Pharmaceutical Quality System (PQS) Advantages for a Global Operation in the Implementation of Q8, 9, and 10

Transcription

1 Pharmaceutical Quality System (PQS) Advantages for a Global Operation in the Implementation of Q8, 9, and 10 WCBP 2011 Sunset Plenary Session January 10, 2011 Joseph C. Famulare Senior Director Global Quality and Compliance Genentech, Inc.

2 Outline Slide 2 ICH Vision for Pharmaceutical Quality Regulatory Expectations Implementation of Q10 at Genentech/Roche Conclusions

3 An ICH Vision for Pharmaceutical Quality Slide 3 The Regulatory System Quality Risk Management (Q9) Quality System Management Quality Risk Management Pharmaceutical Development Pharmaceutical Development (Q8 & Q8R) Existing GMP Existing GMP s Pharmaceutical Quality System / PQS (Q10) Drug Substance Guidance (Q11) Step 2 Spring 2011? Source: Jacques Morénas, ISPE, Nov 2007

4 ICH Guidance History Slide 4 1. ICH Q8 - Pharmaceutical Development (2006; revised 2009) describes the suggested contents for the pharmaceutical development section of a regulatory submission in the ICH M4 common technical document (CTD) format; indicates areas where the provision of greater understanding of pharmaceutical and manufacturing sciences can create a basis for flexible regulatory approaches. Q8(R) includes concepts of Quality by Design (QbD) and examples of design space. 2. ICH Q9 Quality Risk Management (2006) provides principles and examples of tools for quality risk management that can be applied to all aspects of pharmaceutical quality throughout the lifecycle of drug substances, drug products, and biological and biotechnological products; intended to enable regulators and industry to make more effective and consistent risk based decisions. 3. ICH Q10 Pharmaceutical Quality System (2009) intended to provide a comprehensive approach to an effective pharmaceutical quality system that is based on ISO concepts, includes applicable GMP regulations and complements ICH guidance on Q8 and Q9.

5 Q9 Goal is to reduce patient risk Slide 5 Design Opportunities to impact risk using quality risk management Q9 Process Materials Manufacturing Facilities Distribution Q8 Q10 Patient

6 Q10 Pharmaceutical Quality System PQS Slide 6 Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation Investigational products GMP Management Responsibilities Process Performance & Product Quality Monitoring System PQS Corrective Action / Preventive Action (CA/PA) System elements Change Management System Management Review Enablers Knowledge Management Quality Risk Management

7 Regulatory Landscape and Need for Integrated Product Quality Management Slide 7 Guidance for Industry: Q10 Pharmaceutical Quality System (April 2009), Process Performance and Product Quality Monitoring System Pharmaceutical companies should plan and execute a system for the monitoring of process performance and product quality to ensure a state of control is maintained. Use quality risk management to establish the control strategy. Provide the tools (e.g., data management and statistical tools) for measurement and analysis of parameters and attributes identified in the control strategy Verify continued operation within a state of control Identify sources of variation affecting process performance and product quality for potential continual improvement activities. Include feedback on product quality from both internal and external sources, e.g. complaints, product rejections, non-conformances, recalls, deviations, audits and inspection inspections and findings;

8 Q10 - Where the PQS Applies Slide 8 Product Life Cycle Pharmaceutical Development Technology Transfer Commercial Manufacturing Product Discontinuation Pharmaceutical Quality System (PQS) Operations Make Assess Release PQS

9 Q10 PQS Slide 9 Q10 encompasses the entire product lifecycle and can be applied whether or not QbD is employed. Documentation Training and education Outsourced activities / purchased materials Control Strategy Use quality risk management to establish using parameters and attributes and related facility and equipment operating conditions Monitoring / Handling Quality Defects (CAPA) The level of effort of the investigation should be commensurate with the level of risk. Result should be product and process improvements

10 Q10 PQS Slide 10 Auditing / Inspection For regulators For companies Periodic review Change management / change control Driven by innovation, continual improvement, the outputs of process performance and product quality monitoring, and CAPA Level and formality commensurate with risk Continual improvement an opportunity to optimize scienceand risk-based post-approval change process

11 PQS Management Responsibilities & Expectations 11

12 Outline Slide 12 ICH Vision for Pharmaceutical Quality Regulatory Expectations Implementation of Q10 at Genentech/Roche Conclusions

13 Performance Expectations of the PQS Health Authorities expecting ICH Q8-10 implementation EU moving in direction of making ICH Q10 elements enforceable as directives More emphasis on role of management QRM and KM are expected to be integrate in PQS PQS is expected to be applied consistently across a company 13

14 FDA Performance Expectations of the PQS Slide 14 Establish and Maintain State of Control (Systemic, Comprehensive and Global) It is our [FDA] expectation that firms take a systematic approach to correcting and complying with CGMP to ensure the identity, strength, quality, and purity of their drug products. In your response to this [warning] letter, please include an explanation of how you intend to implement, support, and sustain a comprehensive quality system at your firm that is consistent with CGMP. It appears that you have not taken a global quality systems approach to corrective actions at your firm It is your responsibility to review your operations at all facilities and apply appropriate corrective actions to address deficiencies present at multiple sites. Source: 2010 FDA Warning Letters, at

