FDA's New Validation Approach - The Life Cycle Approach

GMP News No. 728

GMP News
15 May 2006

FDA's New Validation Approach – The Life Cycle Approach

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:

Get an overview of the cGMP requirements on the whole range of validation/qualification - in the European Compliance Academy's 3-day GMP Education Course The Validation Manager, Vienna, Austria, 31 May to 2 June 2006.

Sven Pommeranz
On behalf of the European Compliance Academy

Cookies help us in providing our services. By using our services, you agree that we use cookies. Further information


Go back

GMP Conferences by Topics

Cookies help us in providing our services. By using our services, you agree that we use cookies. Further information