Annex 1 Quality & Compliance August 2022 Update

by: Giovanna Cantoni, CQV & GMP Advisor Associate Partner @PQE Group

August 2022 update on the Annex 1 

Following a long review period, the new Annex 1 was released in August 2022 and it is now time to consider the different new and renewed requests and the impact of these requirements on our own facility and organization.

A little bit of history

The last version, in force until 22 August 2022, was released in 2009; it was in use for more than 10 years. Then, approximately five years ago, a first version of an updated Annex 1 was published with the goal of collecting comments from the pharmaceutical industry. No limit to comments was announced.

It should be mentioned that major changes were foreseen in the updated version; to give an idea of the changes, the earlier version contained more than 20 pages while the updated one has more than 60 pages.

The 2017 updated document was the object of many discussions and disputes in the pharma community and a correspondent volume of comments and amendment requests were sent to the agency. This cumbersome amount of information took some time to be accepted, implemented and justified.

Then, in 2020 the updated Annex with comments incorporated was released for comment but open only to specific institutions.

The massive quantity of new information and subsequently requested new content contained in the new document is also due to the fact that in the past years, important implementation from a technical point of view has been developed to grant a more reliable aseptic condition along with the various processes where a sterile condition is required.

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Primary key points and possible impact on the pharma industry

As already mentioned above, the new Annex 1 contains many references to new technologies and their application to sterile manufacturing facilities.

Furthermore, a completely different approach to define sterility has been suggested and requested. In fact, instead of considering sterility assurance as an issue to be evaluated only in Grade A and B manufacturing areas, the approach to be considered and applied to assure the sterility of the final product is now a holistic approach. This approach takes into consideration all the steps involved in the process, from the entrance of raw material in the facility, the management of the equipment and the environment of all the manufacturing areas up to the final delivery of the product.

Following this approach, a new document is requested to justify and consider all the operations involved in the manufacturing of the final sterile product. The document is already well known to the pharma community as the Contamination Control Strategy, a document that considers all the strategies used throughout the manufacturing process to control and avoid microbiological contamination.

Additionally, to define measures allowing us to prevent microbial, particulate and endotoxin/pyrogen contamination in the final product, the principles of quality risk management (QRM) should be applied.

Considering the technological advancements

As already mentioned earlier, the new Annex 1 takes into consideration the fact that technology has improved in the last 10-15 years and in particular, equipment such as isolators and RABS have been implemented with high levels of automation, requiring human intervention only during abnormalities in the manufacturing process. The core of the document is the encouragement in the use and/or implementation of these new, highly automated technologies and limiting human intervention during the process, aiming to limit the risk of contamination of the final product.

Use of isolators and/or RABS also defines a better work environment for personnel who can act as equipment supervisor and deliver only spot actions in Grade C cleanrooms, where lighter gowning is required and consequently, a more comfortable way of job execution will be in place.

Annex 1 also suggests implementation related to Pharmaceutical Quality System (PQS) by adding special requests for PQS of sterile facilities. Examples of additional requests include: an effective Risk Management System integrated in all areas of the product life cycle, appropriate knowledge and expertise of the sterile manufacturing process, root cause analysis applied to all procedures, and process or equipment failures to identify possible risks for the product.

Typically, small facility sites with older equipment tend to be more concerned with the new requirements for facility and equipment design, while larger and/or newer sites are more concerned with quality system management, which is also a fundamental aspect strongly emphasized in the new Annex 1.

In Conclusion

The 2022 Annex 1 is a complete document that is applicable to all processes as a whole and as such, should to be considered when verifying and implementing contamination measures to assure the sterility of final products.

All the above-mentioned topics and much more are part of the services that PQE can offer their customers to support them in this “new” world by providing a multidisciplinary team of people having different expertise to cover all the different areas: microbiology, engineering, quality, qualification and validation.

Are you ready for change?

PQE Group can support your business in reaching the compliance for your products as well as in implementing new procedures, tools and software.

To get more information or support, check our Quality Compliance dedicated page or get in touch with us to find the most suitable solution for your company.

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