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Feedback from Pierre Devaux on the new Annex 1

The A3P Association Congress has closed its doors! What should we remember about the new Annex 1 and its implementation?

Manufacturers of primary packaging items and PM (including excipients) have to align with the text. The SCC is the document to drive sterility assurance (SA). Based on the surveys conducted during our workshop 1, only 3 of the 26 production sites present already have a completed 1st version.

To reassure everyone, an A3P Association guide will be published by our ICG. However, this is one proposal among others. There is no single model, no two sites are alike. Furthermore, it is requested that the same document be produced for the risks of Cross Conta and biological contamination.

In chapter 3, microbiology skills are more than essential to control the quality of your investigations and the microbio lab actors are strengthened. Chapter 4, the cleaning and disinfection operations of all our production surfaces are essential and must be supported by RAs. This subject was the subject of many slides in Mr Sarakha’s presentation. The management and monitoring of 5 micron particles still appears unclear.

For utilities, it is essential to identify and control your critical fluids by monitoring the capability of their production and distribution processes via well defined and stable CPP/CQA. Chapter 7 staff must be provided with tailor-made training for all of the ZAC’s activities, always with this microbiological “knowledge” in mind.

With regard to aseptic processes, the absence of PUPSIT, including by Design via a relevant risk analysis, seems perilous in view of the various exchanges we have had on the podium on the subject. Dominique Sierakowski also explained in a remarkable way to the ANSM the complicated regulatory situation with regard to lyos, the vacuum sterilisation of lyos accelerating their ageing. It is important to note that point 8.123 is the only one in the document that is tolerated by a 2-year implementation period.

The design of the distribution lines must be integrated into the design of your APS processes, which is not sufficiently the case at present, as even open isolators provide much greater safety with regard to the critical zone than a revamped conventional line! Monitoring activities are relevant but not a panacea to guarantee your control.

For chapter 10, it should be noted that contrary to what is stated in 10.6, it does not seem necessary to have a class D around your closed isolators to perform the sterility test. There are so many other issues to discuss. In any case, this promises a lot of discussion and definition of relevant and well justified action plans in the coming weeks.

We will be there for you!