Validation study: Why Three batch for validation study?

In
this article we will try to understand the fundamental concept of three batches for
Validation study; or more correctly we say Process performance qualification (PPQ).
This is very important to know “what we are doing and why we are doing” to come on fruitful conclusion. So, we will continue the topic with the small
background on regulatory requirements.

In
the world of pharmaceutical manufacturing, Validation of manufacturing
processes is a requirement of the Current Good Manufacturing Practice (CGMP)
regulations (21 CFR 211.100 and 211.110) and
is considered an enforceable element of current good manufacturing practice for
active pharmaceutical ingredients (APIs) under the broader statutory CGMP
provisions of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.

A
validated manufacturing process has a high level of scientific assurance that it
will reliably produce acceptable product. The proof of validation is obtained
through rational experimental design and the evaluation of data, preferably beginning
from the process development phase and continuing through the commercial
production phase.

Before
the commercial distribution begins, a manufacturer is expected to have
accumulated enough data and knowledge about the commercial production process
to support post-approval product distribution. 

Normally, this is achieved after
satisfactory product and process development, scale-up studies, equipment and
system qualification, and the successful completion of the initial conformance
batches. Conformance batches (sometimes referred to as “validation”
batches and demonstration batches) are prepared to demonstrate that, under
normal conditions and defined ranges of operating parameters, the commercial
scale process appears to make acceptable product.

Generally
it is considered; three batches are required for validation study

• If
  we get the desired quality in the first batch, it is accidental, second batch
  quality is regulator and quality in the third batch is validation. 

• For statistically
  evaluation and to prove reproducibility, as two data points would not show
  fluctuation (if any) it will always give a straight line and no conclusive
  remark.

• No regulatory agency defines minimum or maximum no. of batch for
  validation study.

• If three batch meets quality requirement as per established
  specification or acceptance criteria; 

Fig. 02: Validation-Three batch concept