In our GMP
News of 27 April we wrote about an article on process validation from
the online forum of the US edition of Pharmaceutical Technology. A
follow-up article picks up the topic again and gives an outlook on changes
to the CMC part of the dossier for a marketing authorisation. In the
following we have summarised the most important points for you:
With its "cGMP for the 21st Century" initiative, the FDA has
begun to change its process validation concept. To date, process
validation is associated with 3 validation runs. This number stems among
others from a Compliance Policy Guide (CPG) on process validation dating
back to 1993. This guide was revised in 2004. The new CPG does not define
a number of necessary process validation runs any more. Validation is
considered to be a life cycle approach, therefore, the CPG does not use
the term "validation runs" any longer.
Brian Hasselbalch from FDA's Office of Compliance commented that the
focus of process validation is too much on the number of
replicant runs. He considers this to be a step away from the original idea
of validation. The original principle had a strong design and development
element to it. Full-scale runs in fact only make sense if based on good design and
careful development activities. Hasselbalch
desires that design, development and process capability be verified during
routine production. However, he acknowledges that even well-designed and
well-developed processes might need optimisation. And he adds that
processes may need to be optimised in order to improve yield or quality.
Here it remains to be hoped that the planned revision of the FDA Guideline on General
Principles of Process Validation will facilitate post-approval changes.
In connection with this, the CMC part of the dossier is also intended
to be changed so that it will be easier to review the documentation. A
pilot programme on this issue has already been launched. In this context,
the implementation of Design of Experiments (DoE) is mentioned, a
method that - when applied correctly - can lead to wider specification
limits than hitherto possible. Another tool is design space, which is also
meant to facilitate post-approval changes. In order to be able to assess
this design space correctly within the framework of the registration
process, the FDA is hiring experts on pharmaceutical development,
engineering and physical pharmacy. In the future, the review will be done
by a whole team of experts, not by a single reviewer. The Agency's
priority objective is not to be in the way of pharmaceutical innovations
and process improvements. For the same reason, a draft guideline on
comparability protocols is being revised.
In the future, the FDA intends to shift responsibility for compliance
to the companies. However, relief with regard to post-approval changes
requires a good GMP compliance of the companies in question.
"Old-style validation" will remain possible where the
above-mentioned conditions cannot be fulfilled. In these cases, the
FDA still expects the companies to evaluate the data obtained from the
manufactured batches so that they get to understand their manufacturing
processes better.
Yet the FDA hopes that "soon no one will want to do it the
old way".
If you would like to read the complete article, please click here:
http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=185843
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