B asic Principles of PHARMACEUTICAL QUALITY SYSTEM ( PQS )- ICH Q10

1. Basic Principles of PHARMACEUTICAL QUALITY SYSTEM (PQS)-ICH Q10 Pharm (Mrs). Uche Sonny-Afoekelu, M.Sc.(PH), MPCPharm Assistant Director, Compliance Division Drug Evaluation and Research Directorate, NAFDAC US-A

2. OUTLINE • Introduction- What is quality? • Relationship between different levels of quality • What is ICH Q10? • Philosophy and essential elements of the quality system in pharmaceutical manufacturing • Objectives of Pharmaceutical Quality System (PQS) • Applications of PQS US-A

3. INTRODUCTION • What is Quality? Degree to which a set of inherent characteristics fulfills requirements- ISO Degree- refers to a level which a product or service satisfies. So depending on the level of satisfaction, a product may be termed as excellent, good or poor quality product US-A

4. INTRODUCTION…..2 • Inherent characteristics: Those features that are a part of the product and are responsible for achieving satisfaction • Requirements: Refers to the needs of the customer, needs of the organization, and those of other interested parties eg Regulatory Bodies US-A

5. INTRODUCTION…..3Examples of quality components • AREA • Airlines • Healthcare • Food services • Pharmaceutical Quality System • QUALITY COMPONENTS • On-time, comfortable, low-cost service • Correct diagnosis, minimum wait time, low cost • Good taste, free from contamination, fast delivery, good environment • ???????????? US-A

6. INTRODUCTION….4 • Every Pharmaceutical product has established identity, strength, purity and other quality characteristics designed to ensure the required levels of safety and effectiveness. • In this Presentation, achieving quality means achieving these characteristics for a product. US-A

7. Relationship between different levels of quality • Quality management, defining the overall policy of the organization towards quality, is over everything else. • Next comes quality assurance, which is the concept that ensures the policy is achieved. • GMP is part of quality assurance. It deals with the risks that cannot be tested. It builds quality into the product. • Quality control is a part of GMP. It is that part of GMP that is focused on testing of the environment and facilities, as well as the testing of the materials, components and product in accordance with standards. US-A

8. Quality relationships Quality Management / PQS Quality Assurance GMP Production and Quality Control

9. GMP – PICs Guide QUALITYMANAGEMENT QUALITY UNIT PRODUCTION MANAGEMENT PEOPLE PRODUCTS & MATERIALS EQUIPMENT FACILITIES

10. FDA – 6 Systems Approach of PQS Quality System Production System Facilities & Equipment System Laboratory Controls System Materials System Packaging & Labeling System

11. Q8 Q9 Q10 New Era With New Challenges “risk-based” concepts and principles of ICH Ref: ICH

12. How did ICH Q10 Originate? • ICH Q10 was created from aspects of regional GMPs, ICH Q7 “GMP Guide for APIs”, and ISO 9000 (and related guidelines). ICH Q10 augments GMP by describing specific quality system elements and management responsibilities. • ICH Q10 provides a harmonized model for a pharmaceutical quality system throughout the product lifecycle and is intended to be used together with regional GMP requirements. • GMPs don’t explicitly address all stages of product lifecycle (e.g. Development). The quality system elements and management responsibilities described in Q10 promote the use of science and risk based approaches at each lifecycle stage, thereby encouraging continual improvement across the entire product lifecycle.

13. to IHow did ICH Q10 Originate?......2CH Q10 Conti... • ICH Q10 describes a comprehensive approach to Pharmaceutical Quality System • It includes Good Manufacturing Practice (GMP) regulations • It is harmonized with ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management” • It allows Industry & Regulatory to enhance the Quality and Availability of medicines around the Globe in the interest of Public Health 19

14. What is ICH Q10? • ICH Q10 is not intended to create any new regulatory requirements • It only helps in maintaining product quality and compliance at all stages of product life cycle • It helps innovation and continual improvement in pharmaceutical manufacturing • GMPs do not explicitly address all stages of the product life cycle (e.g., development) and ICH Q10 is intended to encourage the use of science and risk based approaches at each lifecycle stage thereby promoting continual improvement across the entire product life cycle.

