The European Commission has passed and published the final version of Annex 13 ("Investigational Medicinal Products") to the EC GMP Guide. The new Annex will come into force in July 2010.
Apart from editorial changes, the revised version gets several important new features. These are, among other things, additions and clarifications on the following topics:
Reconstitutions are to be understood as processes, like dissolving or dispensing finished and released investigational medicinal products for ensuring immediate application or mixing investigational medicinal products with other substances if this is necessary for the application. It is clarified that this reconstitution of investigational medicinal products does not require a manufacturing authorisation. Reconstitution is distinguished from blending a substance with an active ingredient to produce an IMP. The latter equals manufacture and requires a corresponding authorisation.
Independence between quality control and production: this must also be ensured in small companies with a low number of employees (Section 3).
The section on reference samples and retention samples (Sections 36 and 37) mirrors the requirements of Annex 19. Furthermore, the retention period for samples of investigational medicinal products is defined; these are meant to be kept two years after completion or cancellation of the last clinical trial together with the corresponding batch. The storage location shall be laid down in the contract between sponsor and manufacturer and may, under certain conditions, be situated outside the EU or the European Economic Area.
The two-step release procedure (Section 43) shall be documented under the sponsor's responsibility and kept in the corresponding clinical trial's documentation. The sponsor is also responsible that the details of the application for a clinical trial, to which the Qualified Person must have access, are identical to those accepted by the authority. Here, the Annex recommends an established procedure for making changes to the Product Specification File (PSF) and a contractual agreement between sponsor and Qualified Person. The investigational medicinal product must not be applied and has to remain under the control of the sponsor until this two-step procedure is completed.
What is completely new is Attachment 3, which includes a harmonised template for documenting the certification of the batch (step 1).
On behalf of the European Compliance Academy (ECA)