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Revisiting Annex 1: Comprehensive Changes and Their Impact on Sterile Manufacturing and Quality Ris

Updated: Feb 13



Are you confident that your risk management strategy addresses the Annex 1 requirements? Are your processes validated and continuously maintained in a validated state? Can you affirm the adequacy of your contamination controls?


The European Union Eudralex - Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, specifically Annex 1, focuses on the Manufacture of Sterile Medicinal Products. This guide, jointly revised by the Pharmaceutical Inspection Co-operation Scheme (PIC/S), European Medicines Agency Inspectors’ Working Group (IWG), the European Commission (EC), and the World Health Organization (WHO), was published by the EC on August 22, 2022, and by PIC/S on September 9, 2022.


Since its initial publication in 1971, based on a PIC/S recommendation, Annex 1 has been instrumental in ensuring the sterility of medicinal products for patient benefit by outlining the minimum controls required to protect sterile products during manufacturing.




Manufacturers supplying sterile products to the European market are obligated to adhere to these guidelines to minimize microbial, particulate, and pyrogen contamination risks in the final product.

This guide, being the first full revision, provides more detailed requirements for sterile manufacturing and wholly incorporates the principles of Quality Risk Management. It elucidates how manufacturers can leverage enhanced process understanding, using innovative tools as outlined in the Quality Risk Management ICH Q9(R1) and ICH Q10 Pharmaceutical Quality System guidelines.


Mirroring the FDA's trend since 2006, this guideline emphasizes applying a risk-based approach to Quality and Compliance. The expectation is for proactive management of the manufacturing process, associated activities, equipment, and facilities using QRM principles to identify potential risks to quality.


Abouth the Author


Elizabeth Plaza, R. PH


Elizabeth-Plaza

Boasts over 35 years in the bio-pharmaceutical field, starting as a PD Scientist and later leading consulting ventures since 1993, focusing on compliance, project management, technology transfer and validation. Overseen 3000+ resources, completed 10000+ projects, including 1000+ in tech transfer & validation life cycle management. Currently leads a Third Party Consultant firm qualified as set forth in 21 CFR 211.34 to help establishments in meeting cGMP requirements. Co-authored PDA Technical Report #60 on Process Validation.



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