15. Scope of ICH Q10 • ICH Q10 can be implemented throughout the different stages of a product lifecycle. • Development Stage • Technology Transfer Stage • Manufacturing Stage • Discontinuation Stage

16. ICH Q10 I(PQS GMP Pharmaceutical Development Technology Transfer CommercialManufacturing Discontinuation Investigational products Management Responsibilities Process Performance & Product Quality Monitoring System Corrective Action / Preventive Action (CAPA) System Change Management System Management Review PQS elements Knowledge Management Enablers Quality Risk Management 33

17. Objectives of PQS • Achieve Product Realization: To establish, implement & maintain a system that allows the delivery of products with quality attributes appropriate to meet the needs of patient & other stake holders. (2) Establish & Maintain a State of Control:To develop & use effective monitoring & control systems for process performance & product quality, thereby providing assurance of continued suitability and capability of processes. Quality Risk Management (QRM) can be useful in identifying the monitoring and control systems (3) Facilitate Continual Improvement:To identify and implement appropriate product quality improvements, process improvements, variability reduction, innovation & quality system enhancements, thereby increasing the ability to fulfill quality needs consistently. QRM can be useful for identifying & prioritizing areas for continual improvement.

18. Objectives of PQS • What is the Objective of any System? • (Using ICH Q10 as an example) Product Realization State of Control Continual Improvement Compliance ORGANIZATIONAL OPTIMIZATION Development + Tech transfer + Commercial + Discontinuation System Boundaries ie full Life Cycle “Quality is a side effect of a system that is running well”

19. GMPs without a Modern Framework will Limit Improvements • GMPs provide guidance on the manufacturing and control of pharmaceutical product • GMPs do not drive lifecycle approach to quality • GMPs do not specifically address proactive continual improvement • GMPs only briefly mention management responsibility • GMPs are reactive, PQS is more proactive

20. Philosophy of the Quality System in Pharmaceutical manufacturing • The overarching philosophy is that • Quality should be built into the product, and testing alone cannot be relied on to ensure product quality ! • Implies QUALITY BY DESIGN (QbD) (Build Quality into your products, design risk out of your processes)! US-A

21. Philosophy of the PQS…2 • The PQS (formerly referred to as Quality management system) is described in ICH Q10 • It is based on ISO (International Organization for Standardization ) quality concepts. • It includes the concepts of QA, GMP, QC, QRM- which are interrelated aspects of Quality Management. US-A

22. Philosophy of the PQS…3 • Quality Management is a management function • It determines and implements the quality policy which is the overall intention and direction of an organization regarding quality • It is formally expressed and authorized by top (senior) management • Senior management has the ultimate responsibility to ensure an effective PQS US-A

23. Philosophy of the PQS…4 • Quality Manual • A quality manual should be established and should contain the description of the PQS. The description should include: • The quality policy • Scope of the PQS • Identification of the PQS system processes, their linkages and interdependencies. Process maps and flow charts can be useful. • Management responsibilities within the PQS US-A

24. Philosophy of the PQS…5 • Paradigm shift in Quality (ICH Q8, ICH Q9, and ICH Q10) • ICH Q10 is a model for a Pharmaceutical Quality System that can be implemented throughout the different stages of a product life cycle. US-A

25. Philosophy of the PQS…6 • Implementation of ICH Q10 throughout product life cycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities US-A

26. Product lifecycle • Pharmaceutical Development: • Goal: To design a product and its manufacturing process to consistently deliver the intended performance and meet the needs of the patients, healthcare professionals, regulatory authorities. • Drug Substance development • Formulation Development • Manufacture of investigational products • Delivery system development • Manufacturing process development and scale up • Analytical method development US-A

27. Product Lifecycle… 2 • Technology transfer • Goal: To transfer Product and Process knowledge • Between development and manufacturing, • Within manufacturing sites • Between manufacturing sites ……. to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and on-going continual improvement US-A

28. Product Lifecycle…3 • Commercial manufacturing • Goal: To achieve product realization, establish and maintain a state of control and facilitate continual improvement • Acquisition and control of materials • Provision of facilities, utilities, and equipment • Production (including packaging and labeling) • Quality control and assurance • Release • Storage • Distribution US-A

