Effects Of Annex 1 Revisions On Manufacturing Operations: An Overview Of Updated Best Practices

By Jaime Rain, MMB, Director, Quality Control, Kymanox Corporation, Morrisville, North Carolina

The revisions to European Union (EU) Annex 1 set the stage for the future direction of the pharmaceutical/biotechnology industry. This document is one of the main EU regulatory guidelines for Risk Management and Contamination Control (Eudralex Volume 4, EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Annex 1: Manufacture of Sterile Medicinal Products) and also serves as the blueprint for the strategies and policies implemented by the many pharmaceutical/biotechnology companies in the United States (US), as US companies frequently consider the EU market.

EU Annex 1 recently underwent a significant revision and was made effective in late August of 2022. The final document expanded the content from 16 to over 50 pages and includes new regulatory requirements as well as details and clarifications from the previous version of Annex 1 (2008). The industry is expected to be in compliance with the revision by 25 August 2023, with the exception of a single requirement related to lyophilizer sterilization where the industry has until 25 August 2024. As a result, many companies across the EU and US are now seeking advice on the implementation of Annex 1. Companies that do not have commercial products marketed in the EU, or those who manufacture Active Pharmaceutical Ingredients (APIs) or drug substance only, should not ignore the document since it provides best practice guidelines that will improve a company’s aseptic manufacturing processes. Additionally, the FDA will likely implement similar requirements in time. Instead, Annex 1 should serve as a point of reference for companies to align with the updated regulatory expectations.

This article, although not exhaustive, discusses some of the key takeaways and interesting changes in Annex 1 for risk management and contamination control strategies.