Quality Manager Ms. Christine Mundkur Mr. Takayoshi Matsumura Eisai, Assistant Manager, Corporate QA Department Mr. Tetsuhito Takarada Mochida Pharm. Deputy Director, Quality Control Mr. Hideo Sasaki(alternate) Nippon Shinyaka Co Ltd, Manager Anal. Chem. Sect. Mr. Frederick Razzaghi Lilly, GB, Senior Quality Consultant, Corporate QS Dr. Stephan Rönninger Consumer Health Product Association Dr. Sabine Kopp QA & Safety Medicines, WHO Dr. Urs Kopp Head of Inspectorate, Swissmedic prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 12

History ICH Q 9 QUALITY RISK MANAGEMENT Result of ICH Q 9 EWG Meeting Chicago November, 6. -8. 2005 Points of discussion and changes to the step 2 document · Separate the “How to do? ” (annex) from the “What to do? ” (text) and move the tools examples to the annex · Modify original diagram in section 4 > Take an alternative proposal showing communication routes · Move “continuous improvement” to Annex II. 1 (see ICH Q 10) · Reduce complexity by combining and re-wording the individual sections > “formal” and “informal” risk management referenced > “detectability” as an element in several chapters prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 13

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Expert Working Group (EWG) as of ICH Step 4 Dr. H. Gregg Claycamp (Rapporteur) Dr. Georgia Keresty Director Scientific Support Staff Mr. A. D’Sa Compliance Officer, CDER Ms. Diana Kolaitis District field inspector Centocor, Inc. , Global. Biologics. Supply Vice President, Worldwide Quality Mr. Tobias Massa Bristol-Myers Squibb Vice president Global Regulatory Sciences-CMC Dr. Yukio Hiyama Ms. Emer Cooke Chief, Third Section: Division of Drugs Ichiro Tsunoi Assistant Director, Office of Compliance, Pharm. & Food Safety Bureau, MHLW Tamiji Nakanishi Reviewer, Office of New Drugs I, PMDA Mayumi Shikano Review Director, Office of Biologics, PMDA Head of sector Inspections EMEA Expert Working Group ( EWG ) Dr. Jacques Morenas Inspection and Companies Directorate AFSSAPS, FEMEA, PIC/S Yoshihiro Matsuda Reviewer, Office of New Drug I, PMDA Yukio Saito GMP Inspector, PMDA Takashi Nagashima GMP Expert, PMDA Ms. Diana Dowthwaite Compliance and Enforcement Coordination division, Health prod. & Food Branch Inspectorate Health CDN Ms. Christine Mundkur International Generic Pharmaceutical Alliance Mr. Frederick Razzaghi Mr. Malcolm Holmes GSK, UK, Global Quality Assurance, Director Dr. Stephan Rönninger F. Hoffmann-La Roche, CH, Global Quality Manager Consumer Health Product Association Mr. Takayoshi Matsumura Dr. Sabine Kopp Mr. Tetsuhito Takarada Dr. Markus-Peter Müller Eisai, Assistant Manager, Corporate QA Department QA & Safety Medicines, WHO Mochida Pharm. Deputy Director, Quality Control Head of QM-Inspectorate, Swissmedic Mr. Hideo Sasaki Nippon Shinyaka Co Ltd, Manager Anal. Chem. Sect. prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 14

History ICH Q 9 QUALITY RISK MANAGEMENT Publication and implementation of ICH Q 9 Legal position of ICH Q 9 · US / FDA: - Guidance for Industry (June 2006) - By law, guidance documents are not enforceable or binding FDA will use the document internally in this spirit, as well · Japan / MHLW: - Product GMP Guideline “Annex”: ICH Guidelines · EU / EMEA: EUDRALEX Volume 4 - Medicinal Products for Human and Veterinary Use : Good Manufacturing Practice - EU-GMP Vol. 4, Annex 20 - Teams established to update chapters of EU-GMP, Nf. G etc. prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 15

History ICH Q 9 QUALITY RISK MANAGEMENT European legal position of ICH Q 9 Publication of the document in EU for comments: · “It should be borne in mind that this guideline does not introduce new requirements or expectations but should be considered a resource document that can be used together with existing quality-related guidelines when a risk-based approach is appropriate. ” · “Therefore, as well as complementing GMP guidelines, the document should be seen as also complementing and supporting existing and future guidelines published by CHMP and CVMP concerning the quality of medicinal products. ” EU-Publication of Step 2 document prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 16

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Briefing Pack July 2006 Authors Reviewers · · · · E. Cooke, EMEA · Y. Hiyama, MHLW · D. Horowitz, FDA · G. Keresty, Centocor · U. Kopp, Swissmedic · J. Morénas, AFSSAPS · C. Mundkur, Barr Laboratories · M. -P. Müller, Swissmedic · F. Razzaghi, CHPA Supported by EFPIA and JPMA ICH Q 9 topic groups S. Rönninger, Roche (Chair) G. Claycamp, FDA P. Gough, former Lilly M. Holmes, GSK T. Matsumura, Eisai Co. H. Sasaki, Nippon Shinyaku T. Takarada, Mochida Pharm. prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 17

History ICH Q 9 QUALITY RISK MANAGEMENT ICH Q 9 Briefing Pack ICH EWG members published a set of slides with more details on possible implementations > ICH homepage: www. ich. org -> -> scroll down to ICH Q 9 · On the ICH Q 9 Document > > > Background History Content Tools Applications Current direct link: http: //www. ich. org/cache/html/3157 -272 -1. html · Additional features > Senior Management Training > Frequently Asked Questions (Q&A) prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 18

History ICH Q 9 QUALITY RISK MANAGEMENT Optional but can benefit from its use! prepared by some members of the ICH Q 9 EWG for example only; not an official policy/guidance July 2006, slide 19