Quality Assurance and Regulatory Compliance for Pharmaceutical Product

1. Quality Assurance and Regulatory Compliance for Pharmaceutical Product Prof. Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010, Karnataka, India E-mail: bknanjwade@yahoo.co.in Cell No: 00919742431000 Maharashtra College of Pharmacy, Nilanga

2. Quality Assurance Quality assurance is a wide ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. QA is the heart and soulof quality control QA = QC + GMP Maharashtra College of Pharmacy, Nilanga

3. The System of Quality Assurance • Pharmaceutical products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical practice (GCP) • Product and control operations are clearly specified in a written form and GMP requirements are adopted Maharashtra College of Pharmacy, Nilanga

4. The System of Quality Assurance • Managerial responsibilities are clearly specified in job description • Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials. • All necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out. Maharashtra College of Pharmacy, Nilanga

5. The System of Quality Assurance • The finished products is correctly processed and checked according to the defined procedures. • Pharmaceutical products are not sold or supplied before the authorized persons have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other regulations relevant to the production, control and release of pharmaceutical products Maharashtra College of Pharmacy, Nilanga

6. The System of Quality Assurance • Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are stored by the manufacturer, distributed and subsequently handled so that quality is maintained throughout their shelf-life. • There is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the quality assurance system Maharashtra College of Pharmacy, Nilanga

7. The System of Quality Assurance • Deviation are reported, investigated and recorded • There is a system for approving changes that may have an impact on product quality • Regular evaluations of the quality of pharmaceutical products should be conducted with the objective of verifying the consistency of the process and ensuring its continuous improvement. Maharashtra College of Pharmacy, Nilanga

8. Quality relationships QA GMP QC Maharashtra College of Pharmacy, Nilanga

9. Quality Assurance It is the sum total of the organized arrangements with the objective of ensuring that products will be of the quality required for their intended use Maharashtra College of Pharmacy, Nilanga

10. Good Manufacturing Practice Is that part of Quality Assurance aimed at ensuring that products are consistently manufactured to a quality appropriate to their intended use Maharashtra College of Pharmacy, Nilanga

11. Good Manufacturing Practice GMP Covers all aspects of production including • Raw or starting materials • Finished products • Premises and environment • Equipment • personnel • Training • Hygiene Maharashtra College of Pharmacy, Nilanga

12. GOOD MANUFACTURING PRACTICE Maharashtra College of Pharmacy, Nilanga

13. Quality Control Is that part of GMP concerned with sampling, specification & testing, documentation & release procedures which ensure that the necessary & relevant tests are performed & the product is released for use only after ascertaining it’s quality Maharashtra College of Pharmacy, Nilanga

14. QC is that part of GMP which is concerned with sampling, specifications, testing and with in the organization, documentation,and release procedures which ensure that the necessary and relevant tests are carried out QA and QC • QA is the sum total of organized arrangements made with the object of ensuring that product will be of the Quality required by their intended use. Maharashtra College of Pharmacy, Nilanga

15. Operational laboratory techniques and activities used to fulfill the requirement of Quality QA and QC • All those planned or systematic actions necessary to provide adequate confidence that a product will satisfy the requirements for quality Maharashtra College of Pharmacy, Nilanga

16. QC is lab based QA and QC • QA is company based Maharashtra College of Pharmacy, Nilanga

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19. Quality Assurance-Highlights • In process quality checking in manufacturing • Validation of facilities, equipments, process, products and cleaning • Complaint handling • Storage of quality records and control samples • Stability studies Maharashtra College of Pharmacy, Nilanga

20. Quality Assurance Activities • Technology Transfer • Validation • Documentation Control • Assuring Quality of Products • Quality Improvement Plans Maharashtra College of Pharmacy, Nilanga

21. 1. Technology Transfer • Receipt of product design documents from R & D Department • Distribution of documents to different departments • Checking and approval of documents generated based on R & D documents i.e. batch manufacturing record • Scale‐up and validation of product Maharashtra College of Pharmacy, Nilanga

22. 2. Validation • Preparation of validation plans for facility, equipments/process including cleaning • Approval of protocol for validation of facility /equipment /product /process • Team member for execution of validation of facility/equipment/ product/process Maharashtra College of Pharmacy, Nilanga

23. 3. Documentation Control • Controlled distribution and archiving of documents • Control of changes made by proper change control procedure • Approval of all documents Maharashtra College of Pharmacy, Nilanga

24. 4. Assuring Quality of Products • cGMP training • SOP compliance • Audit of facility for compliance • Line clearance • In‐process counter checks • Critical sampling • Record verification • Release of batch for marketing • Investigation of market complaints Maharashtra College of Pharmacy, Nilanga

25. 5. Quality Improvement Plans • To take Feedback from different departments • Proposals for corrective and preventive actions • Annual Products review • Trend analysis of various quality parameters for products, environment and water Maharashtra College of Pharmacy, Nilanga

26. FACTORS IN DRUG QUALITY ASSURANCE Import & Export Control Legislative Framework -Regulations Packaging Human Resources- Professionals Labeling & Product Information DRUG PRODUCT QUALITY Raw Materials- Active & Inactive QC & Analysis Transport Distribution Dispensing & Use Manufacturing Processes & Procedures Storage Maharashtra College of Pharmacy, Nilanga