29. Product lifecycle…. 4 • Product discontinuation • Goal: To manage the terminal stage of the product life cycle effectively. • Retention of Documentation • Sample Retention • Continued product assessment (complaints handling and stability) • Reporting in accordance with Regulatory requirements US-A

30. ELEMENTS OF THE PQS 1) Process performance and product quality monitoring system 2) Corrective action and preventive action system 3) Change management system 4) Management review of process performance and product quality US-A

31. Elements of the PQS….2 • These elements should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognizing the differences among the stages and the different goals of each stage US-A

32. 1) Process performance and product quality monitoring • 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. • An effective monitoring system • provides assurance of the continued capability of processes and controls to produce a product of desired quality • Identifies areas for continual improvement US-A

34. Application of Process Performance and Product Quality Monitoring System throughout Product Lifecycle Pharmaceutical Development • Process and product knowledge generated and process and product monitoring conducted throughout development can be used to establish control strategy for manufacturing US-A

35. Application of Process Performance and Product Quality Monitoring System throughout Product Lifecycle • Technology transfer • Monitoring during scale up activities can provide a preliminary indication of process performance and the successful integration into manufacturing • Knowledge obtained during transfer and scale- up activities can be useful in further developing the control strategy US-A

36. Application of Process Performance and Product Quality Monitoring System throughout Product Lifecycle • Commercial manufacturing • A well defined system for process performance and product quality monitoring should be applied to assure performance within a state of control and to identify improvement areas US-A

37. Application of Process Performance and Product Quality Monitoring System throughout Product Lifecycle • Product discontinuation • Once manufacturing ceases, monitoring such as stability testing should continue to completion of the studies. • Appropriate action on marketed products should continue to be executed according to regional regulations US-A

38. 2) Corrective Action and Preventive Action System • The Pharmaceutical company should have a system for implementing corrective and preventive actions resulting from the investigation of complaints, product rejections, non conformances, recalls, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring US-A

39. Correction, Corrective and Preventive Action • Correction: Any action taken to eliminate a non-conformity • Corrective Action: Action to eliminate the cause of a detected non-conformity or other undesirable situation. Note: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence (ISO 9000:2005) • Preventive Action: Action to eliminate the cause of potential non-conformity or other undesirable potential situation. Note: Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence (ISO 9000:2005)

40. Corrective Action and Preventive Action System…2 • A structured approach to the investigation process should be used with the objective of finding the root cause • CAPA methodology should result in product and process improvements and enhanced product and process understanding US-A

42. Application of Corrective Action and Preventive action system throughout the product lifecycle • Pharmaceutical Development • Product or process variability is explored. CAPA methodology is useful where corrective actions and preventive actions are incorporated into the iterative design and development process US-A

43. Application of Corrective Action and Preventive action system throughout the product lifecycle • Technology Transfer • CAPA can be used as an effective system for feedback, feedforward, and continual improvement. US-A

44. Application of Corrective Action and Preventive action system throughout the product lifecycle • Commercial Manufacturing • CAPA should be used and the effectiveness of the actions should be evaluated US-A

45. Application of Corrective Action and Preventive action system throughout the product lifecycle • Product Discontinuation • CAPA should be continued after the product is discontinued. • The impact on product remaining on the market should be considered, as well as other products that might be affected US-A

46. Change Management • Change Management: A systematic approach to proposing, evaluating, approving, implementing & reviewing changes. It Should Include • Quality risk management to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk

47. Change Management….2 • Innovation, continual improvement, the output of process performance and product quality monitoring, and CAPA drive change. • To evaluate, approve and implement these changes properly, a company should have an effective change management system (CMS) • The CMS should provide a high degree of assurance that there are no unintended consequences of the change US-A

48. Change Management…3 • Proposed changes should be evaluated relative to the marketing authorization including design space, to determine whether a change to regulatory filling is required under regional requirements • Proposed change should be evaluated by experts in contributing their experience and knowledge

49. Change Management…4 • After implementation, evaluation of change should be under taken to confirm that the change objectives were achieved and there was no deleterious impact on product quality