Revised December 2011
These procedures and guidelines have been elaborated by a panel of experts from various OMCLs under the aegis of the EDQM and endorsed by the plenary network of Official Control Authority Batch Release laboratories after public enquiry. The procedures outlined in this book are to be used for application of Official Control Authority Batch Release in the EU/EEA within the prescriptions outlined in article 114 of Directive 2001/83/EC, as amended by Directive 2004/27/EC. The product specific guidelines which follow take into account the current state of the art in methodology and techniques for the quality control of blood derived medicinal products and vaccines as detailed in the Marketing Authorisation applications which, as indicated in the annex 1 of 2001/83/EC (amended by 2003/63/EC), shall include reference to the European Pharmacopoeia and therefore wherever appropriate they are based on the monographs, general chapters and methods in the European Pharmacopoeia. They are intended to be used by manufacturers and OMCLs for the Official Control Authority Batch Release of blood derived medicinal products and vaccines for human use as appropriate and are applicable as noted on each cover page.
Any modifications must first pass through a system of consultation and approval by the appropriate authorities before being applied. A form for requesting changes to existing guidelines can be found at the end of this book. A complete set of guidelines including a version of this text is also available electronically on the internet at http://www.edqm.eu to be applied by users in the context of the Rules Governing Medicines in Europe Volume III, published by the EU Commission, Directorate General for Health and Consumers (http://ec.europa.eu/health/human-use/legal-framework/index_en.htm).
We wish to remind the readers/users that all 27 EU Member States and the 3 EEA partners, may decide to apply Official Control Authority Batch Release in accordance with article 114 of Directive 2001/83/EC, as amended by Directive 2004/27/EC. All the procedures and guidelines for the running of OCABR throughout the network will apply equally to all Member States and as such, where applied, Official Control Authority Batch Release will be mutually recognised throughout the full EU territory.
It is also recalled that since June 1st, 2002 any Official Control Authority Batch Release Certificate issued in the EU/EEA for a batch of product released following the procedures and product specific guidelines outlined here will also be valid in Switzerland in application of the Mutual Recognition Agreement (MRA) between that country and the EU (Chapter 15 of Annex 1).
Reciprocally, Official Control Authority Batch Release performed in Switzerland according to their specific procedure and resulting in issue of a Batch Release Certificate with reference to the MRA will be recognised within the EU/EEA. Detailed information can be obtained at www.swissmedic.ch.
From January 1, 2007, the agreements related to this MRA are extended to the entire expanded European Union wherever OCABR is applicable.
Furthermore, an Agreement on Conformity Assessment and Acceptance of Industrial Products (ACAA) with Israel is currently under development. With respect to OCABR this agreement will initially cover the field of human vaccines only. In this context Mutual Recognition of results obtained through applying the EU regulation, procedures and guidance on OCABR will be applicable between Israel and EU/EEA Member States.
At the time of publication, the official date of application is not known however it should be announced on the EU Commission Website and will be communicated via the EDQM website as soon as the decision is made public.
The ACAA agreement does not extend de facto to MRA partners.
NOTE TO USERS
Chaque guideline individuel est clairement identifié sur la page titre. Par souci de continuité et de transparence, les anciens noms des guidelines et d’autres informations d’ordre rédactionnel sont fournies.
The Administrative Procedure for Official Control Authority Batch Release contains an update to the procedure section to facilitate the transfer of information concerning approved variations to Marketing Authorisations from the MAH to the OMCL performing OCABR in a timely manner. It also has an update in annex V, the template for OCABR annual reports by the OMCLs. The updated document is in force from 1 January 2012.
Users are also reminded that Annex III, the list of official contacts for OCABR, is continuously updated as soon as changes in contact details are made known to EDQM. The most recent contact details for the network of EU/EEA and MRA partners are found exclusively on the EDQM website (http://www.edqm.eu). It is therefore advised to regularly visit the website to ensure that users have the most recent version.
