Pursuant to section 32 'Official batch testing' of the Medicinal Products Act (Arzneimittelgesetz, AMG), the batch (production unit) of a vaccine, serum, or allergen may only be placed on the market in Germany if an official batch test has been carried out and the batch has been released by the competent higher federal authority, which is the Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines. The directives of the European Union and the European Pharmacopoeia supplement this national legislation.
Updated: 11.11.2024
The Paul-Ehrlich-Institut checks whether the batch has been produced and tested in accordance with the manufacturing and control methods that comply with the prevailing standard of scientific knowledge and the requirements of the marketing authorisation. Like other European Official Medicines Control Laboratories (OMCLs), the Institute conducts tests of vaccines, plasma-derived products, and immunoglobulins on the basis of product specific Guidelines for Official Control Authority Batch Release (OCABRs). These guidelines specify which experimental tests are necessary and which documents the pharmaceutical company must submit together with the application for batch testing. The test specifications are set forth by the European Directorate for the Quality of Medicines and HealthCare (EDQM).
Updated: 11.11.2024
The selection of samples for batch testing is carried out by the manufacturer in accordance with clearly defined specifications, which are described in the product specific Guidelines for Official Control Authority Batch Release (OCABRs). These guidelines are issued and regularly updated by the European Directorate for the Quality of Medicines and HealthCare (EDQM). Samples must be representative of the entire batch to ensure meaningful testing.
Updated: 17.12.2020
The procedure for batch release by the Official Medicines Control Laboratories (OMCLs) within the EU – to which the Paul-Ehrlich-Institut belongs – includes a critical assessment of the manufacturer's production and control protocol and usually an examination of samples submitted by the manufacturer in accordance with the Official Control Authority Batch Release Guidelines (OCABRs). The parameters to be tested are specific to each product.
For example, the experimental batch tests to be carried out by the OMCLs for mRNA vaccines comprise the following quality indicators:
Updated: 11.11.2024
Section 32 of the Medicinal Products Act (AMG) stipulates that the higher federal authority responsible for the medicinal products subject to batch testing – in Germany the Paul-Ehrlich-Institut – must reach a decision on the release within two months of receipt of the batch sample to be tested. However, it is rare that the entire statutory period is needed to complete testing. One part of the batch testing requires only a review of the submitted documents, which is completed quickly. The experimental testing takes from a few days to a few weeks.
Batch testing often takes place in parallel with the tests that the manufacturer carries out themselves. This can save time, as both types of tests are running at the same time.
Batch testing always precedes batch release. Only fully tested batches can be released by the Paul-Ehrlich-Institut for the German market.
Updated: 11.11.2024
Yes.
The marketing authorisation documents for each medicinal product set out detailed guidelines for the manufacturing steps and checks required to ensure a consistently high level of quality for each batch. The marketing authorisation documents also contain the specifications (requirements) for batch testing.
In addition to the in-house (experimental) batch testing carried out by the pharmaceutical company, there is usually further testing – also experimental – done by Official Medicines Control Laboratories (OMCLs) in the EU on samples from each batch that is produced. The Paul-Ehrlich-Institut acts as an OMCL for certain medicinal products, including various vaccines.
OMCLs test batches according to the predetermined specifications. The Paul-Ehrlich-Institut only grants national batch release for the German market if the medicinal product meets the criteria and specifications laid out in the marketing authorisation documents and the manufacturer’s manufacturing process documentation is complete and correct, including the quality checks. This ensures a high level of quality for each batch. The specifications only allow for differences between individual batches within a narrow range.
Updated: 11.11.2024
Yes. Pursuant to section 32 of the Medicinal Products Act (Arzneimittelgesetz, AMG), vaccines, sera, and allergens require an official batch test before these medicinal products can be placed on the market in Germany. Since these medicinal products fall within the remit of the Paul-Ehrlich-Institut, the Institute carries out the official batch release in Germany.
However, the Paul-Ehrlich-Institut does not necessarily have to carry out the batch testing itself. It also recognises the results of other EU Official Medicinal Laboratories (OMCLs) responsible for the medicinal product and releases batches on this basis, provided that the tests comply with European standards.
Updated: 11.11.2024
After an official batch release is issued, the medicinal product can be placed on the market and used in Germany.
Updated: 11.11.2024
The Paul-Ehrlich-Institut will deny batch release if the criteria and specifications set out in the marketing authorisation documents are not met. However, this is very rare because strict quality controls are carried out by the manufacturer during the entire production process. These controls reveal potential deficiencies at an early stage. Medicinal products that reach the manufacturer for final product testing have therefore already been intensively monitored and are very likely to meet the quality standards required in the marketing authorisation documents.
The manufacturer must prepare and submit a testing report for each batch in order to apply for batch release. If a batch of a medicinal product shows deficiencies in the context of these tests, the Paul-Ehrlich-Institut will refuse official batch release for the batch.
As a rule, a manufacturer will not even apply for batch release from the Paul-Ehrlich-Institut if it has already been determined in advance that the batch does not meet the required product specifications.
Updated: 11.11.2024
