Initiation of Validation Design Review Who Validates? What Process to Validate? Process Validation Decision Tree When to Validate? Prospective Validation Concurrent Validation Retrospective Validation Process Validation Steps 19
Design Review Process validation is reliant upon design review of the product to determine the design controls and process specifications derived from the design output for each product or process that needs to be validated. Processes are developed according to design controls in 21 CF 820.30 and the process specifications (parameters) are derived from the specifications for the device. These parameters must be documented in the device master record per 820.30, 820.40, and 820.181. Thus, 21 CFR 820 regulation is highly relevant to process validation and must be completed prior to process validation 20
Who Validates? A team is typically used to plan and perform the validation of a process including members from many different departments. Alternatively, or in addition, an individual or company skilled specifically in validation processes may also be hired to carry out and complete validation processes. Typically, members of the validation team include (GHTF study grp 3): Quality Assurance Engineering Manufacturing Research & Development Regulatory Affairs Clinical Engineering Purchasing/Planning Marketing Technical services Laboratory individuals Product development Statistician 21
The team will plan the following validation activities and document them in the validation master plan (GHTF study grp 3): Define requirements Identify and describe processes to be validated Specify process parameters and desired output Criteria for a successful study Length and duration of the study Decide on verification or validation Create a master validation plan Select methods and tools for validation Create validation protocols Perform IQ, OQ, PQ (traditional) and document results or PD,PPQ, CPV (new lifecycle) Determine continuous process controls Control the process continuously 22
What Process to Validate? Each process should have a specification describing both the process parameters and the output desired. Based on this the manufacturer can decide whether the output can be verified by monitoring or measurement or if verification alone is not sufficient then the process should be validated. Risk analysis should be used to decide this. Also changes in the processes that formerly were only verified may result in the need to validate and would need to be re-evaluated. According to 21 CFR 820.75(a) when process results cannot be fully verified during routine production by inspection and test (ie, measuring length, checking ph etc), then the process must be validated according to established procedures. This is especially important when the routine end-product tests do not reveal all variations in safety and efficacy that may occur in the finished devices. Also, if clinical or destructive testing would be required to show that the manufacturing process was successful and produced the desired product then process validation is necessary. Finally, if the process capability is not known, or if the process is 23
suspected of barely capable of meeting device specifications, a non-robust process would need to be validated. Just so you know The new FDA principle of Quality Assurance (Jan. 2011) is based on the principle that quality cannot be adequately assured merely by in-process and finished-product inspection or testing and has to be built into the product. These new principles will be incorporated in the steps of this book. 24
Process Validation Decision Tree (GHTF study grp 3, Jan 2004) Is Process Output Verifiable? Yes No Validate Is Verification sufficient and Cost Effective? Yes Verify and Control Process Output No Redesign Product and/or Process Figure 1. The Process validation decision tree can be followed by a manufacturer to decide whether a process needs to be validated. Examples of processes to be validated (GHTF study grp 3): Sterilization processes Clean room ambient conditions Aseptic filling processes Sterile packaging sealing process Lyophilization process 25