Quality Management

1. Basic Principles of GMP Quality Management Section 1 and 2

2. Quality Management Objectives • To understand key issues in quality assurance/good manufacturing practices/quality control. • To understand specific requirements on quality management and quality assurance including: • Organization • Procedures, processes and resources. • To develop actions to resolve your current problems.

3. Quality Management Quality relationships Quality Management Quality Assurance GMP Production and Quality Control Section 1 and 2

4. Quality Management Philosophy and essential elements • What is Quality Management? • The aspect of management function that determines and implements the “quality policy” • The overall intention and direction regarding quality, as formally expressed and authorized by top management

5. Quality Management Quality Management • The basic elements are: • An appropriate infrastructure or “quality system” encompassing the organization structure, procedures, processes and resources • The systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality” The totality of these actions is termed “Quality Assurance”

6. Quality Management Quality Management • Quality assurance is a management tool • In contractual situations, it also serves to generate confidence in a supplier • QA, GMP and Quality Control are interrelated aspects of Quality Management • They are described on the following slides in order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products

7. Quality Management Principles of Quality Assurance (QA) • Wide-ranging concept • covers all matters that individually or collectively influence the quality of a product • Totality of the arrangements • to ensure that the drug is of the right quality for the intended use • Quality Assurance incorporates GMP • also product design and development 1.1

8. Quality Management QA System should ensure that: • Products are designed and developed in accordance with GLP, GCP, and GMP • Production and control operations are clearly specified in SOPs • Managerial responsibilities are clearly specified in job descriptions • Systems ensure that the correct starting and packaging materials are used 1.2

9. Quality Management QA System should ensure: • Starting materials, intermediate products, bulk products are controlled • In-process controls, calibrations, and validations are carried out • Finished products are correctly processed and checked • Products are not sold or supplied before release by authorized persons • Systems ensure that products are appropriately stored and distributed 1.2

10. Quality Management QA System should ensure: • Self-inspection and/or quality audits are done regularly • Deviations are reported, investigated and recorded • Changes are controlled • Systems are followed to verify the consistency of processes and ensuring continuous improvement • Quality Risk Management is implemented 1.2

11. Quality Management Quality Assurance • Products must: • safety, quality and efficacy requirements - fit for their intended use • comply with the requirements of the marketing authorization • Senior management is responsible - and all staff must be committed to achieve this. • Relies on a comprehensively designed, documented, correctly implemented system of QA incorporating GMP and QC. • Relies on competent personnel, suitable and sufficient premises, equipment and facilities. 1.3

12. Quality Management Quality Assurance • Manufacturers should manage quality risks. Quality Risk Management (QRM) is a systematic process for: • assessment, control, communication and review of risks to the quality of the medicinal product. • QRM: • can be applied both proactively and retrospectively • Should be based on scientific knowledge and experience with the process • Should be linked to the protection of the patient 1.4 – 1.5

13. Quality Risk Management (ICH Q9) Advanced training workshop for GMP inspectors Nairobi , 9-12 May, 2011

14. Quality Management Quality Assurance • Quality Risk Management follows a cycle of assessment, control, communication and review. • An appropriatetoolshouldbeused in riskassessment, such as: • Fault Tree Analysis (FTA) • Hazard and Operational Studies (HAZOP) • Failure Mode and Effect Analysis (FMEA) • Hazard Analysis and Criticality Analysis (HACCP) • Failure Mode, Effect, and Criticality Analysis (FMECA) 1.3

15. Quality Management Failure Mode Effect Analysis • Breakdown in manageable steps • Process and product understanding needed • Evaluate failure mode and effect on outcome • Eliminate, contain, reduce, control • (Identify mode, cause, effect)

16. Quality Management Quality Assurance Product quality review (PQR) • Regular, periodic or rolling quality reviews of all medicinal products • Normallyannually • Objective: • Verifying the consistency of the existing process • appropriateness of current specifications for both starting materials and finished product • highlight any trends • identify product and process improvements. 1.6

17. Quality Management Quality Assurance • PQR should include at least a review of: • starting materials and packaging materials (especially from new sources) • critical in-process controls and finished product results • all batch failures and their investigation • deviations or non-conformances (and investigations and CAPAs) • all changes made to the processes or analytical methods • dossier variations submitted, granted or refused • results of the stability monitoring programme and any adverse trends 1.6

18. Quality Management Quality Assurance • PQR shouldinclude (cont).: • quality-related returns, complaints and recalls and the investigations • adequacy of previous corrective actions on product process or equipment • Post marketing commitments • qualification status of relevant equipment and utilities • technical agreements 1.6

19. Quality Management Quality Assurance • Results should be reviewed- assessment should be made whether CAPA or revalidation should be undertaken • CAPA completed in a timely and effective manner – verified • Product types can be grouped • Agreements in case of contracted parties • PQR in a timely manner and verified for accuracy 1.6

20. Quality Management Quality Assurance When inspecting PQR, also verify: • Correctness of data transferred • Trending of results • Calculations such as process capability index (CpK) - where appropriate • Accuracy in terms of APIs reflected, approved suppliers used, number of batches, variations, changes, complaints etc. • CAPAs and conclusion

21. Quality Management Good Manufacturing Practices (GMP) • That part of QA that ensures that products are consistently produced and controlled • Quality standards • Marketing authorization • Aim: Diminishing risks that cannot be controlled by testing of product • Contamination and cross-contamination • Mix-ups (confusion) 2.1

22. Quality Management Basic Requirements for GMP – I • Clearly defined and systematically reviewed processes • Qualification and validation is performed • Appropriate resources are provided: • Qualified and trained personnel • Premises, space, equipment and services • Materials, containers, labels • Procedures, storage, transport • Laboratories and in-process control 2.1 a - c

23. Quality Management Basic Requirements for GMP – I • Clear, written instructions and procedures • Trained operators • Records of actions, deviations and investigations • Records for manufacture and distribution • Proper storage and distribution • Systems for complaints and recalls 2.1 d - j

24. Quality Management Group session – I • How many GMP deficiencies can you find in the photographs in the handout?

25. Quality Management Group session II • Imagine you are inspecting a pharmaceutical company for compliance with GMP • Consider the situations in the next slides which may have impact on a company’s quality management programme • Describe the action to be taken in each case

26. Quality Management Issues – I • Quality Management manual not established in writing • Limited human resources • Lack of qualified people • Processes not properly validated • Poor SOPs or standard batch documentation • More consideration to cost than quality • Family members in key positions of authority

27. Quality Management Issues – II • Substandard materials deliberately purchased • Technical staff not involved in purchasing • Inability to re-export substandard materials • Owner insists on selling rejects • Corruption • No commitment to training