Process Validation Template Guidance & compliance publication: General Principles & Practices introduces a life cycle approach to process verification. While the guidelines no longer think the use of traditional three-batch process validation template appropriate, it does not stipulate the number of validation batches appropriate for a prospective validation protocol, nor does it provide a rationale to determine it. This could; and has, left many manufacturers in a dilemma
The way forward must be by utilizing a continuing activity that constantly verifies process compliance?
The secret to success is going to be in selecting the single parameter robust enough to be used as yard stick for the process efficacy. Once this can be achieved preventative measures will become routine practice as operators use predictive analysis to execute routine maintenance - before product drifts out production tolerances. The whole process qualification; even for life cycle evaluation, can be monitored with suitable data capture systems. Which will be be used in product release and simplification of end-product release analysis and process validation template.
For the Process Validation template to be successfully executed then critical quality characteristics and critical process parameters must be derived from research and development scale-up, or existing commercial production history. If these parameters do not exist, it is necessary to establish them through either designed experiments or planned review of commercial history prior to the start of process qualification.
Although often combined in the same protocol, the purposes of PQ and PV for products differ. PQ starts to address the ruggedness of each of the process steps While PV puts all the parts together to verify that the process can consistently and accurately be replicated.
The performance of certain support processes can be proven for multiple products without having any product involved. Examples of these include sterilization of stoppers and glassware, aseptic processes, and cleaning validation. The specifics of these are discussed in other chapters.
This section will briefly discuss the determination of critical process validation template parameters, since the establishment of these critical process parameters is one of the most important requirements for successful process qualification. The primary objective of each unit operation is identified as it relates to the critical quality characteristics of the product. Acceptance criteria are defined for the critical quality characteristics based on the allowable variation in the process step, relevant to its location in the process. That is, steps become more important as the process moves closer to the bulk drug substance and drug product since there are fewer opportunities to improve product quality.
A risk assessment, based on the margin between the normal operating range (NOR) and the proven acceptable range (PAR), should be performed to evaluate the likelihood that a parameter will cause batch failure. If the parameter is deemed to have a high likelihood to cause hatch failure and it is a difficult parameter to control, it is deemed critical. In other words, the normal operating range is close to the proven acceptable range. If the risk is low because the proven acceptable range is relatively large and the parameter is easily controlled, the parameter is still of interest, hut it does not need to be evaluated during process validation template generation. These are deemed “quality” or “important” parameters”.
A prospective process validation template must include manufacturing, sampling, and testing validation batches according to a pre-approved test protocol Validation batches are not released until all batches specified in the protocol have been manufactured, all tests have been executed, all results have been reviewed, deviations addressed, all acceptance criteria are met, test reports have been written and approved and all change requests have been closed. The system owner must justify any exception to the above conditions and the justifications must he reviewed and approved by QA.
The following is a checklist of knowledge that must be available prior to starting PQ and/or PV:
· Critical Characteristics & associated limits must be established
· Critical parameters & associated limits must be established
· Rationale for non-critical process parameters
· Process description and process drawings
· Equipment and materials requirements
· Proposed hatch records and standard operating procedures
Initialization of cleaning process qualification.
Recommended in-process validation template of controls.
· Data to support upper control limit and lower control limit.
· Validated analytical methods
· References to development studies
· Reference to previous process validation templates, if any
· PQ/PV protocols available prior to execution.
Before reaching the conclusion that process validation TEMPLATE has been successfully completed, it is necessary to demonstrate that the specified process has not adversely affected the finished product. Where possible, product process qualification, verification testing should include testing under conditions that simulate actual use. Product process qualification testing should be conducted using product manufactured from the same type of production equipment, methods and procedures that will be used for routine production. Otherwise, the qualified product may not be representative of production units and cannot be used as evidence that the manufacturing process validation will produce a product that meets the pre-determined specifications and quality attributes.