INTRODUCTION TO PHARMACEUTICAL VALIDATION SCOPE and MERITS OF VALIDATION.pptx

Pharmaceutical validation for manufacure of quality products and documentation.

1. Guided by, Dr. A.B.Gangurde Head of Department Department of Pharmaceutics INTRODUCTION TO PHARMACEUTICAL VALIDATION,SCOPE &MERITS OF VALIDATION. Presented By , DEORE SEJAL SURESH F.Y.M.Pharmacy Department of Pharmaceutics

2. Contents: Introduction Need of validation Types of validation Prospective validation (or premarket validation ) Retrospective validation Concurrent validation Revalidation Importance of validation Scope of validation Merits of validation Conclusion for validation References

3. Introduction: The concept of validation was first proposed by two Food and Drug Administration (FDA) officials . Byers and Bud Loftus, in the mid 1979s in(USA )order to improve the quality of pharmaceuticals. It was proposed in direct response to several problems in the sterility of large volume parenteral market . The first validation activities were focused on the processes involved in making these products, but quickly spread to associated processes including environmental control, media fill, equipment sanitization and purified water production .

4. Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages . In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.

5. Definition: Validation is the documented act of proving that any procedure, process, equipment, material, activity or system actually leads to the expected result . ISO definition :Validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled.

6. NEED FOR VALIDATION: Customer satisfaction. Customer mandated . Product liability . Control production cost. Development of new generation Safety .

7. Customer satisfaction : CUSTOMER SATISFACTION : Customer satisfaction is defined as a measurement that determines how happy customers are with a company’s products, services, & capabilities . Customer satisfaction information ,including surveys and ratings, can help a company determine how to best improve or changes its products and services.

8. CUSTOMER MANDATE: Customer mandate means the forms completed by the client at the time the account is opened or as amended by agreement between the client and the bank from time to time.

9. PRODUCT LIABILITY: Product liability is a doctrine that gives plaintiffs a cause of action if they encounter a defective consumer item.

10. CONTROL PRODUCTION COST: Production cost is based on the actual performance during production. Production cost control is done by comparison of actual cost with the standard cost, budget cost or aimed cost.

11. DEVELOPMENT OF NEW GENERATION SAFETY: In future validation play’s important role in development for new pharmaceutical product .

12. TYPES OF VALIDATION :

13. PROCESS VALIDATION : As per FDA, the process validation is defined as: “ The collection of data from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.”

14. Process validation life cycle/flow chart:

15. TYPES OF PROCESS VALIDATION:

16. PROSPECTIVE VALIDATION: This is performed for all new equipment, product and processes . It is a proactive approach of documenting of design, specification and performance before the system is operational . This is the most defendable type of validation. It is compulsory for sterile products. The activity continuous till first 3 batches are manufactured at full scale .

17. STEPS IN PROSPECTIVE VALIDATION :

18. RETROSPECTIVE VALIDATION: Retrospective validation is used for facilities, processes, and process controls in operation use that have not undergone a formally documented validation process . Validation of these facilities, processes, and process controls is possible using historical data to provide the necessary documentary evidence . Therefore , this type of validation is only acceptable for well-established processes and will be inappropriate where there have been recent changes in the composition of product, operating processes, or equipment . This approach is rarely been used today because it's very unlikely that any existing product hasn't been subjected to the Prospective validation process. It is used only for the audit of a validated process.

19. CONCURRENT VALIDATION: Concurrent validation is used for establishing documented evidence that a facility and processes do what they claim to do, based on information generated during actual imputation of the process . This approach involves monitoring of critical processing steps and end product testing of current production, to show that the manufacturing process is in a state of control .

20. 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. Possible reasons for starting the revalidation process include : The transfer of a product from one plant to another . Changes to the product, the plant, the manufacturing process, the cleaning process, or other changes that could affect product quality.

21. The necessity of periodic checking of the validation. results . Significant (usually order of magnitude) increase or decrease in batch size . Sequential batches that fail to meet product and process specifications . The scope of revalidation procedures depends on the extent of the changes and the effect upon the product .

22. CLEANING VALIDATION: Definition : "A process of attaining and documenting sufficient evidence to give reasonable assurance, given the current state of Science and Technology, that the cleaning process under consideration does, and/or will do, what it purpose is to do."

23. OBJECTIVE:

24. Source of contamination: Cross contamination of one product into another . Product contamination by a foreign material . Microbial contamination . Cleaning methods : Manual cleaning method . Semi automated procedures . Fully automated procedures .

25. Factors Influencing Cleaning validation: Product. Equipment. Facilities. Cleaning methods . Cleaning agents . Sampling. Testing , Limits, and acceptance criteria .

