Number of Manufacturing Lots for Process Validation

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ncwalker

My dear, the way 2016 went, I don't think those actual details even matter any more.
 

MasterBB

Involved In Discussions
Three is not a magic number…The past and the present and the future. You no longer get three as a magic number.

The approach to PQ should be based on the overall product and process understanding.

The PQ lots should be manufactured under normal conditions by personal expected to routinely perform each step.

The manufacturer should judge whether it has gained sufficient understanding to provide a HIGH degree of assurance in its process to justify commercial distribution of the product.

The requirement for testing from the first three production lots or batches has been deleted...
Preamble comment #85

The challenges should be repeated enough times to assure that the results are meaningful and consistent.
GHTF Guidance Section 5.5 PQ

See Question 5 on the from FDA website. (I cannot post links if you want the link direct message me)

Do CGMPs require three successful process validation batches before a new active pharmaceutical ingredient (API) or a finished drug product is released for distribution?

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 became prevalent in part because of language used in past Agency guidance. FDA's process validation guidance now recommends a product lifecycle approach. 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 an 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 the 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 that 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.

Can you please send me the link?
 
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