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28. Quality Assurance Highlights • In process quality checking in manufacturing • Validation of facilities, equipments, process, products and cleaning • Complaint handling • Storage of quality records and control samples • Stability studies Maharashtra College of Pharmacy, Nilanga

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30. Equipment /Instrument Qualification • Before a process can be validated the equipment, facilities & services used in that process must themselves be validated such an operation is referred to as qualification • Qualification therefore, an integral part of process validation which in turn is part of GMP Maharashtra College of Pharmacy, Nilanga

31. Equipment /Instrument Qualification Maharashtra College of Pharmacy, Nilanga

32. Equipment /Instrument Qualification Maharashtra College of Pharmacy, Nilanga

33. Why to qualify If the instrument is not qualified prior to use & if a problem occurs, the source of problem will be difficult to identify. Maharashtra College of Pharmacy, Nilanga

34. Qualification Involves Maharashtra College of Pharmacy, Nilanga

35. Details Record in Change Control • Request for change • Change control No. • Date • Change related to product/document/system/facility • Concerned documents with number • Description of change • Reason for change • Impact of change Maharashtra College of Pharmacy, Nilanga

36. Details Record in Change Control • Proposed methodology for implementation • Category of change • Type of change • Comparison criteria for evaluation of the change • Assessment of impact of change • Approval of change • Implementation of change • Closure of change Maharashtra College of Pharmacy, Nilanga

37. Details Recorded in Deviation Approval • Deviation no. • Deviation related to • Concerned identity number (Batch No., Code No. etc) • Type of deviation (Planed/Unplaned) • Description of deviation • Reason/Investigation with document • Category of deviation • Root cause analysis Maharashtra College of Pharmacy, Nilanga

38. Details Recorded in Deviation Approval • Impact of deviation (on batches, Products, Items, etc) • Immediate action • CAPA (Corrective and Preventive Action) • Impact of CAPA • Intimation to concerned • Comments from concerned • Periodic review • Final review • Deviation close-out • Evaluation of implemented CAPA Maharashtra College of Pharmacy, Nilanga

39. Details Recorded In Out of Specification Report • OOS No. (Out of Specification) • Reporting of OOS • Information of OOS to immediate senior • Assessment of analytical data by immediate senior • Discussion between analyst and immediate senior • Sampling and analysis • Data compilation • Assignable cause identification • Full scale OOS investigation (Cause not identified) • Evaluation • Conclusion • CAPA • OOS results summary Maharashtra College of Pharmacy, Nilanga

40. Area of Self Inspection • Personal & Personal details • Premises including personnel facilities • Maintenance of building & equipment • Storage of starting material & finished products (Stores) • Equipment • Production & In-process controls • Cephalosporin Mfg & Packing • Manufacturing • Packing • Quality control • Documentation • Sanitation & Hygiene • Validation and revalidation program Maharashtra College of Pharmacy, Nilanga

41. Areas of Self Inspection • Calibration of instruments or measurement system • Recall procedure • Complaints management • Labels control • Computerized system • Engineering • Documents related to regulatory affairs • Discarding of residues • Quality assurance • Control on contract analysis • Results of previous self inspection, quality audit and any corrective steps taken Maharashtra College of Pharmacy, Nilanga

42. Details Recorded in Complaint Investigation Report • Complaint No. • Product Name • Manufacturing and Expiry of product • Source of complaint • Date of receipt of complaint • Nature of complaint • Category of complaint Maharashtra College of Pharmacy, Nilanga

43. Details Recorded in Complaint Investigation Report • Investigation • Impact of complaint on other batches/products • Batches/Products • Review • CAPA • Impact of CAPA • Implementation of Preventive action • Close out of complaint Maharashtra College of Pharmacy, Nilanga

44. Acceptance Criteria RPN: Risk Priority Number Maharashtra College of Pharmacy, Nilanga

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46. ROOT CAUSE ANALYSIS Maharashtra College of Pharmacy, Nilanga

47. Regulatory Compliance For Pharmaceutical Product Maharashtra College of Pharmacy, Nilanga

48. Regulatory Requirements • Regulatory requirements are part of the process of drug discovery and drug development. • Regulatory requirements describe what is necessary for a new drug to be approved for marketing in any particular country. • In the US, it is the function of the Food and Drug Administration (FDA) to establish these regulatory requirements. • The European Medicines Agency (EMA) and • Japanese Pharmaceuticals and Medical Devices Agency (PMDA) are also important regulatory authorities in drug development. These three agencies oversee the three largest markets for drug sales Maharashtra College of Pharmacy, Nilanga

49. Regulatory Compliance • In general, compliance means conforming to a rule, such as a specification, policy, standard or law. • Regulatory compliance describes the goal that corporations or public agencies aspire to in their efforts to ensure that personnel are aware of and take steps to comply with relevant laws and regulations. Maharashtra College of Pharmacy, Nilanga

50. Pharmaceutical Product Quality Cannot Be Tested in - It Is Built in • Pharmaceutical product quality is assured by • Comprehensive development program • Extensive manufacturing and environmental controls • Rigorous validation procedures and requirements • Compliance to regulatory requirements • The high quality thus built into the final product is ensured through in-process controls and verified in a series of confirmatory tests before each manufactured batch is released to the market Maharashtra College of Pharmacy, Nilanga