VALIDATION & PERSONNEL

1. VALIDATION & PERSONNEL • GUIDED BY: DR.N.P. CHOTAI • PREPARED &PRESENTED BY: VISHAL B,NAKRANI M.PHARM(Q.A.,2nd SEM.) ID.NO:05PH912 DATE:31/05/06

2. Content: • Validation definition • Advantage of validation • Protocol development • GMP Inspector’s check list for validation • Personnel • Validation Working Groups • Reference

3. Validation WHO validation definition • The documented act of proving that any procedure, process, equipment, material, activity or system actually leads to the expected results.

4. The WHO GMP Guidelines state: Validation studies are an essential part of good manufacturing practice and should be conducted in accordance with predefined protocols. • written report • process and procedures • processing • testing • cleaning procedures

5. Functionality, consistency and repeatability is confirmed by validation

6. Validation as such does not improve the process but it confirms and assuresthat the process • Has been well developed • It is well maintained • It operates as it should

7. Advantages of validation: • During the process the knowledge of process increases • Assures the repeatability of the process • Assures the fluency of production • Assures that the product is continuously produce according to the marketing authorisation

8. Decreases the risk of the manufacturing problems • Decreases the expenses caused by the failures in production • Decreases the risks of failing in GMP • Decreases the expenses of the every day production even though the validation itself will create expenses

9. Protocol development Each stage in the validation of the overall process should proceed in accordance with a pre-established and formally approved detailed, written protocol, or series of related protocols. Protocols should have a Title, Date and a unique Identification or Reference Number. They should be formally authorized/approved by persons with the competence and authority to do so.

10. It should specify the objectives and scope of the study. Like, a clear and precise definition of the process, equipment, system or sub-system which is to be the subject of the study, with details of performance characteristics.

12. GMP Inspector’s check list for validation (1) Check that the manufacturer has: A VMP and multi-functional team for validation Planned approach , defined requirements Identified and described processes Analyse the amount of validation work to perform

13. GMP Inspector’s check list for validation (2) Check that the manufacturer has: • Selected methods and tools for validation • Created protocols • Performed DQ, IQ, OQ, PQ and documented results • Exerted change control, set revalidation time

14. Validation - Logical entity: • protocol + • procedure + • report

15. Personnel Personnel actually performing any validation studies, and in routine operation can have so crucial an effect on the quality of the end-product, it is appropriate and necessary to consider both these aspects of personnel involvement. Appropriately qualified personnel should ensure that the protocol and the testing methodology are properly evaluated and certified.

16. All personnel conducting tests should be trained and experienced in the use of the instruments, measuring devices and materials used. • Engineering/maintenance personnel should be fully trained and competent in the operation and maintenance of the machines, equipment, and air control systems involved. • Any operators involved in performing a validation study should adopt the same techniques, disciplines, and standards of hygiene, clothing and behavior as in normal routine manufacture.

17. It is therefore vital that all personnel involved in validation are trained, and fully understand, the concepts and principles of GMP, and validation. • They must understand the importance of personal hygiene and cleanliness, and be made fully aware of the possible hazardous consequences of product contamination. • Operators should be provided with suitable Clean Room clothing and trained in appropriate gowning technique.

18. The type of clothing to be worn, and gowning process should be defined in written procedures, available to the operators, and preferably displayed in the changing room. • The same clothing/gowning standards should be observed during validation studies as in routine production, and vice versa.

19. Validation Working Groups The executive part of the validation work should be delegated to dedicated personnel: • Director of validation • Manager or senior manager of validation • A representative from quality assurance • A representative from technical services • A representative from research & development • A representative from quality control • A representative from production

20. Director of validation • Primary responsibility: • Directs company-wide process validation program. • Directs company-wide cleaning validation program. • Reviews and/or approves Master Batch Records for development and Production, as required. • support company-wide equipment qualification and validation program.

21. • Supports company-wide computer system validation program. •Supports company-wide activities associated with development of new technology, improvement of existing technology and utilizing newer, more automated equipment and processes. •Supports company management in evaluation of new products, technology and equipment.

22. Essential functions: • Designs, implements and oversees company-wide programs for process and cleaning validation. • Ensures that the system is in compliance with federal and industry guidelines, and that each system is documented and tracked in an orderly manner. • Designs, implements and oversees studies aimed to determine whether process or systems meet or exceed the specifications of its design, is suitable for its intended application, conforms to cGMP requirements, satisfies concerns of regulatory agencies and meets company goals established for quality.

