2020 Annex 1 draft: new challenges for sterile manufacturers

by PQE Group


The second draft of GMP Annex 1 is about to be released. The document, a milestone standard for all sterile manufacturers, has been widely revised and extended, with important insights and implementations for the sterility assurance of the finished products. Should all manufacturers get ready to be compliant with the approaching news from Annex 1? The answer is of course “Yes”. Let’s have a look to all the main changes and what they bring for manufacturing companies.

2020 Annex 1 draft new challenges for sterile manufacturers - int

Significant Addings related to Risk Assessment Approach. New Contamination Control Strategy document


Let’s see the main implementations, with respect to the current Annex 1 edition. The 2020 Annex 1 draft results to be widely expanded in many sections, and the added news are many and significant. One first aspect, catching the eye of any interested reader, is the strong attention paid to PQS and Quality Risk Management: ICH Q9 and ICH Q10 are now globally accepted and implemented. Manufacturers are now more than ever requested to improve their management system for risk assessment, investigations, CAPAs implementation and monitoring. And most of all, they are requested to improve their risk assessment approach, extending it to every aspect of sterile manufacturing. This new global, site-wide approach to the contamination risk assessment is reflected in the strong focus on the implementation of Contamination Control Strategy: a newly requested document where any aspect, having an impact on the sterility assurance of sterile products, must be assessed with a holistic approach: cleanroom design, material/personnel flows, closed systems implementation, environmental monitoring and data trend, disinfection, utilities management, and so on.


Re-thinking Cleanrooms’ layouts. Aseptic Processing controls enhanced.


The new Annex 1 draft requests the sterile manufacturers to re-think their cleanrooms layout, with new approaches to the design of environmental monitoring plans of the critical areas, changing rooms, HVAC system and cleanroom qualification. And new technologies are now mentioned for the protection of the most critical steps of aseptic processing: the implementation and use of RABS, isolators and closed systems is now dramatically encouraged.

Most of all, aseptic processing is approached with deeper insights on the most critical aspects for microbial contamination containment. Manufacturers are now requested to be aware of their need for (just to mention the most relevant ones):

  • a strong sterile personnel training and qualification program
  • a risk-based approach to sterility assurance and environmental monitoring
  • a scientific justification for time controls on sterile processing
  • a close control to material and operators flows in and out from cleanrooms.

But the list doesn’t stop here, because the new draft Annex 1 also introduces important news about aseptic process simulation (aka media fill). The requirements for media fill execution are much more detailed in terms of acceptance criteria, performance parameters, operational aspects to be challenged. Manufacturers are thus forced to have, or gain, deeper knowledge and skills on every asepct of their aseptic processing.


Personnel, Critical Defects: a better definition for Visual Inspections.


Visual inspection is another production step poorly detailed in the current edition and now much better defined: critical defects must be listed, monitored and trended, and dedicated personnel is now requested to be qualified and periodically assessed for their ability to reliably detect such defects. And last but not least, in a list that could be much longer, alternative rapid microbial methods are now mentioned and their adoption foreseen: such methods (not only for environmental monitoring and sterility test) show important advantages, with respect to the currently used ones, but need strong and skilled efforts for their set-up and validation, to be reliably applied.


In conclusion, the new Annex 1 is going to request manufacturers to adopt an overall risk assessment approach and build a robust and scientifically-based management system for the sterility assurance of their products. A lot of operational aspects of sterile production are now much more detailed and cleared, and new challenges are arriving for sterile manufacturers to get compliance with GMP guidelines, not only related with equipment and cleanrooms but also with their quality personnel skills and background.


Any issue with sterile manufacturing?

PQE Group staff comprises experienced and skilled experts that can support you in the goal for compliance in every aspect of your aseptic manufacturing: sterility assurance strategies, quality compliance, microbial monitoring, cleanroom design and revamping, equipment qualification, critical system validation, analytical methods selection and validation, and many others.

Visit our Technical Qualification services page or contact us to find the most suitable solution for your company.