ICH Q10 Pharmaceutical Quality System

Transcription

1 Safeguarding public health ICH Q10 Pharmaceutical Quality System An EU Regulator s Perspective

2 Presentation overview Why does Q10 exist and what were the desired outcomes Content of the Q10 step 2 document & current status Potential benefits of Q10 and Q8, Q9, Q10 together, for both Industry and the regulator Challenges to a successful outcome Slide 2

3 Why Q10? Increasing recognition that: - Globally Pharmaceutical Manufacturing was highly inefficient compared to other science based industries - Regulatory processes perceived as inflexible particularly with respect to post marketing change - Innovation and improvement stifled - Risk averse compliance focus against perceived non science or risk-based regulations / guidance - Toleration of the status quo. Cost pressures for industry and regulators - Margins / resources reduced - Drive for better efficiency - Ever more global and complex supply chains Slide 3

4 Why Q10? The period PWC report 2001 Low Process Capability in Pharmaceutical Manufacturing Low utilisation levels (15% in some cases) Scrap and rework at 5-10% is accepted Time to effectiveness is not challenged Cost of Quality > 20% You need to improve..other high-tech industries have achieved enormous product gains in manufacturing in the last 25 years. We should expect nothing less from the Pharmaceutical Industry. Mark McLellan ex FDA Commissioner Slide 4

5 What has changed since 2001? IBM report 2005 The metamorphosis of manufacturing On time supply 60-80% Right First Time 85-95% Process control level 1 to sigma processes Better process design and control and Continual Improvement could give 4.5 sigma Potential cost benefits of >$10* billion a year * Various studies indicate $10-90 billion A general political environment of demands for better regulation across all governmental activities Slide 5

6 ICH Q10 -The vision Describe a modern quality system needed to establish and maintain a state of control that can ensure the realisation of a quality drug product and facilitate continual improvement over the life cycle of a drug product. Promote a paradigm shift from discreet GMP compliance systems at each stage of the product lifecycle to a global QS approach over the entire lifecycle of the product. Slide 6

7 ICH Q10 -The vision continued.. And if adopted by industry (on a voluntary basis) would: Complement and serves as a bridge between regional GMP regulations. Facilitate application of ICH Q8, Q9 Links development and manufacturing through product the lifecycle Facilitate continual improvement in pharmaceutical manufacturing Be based upon the well accepted ISO 9000 structure within a pharmaceutical context Facilitate appropriate levels of regulatory scrutiny Post approval change Inspections Slide 7

8 ICH Q10 -The vision continued.. Would provide a harmonised model for a Pharmaceutical Quality System that if adopted by industry (on a voluntary basis) would: Leverage knowledge and encourage a preventive action culture, which ensures actions are taken before a problem / issue arises Improve quality monitoring and review (e.g. data evaluation, statistical process control and process capability measurements), which form the basis for continual improvement of processes Provide greater assurance that there is no unintended consequence as a result of continual improvement activities Slide 8

9 GMPs and ICH Q10 Q10 is not a harmonised GMP Regional GMPs do not currently apply across all life cycle but GMPs do provide guidance on manufacture and control of pharmaceutical products GMPs do provide guidance on most of the essential elements of a Quality Assurance System GMPs address CAPA but not proactive continual improvement GMPs touch on management responsibilities GMPs do not address the system needed to bring a quality product to market However, GMPs are a critical element of an effective Pharmaceutical Quality System Optional model but having a QMS isn t!! Slide 9

10 Q10 (Step 2) History and status Final Concept Paper, September 2005 Final Business Plan, October 2005 Step 2 May 2007 Consultation (Step 3) : EU: Transmission to CHMP and to Interested Parties May Issued as EMEA/CHMP/ICH/214732/2007. Deadline for comments: November MHLW: Released for consultation 13th July 2007, PFSB/ELD, deadline for comments 1st October 2007 FDA: Published in the Federal Register July 13, 2007, Volume 72, No. 134, pages Deadline for comments October 11, 2007 Slide 10

11 Q10 (Step 2) Structure and Content Introduction Pharmaceutical Quality System Management Responsibility Management and Continual Improvement of Product Quality Management and Continual Improvement of the Pharmaceutical Quality System Slide 11

12 Product Lifecycle Early Stage Late Stage Commercial Product Discontinuation Product & Process Development Manufacturing Principles (& Supporting Tools) Knowledge Management (Science) Quality Risk Management Quality Management Management Responsibilities Q10 Pharmaceutical Quality System Elements Process and Product Quality Monitoring CAPA Change Management Management Review GMPs Quality System Foundations Quality, Laboratory Controls, Production Facilities & Equipment, Materials, Packaging & Labelling Slide 12

