Validation, scope of validation, URS , WHO GUIDELINES FOR VALIDATION

Validation

1. Presented to: Prof. H.S. keerthy Department of Pharmaceutics MALLIGE COLLEGE OF PHARMACY Presented By: Manikant Prasad Shah Mpharm II Sem. validation

2. WHAT IS VALIDATION? According to WHO- It is the establishment of documented evidence that a system it is supposed to do. According to US FDA- The process of establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product with its predetermined specifications and quality attributes.

3. Merits of 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.

4. Scope of validation: Selection of raw material i.e. raw materials of desired quality attributes Product design based on the expected performance Process design to build the desired quality attributes in the product Design of control parameters, such as change control, acceptance criteria, tolerance limits, etc. In process quality control parameters and sampling plans Finished product testing or evaluation criteria Validation of related analytical process Validation of related system, facility and equipment Personnel training Validation involves careful determination of criteria variable of the process , such as moisture content of granules, drying temperature of time, etc. and then establishment of acceptable range and tolerance limit for the same. A careful and continuous control of these variables will ensure consistent product quality,

5. Relationship between validation and qualification: Qualification and validation are essentially the same. The term qualification is normally used for equipment and utilities, and validation is for systems and processes. In this sense, qualification can be seen as part of validation.

6. Validation Master plan- A Validation Master Plan is a document that summarises the firm’s overall philosophy, intention and approaches to be used for establishing performance adequacy. A tool to track progress Assignment of responsibility and team work It identifies acceptance criteria before the start of validation

7. V model for validation:

8. Urs , fat & sat: User R equirement S pecifications- Manufacturers should prepare a document that describes, for example , the utility or equipment to be sourced. The requirements and specifications for the utility or equipment should be defined by the user and documented in the URS. Factory Acceptance T est and Site A cceptance Test- Where appropriate, FAT and SAT should be performed to verify the suitability of the system at site, prior to the subsequent stages of qualification . This should be appropriately documented .

9. WHO guidelines for validation of equipment: All equipment, instruments and other devices used to measure the physical properties of substances must be regularly calibrated, validated and verified . Specific procedures must be established for each type of equipment, instrument and other device, having regard to the extent to which they are used, verified and calibrated at regular intervals according to the SOP. For example: (a) pH meters are verified with standard certified buffer solutions at least once a day; (b) infrared spectrophotometers require verification at least once a day and calibration at regular intervals.

10. Only authorized personnel should operate equipment, instruments and devices. Up-to-date instructions must be there. Includes any relevant manuals ( provided by the manufacturer) must be readily available for use by the appropriate laboratory personnel (e.g. a copy of these instructions should be placed beside each apparatus, together with a schedule of the dates on which it is due for verification and/or calibration). The results of the verification must be recorded on a control chart, forming the basis for the timing of calibration. 4. Each item of equipment, instrument or other device used for testing , verification and calibration must, when practicable , be uniquely identified.

11. 5. Records must be kept of each item of equipment, instrument or other device used to perform testing, verification and/or calibration. The records must include at least the following: the identity of the equipment, instrument or other device; the manufacturer’s name, the type identification, serial number or other unique identification ; the verification and/or calibration required to comply with the specifications; the current location, where appropriate the manufacturer’s instructions, if available, or an indication of their location ; the dates, results and copies of reports, verifications and certificates of all calibrations, adjustments, acceptance criteria, and the due date of the next verification and/or calibration ; the maintenance carried out to date and the maintenance plan ; a history of any damage, malfunction, modification or repair.

12. Types of validation:

13. Types of validation: Prospective validation- Establishing documented evidences during development stage of process based on a predefined protocol. It is done prior to distribution of a new product or whenever there is a major change in the product characteristics. Compulsory for sterile products. The activity continues till the first 3 batches are manufactures at full scale.

14. Steps in prospective validation: Formation of validation team Preparation of validation master plan and validation protocol Formulation development (preformulation studies and optimization) Process development (process design, control & challenges in critical parameters etc.) Facility development (building, support systems, staff) Process qualification (checked for worst case conditions o ensure reproducibility) Product qualification Change control

15. 2. Concurrent Process validation- Carried out during normal production. It is useful only if process is well understood during development stage. The nature and specifications of subsequent in- process and final tests are based on the evaluation of the results of such monitoring.

16. 3. Retrospective process validation (based on analysis of historical data)- Carried out on the basis of database generated during previous production of the product. Recorded difficulties, variation and failures in production are analysed to determine the limits of process parameters. Thus, it is useful in establishing priorities for validation.

17. 4. Revalidation- It is needed to ensure that the changes in process or in process environment do not adversely affect the process characteristic and product quality. Revalidation is required when:- There is major change in facility, equipment, process etc. Periodic revalidation is scheduled at regular interval to control and identify a gradual change in the process.

18. Dq , iq , oq , pq processes:

19. Design qualification-   Design Qualification protocol is used at the stage where a design that has been developed from the  VMP /  URS /   cGMP etc, is reviewed and documented by competent persons to ensure that the designed equipment, if built, will satisfy all the detailed specified requirements, as contained in the VP and URS. 

20. Installation qualification: defined by the FDA as, establishing by objective evidence that all key aspects of the process equipment and ancillary system installation adhere to the manufacturer’s approved specification. It includes:- Examining documentation of equipment design, identification no., description etc Establishment of critical support system(air, ventilation, electricity, drainage etc) Ancillary equipments , spare parts are also accounted Design of SOPs for operation, calibration, maintenance, cleaning. Reference nos. are given to them. Log books are prepared Details of the preventive maintenance procedure is documented. Before OQ, IQ datas are reviewed and approved.

21. Operational qualification: The Operational Qualification Protocol is a collection of test cases used to verify the proper functioning of a system. The operational qualification test requirements are defined in the Functional Requirements Specification. Operational Qualification is usually performed before the system is released for use. It includes:- Tests are done in normal conditions and worst case conditions Testing procedure is prepared Sampling plan is established and verified using a placebo batch Checks and calibration of sensors, probes, gauges, recorders, pressure, temperature etc Requirements for training of personnel involves is identified and training schedule is finalized and documented. The completion of satisfactory IQ and OQ permits a formal release of equipments for the next stage.

22. Process qualification: Process qualification  is the qualification of manufacturing and production processes to confirm they are able to operate at a certain standard during commercial manufacturing. Data covering critical process parameters must be recorded and analyzed to ensure critical quality attributes can be guaranteed throughout production. Once all processes have been qualified the manufacturer should have a complete understanding of the process design and have a framework in place to routinely monitor operations. Only after process qualification has been completed can the manufacturing process begin production for commercial use .

23. Equipment approval: Once approved, the equipment is handed over to project co-ordinator by project manager. All engineering and technical documents are handed over to the operating department.

24. Change control: Process may be subjected to changes like change in the spare part of an equipment that can affect product quality; so criteria for acceptance is decided and its implementation procedure is established.

25. References: Pharmaceutical Process Validation; Wachter H. Alfred; Nash Robert; Marcel D ekker Inc.; vol 129; 3 rd edition; New York http:// www.who.int/medicines/areas/quality_safety/quality_assurance/validation-2016_05_17.pdf WHO Technical report, no. 902, 36 th report Pharmaceutical Master Validation Plan; Haider Imitiaz;1 st Indian Reprint

26. THANK YOU!