2th of August 2023

Revision of Annex 1 - New approaches are required soon! A challenge for your company?

Get an overview about the most important upcoming changes

The revision of Annex 1 of the EU GMP Guideline will be effective this year. It faces companies in the pharmaceutical and biotech industry new challenges. This concerns minor changes, which are reflected for example in the gowning regulations for cleanrooms, as well as more extensive requirements, which may even necessitate a revision of the entire quality assurance and quality control system.


Due date for the implementation of these changes will be 25. August 2023!

The new revision continues and extents the commitment to the risk-based approach. This is leads to the requirement for quality risk management (QRM) covering the entire quality-relevant field of activity, as already described in the ICH Q9 and ICH Q10 guidelines. For the first time, however, the implementation of a Contamination Control Strategy (CCS) is explicitly required. This should describe all aspects of both contamination and cross-contamination prevention.

Part of this concept could be the use of Restricted Access Barrier Systems (RABS), isolators and robotic systems as well as rapid or alternative methods and continuous systems for determining microbiological contamination. According to the new guidelines, their use in production should be considered in any case.
It should be noted that new - partially stricter - specifications have also been made for the use of RABS and isolators. For the first time, for example, a distinction is made between open and closed isolators.

In general, the principle of "first air" now applies to aseptic handling of open product or material and explicitly also to the production of aseptic connections – with only a few exceptions. This means that filtered air must meet the product or product contact surface uninterrupted. Proof must be provided by flow visualizations both at rest and in operation. 

Other aspects such as gassing, and particle measurements are also now regulated more precisely. For potential sources of particle emissions now proved materials must be used which are emitting as low particles as possible. This applies both to the materials used for the construction and to items and equipment used within the cleanroom.

For sterile filtration, a "Pre-Use Post Sterilization" integrity test (PUPSIT) i.e., ensuring the integrity of sterilized filters before use, is to be carried out in the future.

For the first time, parenteral products do require a "defect library" for defects in primary packaging materials.

The revision of Annex 1 of the EU GMP Guidelines also specifies an additional requirement for the use of lyophilizing chambers for the lyophilization of a pharmaceutical product: In the future, the loading and unloading process must be carried out as far as possible without intervention by the operating personnel and, moreover, under cleanroom class A conditions throughout.


Businessman ticks off checkboxes

Valicare experts check the current state.

Valicare GmbH has been working for many years for renowned customers in the field of sterile manufacturing and filling of pharmaceuticals. With our team of experts, the described challenges turn into opportunities for you and your company. We help you to analyze the current state and to define suitable risk-based measures. And if desired, our team will also assist you in implementing the measures.

Questions? Then call us!

Author: Alexander Linack,GMP Validation Expert/Consultant

Further links:
Annex 1
"Lets talk about Annex 1" of our parent company, Syntegon Technology GmbH

Ellen Sons Brinkmann

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Dr. Ellen Sons-Brinkmann
Tel: +49 69 153 293 709
Mail.: ellen.sons-brinkmann@valicare.com