5/6 October 2023
On February 20, the long-awaited revised draft of Annex 1 (Manufacture of Sterile Products) was published. The revised Annex 1 will not be an independent EU document, but should also apply directly to the PIC/S guidelines. So the planned revision will replace the current versions of EU-GMP Annex 1 and the PIC/S document PE 009 -11 "Manufacture of sterile Medicinal Products". This is why the draft does not contain any direct references to the term "Qualified Person" (QP); the QP is called here "Person responsible for the quality release of sterile medicines" (3.1 vii). Nevertheless, the term "batch release" was substituted by the term "batch certification", which is now closer to the wording used in Annex 16.
In general, the document will be much more extensive and contain some new rules and additions. There are also some things to consider for QPs:
It doesn't really come as a surprise that this so called responsible person should have "appropriate access to manufacturing and quality information and possess adequate knowledge and experience in the manufacture of sterile dosage forms and their critical quality attributes."
But also a few things which need to be considered in the batch certification process are described directly:
Where used for aseptic manufacturing, confirmation of the integrity of the final sterilization gas filter should be considered as part of the batch certification process [7.15].
Sterilization records should be available for each sterilisation run. These should be reviewed and approved as part of the batch certification procedure [8.35].
Lyophilizer integrity testing results should be part of the batch certification [8.113]
According to Annex 1, the environmental and process monitoring program should be part of an overall contamination control strategy (CCS). The goal is to minimise the risk of both microbial and particulate contamination. Here, the information from the CCS systems should be "used for routine batch certification and for periodic assessment during process review or investigations" [9.3].
The monitoring results including trends "should be considered when reviewing batch documentation for finished product batch certification". [9.13, 10.10]
"A bioburden assay should be performed on each batch for both aseptically filled product and terminally sterilized products and the results considered as part of the final batch review". [10.3]
In those cases where Parametric Release is performed (and has been authorised), a "robust system should be applied to the product lifecycle validation and the routine monitoring of the manufacturing process. This system should be periodically reviewed". [8.53]