15 FDA Performance Expectations of the PQS Slide 15 Management Commitment It is our expectation that firm s senior management ensure a systematic approach to designing their products, processes, and quality systems, and require that deviations and flaws are promptly identified and corrected to assure the identity, strength, quality, and purity of their drug products. Be advised that FDA expects that your corporate management will undertake a comprehensive evaluation of manufacturing operations to ensure compliance with CGMP. Source: 2010 FDA Warning Letters, at

16 Outline Slide 16 ICH Vision for Pharmaceutical Quality Regulatory Expectations Implementation of Q10 at Genentech/Roche Conclusions

17 Quality Philosophy & Prioritization Principles Slide 17 Quality Philosophy Quality is every patient s right and every employee s responsibility. Quality provides a competitive advantage and is engrained in everything we do, from concept through continuous improvement. Because our products touch human lives, quality is the true measure of our success. Our People Our Patients Our Prioritization Principles 1. Right to Operate 2. Quality Supply to Patients 3. Contribution to Target

18 Global Technical Operations Slide 18 Over 20 Plant Operations at 17 sites, about 12,000 employees North America Hillsboro Vacaville South San Francisco Boulder Florence Oceanside Toluca a Mannheim Clarecastle Penzberg Leganés Basel/Kaiseraugst Segrate Europe & Africa Shanghai Singapore Asia Pacific Latin America PLUS: Over 200 contract manufacturing organizations (CMOs) Rio 420 Solid Dosage Drug Product Small Molecules Drug Substance Isando Sterile Drug Product Biologics Drug Substance

19 Implementation of Modern Quality Systems Slide 19 Why One Pharmaceutical Quality System (PQS)? Health Authority Requirements & Standardization LEAN Quality Process Expectations One Company One PQS Network Wide Integrated with the Business Knowledge Management Reduce Product & Patient Risk Drive Down Costs

20 Implementation of Modern Quality Systems Slide 20 Product Quality Management - Deliver an End to End (E2E) view of product quality for all Commercial products - Critical to: maintaining quality supply to patients product consistency across sites our right to operate - End to End means that the product quality: is managed throughout the product value stream includes both API and drug product is managed throughout Product Life Cycle (Q10 enabler- Process Performance and Product Quality Monitoring) - Success requires knowledge transfer from Clinical to Commercial

21 Product Quality Management: Fundamental Elements Slide 21 Product Complaints Early warning signals of product quality issues in the field Product Assessment & Trending Proactive assessment of product quality attributes across the manufacturing process Product Quality Stewards Single point of Contact for Quality to key stakeholders Routine health assessment of product to address trends Planning provides foresight and proactive approach QC testing network support Harmonized approach to test method execution & support Scalability & flexibility to balance test workload across network Analytical methods management Scientific rigor engrained in analytical method performance Product control systems based on science Seamless product transfers & assessment of consistency

22 Implementation of Modern Quality Systems Slide 22 Product Quality Steward Model - Dedicated resources overlooking each product to assure quality integrating activities - across all sites (Mfg, QC, QA, etc) - Single point of contact: from raw materials to distribution across all technical disciplines Quality and the rest of the organization - Early warning for product quality issues - Quality improvement activities are implemented across the network

23 Opportunities for Global Implementation Slide 23 Better understanding of a company s capability and profile across a global network i.e., more assurance by regulators of consistent processes and global implementation; Companies can provide more assurance site to site for producing consistent products and analytical procedures in a global network environment; and Enhanced ability for regulators to leverage shared assessments, inspections based on common standards globally for new products, changes, and site transfers.

24 Design of the PQS One Document Hierarchy In Alignment with ICH Q10: Four Categories to Organize PQS Documents Quality Policy Process Maps, Flow Charts and Visual Aids Quality Requirements Global Standards & Processes Standard Operating Procedures Other Document Types PQS involves IT Tools, business processes and common requirements described in QRs / GSPs 24

25 Cost of Quality Slide 25

26 Cost of Quality Slide 26 Encompasses the costs of creating a quality product and service More importantly it incorporates and focuses on the cost of NOT creating a quality product or service Encompasses Right First Time Principles to drive better quality decisions and improve the quality throughout processes

27 Cost of Quality Slide 27 Need to establish metrics including costs: Investigations Rejects product removal actions Labor and Time involved Too often the focus is on getting the product released, but not enough focus on getting to the root cause and preventing the issues from reoccurring. If conducting multiple investigations to deal with the same issues over and over again, is money really being spent wisely? The Cost of Quality quantification provides a business case for well thought out preventive action."

28 Quality Compliance Risk Slide 28 Use of Quality Risk Management to utilize findings from inspections, audits, and trending data and to eliminate or mitigate risks Risk Assessment Mitigation Planning Reporting 28

29 Conclusion PQS is the foundation for quality products PQS covers All of Supply Chain from raw materials to distribution Own production and outsourced From pre-clinical through commercial to decommissioning GMPs and should be integrated with business processes and supported by tools For multi site companies PQS consistency is achieved through standardization, common IT tools and management oversight ICH Q10 has increased expectations to Senior Management within PQS and to using the enablers QRM & Knowledge Management Quality is an attribute not just a function 29

30 Slide 30 Acknowledgements Stephen Mahoney Genentech Jennifer Magnani Genentech Ann Gillian Roche Deb Bailey Genentech Ron Taticek - Genentech

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