Do CGMPs require three successful process validation batches before a new product is released for distribution?
ICH Q7 of 21CFR not demands for the same, but every one following the same logic universally? Is there any other guideline reference?
Views welcome from the forum
Thanks
[quote=jyopravel]Do CGMPs require three successful process validation batches before a new product is released for distribution?
ICH Q7 of 21CFR not demands for the same, but every one following the same logic universally? Is there any other guideline reference?
Views welcome from the forum
Thanks[/quote]
FDA given the clarification for the above quote:
“No. Neither the CGMP regulations nor FDA policy specifies a minimum number of batches to validate a manufacturing process. The current industry guidance on APIs (see ICH Q7A for APIs) also does not specify a specific number of batches for process validation. FDA recognizes that validating a manufacturing process, or a change to a process, cannot be reduced to so simplistic a formula as the completion of three successful full scale batches. The agency acknowledges that the idea of three validation batches has become prevalent, in part due to language in its own guidance documents. However, FDA is now clarifying current expectations on process validation. The 1987 Guideline of General Principles of Process Validation is currently being revised to address this issue. The emphasis for demonstrating validated processes is placed on the manufacturer’s process design and development studies in addition to its demonstration of reproducibility at scale, a goal that has always been expected. However, a minimum number of conformance (a.k.a. validation) batches necessary to validate the manufacturing processes is not specified. The manufacturer is expected to have a sound rationale for its choices in this regard. The agency encourages the use of science based approaches to process validation.
In March 2004, FDA revised the Compliance Policy Guide (CPG) (Sec. 490.100) on Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients Subject to Pre-Market Approval. The CPG describes the concept that, after having identified and establishing control of all critical sources of variability, conformance batches are prepared to demonstrate that under normal conditions and operating parameters, the process results in the production of acceptable product. Successful completion of the initial conformance batches would normally be expected before commercial distribution begins, but some possible exceptions are described in the CPG. For example, although the CPG does not specifically mention concurrent validation for an API in short supply, the agency would consider the use of concurrent validation when it is necessary to address a true short-supply situation, and if the concurrent validation study conforms to the conditions identified in the CPG (See paragraph 4. a-c).
The conditions outlined in the CPG include expanded testing for each batch intended to address a short-supply situation. Expanded testing, conducted according to an established validation protocol could provide added assurance that the batch meets all established and appropriate criteria before the API is used in the finished drug product. Additionally, confidence in the API manufacturing process may be gained by enhanced sampling (larger sample size representative of batch) and perhaps the testing of additional attributes. Validated analytical methods are needed for testing every batch, including validation batches. The agency would also expect the manufacturer to use a validation protocol which includes a review and final report after multiple batches are completed, even though the earlier batches may have been distributed or used in the finished drug product”.
Thanks
3 batches is based on statistical evaluation.There is no hard and fast rule.
Sir,
A this is a very good discussion overg the thread.
Sir i wanted to ask one thing, that if we go for process validation with 1 commercial batch size and collect the respective data for the same is it OK.
Because as mentioned in the new FDA guideline for process validation 2011 they have not mentioned to provide data for consecutive batches or anything.
Yes even One commercial batch can be justified [Assumption, that you have gained more understaing of the Process, Product and Control strategy and overall risk is low]
[quote=nisshil]Sir,
A this is a very good discussion overg the thread.
Sir i wanted to ask one thing, that if we go for process validation with 1 commercial batch size and collect the respective data for the same is it OK.
Because as mentioned in the new FDA guideline for process validation 2011 they have not mentioned to provide data for consecutive batches or anything.[/quote]