According to the European Directives 2001/83/EC and 2004/27/EC, EU Member States may require to test batches of immunological medicinal products or medicinal products derived from human plasma by an Official Medicines Control Laboratory (OMCL) before these can be marketed. A Batch Release Certificate is issued when the results are satisfactory. This is known as "Official Control Authority Batch Release" (OCABR) and consists of analytical controls and document review which are additional to the routine release testing that must be carried out by the manufacturer for each single batch. The Directives require Member States to recognize OCABR carried out by other Member States. This means that once a batch is released by the competent authority of one Member State, OCABR is valid for all other Member States, which is also known as mutual recognition.
Although the process of batch release in Europe is straightforward and clearly laid down in directives, it is sometimes a lengthy process. Sometimes more than one year should be taken into account between the intention of putting a vaccine on the market and the first available commercial batch. Since OCABR in EU is obligatory, it is the company’s responsibility to choose an OMCL belonging to the OMCL network. This choice, which is free, should be made before filing of the MA application. The initial process involves the transfer of the analytical methods for those tests that will be performed by the OMCL. Regarding the set of the tests to be performed by the OMCL, this is finally decided by EDQM and depends whether or not an OCABR guideline for the type of product in question is already in force. For the method transfer, many aspects should be taken into account such as for instance OMCL equipment availability, structural differences of equipment (between manufacturer and OMCL), shipment of samples and reagents,…. Assay variability and possible changes in analytical methods and specifications during the registration procedure should also be closely monitored. The OMCLs also operate under a quality assurance system according to ISO17025 norm.
Once the method validation has been successfully completed and the company has obtained its MA, commercial batches can be put on the market. The OMCL release testing is a process that normally takes up to 60 calendar days. This release procedure, as mentioned above, involves one or several tests on final lot and sometimes on bulks and intermediates, as well as a critical protocol review of the manufacturer’s data. After testing and protocol review, the OMCL will issue a certificate of compliance, or in case of unsatisfactory test results, a certificate of non-compliance. The issuing of a non-compliance certificate is a rare event under normal circumstances and involves a thorough investigation from the side of the OMCL.
Finally, it should not be forgotten that, even when the method transfer has been completed and batch release is being performed on a routine basis, strict follow-up and close interactions between manufacturer and OMCL remain of utmost importance. The OMCL performing OCABR should always be notified of all relevant approved variations that have an impact on product specifications or on relevant batch record data (which are usually supplied in section 3 of the protocol). Important modifications of the manufacturing and testing procedures, changes in reagents and standards, and technical problems (both manufacturer and OMCL) should be shared as soon as possible in order to guarantee a continuous batch release and to prevent potential out-of-stock situations.
