Batch Release for Human Biologicals: vaccines, blood and plasma derivatives
COVID-19 related: Information on OCABR activity for COVID-19 vaccines; guidelines and more
- Background: OCABR Network for Human Biologicals
- Legal framework
- The procedure
- Product-specific guidelines
- NEW: Questions and answers on the OCABR procedure
This network is an important forum for the confidential exchange of quality and technical information on human biological medicinal products and related methods and is a key link in the regulatory chain. As mandated by the European Commission, the EDQM acts as its Secretariat. It is a specific network within the General European OMCL Network, thus subject to its operating rules. It is supervised by an elected advisory group consisting of six representatives (three for blood and three for vaccines) from different member states. A plenary meeting is held annually bringing together all the representatives (their details are available in a contact list) to review the years' activities and to discuss any relevant issues. This meeting also serves as an opportunity to officially adopt the Official Control Authority Batch Release (OCABR) procedures and guidelines, which - like all other OMCL Network activities - must be approved by all the networks' members.
As part of the regulation of biological medicinal products, Article 114 of Directive 2001/83/EC relating to medicinal products for human use, as amended by Directive 2004/27/EC, of the European Parliament and of the Council provides that a member state laboratory may, but is not required to, test a batch of an immunological medicinal product or a medicinal product derived from human blood or plasma before it is placed on the market. OCABR performed by any given member state must be mutually recognised by all other member states requiring OCABR for that product.
This legislation concerns EU/EEA member states and is also applied by any state having signed a formal agreement which includes recognition of OCABR with the EU. Currently, Switzerland has done so via a Mutual Recognition Agreement (MRA) for both the human blood and plasma derived medicinal products and human vaccines fields. In addition, an Agreement on Conformity Assessment and Acceptance of Industrial Products (ACAA) was ratified between the EU and Israel and includes OCABR in the field of vaccines for human use.
The core administrative procedure for OCABR for Human Biological Medicinal Products is the EU Administrative Procedure for Official Control Authority Batch Release. This is used by OMCLs when implementing OCABR at the national level. It is also intended for use by marketing authorisation holders (MAHs). It provides guidance on documents used for communication between MAHs and OMCLs and describes the steps involved in the OCABR process, which are summarised below.
The member state informs the MAH that its authorised human biological medicinal product is subject to OCABR. Samples of the batch to be released are sent, along with production and control protocols, to an OMCL within the EU/EEA. If the results are satisfactory, the Competent Authority (CA) issues an "Official Control Authority Batch Release Certificate" to the MAH. This certificate means that the batch has been examined and tested by an OMCL in accordance with the OCABR guidelines pertaining to the medicinal product and is in compliance with the approved specifications laid down in the relevant monographs of the European Pharmacopoeia and in the relevant marketing authorisation (MA). The MAH must provide a copy of the OCABR Certificate to the Competent Authority of the member state where the batch will be marketed. The certificate is recognised by all members of the network.
If the results are unsatisfactory, the batch is given a certificate of non-compliance and may not be placed on the market. All members of the OCABR network are informed.
Manufacturers with medicinal products potentially subject to OCABR according to Article 114 of Directive 2001/83/EC as amended should make contact with (an) OMCL(s) as early as possible. As noted in the European Medicines Agency (EMA) pre-authorisation procedural advice for users of the centralised procedure (question 66), it is strongly recommended for an applicant to enter into early collaboration with the OMCL(s). This collaboration should ideally begin at least one year before submission of the Marketing Authorisation Application in order to allow for exchange of information between the OMCL and the applicant, which should be considered in the development of the testing methodology. It is advisable that this activity also be undertaken with a second OMCL and that applicants seriously consider the nomination of two such OMCLs for batch release of the authorised product to the market, to secure the supply chain and minimise the risk of shortage.
A list of the OMCLs that may be in a position to provide EU OCABR certificates for different products is available to manufacturers from EDQM on request at BatchRelease@edqm.eu.
In addition to the Administrative Procedure, a series of product-specific guidelines exist. They are elaborated by a panel of experts from various OMCLs under the aegis of the EDQM. These documents facilitate OMCLs in meeting the requirements of Directive 2001/83/EC, as amended by Directive 2004/27/EC. They ensure a common approach to testing in all OMCLs throughout the EU/EEA and transparency for all users of the system. The guidelines are adopted only after consultation within the network and where appropriate after a public enquiry involving interested parties.
The procedures and guidelines for running OCABR apply equally in all member states.
OCABR guidelines and procedures are available exclusively on our website. The complete list is presented in a table from which the files may be downloaded. The guidelines will be updated on an ongoing basis, as necessary. New and revised versions will be placed on the website within one month of their date of entry into force. Users are encouraged to visit the site regularly to ensure they are using the most recent versions. Highlights of recent additions and revision updates can be found in the right-hand menu.
New Guideline (in force from 4 May 2022)
COVID-19 pandemic vaccine, Inactivated (section 2 only)
New Guideline (in force from 21 March 2022)
COVID-19 pandemic vaccine (Recombinant Spike Protein) (full guideline)
Revised Guideline (in force from 21 March 2022)
Multivalent Pneumococcal Polysaccharide Conjugate Vaccine
New Guideline (in force from 21 January 2022)
Recombinant Influenza vaccine
Revised Guidelines (in force from 21 January 2022)
Hepatitis B (rDNA) vaccine
Varicella (rDNA) vaccine
Revised Guideline (in force from 30 November 2021)
COVID-19 pandemic vaccine (Recombinant Spike Protein) (section 2 only)
Revised Guideline (in force from 1 July 2021)
Human Papillomavirus (rDNA) vaccine
Revised Guidelines (in force from 1 June 2021)
Vaccine guidelines to remove the identity test on bulk purified HBsAg (5 guidelines)
Obsolete Guidelines (from 1 June 2021)
Diphtheria, Tetanus, Pertussis (Whole Cell) and Poliomyelitis (Inactivated) vaccine
Diphtheria, Tetanus, Pertussis (Whole Cell), Poliomyelitis (Inactivated) with separate Haemophilus Type B Conjugate vaccine
Revised Guideline (in force from 1 May 2021)
Hepatitis B (rDNA) vaccine
New Guidelines (in force from 1 May 2021)
Pandemic COVID-19 Vaccine (Non-Replicating Adenovirus-Vectored Vaccine) (full version)
COVID-19 pandemic vaccine (mRNA Vaccine) (full guideline)
- Annex III of EU Administrative Procedure for Official Control Authority Batch Release: Human OCABR contact list (11/04/2022)
- Administrative Procedure for European OMCL Certification of Compliance of Batches under Article 58 (10/12/2012)
- OCABR Human Biologicals Flowchart (revised December 2010)
- "The EU/EAA Network for Official Control Authority Batch Release of Biologicals for Human Use", The Regulatory Affairs Journal, June 2002