The Pharmaceutical Quality System Final

nullThe Pharmaceutical Quality SystemThe Pharmaceutical Quality SystemJoe Famulare – FDA Gerry Migliaccio – Pfizer February 28, 2007Discussion TopicsDiscussion TopicsIndustry Perspective on the Pharmaceutical Quality System – Gerry FDA perspective on the Pharmaceutical Quality System and the FDA Quality System Guidance– Joe ICH Q10 Overview and Management Responsibility - Gerry Management and Continual Improvement of Product Quality and the Quality System – Joe Q&AIndustry Perspective on the Pharmaceutical Quality SystemIndustry Perspective on the Pharmaceutical Quality SystemIndustry Perspective on the Pharmaceutical Quality SystemIndustry Perspective on the Pharmaceutical Quality SystemIndustry and regulators agree that compliance with GMP assures quality, but certain principles and elements must be built on to GMPS to establish a comprehensive pharmaceutical quality system and: Promote a lifecycle approach to product quality. Promote innovation and continual improvement. Provide opportunity to optimize regulatory processes. These principles and elements are no more than common sense and good business practice.Why Industry Supports Pharmaceutical Quality Systems Guidance?Why Industry Supports Pharmaceutical Quality Systems Guidance?Industry is global A harmonized regulatory authority perspective on a modern effective pharmaceutical quality system is essential to: Facilitate innovation and continual improvement Harmonize and streamline regulatory processes FDA perspective on the Pharmaceutical Quality System and the FDA Quality System GuidanceFDA perspective on the Pharmaceutical Quality System and the FDA Quality System GuidanceQuality System Guidance Development Quality System Guidance Development cGMP Initiative For the 21st Century - August 2002 - August 2004 Comparison of Quality Systems Approaches (Evaluation of Quality Systems) ISO standards, EU, PIC/S, U.S., Non–pharmaceutical Quality Standards (QSR’s, HAACP) Guidance describes a comprehensive quality system model and how CGMP regulations correlate to QS elements If implementing a comprehensive quality system, this guidance can help achieve compliance with CGMPs Final Guidance issued September ‘06Intent of the FDA Quality Systems Guidance Intent of the FDA Quality Systems Guidance Implement a modern, comprehensive and robust quality system, consistent with CGMPs that, defines a state of control to: Facilitate the consistent production of high quality, safe and efficacious product Facilitate change control - continuous improvement Facilitate quality by design - building in quality to process and product Facilitate adoption of risk management Facilitate harmonization with other quality systems FDA Quality Systems GuidanceFDA Quality Systems GuidanceThe FDA has concluded that modern quality systems, when coupled with manufacturing process and product knowledge and the use of effective risk management practices, can handle many types of changes to facilities, equipment, and processes without the need for prior approval regulatory submissions. Manufacturers with a robust quality system and appropriate process knowledge can implement many types of improvements. In addition, an effective quality system, by lowering the risk of manufacturing problems, may result in shorter and fewer FDA inspections.FDA Quality Systems GuidanceFDA Quality Systems GuidanceA quality system can provide the necessary framework for implementing quality by design (building in quality from the development phase and throughout a product’s life cycle), continual improvement, and risk management in the drug manufacturing process. A quality system adopted by a manufacturer can be tailored to fit the specific environment, taking into account factors such as scope of operations, complexity of processes, and appropriate use of finite resources. FDA Quality Systems GuidanceFDA Quality Systems GuidanceCGMPs and the Concepts of Modern Quality Systems CGMPs and the Concepts of Modern Quality Systems Quality Quality by Design and Product Development Quality Risk Management CAPA (Corrective and Preventative Action) Change Control The Quality UnitThe Quality Systems ModelThe Quality Systems ModelManagement Responsibilities Resources Manufacturing Evaluation ActivitiesResult Result Continual Improvement – On going activities to evaluate and positively change products, processes and the quality system to increase effectiveness.Measures of Success Science-based approaches Decisions based on an understanding of the intended use of a product Proper identification and control of areas of potential process weakness Responsive deviation and investigation systems that lead to timely remediation Sound methods for assessing and reducing risk Well-defined processes and products, starting from development and extending throughout the product life cycle Systems for careful analysis of product quality Supportive management (philosophically and financially) ICH Q10ICH Q10Q10 OverviewQ10 OverviewIntroduction Establish a tripartite guideline for a pharmaceutical quality system. The guideline: Provides a means to maximize the benefits of implementing Q8 and Q9. Demonstrates industry and regulatory authority commitment to a pharmaceutical quality system. Facilitates innovation and continual improvement over the product lifecycle. Q10 ObjectivesQ10 ObjectivesAchieve Product Realization To consistently provide a product of the quality necessary to meet the requirements of patients, health care professionals, regulatory authorities and internal customers. Establish