The model protocol, present in all guidelines, is provided for use by the manufacturer. It is meant to help ensure complete and harmonised protocol submission. An attempt has been made to list all appropriate production steps and controls as required by the Marketing Authorisation and the relevant monograph(s) of the Ph Eur. It is possible however that a protocol for a specific product may differ in detail from the model provided. The essential point is that all relevant details demonstrating compliance with the Marketing Authorisation and the Ph Eur monograph(s) (where existing) for a particular product should be given in the protocol submitted by the manufacturer. This is explained clearly in section 3 of all guidelines.
To complete the set of references for OCABR to match the current market situation new guidelines have been added as indicated below. All additions and revisions are also noted in the table of contents and an indication of the revision is given on each cover page. In this context additional guidelines are currently being developed in accordance with the procedures in place in the OCABR network.
All product specific guidelines for both Blood Derived Medicinal Products and Vaccines have be updated in section 4 in parallel with the update to the Administrative Procedure for Official Control Authority Batch Release to facilitate the transfer of information concerning approved variations to Marketing Authorisations from the MAH to the OMCL performing OCABR in a timely manner. Those guidelines not already updated recently have also undergone editorial revision to bring them more in line with the model templates. All updated guidelines come into force on 1 January 2012.
In addition, the following additions or revisions are notable.
GUIDELINES FOR VACCINES
There are 2 new guidelines which came into force 1 July 2011. They were published on the website in June 2011. The guidelines are included for the first time in this book (reissued with a new PA/PH number to include the section 4 revision):
• Live attenuated influenza vaccine produced on eggs
• Haemophilus Type B, Meningococcal C conjugate combined vaccine
A number of revisions also came into force on 1 July 2011 and were made available on the website (they are reissued under a new PA/PH number with the addition section 4 revision):
• Monovalent or multivalent or multivalent meningococcal polysaccharide conjugate vaccine (formerly Meningococcal C Polysaccharide Protein Conjugate Vaccine) was updated to accommodate a new multi serotype vaccine.
The following vaccines were updated in line with the European Pharmacopeia monographs with respect to reference to thermal stability and adopted by fast track procedure.
• BCG vaccine
• Measles vaccine
• Mumps vaccine
• Rubella vaccine
• Measles, Mumps and/or Rubella Component Combined vaccine
• Measles, Mumps, Rubella, Varicella Combined vaccine
• Vaccine containing Vaccinia Virus produced in Cell Culture (Smallpox Vaccine)
• Yellow fever vaccine
The following guidelines were updated in line with revisions to the relevant Ph. Eur. monographs, adopted by fast track procedure and circulated to the manufacturers’ associations and the OCABR Network for information. The revisions related to the monograph come into force on 1 January 2012 (they are reissued under a new PA/PH number with the addition section 4 revision):
• Hepatitis A (inactivated) and Typhoid Polysaccharide combined vaccine
• Hepatitis A (inactivated) and Typhoid Polysaccharide combined vaccine (adsorbed) for mix-at-use format products
• Poliomyelitis vaccine (Oral) (OPV) trivalent vaccine was updated in line with the European Pharmacopeia monographs with respect to reference to thermal stability;
• Pandemic Influenza vaccine was updated to include a reference to the guideline for live attenuated influenza vaccine.
Both of these revisions were added concurrently with the update to section 4 and come into force on 1 January, 2012.
Guidelines for human blood and plasma derivatives
There are no additional revisions or new guidelines.
Please note that guideline updates may occur during the year to respond to the needs of the system. In such cases the guideline update is published on the EDQM website as soon as possible after final adoption and a notification is also sent through relevant manufacturers’ associations and to the OCABR network.
Guideline additions/revisions adopted mid-year will be published in the OCABR book at the end of the given year. Users are encouraged to refer to the EDQM website periodically to check for update announcements.
In the context of Article 58 of CEC Council Regulation 726/204 a procedure has been developed through a close collaboration between the WHO, EDQM and the EMA to facilitate the possibility of certification of batches by European OMCLs for biologicals destined to 3rd (non EU) countries. The procedure is presented here for information for potential users.
A template for requesting revisions to any of the published procedures or guidelines and contact details for the EDQM secretariat responsible for OCABR are available at the end of this book and on the EDQM website. Please ensure that any request for changes submitted is substantiated with supportive data and results as appropriate.
© European Directorate for the Quality of Medicines & HealthCare