5.1 Process validation shall be completed prior to the distribution and sale of the medicinal product (Prospective validation). In exceptional cases where this is not feasible, processes may need to be validated during routine production (concurrent validation). Additionally, processes that have been in use for an extended period should be validated (retrospective validation).
5.2 Facilities, systems and equipment to be used for process validation should have been qualified and analytical testing methods should be validated. Personnel involve in process validation should have been appropriately trained.
5.3 All new processes developed In-House or transferred from other sites will be validated prospectively. In general, process validation requires a minimum of three consecutive commercial batches. These batches should match the size of the intended industrial scale production batches
5.4 Depending on product complexities and recommendation from R & D / Customer, optimization batches (viz. scale up batch or feasibility batch) may not be required. In such cases, if first validation batch is manufactured without any change in critical process parameters; it shall follow with next two validation batches.
5.5 Process validation for a product shall include the challenging of the process parameters. Each step shall be evaluated to determine the critical factors /parameters that may affect the quality of the finished product.
5.6 The process validation protocol should be prepared and approved prior to Manufacturing.
5.7 Validation batches can be released for distribution after the validation data has been reviewed and found acceptable by the validation team.
5.8 Process validation protocols shall be prepared prior to execution of validation. It consist of following but not limited to.
5.8.1 Table of Content.
5.8.2 Protocol Approval.
5.8.3 Objective.
5.8.4 Scope.
5.8.5 Responsibility and Identification of Execution Team.
5.8.6 Validation Study.
5.8.7 Product Information.
5.8.8 Manufacturing Formula.
5.8.9 List of Manufacturing Equipments.
5.8.10 Equipment Qualification Matrix.
5.8.11 Manufacturing Procedure.
5.8.12 Process Flow Diagram.
5.8.13 Critical Process Steps.
5.8.14 Test Program and Acceptance Criteria.
5.8.15 Sampling Points.
5.8.16 Deviation/Incidents (if any).
5.8.17 List of Supporting Documents.
5.8.18 Abbreviations.
5.8.19 Annexures.
5.9 Process validation report shall be prepared and may consist of the following but not limited to.
5.9.1 Table of Content.
5.9.2 Report Approval.
5.9.3 Objective.
5.9.4 Scope.
5.9.5 Product Information.
5.9.6 Batch Details.
5.9.7 Study Details.
5.9.8 Product Results.
5.9.9 Deviations/Incidents (if any).
5.9.10 List of Supporting Documents.
5.9.11 Abbreviations.
5.9.12 Summary.
5.9.13 Conclusion.
5.9.14 Annexures.
5.10 The validation of the Product /Process shall involve following types of techniques depending upon the approach used to carry out validation activity.
5.10.1 Prospective Validation:
5.10.1.1 This validation activity shall be undertaken before the commercial distribution of the batch and in association with the technology transfer from Formulation research and Development to production.
5.10.1.2 Validation shall be under taken when a new product or a product manufactured by revised formula / revision in manufacturing procedure where in the revision is expected to alter the product characteristics.
5.10.2 Concurrent validation:
5.10.2.1 In exceptional circumstances, it may be acceptable not to complete a validation programme before routine production starts.
5.10.2.2 The decision to carry out concurrent validation must be justified, documented and approved by authorized personnel.
5.10.2.3 Documentation requirements for concurrent validation are the same as specified for prospective validation.
5.10.3 Retrospective validation:
5.10.3.1 Retrospective validation is only acceptable for well-established processes and will be inappropriate where there have been recent changes in the composition of the product, operating procedures or equipment.
5.10.3.2 Validation of such processes should be based on historical data. The process require the preparation of a protocol and the reporting of the results of the data review, leading to a conclusion and a recommendation.
5.10.3.3 The source of data for this validation should include, but not be limited to batch processing and packaging records, process control charts, maintenance logbooks, records of personnel changes, process capability studies, finished product data, including trend charts and stability study results.
5.10.3.4 Batches selected for retrospective validation should be representative of all batches made during the review period, including any batch that failed to meet specifications and should be sufficient in number to demonstrate process consistency.
5.10.3.5 For retrospective validation, generally data from ten to thirty consecutive batches should be examined to assess process consistency, but fewer batches may be examined if justified.
5.11 A product / process will be considered validated, when 3 consecutive commercial scale batches meet the acceptance criteria established in the validation protocol.
5.12 In case one of the batches fails to meet the acceptance criteria the subsequent 3 consecutive batches shall be validated.
5.13 If a batch fails to meet acceptance criteria, investigation of the cause of failure must be conducted and corrective action shall be implemented.
5.14 Validated systems / equipment’s / process are considered to be in a state of control. As long as conditions and control parameters remain unchanged, they will maintain their validated state. Any modifications shall be managed through a “change control programme”.
5.15 Validation batches shall be subjected to stability studies.
5.16 Revalidation: Revalidation shall be carried out to a validated process in any of the following circumstances.
5.16.1 Change of formulae, procedure or quality of raw materials.
5.16.2 Change of equipment, installation of new equipment, major changes in the machinery or apparatus and breakdowns.
5.16.3 Major changes in process parameters.
5.16.4 Change In facility and installations which influence the process.
5.16.5 On appearance of negative quality trends.
Note: The extent of revalidation will depend on the nature and significance of the change.
5.17 Numbering of process validation protocol / report:
5.17.1 QA department shall assign the process validation protocol / report numbers.
5.17.2 This is a unique number given to each process validation protocol and its corresponding report(s).