EVALUATION SEMINAR PRESENTATION

1. EVALUATION SEMINAR PRESENTATION VALIDATION-DESIGN, DEVELOPMENT OF PROCESS VALIDATION, METHODS FOR PHARMACEUTICAL OPERATIONS INVOLVED IN THE PRODUCTION OF PHARMACEUTICAL DOSAGE FORMS. PRESENTED BY: P.SHARATH CHANDRA M.PHARM(SECOND YEAR) DEPT. OF PHARMACEUTICS KLE UNIVERSITY’S COLLEGE OF PHARMACY,BELGAUM

2. INTRODUCTION: • The concept of Validation was first proposed by two Food and Drug Administration (FDA) officials, Ted Byers and Bud Loftus, in the mid 1970’s in order to improve the quality of Pharmaceuticals. • USFDA Definition for Process validation: • Process validation is establishing documented evidence which provides a high degree of assurance that a specific process (such as the manufacture of pharmaceutical dosage forms) will consistently produce a product meeting its predetermined specifications and quality characteristics.

3. General view of Process Validation

4. Why Is Validation Required ? • It would not be feasible to use the equipments without knowing whether it will produce the product we wanted or not. • The pharmaceutical industry uses expensive materials, sophisticated facilities & equipments and highly qualified personnel. • The efficient use of these resources is necessary for the continued success of the industry. The cost of product failures, rejects, reworks, and recalls, complaints are the significant parts of the total production cost. • Detailed study and control of the manufacturing process- validation is necessary if failure to be reduced and productivity improved.

5. Responsible Authorities For Validation

6. Process validation timeline for a new process

7. Elements Of Validation

8. Types Of Process Validation

9. A) Prospective validation: Prospective validation life cycle

10. B) Retrospective validation: Retrospective validation life cycle

11. C) Concurrent validation: Concurrent validation life cycle

12. D) Revalidation: • Revalidation means repeating the original validation effort or any part of it, and includes investigative review of existing performance data. • This approach is essential to maintain the validated status of the plant, equipment, manufacturing processes and computer systems. • Change Control: • Written procedures should be in place to describe the actions to be taken if a change is proposed to a product component, process equipment, process environment, processing site. • All changes must be formally requested, documented and accepted by the validation team.

13. Validation Protocol • A written plan stating how validation will be conducted, including test parameters, product characteristics, production and packaging equipment, and decision points on what constitutes acceptable test results. Validation Master Plan • A comprehensive document describing the applicable validation requirements for a given facility, and providing a plan for meeting those requirements. • The VMP provides a “road map” for validation, to establish a sequence of events followed by facilities audits and inspections.

14. Contents of Validation Protocol 1. Title  2. Objective & Scope  3. Responsibility 4. Protocol Approval 5. Validation Team  6. Product Composition   7. Process Flow Chart  8. Manufacturing Process 9. Review of Equipments / Utilities   10. Review of Raw Materials and Packing Materials  11. Review of Analytical and Batch Manufacturing Records 12. Review of Batch Quantities for Validation (Raw Materials) 13. Review of Batch Quantities for Validation (Packing Materials)    14. HSE Requirements  15. Review of Process Parameters 16. Validation Procedure    17. Sampling Location   18. Documentation 19. Acceptance Criteria   20. Summary 21. Conclusion

15. Content and Format of Validation Master Plan • Introduction: Validation policy, Scope, Location and Schedule • Organizational structure: Personnel responsibilities • Plant/ process /product description: Rational for inclusions or exclusions and extent of validation. • Specific process considerations that are critical and those requiring extra attention. • List of products/ processes/ systems to be validated, summarized in a matrix format, validation approach. • Re-validation activities, actual status and future planning. • Key acceptance criteria • Documentation format • Reference to the required SOP’s • Time plans of each validation project and sub-project.

17. Validation of Granulation process

18. 1) Equipment Validation • Various equipment utilized in granulation process are 1) Mixer/Granulation 2) Dryer 3) Blender 4) Mills 5) Sieves • In an ideal situation the equipment used to manufacture dosage forms would be selected based upon such factors asformulation,safety requirements,handling or production efficiencies and commercial demands.

