New EU GMP Annex 1 Implementation

After almost 15 years, the 2008 version of the EU Good Manufacturing Practices (GMP) Annex 1: Manufacture of Sterile Medicinal Products, was updated and significantly expanded on 2022, with the objective of eliminating ambiguities and take into consideration technological advances like the rising use of Single Use systems and technologies.

The final deadline for implementing this revised regulation is August 25th, 2023. This will have a significant regulatory impact in the industry so we would like to take a moment to outline the key aspects that affect the SUS industry and what solutions Venair offers to ensure that our clients can confidently validate and qualify our products as a part of their Contamination Control Strategies (CCS).

Venair ensures a strict sterility program

First and foremost, a reliable sterilization methodology is of capital importance as described in point 8.134 in the new updated normative, where biomanufacturers are commended to verify the sterility assurance of their suppliers as a part of their supplier qualification.

Venair puts great focus is this prerogative with a robust Sterility Program in accordance with ISO 11137 than ensures that all our products shipped with a sterile claim (Certificate Levels 2, 3, 4 and 9*) are sterile with a SAL 10^-6 and that all sterilization processes are well documented and traceable.

Besides, to preserve the sterility barrier shipment, Venair has incorporated a validated packaging and transport configuration, fully compliant with ISO 11167-1 and ISO 11167-2 standards.

The EU GMP Annex 1 and the SUS system

The new updated EU GMP annex 1 notably incorporates for the first time the SUS and some specific requirements suppliers and biomanufacturers must met when using this technology. Integrity of all closed and single-use system in considered of critical importance to maintain the sterility, safety, and functionality of the production processes and therefore there is a strong focus in how the supplier validate the integrity of their systems.

At Venair, we address these concerns by providing the option to perform non-destructive integrity/leak tests in the whole SUS with our certificates of level 4. This encompasses an evaluation of the particular assembly and the formulation of an appropriate integrity/leak test, in accordance with the principles outlined in the ASTM 3336-22 Standard Test Method for Physical Integrity Testing of Single-Use Systems.

Other regulatory concerns

Naturally, extractables and leachables (E&L) are one of the main concerns when using SUS and the updated GMP Annex 1 advises their evaluation.

To ensure that all E&L concerns are addressed, Venair uses validated and chemically characterized components for our SUS systems from reliable providers. Besides, all Venair Biotech products undergo rigorous validation, including biocompatibility tests and an extractables study following USP 665 guidelines.

Finally, particles or endotoxin contamination should also be considered when producing a sterile product under the new Annex 1.

Venair manufactures all its products in an Iso Class 7 clean room. Furthermore, our Certification levels 3 and 4 provide the option to conduct USP 85 (endotoxins) and USP 788 (subvisible particles) testing before lot release.

Conclusions

In conclusion, the new EU GMP Annex 1 brings significant changes to sterility assurance and quality in the pharmaceutical and biotech industries. Venair is fully prepared to meet these regulations through a robust Sterility Program, a comprehensive integrity testing for Single-Use Systems (SUS) and a proactive approach in other regulatory concerns like particles, E&L, etc.