26. EQUIPMENT VALIDATION: Definition : As per FDA, "Action of proving that any equipment works correctly and leads to the expected result is equipment validation. It is not a single step activity but instead result from many discrete activities. “ Steps involved : User requirement specification Design qualification Installation qualifications Operational qualifications Performance qualification

27. VALIDATION OF ANALYTICAL METHODS: Definition : "The process by, which it is established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical application ". Accuracy : The closeness of test results obtained by that method to the true value. This accuracy should be established across its range . Precision : The degree of agreement among individual test results when the method is applied repeatedly to multiple sampling of a homogenous sample.

28. Specificity: The ability to assess unequivocally the analyte in the presence of components that may be expected to be present, such as impurities, degradation products and matrix components. Limit of Quantitation: A characteristic of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk substances and degradation products in finished pharmaceuticals. It is the lowest amount of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions.

29. Range: Interval between the upper and lower of analyte (including these levels) that have been demonstrated to be determined with a suitable level of precision, accuracy and linearity using the method as written. The range is normally expressed in the same units as test results obtained by the analytical method (e.g. Percentage, parts per million, etc .) Ruggedness : The degree of reproducibility of test results obtained by the analysis of the same sample under a variety of conditions such as different laboratories, different analysts, different instruments, different lots of reagents, different elapsed assay times, different assay temperatures, different days, etc.

30. SCOPE OF VALIDATION: Validation requires an appropriate and sufficient infrastructure including:-organization, documentation, personnel and finances . Involvement of management and quality assurance personnel Personnel with appropriate qualifications and experience Extensive preparation and planning before validation is performed . A specific programme for validation activities in place.

31. Validation done in a structured way according to documentation including procedures and protocols . Validation should be performed:-for new premises, equipment, utilities and systems, and processes and procedures; at periodic intervals; and-when major changes have been made . Validation in accordance with written protocols.

32. A written report on the outcome to be produced . Validation over a period of time, e.g.-at least three consecutive batches (full production scale) to demonstrate consistency. Process , materials and equipment to prove consistent yield of a product of the required quality . Manufacturers to identify what validation work is needed. Significant changes (facilities, equipment, processes) - should be validated Risk assessment approach used to determine the scope and extent of validation needed.

33. MERITS 0F VALIDATION : Assurance of quality compliance . Optimization of resources and manufacture product at lowest possible cost . Fewer failures, fewer rejects, fewer retests, fewer reworks, fewer wastage . It is a practice that must be followed for manufacturing, distribution, selling or license . Efficient production operation .

34. CONCLUSION FOR VALIDATION: Validation has been proven assurance for the process efficiency and sturdiness and it is the full fledged quality attributing tool for the pharmaceutical industries . Validation is the commonest word in the areas of drug development, manufacturing and specification of finished products. It also renders reduction in the cost linked with process monitoring, sampling and testing . Apart from all the consistency and reliability of a validated process to produce a quality product, it is very important for an industry.

35. REFERENCES: Fundamental of quality assurance techniques...by Ramesh Sawant and Sandip Hapse, First edition Dec 2011, Career publications . Pharmaceutical Quality Assurance...by Manohar Potdar, Second edition Dec 2007, Nirali Prakashan . IJRPC 2011 An overview of pharmaceutical validation: quality assurance view point' by Nandhakumar et al . IJPR Review Article An Overview of pharmaceutical Validation and Process Controls in Drug Development" Elsie Jatto and Augustine O. Okhamafe . P . P. Sharma, "Validation in Pharmaceutical Industry- concepts, approaches & guidelines", 1 edition, 2007 Vandana Publication House .

36. B . T. Loftus & R. A. Nash, "Pharmaceutical Process Validation", Drugs and Pharm Sci. Series, Vol. 129, 3rd Ed., Marcel Dekker Inc., N.Y . https://www.slideshare.net/Manikant PrasadShah /validation-scope- of-validation- urs -who-guidelines-for-validation https ://www.slideshare.net/shettyue/new-who-guidance-on-process-validation https ://www.slideshare.net/Anshul2593/ich-guidelines-72292250https://www.slideshare.net/rks19761/pharmaceutical-process- validation?next slideshow-1 https ://www.slideshare.net/dalvirabul16/pharmaceutical-validation-ppt https ://www.slideshare.net/sagarsavale 1/cleaning-validation- 62056468

37. https://www.who.int/medicines/areas/quality safety/quality assurance/Supplementary GMP Validation TRS937Annex4.pdf?ua https:// www.slideshare.net/ssuserfe3019/ich-who-guidelines .