EMEA publishes new Q and As on PAT

One of the most useful resources with regard to current GMP interpretation in Europe are the Questions and Answers published by EMEA. These Q and As exist for GMP/GDP, GCP as well as for questions related to the Quality Working Party. Since 2006 there has also been a section about Process Analytical Technology (PAT) on the website. On 26 March 2009 three questions were published focusing on design space, validation strategy and inspections. Below you will find the information.

Design Space

What are the views of the EMEA PAT team on the overall applicability of the concept of "Process Signature", and in particular, in expanding the design space in the post-approval phase?

Currently there is no universally accepted definition of the term "Process Signature" and therefore applicants will have to carefully describe what they mean in any regulatory submission. However we have noted that the concept of "Process signature" may have applicability in controlling manufacturing processes. From this we see the process signature as a possible means of demonstrating that a process is operating within an approved design space. However, as far as expanding the design space in the post-approval phase is concerned, a number of factors, including how the process signature is being used, what has been accepted and agreed to in the submission and how it is proposed to expand the design space would need to be considered. Extensions to the design space are subject to prior regulatory approval, but when more experience with process signatures is gained in the future, this might be reconsidered.

Validation Strategy

If a PAT method is being used, but not for quality control purposes, what level of validation would be considered to be "appropriate"?

Any PAT method must be shown to be "fit for purpose" and this together with a Quality Risk Management approach will dictate the level of validation required. If the method is not for a quality control, for the information that is being gathered to be meaningful and have value (dictated by what use is being made of the information) the applicant must have confidence that the results are relevant and repeatable and consequently carry out appropriate validation to confirm this.


What will be the expectations of an inspector when conducting a pre-authorisation inspection of raw data supporting the Design Space or PAT elements of a submission?

The focus of such inspection, if requested, is likely to concentrate on data supporting the "critical process parameters" and the "design space" ranges. Consequently, this information should be available for inspection.
It is acknowledged that some laboratory experiments will not have been carried out in accordance with full GMP requirements and that there would be no need to repeat every one of these under GMP conditions. However it would be expected that raw data would be documented according to a pre-defined archiving strategy and traceable as a matter of good scientific discipline. It is nevertheless recommended that the development work is carried out within a quality system environment such as that described in ICH Q10. Where experiments are key to establishing critical process parameters and design space, it would be expected that these would be verified by repetition and under GMP conditions but it would be anticipated that the majority of these would actually form part of the normal progression and verification of the proposal into the production environment.

The University of Heidelberg is organising the Quality by Design and PAT Conference 2009. This major event will be co-sponsored by ECA. Speakers from FDA, EMEA are invited for the Conference on 29 September to 1 October 2009. The programme will be available at www.pat-conference.org

Source: EMEA - Inspections - What´s New in Inspections

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