13 Pharmaceutical Quality System Introduction Scope Relationship of ICH Q10 to Regional GMP Requirements, ISO Standards and ICH Q7 Relationship of ICH Q10 to Regulatory Approaches ICH Q10 Objectives Enablers Design and Content Considerations Quality Manual Slide 13

14 Management Responsibility Management Commitment Quality Policy Quality Planning Resource Management Internal Communication Management Review Oversight of Outsourced Activities Slide 14

15 How might industry and regulators use Q10? To demonstrate an effective quality system to regulatory authorities probably via inspections The company and/or site should have systems in place to: - Identify what is critical to quality (Q8 & Q9) - Establish appropriate controls - Assess and mitigate the risk of quality failures - Implement continual improvement changes A Q10/Q9 site or company has the potential to be considered lower risk - Fewer inspections? - Inspection depth and frequency - The intensity of regulatory inspections commensurate with the level of risk from degree of product & process understanding, QRM and PQS present Slide 15

16 How might industry and regulators use Q 10 with Q8 & Q9? Opportunity for: Increased use of risk-based approaches for regulatory inspections To facilitate science-based pharmaceutical quality assessment To optimize science and risk-based post-approval change processes to maximize benefits from innovation and continual improvement To enable innovative approaches to process validation establish real-time release mechanisms Slide 16

17 Quality Risk Management Existing GMPs Regulatory System Quality System Well designed and understood processes Quality Risk Management Q9 Pharmaceutical Developm ent Q8 Pharmaceutical Quality System Q10 Together Q8, Q9, Q10 = product & process understanding with risk management applied within a robust quality system Opportunity for: Review Changes Inspections Slide 17

18 Challenges to future successful implantation Trust and culture change enhanced two-way trust Clear understanding of the stakeholders needs and options Industry Regulator trust and openness in working together towards the new vision learning together Culture change in both Industry and Regulators - Overcome internal conservatism and silo thinking - Organisational change management resistance to change, new competencies needed, e-access to data Harmonisation and mutual understanding ICH members & observers, ROW, Emerging markets Big Pharma is a globally operation, but with often with regional / national regulatory processes Slide 18

19 Challenges to future successful implantation Will Industry really be comfortable with the life cycle approach? Inspection of product transfer activities may take GMP Inspectors into Development? Will the approach disadvantage Small and Medium Enterprises? What is the scope of the QMS? Site or Enterprise? Will Q10 ultimately raise the bar for general expectations for the QMS for manufacturing GMPs and become the de facto standard for all? Slide 19

20 Challenges to future successful implantation What s new in Q10 Not a great deal in terms of principles. It brings into a harmonised document to what better companies do already. How will Q10 be eventually adopted? - as a revision to the EU Guide? As an Annex? How many companies will require re-engineering of their QMS? Will adoption deliver Industry s desire for regulatory flexibility? Will it really be a facilitator for change or will the industry s conservativism to change mean that continual improvement will still be stunted? Revision of the Variations Regulations Commission Regulation (EC) No 1084/ Enablers for this are ICH Q8, Q9 and the Commission s own Better Regulation initiative All too early to tell at this stage Slide 20

21 In Conclusion EU regulators firmly believe that effective and robust Quality Risk Management underpinned by an effective quality system is key to the successful implementation of the «new» concepts described in Q 8 EU Regulators are committed to safeguarding public health but are also committed to leaving sufficient flexibility to industry and to avoiding an increase in requirements. EU Regulators are committed to fostering innovation! Slide 21

22 Safeguarding public health Crown copyright 2007 The materials featured within these MHRA presentation notes and delegate pack are subject to Crown copyright protection for this event. Any other copy or use of Crown copyright materials featured in this presentation, in any form or medium, is subject to prior approval of the MHRA which has Delegated Authority from Her Majesty's Stationery Office (HMSO) to administer Crown copyright for MHRA originated material. Applications should be in writing, clearly stating the proposed use/reuse of the information, and should be sent to the MHRA at the following address: Conference and Education Function, 16 th Floor, MHRA, 1 Nine Elms Lane, London SW8 5NQ. Fax or speakers@mhra.gsi.gov.uk. You may not sell or resell any information reproduced to any third party without prior agreement. The permission to reproduce Crown copyright protected material does not extend to any material in this pack which is subject to a separate licence or is the copyright of a third party. Authorisation to reproduce such material must be obtained from the copyright holders concerned. Slide 22