![DEFINITION(S)
• Process design: Defining the commercial manufacturing process
based on knowledge gained through development and scale-up
activities.
• Process qualification: Confirming that the manufacturing
process as designed is capable of reproducible commercial
manufacturing.
• Continued Process Verification [CPV]: Assuring that during
routine commercial manufacturing the process remains in a state of
control (ie) in validated state.
• Lifecycle: All phases in the life of product, from the initial
development through marketing until the product discontinuation.
• Control Strategy: A planned set of controls, derived from
current product and process understanding that ensures process
performance and product quality.](https://image.slidesharecdn.com/processvalidation-180103034353/85/Process-validation-24-320.jpg)
Process validation
- 1. A B H I S H E K K U M A R A W A S T H I A Practical Approach to Process Validation
- 2. What is Process validation? In January 2011 FDA issued the guidance for industry: “Process Validation general principal & practices” to replace the process validation guide from 1987. This guidance aligns process validation activities with a product lifecycle concept and existing FDA guidance/ICH guidance. Process validation aligns Life cycle concept Quality Risk Management(Q9) Pharmaceutical Development(Q8) Quality Management system(Q10)
- 3. Definition Process validation is defined as collection and evaluation of data, from the process design stage throughout commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.
- 4. Principle of Process Validation 1.Quality, safety, and efficacy are designed or built into the product. 2.Quality cannot be adequately assured merely by in- process and finished-product inspection or testing. 3.Each step of a manufacturing process is controlled to assure that the finished product meets all quality attributes including specifications.
- 5. Purpose (This guideline is applicable to Process validation activities during) Introduction of new commercial products. Major change for existing process/Equipment. Site changes Continued process verification for existing products.
- 6. Approaches to Process Validation Life cycle approach emphasizes the importance of link between following three stages. Stage I: Process Design Stage II. Process Qualification Stage III. Continued Process Verification.
- 7. Process design? “The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities .” Two main aspects for process design: 1. Building and Capturing Process Knowledge and Understanding 2. Establishing a Strategy for Process Control
- 8. Process qualification? “During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.” Element 1: Design of the facility and qualification of the equipment & utilities. Element 2: Process Performance Qualification
- 9. What does Element 1 includes: Selecting utilities & equipments construction materials, operating principles and performance characteristics based on whether they are appropriate for their specific uses. Verifying that utility systems & equipment are built and installed in compliance with the design specifications. Verifying that equipment and utilities operate in accordance with the process requirements in all anticipate operating ranges, which should include challenging the equipment or system functions while under loads, comparable to that expected during routine production.
- 10. What does Element 2 includes: The activities which shall include as part of element 2 are------ Verification of CPP in the proposed equipments and establishment of their proven acceptable ranges. Examination of process performance through extensive levels of sampling & testing. The cumulative data from all relevant studies (e.g., designed experiments; laboratory, pilot and PPQ batches) shall be used to define process control strategy required for commercial manufacturing.
- 11. Continued Process Verification (CPV) “Ongoing assurance is gained during routine production that the process remains in a state of control.” Monitoring measures such as Statistical Process Control shall be in place for detecting unplanned departures (drift) from the defined process. The data shall be statistically trended to verify that the quality attributes are appropriately controlled throughout the process. Such data shall include CPP, quality of incoming materials, in-process parameters and CQA of finished product. The impact on validated state shall be evaluated during proposal of any minor change or improvement plans.
- 12. As part of CPV, the following variations shall be evaluated for its impact on validated state. Review of Out of Trend Review of Out of Specification Review of Defect complaints Review of Process deviation reports Review of Incident reports Review of process yield variation
- 13. What does PPQ Protocol contains? The manufacturing conditions, including operating parameters, processing limits, and component (raw material) inputs. The data to be collected and when and how it will be evaluated. Tests to be performed (in-process, release, characterization) and acceptance criteria for each significant processing step. The sampling plan, including sampling points, number of samples, and the frequency of sampling for each unit operation and attribute.
- 14. What does PPQ Protocol contains? A description of the statistical methods to be used in analyzing all collected data (e.g., statistical metrics defining both intra-batch and inter-batch variability). Provision for addressing deviations from expected conditions and handling of nonconforming data. Design of facilities and the qualification of utilities and equipment, personnel training and qualification, and verification of material sources . Status of the validation of analytical methods . Review and approval of the protocol by appropriate departments
- 15. PPQ Protocol Execution and Report Discuss and cross-reference all aspects of the protocol. Summarize data collected and analyze the data, as specified by the protocol. Evaluate any unexpected observations and additional data not specified in the protocol. Summarize and discuss all manufacturing nonconformance such as deviations, aberrant test results, or other information Describe in sufficient detail any corrective actions or changes that should be made to existing procedures and controls. Include all appropriate department and quality unit review and approvals.
- 16. The recommendations of life cycle stages to various scenarios shall be as per the following matrix. Scenario Stage-I Stage-II Stage-III Introduction of new commercial products Major change for existing process - Continued process verification for existing products - -
- 17. Establish Quality Target product Profile(QTPP) ↓ Establish Critical Quality Attribute(CQA) ↓ Define manufacturing Process & identify CPP ↓ Risk Assessment and initial categorization of parameter ↓ Lab scale batch ↓ Scale-up Batches ↓ Finalize Parameter based on criticality and establish control strategy ↓ Qualification of Utility, Facility and Equipment ↓ Process performance Qualification ↓ Continued Process verification Design Stage Process Qualification
- 18. QTPP(Quality Target Product Profile) A prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy. Critical Quality Attributes (CQA): A physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality (ICH Q8) Critical Process Parameter (CPP) A process parameter whose variability has an impact on a CQA and therefore should be monitored or controlled to ensure the process produces the desired quality. (ICH Q8)
- 19. Approach to Identify CQAs Consider all DP quality attributes; physical attributes, identification, assay, content uniformity, dissolution and drug release, degradation products, residual solvents, moisture, microbial limits, etc. Critical Material Attribute (CMA)* A physical, chemical, biological or microbiological property or characteristic of an input material that should be within an appropriate limit, range, or distribution to ensure the desired quality of output material. *CMA is not defined in ICH guidance,
- 23. Example: risk matrix for low dose capsule (CQA vs CPP) Sifting/sizing blending lubrication Capsule filling Assay Low Medium Medium Medium Content uniformity High High High High Dissolution Low Low High Low Stability Low Low Low Low
- 24. DEFINITION(S) • Process design: Defining the commercial manufacturing process based on knowledge gained through development and scale-up activities. • Process qualification: Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. • Continued Process Verification [CPV]: Assuring that during routine commercial manufacturing the process remains in a state of control (ie) in validated state. • Lifecycle: All phases in the life of product, from the initial development through marketing until the product discontinuation. • Control Strategy: A planned set of controls, derived from current product and process understanding that ensures process performance and product quality.
- 25. References http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guid ances/default.htm U.S. FOOD and Drug Administration Protecting and Promoting Public health ppt