23. Reviews and gives final approval for written validation protocols and summaries. • Reviews and approves validation section of change control notices to ensure that each process continues to operate within its designed parameters. • Reviews and approves procedures that have been established to revalidate the process in the event of a process or equipment change.

24. Ensures validation protocols and studies are properly documented, archived and stored for timely retrieval. • Discusses validation studies and plans with customers and regulatory agencies as required during reviews or inspections. • Develop and submit quarterly and monthly reports as defined by Manager • Responsible for Master Validation Plans, SOP’s, and Validation Guidelines. Reviews and approves SOP’s in their related area. • Reviews and approves Master Batch Records.

25. Oversees and approves all documents pertaining to company’s quality development program, such as process development protocols and technology assessment summaries. • Designs and evaluates all documents associated with development and implementation of new technology and improvement of existing technologies, such as master batch records, evaluation protocols, summary reports and change control notices. • Participates in other activities, as may be requested, relative to new products and/or new technology transfers.

26. Performs employees performance reviews and submits them for approval in a timely fashion. • Takes any corrective actions required up to and including termination as appropriate and in accordance with company policies and procedures. • Builds and maintains a staff of professional, highly motivated and knowledgeable individuals. • Participates in selection of personnel and provides effective training. • Establishes standards of performance in accordance with company guidelines and evaluates performance against those standards for all staff members.

27. Knowledge/Skills/Abilities • Thorough knowledge and understanding of governmental requirements and industry standards, related to current Good Manufacturing Practices and other appropriate government regulations and requirements as related to essential job functions • Thorough knowledge of current validation compliance, standards, requirements for a Pharmaceutical Industry, both domestic (FDA) and international (ICH). • Ability to establish validation standards, SOP’s and audits meeting current and future FDA requirements • Experience working with and/or leading cross-functional groups

28. Excellent written, verbal and interpersonal communication skills, highly organized and detail-oriented. • Ability to effectively and directly interface with FDA and technical company personnel at various levels • Ability to effectively communicate, directing, guiding personnel who are not direct reports. • A strong scientific experience and knowledge of analytical, research, engineering, manufacturing, quality control and quality assurance.

29. Good computer skills with knowledge of Microsoft Office programs (Word, Excel, Power point ) • Ability to utilize statistical techniques and approaches to reach scientifically sound decisions regarding validation issues • Thorough knowledge and understanding of product formulations, pharmaceutical technology and equipment performance relative to solid dosage forms, liquids and semi-solids.

30. Education/Experience B.S., M.S. or PhD in Industrial Pharmacy, Pharmaceutics, Chemical Engineering or related science area

31. Manager/Senior Manager, Validation Responsibilities: • Responsible for the management of the Validation Department personnel • Responsible for Validation Department budget development and monitoring • Lead and coordinate the qualification and validation efforts for new GMP facilities

32. Ensure that appropriate validation master plans addressing facilities, utilities, equipment, cleaning, and process are established and implemented according to timelines • Manage and coordinate the activities of contractors performing qualification and validation work • Ensure that a validation/re-validation program is established and implemented in the new manufacturing facility and provide program oversight

33. Review, approve, source and/or write validation documents • Provide technical expertise and interpretation on regulations and guidelines as they relate to validation activities • Oversee the development and revision of validation procedures and protocols to ensure that regulatory compliance and company objectives are maintained • Ensure that the Validation Department personnel are appropriately coached, trained and developed for current and anticipated projects • Prepare and assist with the inspections from regulatoryagencies

34. Requirements: • Bachelor’s degree in Engineering, Science or related technological field or equivalent combination of education and experience • Seven to ten years experience of validation experience in a cGMP environment with increasing levels of responsibility for a wide range of validation projects • Thorough knowledge of validation principles, manufacturing processes, quality systems, engineering design fundamentals, regulatory agency expectations and industrial trends • In-depth knowledge of validation requirements (GMP, FDA, etc.) for pharmaceutical manufacturing facilities, equipment and systems

35. Proven track record in managing a validation department with multiple direct reports • Demonstrated ability in effectively managing multiple validation projects simultaneously • Excellent leadership and organization skills to effectively directing and managing validation personnel and contractors in ensuring project completion on time • Excellent verbal and written communication skills including the ability to write, revise, and comment on validation protocols and reports

37. Reference: 1.mednet3.who.int/prequal/pq_pres/ workshop_Russia/M08-Validation02-f_U.ppt 2.siop.org/_Principles/principlesdefault.htm - 16k 3.www.genitope.com/text/G7605.htm - 8k 4. Pharmabiz, Sunday, april09, 2006 5.Validation standard operating procedure

38. THANK YOU