22. 2) Granulation process validation • Validating a granulation process involves identification of critical parameters, which must be controlled to ensure the consistent production of granulation. • Various operations carried out in granulation process are: 1) Mixing /Blending 2) Wet Granulation 3) Drying 4) Milling

23. I) Mixing/Blending: • Factors in creating uniform blending: -Mixing or blending technique -Mixing/ Blending speed -Mixing time -Drug uniformity -Excipients uniformity. -Equipment capacity or load. II) Wet granulation: Parameters considered in wet granulation process are I) Binder addition II) Binder concentration III) Amount of binder solution or granulating solvent IV) Binder solution or granulating solvent addition rate V) Mixing time VI) Granulation end point

24. III) Milling: • To break up the lumps and aggregates and enhance drying of granules • Factors to be considered • Equipment size and capacity • Screen size • Milling speed • Feed rate IV) Drying: Type of drying technique (Tray, Fluid, and Microwave) required for formulation needs to be determined and justified depending on drug formulation properties and equipment availability.

25. Cont….. • Parameters to be considered in drying 1) Inlet and outlet temperature: Inlet temperature is critical to drying efficiency of granules and should be set high enough to maximize drying without affecting chemical or physical stability of granules. 2) Air flow: Sufficient to ensure removal of moisture from wet granules 3) Moisture uniformity: 4) Equipment capability or capacity: Larger load will require more moisture to be removed on drying and will affect the drying time.

26. 3) Final product (granules) Validation:

27. Tablet Compression Factors to consider during compression are: • Tooling • Compression speed • Compression/ejection force • Tablet compression variables • Fill volume • Pre- and compression force • Turntable speed • Dwell time • Granule size and feed • Ejection force, lubrication

28. Tablet Coating • Key areas to consider for tablet coating: • Tablet properties • Equipment type (Conventional or perforated pan and fluid bed coaters) • Coater load • Pan speed • Spray guns • Application/spray rate • Tablet flow: • Inlet/outlet temperature and airflow • Coating solution (The concentration and viscosity of the coating solution) • Coating weight (A minimum and maximum coating weight) • Residual solvent level

29. Regulatory guidance on validation • Guideline on General Principles of Process Validation http://www.fda.gov/cder/guidance/pv.htm • Guidance for Industry: For the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products. CDER CVM November 1994. www.fda.gov/CDER/GUIDANCE/cmc2.pdf • Working Party on Control of Medicines and Inspections • Final Version of Annex 15to the EU Guide to Good Manufacturing Practice • Title: Qualification and validation • http://pharmacos.eudra.org/F2/eudralex/vol-4/pdfs-en/v4an15.pdf • ICH Q7a Section 12 on validation • http://www.fda.gov/cder/meeting/ICH_Q7A/index.htm • A WHO guide to good manufacturing practice (GMP) requirements. Part 2: Validation • Chaloner-Larsson, G., Anderson, R., and Egan, A. 1997. World Health Organization, Geneva.

30. Conclusions • Process validation is a requirement of cGMP regulation for finished pharmaceutical products. • It is a key element in assuring that the quality goals are met. • Successfully validating a process may reduce the dependence upon intensive inprocess and finished product testing. • Validation of a new or existing product involves the efforts of scientists at various stages of the product development life cycle. • Scientificinformation obtained during the preformulation stage can form the basis for a well-designed and comprehensive validation program.

31. References: 1)Nash RA., Wachter A.H., Pharmaceutical Process Validation, 3 rd Edition, Marcel Dekker publication, P.g, 173-182. 2) Lachman L., Lieberman H.A., Kania J.L., The Theory and Practice of Industrial Pharmacy, 3 rdedition, Varghese Publishing House, P.g.No. 318-320. 3) N. K. Jain & S. N. Sharma, A Text Book of Professional Pharmacy, VallabhPrakashan, P.g.no. -295-297 4) Haider S.I., Validation Standard Operating Procedures St. Lucie Press Publishers, P.g. No. 345-353.

32. Thank you