and Maintain a State of Control To use effective monitoring systems for process performance and product quality providing assurance of continued capability of processes. Facilitate Continual Improvement Identification and implementation of necessary product quality improvements, process improvements, variability reduction, innovations, and PQS enhancements, thereby increasing the ability to consistently fulfil quality requirements. Risk Management techniques may be used to identify necessary areas for improvementRelationship of Q10 and GMPsRelationship of Q10 and GMPsQ10 builds upon regional GMPs and ICH Q7. Q10 describes certain quality system elements and management responsibilities that foster continual improvement. Q10 bridges regional GMP regulations and helps to achieve a harmonized lifecycle approach to pharmaceutical quality systems.Relationship of Q10 to Regulatory ApproachesRelationship of Q10 to Regulatory ApproachesRegulatory approaches should be commensurate with the level of process understanding and the effectiveness of the pharmaceutical quality system. The effectiveness of the pharmaceutical quality system will be confirmed during a regulatory inspection of the manufacturing facility. Regulatory approaches will be determined by region. Potential Opportunities to Enhance Regulatory ApproachesPotential Opportunities to Enhance Regulatory ApproachesQ10 Enablers and ElementsQ10 Enablers and ElementsEnabling Principles Knowledge Management Quality Risk Management Pharmaceutical Quality System Elements Process and product quality monitoring system Corrective action and preventive action (CAPA) system Change management system Management review of product qualityManagement ResponsibilitiesManagement Responsibilities Leadership is essential to establish and maintain a company-wide commitment to quality and for the performance of the pharmaceutical quality system.Management ResponsibilityManagement ResponsibilityQuality Policy Pharmaceutical Quality System Oversight Quality Planning Resource Management Internal Communication Management Review Oversight of Outsourced OperationsICH Q 10 Management and Continual Improvement of Product QualityICH Q 10 Management and Continual Improvement of Product QualityFour PQS Elements that Build on Product Quality Process and product quality monitoring system Corrective action and preventive action (CAPA) system Change management system Management review of product qualityICH Q10- Lifecycle Goals ICH Q10- Lifecycle Goals Development Technology Transfer Manufacturing Product Discontinuation ICH Q 10 HighlightsICH Q 10 HighlightsProduct and Process Quality Monitoring System Utilize the knowledge gained in commercial production to continually improve the product and process. Utilize a knowledge management system Identify sources of process variation Use quality risk management to identify and prioritize indicators for monitoring and utilize feed forward feed backward mechanisms. Verify a state of control Provide key inputs to enrich the design space, and to enable innovative approaches to the process validation lifecycle ICH Q 10 HighlightsICH Q 10 HighlightsCorrective and Preventive Actions A system for implementing corrective and preventive actions in place A structured approach for investigations Determination of root cause of deviations and trends Resulting in product and process improvement and increase in process understanding ICH Q 10 HighlightsICH Q 10 HighlightsChange Management Evaluate changes under the principles of quality risk management Refer to the design space and existing product/process knowledge Expertise needed should include development, manufacturing, quality, regulatory and medical to evaluate the impact on product qualityICH Q 10 Highlights ICH Q 10 Highlights Change Management (continued) Set acceptance criteria for change and evaluate after implementation Knowledge gained should be included in the knowledge management system Assess the need for a regulatory system realizing the benefits from using Q8 and 9 principlesICH Q 10 Highlights ICH Q 10 Highlights Management Review of Product and Process Capability Review the results of inspections audits Measures of customer complaints recalls etc. Periodic reviews results of previous reviews and CAPA actions Follow up on previous reviews ICH Q 10 Highlights ICH Q 10 Highlights Management Review of Product and Process Capability (continued) Identify follow up actions including improvements to the product and process, realignment of resources, and capture and dissemination of knowledge from the knowledge management system ICH Q 10 Highlights ICH Q 10 Highlights Management and Continual Improvement of the Pharmaceutical Quality System (PQS) PQS Monitoring Factors impacting the PQS Management Review of the PQSICH Q10 - SummaryICH Q10 - SummaryContinuous Learning and Improvement Much learning takes place through process experience Our 21st Century Regulatory System will facilitate this improvement Flexibility Management and Performance based regulationIntegration: Review and InspectionIntegration: Review and InspectionHow do we more formally transfer our ideas from CDER (Review, Compliance) to ORA? Create a “handshake” from Center to ORA. Similar to technology transfer from R&D to commercial Final critical aspect of implementing desired state will be realized by new continuity between CDER and ORA Inspectional role: Address follow-up on key areas suggested by Center Verify process implementation and state of control Assess Lifecycle improvements Ensure Adequate change controlQ&AQ&A