Annex 1 of the EU GMP evolves to respond to regulatory developments and technological advances. More complete and better structured than the previous version, the revision of Annex 1 broadens its scope.
The objective of the Annex is to provide all manufacturers of medicinal products and sterile active substances with recommendations to avoid microbial, particulate, endotoxin and pyrogen contamination. But some of its principles can also concern the manufacture of non-sterile products but for which the control of these contaminants is important.
In this article, we present the main principles of the revision of the Annex, in particular the Contamination Control Strategy and Quality Risk Management. Then we detail the main elements to take into consideration to bring you into compliance with this regulatory development.
The main principles of the revision of the Annex
Quality Risk Management
The Appendix specifies a general approach to avoid the risks of contamination in the finished product using the principles of Quality Risk Management. These principles already appeared in the previous Annex but the revision reinforces them.
In addition to the pharmaceutical quality system requirements of Chapter 1 of EU GMP, quality risk management becomes a proactive tool and must be structured around the complete life cycle of the product.
The new text imposes specific obligations to limit the risks of contamination:
- Strengthen the optimization, qualification and validation of factories, equipment and processes
- Implement the means to identify, scientifically evaluate and control potential quality risks

- Use appropriate technologies to ensure the protection and control of products against major external sources of contamination such as personnel, materials and the environment
- Implement monitoring processes and systems designed and qualified by personnel with proven expertise in microbiology
The contamination control strategy (CCS)
The principle of the contamination control strategy appears in this new version of the Annex. A contamination control strategy must be implemented on the manufacturing site to evaluate the effectiveness of the control and monitoring measures implemented to ensure the prevention of contamination. CCS therefore consists of a planned set of controls aimed at ensuring product performance and quality.
Manufacturers now have an obligation to adopt monitoring systems and document their strategy. They must adopt scientifically sound and modern methods and are legally required to upgrade. Respect for sterility and other quality aspects concerns the entire production cycle and not just the finished product. The manufacturer must take all necessary precautions to ensure the sterility of products manufactured in its factories.
The revision of Annex 1 of EU GMP calls for the robust implementation of a contamination control strategy.
To comply with it, you must re-evaluate your practices and processes on the various points raised by the text.
- Do you manufacture products that are not intended to be sterile but where the control and reduction of microbial, particulate and endotoxin/pyrogen contamination is considered important?
- Would you like to know the technical differences and characteristics of insulators and RABS?
- Do you have the impression that dressing is always an ordeal both in terms of space and in terms of procedures?
- Do your material flows cross your personal flows too often?
- Do you need help testing the effectiveness of your CTAs?
- Do you need to carry out risk analyzes of your processes or impact analyzes to evaluate modifications?
- Did you answer YES to at least 3 of the questions?
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