EU GMP and Annex 1: The New Version

Changes to Previous Version

The first obvious change is in the number of pages, the outgoing Annex 1 had 16 pages only, the new version has increased in size to 59 pages. There is also a marked difference in the repetition of key words within the new version, for example, the word ‘monitoring’ is mentioned five times more frequently in the 2022 Annex 1. 

As mentioned above there are some key focuses within the new version. Whilst both Annex 1 documents, and GMP in general, talk about minimising the risk of microbial, particulate and pyrogen contamination in a finished product, the new version emphasises the importance of considering facility, personnel, processes and monitoring. This is supported by the use of terms such as quality risk management and pharmaceutical quality systems to manage the process of identifying and controlling risks. The new version clearly provides a broader directive on risks throughout a facility and process, for example consideration around the increased use of RABs and Isolators, blow fill seal technology. All of these factors form the basis for that holistic facility wide approach and the creation of a contamination control strategy (CCS). 

A more obvious change in the new Annex is the revision to Grade A limits for biocontamination. Previously the limits for active samples stated an average of less than one cfu per cubic metre, this was of course open to some interpretation. The Annex 1 is clear, the limit is zero, meaning any event represents a breach and will need a full investigation. Manufacturers will need to recognise this could lead to an increase in resource within QA and/or QC Microbiology to carry out the in investigations and document the findings.  

We have an infographic to explain the key changes between the two documents.