New FDA Developments

This year's event dealt with an interesting spectrum of topics, even though several announced FDA guidance documents could not be presented yet in a printed version. However, most of their content got discussed already.

The conference was strictly focussed on FDA related issues only by topics and choice of speakers. Among the more than 50 speakers, there was none from the European pharmaceutical industry. And, only one speaker from a European competent authority was invited for a presentation: Dr. Joerg Neuhaus from the Cologne Inspectorate is one of the few European GMP inspectors well recognised in the US. As an expert for aseptic processing, biotechnology/blood products and GMPs in development, he is one of the most sought-after specialists.

We asked Dr. Neuhaus to share his impressions on the most interesting topics of the conference. (Oliver Schmidt on behalf of ECA)

Here are his minutes:

The really interesting innovations could be found in relation to those topics on which the US-FDA has published guidances or started initiatives in the recent years. FDA representatives stated that this was due to FDA's intention to finalise the guidance documents first and then to review the corresponding inspection and compliance programs. Therefore, we can expect some interesting surprises in this area soon, clues for which could already be found at the conference.

A number of sessions were held on Process Analytical Technology (PAT). Here, the FDA has not yet come to a finalised position. Obviously, they are looking for the right concepts, still. The fact that currently only 2 PAT projects of industry have obtained FDA's approval and 18 further projects have well progressed in evaluation may be indicative for that.

In the field of process validation, the FDA has developed its expectations further and adopted some of the European positions. Therefore, the 3 validation batches that were mandatory in the past are not considered to be sufficient any longer. Now they are regarded as "conformance batches" only. FDA expects more evidence of quality capability and control of processes from validation now. To reach this aim in validation, a thorough understanding of the process has to be established and maintained following a life cycle concept. It was announced that a draft of a revised process validation guide will be published before the end of 2005. Therefore, it is useful to keep up to date with this development.

Regarding aseptic processing, it could be observed that FDA is definitely changing its paradigm orientating more towards the risks for product and patients. The respective training of FDA inspectors is good in progress. Therefore, immediate effects on the inspection practice may be expected soon. Additionally, the FDA emphasises its intention to reward modern risk minimising technologies. E.g., it is intended to decrease the requirements on isolators in comparison to conventional clean room technology. And, FDA announced to define, among others, a new category of Restricted Access Barriers (RABS) processing devices. These are "almost-isolators", which are intended to be rewarded by reduced requirements, too.

In September 2004, FDA published a "Draft Guidance for Industry: Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice". This document outlines requirements on quality systems for pharmaceutical manufacturers. The document is intended to resolve the discrepancy that FDA's current cGMP regulations (21 CFR 210/211) do not include any references to quality systems. With this draft, the FDA extends the principles of the Quality Systems Inspection Technique (QSIT) concept, which has been successfully established in the field of medical devices (Center for Devices and Radiological Health), to medicinal products and biologicals. It is most probable that the final "Guidance for Industry: Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice" will be published by the end of the year. FDA has stated that it will not wait with its initiative until an ICH Q10 document on quality systems has been published. However, FDA has announced that its own guidance will be withdrawn or modified respectively as soon as ICH has finalised Q10. [ECA: Compare the event: FDA's New Quality Systems and Risk Approach with former FDA Deputy Director Jim Lyda]

Way behind these almost completed projects, there was little progress only on how to revise 21 CFR Part 11 and the corresponding guidances on computerised systems. It needs a lucky star that 2005 will see a publication of first drafts.

In a session on ICH Q10 (Quality Assurance Systems), industry representatives expressed their high demands that the harmonisation of quality assurance systems should be accomplished by a facilitation of regulatory change procedures. However, the ICH process has not yet moved beyond the agreement to tackle Q10. So far, no concept has been developed. Nevertheless, the delegates of the interested parties present at the conference emphasised their intention to expedite the process and to complete it successfully in 12 to 18 months due to the high interest from the industry.

It is remarkable that - during several side discussions - FDA representatives repeatedly emphasised their conviction that a future US PIC/S membership would result in great progresses - not only with regard to harmonisation. The author received information outside the conference that the membership application has been submitted to the PIC/S office meanwhile and the PIC/S member authorities charged with the evaluation have already been selected (UK and France).

In total it can be summarized that US-FDA continues to fill its cGMP Initiative for the 21^st Century and its Risk-Based Approach concept with life more and more. A very positive result!

Author: Dr. Joerg Neuhaus

Some of the interesting lectures held by FDA representatives can be found here.