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.
Why was a revision of Annex 1 of EU GMP necessary?
An expected revision
Annex 1 of the EU GMP provides general recommendations that apply to all manufacturers of sterile medicinal products and sterile active substances located in the European Union or exporting their products to the EU.
After a first publication of the mandatory EU GMPs in 1989, the text was partially revised 3 times: in 1996, 2003 and 2008. But the text has remained as it is since the last revision in 2008. However, in this period Over time, regulations and technologies have evolved profoundly, such that the content of the Annex was no longer in line with the practices of professionals. Consequently, it appeared essential to clarify and update certain points to better guide manufacturers.
A more complete and better structured document
The new revision is more complete than its predecessor. It has 59 pages while the previous version only had 17. The document is also more structured. It includes a table of contents, a glossary and well-defined sections. Already existing sections are extended with additional details. New sections are also emerging to better regulate the practice of manufacturers.
Towards international standards?
The recommendations in the Annex concern not only products manufactured in the EU but also imports into the EU. Its scope therefore goes beyond the strictly European scope. Its design is also part of a desire for international cooperation.
Indeed, the revision of the Annex was developed in collaboration with the WHO, the Convention on Pharmaceutical Inspection and the System of Cooperation in Pharmaceutical Inspection. For the EU, it is a question of remaining in line with the standards of these organizations and moving towards rules accepted at international level.
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.
How does STERIGENE help you find the right solutions for your environment and adapted to your control strategy?
The revision of Annex 1 of EU GMP details precisely the points to take into account in your contamination control strategy. Thanks to our expertise in clean and sterile process engineering, our teams are able to help you meet the requirements of the text on the following points:
Premises and equipment
Our experts meet this requirement with services for the study and qualification of your clean rooms:
qualification of your CTA (air handling units)
Isolation/protection of sterile production with our RABS and isolator designs
Management of incoming and outgoing flows using intelligent airlocks
Staff
For our range of coverings, we offer innovative packaging and materials to enable contamination control even before entering your areas. We also provide specific training to qualify your staff entering the room and ensure that your employees adopt the right behaviors and reflexes when it comes to dressing.
Utilities
STERIGENE offers a wide range of equipment allowing the production of pure fluids (EPU, EPPI, VP) as well as associated storage and distribution systems, produced in compliance with pharmaceutical standards (Annex 1, ASME BPE, etc.).
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Supplier Approval
Our internal procedures and working methods are as close as possible to yours to guarantee you the level of requirements imposed by pharmaceutical standards:
- Robust quality reference
- QUALIOPI certification
- Control of changes
- Optimized logistics platform
- Traceability of materials and finished products
- …
And we choose our suppliers for their expertise and technical support throughout our partnerships.
Process risk management
By combining expertise in our equipment and knowledge of your processes, our risk analyzes will allow you to better understand the risks of your processes.
Validation of sterilization processes
Our performance qualification and cycle optimization services will allow you to carry out your validation files.
Preventive maintenance
The revision of the Annex requires that equipment, utilities and premises (planned and unplanned maintenance) be maintained at a level which will ensure that there is no additional risk of contamination. To meet this requirement, STERIGENE supports you in the development and optimization of your maintenance strategies: expertise, diagnosis, on-site audit, advice and tailor-made services.
Cleaning and disinfection
We help you make the right choice of products and protocols upstream to facilitate the validation of your processes. Our teams help you find your way among the different solutions and combine chemistry and microbiology to implement your decontamination processes. We offer a selection of products tailored to your specific needs:
- detergents for cleaning
- broad spectrum disinfectants
- sporicides
- Different formats: sprays, cans, aerosols, wipes
- ready to use
- sterile and non-sterile
- French made
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?
We can help you, contact us!
