​​​Guidance for manufacturers: Independent control testing (batch release) for the United Kingdom

Last updated 25 September 2024: Updates to this guidance include information about changes to the control testing (batch release) process for Northern Ireland following the agreement of the Windsor Framework.

1. Overview

This guidance is designed to provide information on the certification of batches of immunological medicinal products or medicinal products derived from human blood or plasma products (‘biological medicines’, including plasma pools), in accordance with the Human Medicines Regulations 2012.

Since 1 January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) retains functions as the Official Medicines Control Laboratory (OMCL) for the United Kingdom (Great Britain and Northern Ireland) through NIBSC.

From 1 January 2025, different batch release processes will apply in Northern Ireland following the agreement of the Windsor Framework (see footnote [1]).

1.1 Control testing (independent batch release) following agreement of the Windsor Framework

The Windsor Framework sets out the long-term arrangements for the supply of medicines in Northern Ireland. It will ensure that medicines can be approved and licensed on a UK-wide basis by the MHRA, with medicines using the same packaging and labelling across the UK. It also provides for the disapplication of the EU Falsified Medicines Directive (FMD) safety features for medicines marketed and supplied in Northern Ireland.

These measures will commence on 1 January 2025 UK. This means that from this date:

• Batch release for Northern Ireland will change.
• The same control testing (batch release) procedure will apply across the whole of the UK (Great Britain and Northern Ireland).

This guidance explains the procedure for control testing (batch release) up until 31 December 2024 (see section 2) and from 1 January 2025 (see section 3).

2. Independent batch release until 31 December 2024

2.1 Batches for Great Britain
In Great Britain, most batches of biological medicines require NIBSC certification before they can be placed onto the Great Britain market. The exceptions are batches that were manufactured and certified by a country with whom the UK has a relevant Mutual Recognition Agreement (MRA). The UK has an MRA in place to cover batches manufactured and released in Switzerland or Israel (see footnote [2]).  

The regime for national certification by the NIBSC works as follows up until the 31 December 2024:

• Great Britain carries out its own independent certification of batches of biological medicines at NIBSC. NIBSC applies a risk-based approach to decide when to apply laboratory testing in addition to protocol review ^[2].
• The expectation is that NIBSC will independently test and certify batches that are to be used exclusively in the UK.
• The statutory fees that apply enable NIBSC as the UK OMCL to charge for certification and testing in Great Britain.
• You must inform the MHRA of the intention to place batches of biological medicines on the market in Great Britain at least seven days in advance. Please send a UK Marketing Information Form (MIF) together with copies of the relevant certificate(s) (NIBSC, OCABR or a certificate from a country with which the UK has a Mutual Recognition Agreement) to the email address on the MIF. Further information on the MIF process can be found in guidance on applying to release a vaccine or blood product to market or obtained by emailing MarketingInformationForm@mhra.gov.uk.

2.2 Procedure to follow if you want to market a batch in Great Britain

Unless special MRA arrangements apply (see footnote [2]), you will need to send samples and documentation to NIBSC for all batches that are intended to be used in Great Britain.

Where NIBSC certification is required, please submit samples and manufacturing protocol documentation as soon as available and (if applicable) evidence of previously obtained OCABR batch certification as soon as you have it (see footnote [3]). Please contact us at ControlTesting@mhra.gov.uk to discuss specific arrangements for your product.

NIBSC will endeavour to meet current batch release turnaround times and continue to offer parallel testing, which in most cases means submitting samples ahead of documentation to meet your anticipated release date. The statutory turnaround time for NIBSC certification is 60 days.  However, our real turnaround times are much shorter.

2.2.1 Products supplied from the European Union to Great Britain:

Wholesale dealers in Great Britain that import biological medicines from the EEA will be required to check that each batch has an appropriate NIBSC certificate before placing on the market in Great Britain. Information about certificates issued by NIBSC can be obtained from NIBSC.

See guidance on the responsibilities of wholesalers importing medicines into Great Britain and the new role of the Responsible Person (Import).

2.2.2 Products supplied from Northern Ireland to Great Britain:

Products supplied from Northern Ireland to Great Britain will require the supplying manufacturer or wholesale dealer in Northern Ireland to confirm that a NIBSC or MRA country’s certificate is available before supplying a Great Britain wholesaler or other authorised person in Great Britain, such as a hospital.

See further guidance on obtaining evidence of independent batch release certification and supply of medicines from Northern Ireland to Great Britain.

2.2.3 Biological medicines imported into Great Britain under a Parallel Import Licence:

Products placed on the market in Great Britain under a Parallel Import licence will require a NIBSC certificate. Please follow the guidance above for batches for Great Britain, including the requirement to provide a UK Marketing Information Form and NIBSC certificate in advance of the product being placed on the market. See further guidance on Parallel Import licences.

2.3 Batches for sale or supply in Northern Ireland only

For batches to be placed onto the Northern Ireland market,EU Official Control Authority Batch Release (OCABR) certificates dated on or before 31 December 2024 are accepted, with the exception of batches of vaccines and immunological medicinal products whose OCABR certificate was issued in a different EEA member state to that in which the batch was manufactured. These arrangements apply unless the product is subject to a waiver (for which further details are set out below):

• At least seven days prior to placing the product on the market, you must provide the MHRA with a UK Marketing Information Form and send a copy of the relevant certificate to the email address on the MIF.
• A NIBSC certificate will be required for products marketed in Northern Ireland where there is no OCABR certificate or for batches of vaccines and immunological medicinal products whose OCABR certificate was issued in a different EEA member state to that in which the batch was manufactured, and which are not the subject of a waiver*.

If a NIBSC certificate is required, please follow the guidance above that applies to Great Britain.

2.4 Batches for UK-wide sale or supply      

If a batch of products is placed on both the Great Britain and Northern Ireland markets, it will need a NIBSC certificate for Great Britain and the appropriate certificate for Northern Ireland (see section 2.3 above – batches for sale or supply in Northern Ireland only). If the batch does not have an OCABR certificate we will accept the NIBSC certificate for both Great Britain and Northern Ireland.

2.4.1 Waiver applications

Waivers can be granted for batches of vaccines and immunological medicinal products to be placed onto the Northern Ireland market. A waiver applies when the OCABR certificate was issued in a different EEA State to where the batch was manufactured.

The MHRA/NIBSC may grant product-specific waivers following an application from the product’s Marketing Authorisation Holder.  Submitting one application that lists all products that are already on the Northern Ireland market, is acceptable. However, waivers will be granted, and may in the future be revoked, on a product-by-product basis.

Waiver applications should be sent to ControlTesting@mhra.gov.uk.

Waiver applications may be refused, but the expectation is that most existing vaccines will be granted a waiver on the following terms:

• The product-specific waiver will exempt the Marketing Authorisation Holder from the need for a NIBSC certificate for vaccine batches that are destined for Northern Ireland but are manufactured in a different EEA member state to the one that issued the OCABR certificate, provided that:

• the batch has an OCABR certificate;
• the Marketing Authorisation Holder submits the OCABR certificate and a UK Marketing Information Form for each product batch to the MHRA (marketinginformationform@mhra.gov.uk); and
• the Marketing Authorisation Holder does not place the batch on the Northern Ireland market until they have received confirmation of the MHRA’s acceptance of the batch.

• Waivers will remain in force unless:
• Waiver applications for products new to the Northern Ireland market will be assessed on a case-by-case basis.
• The terms for new products or for products where concerns are raised will be agreed on a case-by case basis.

• the NIBSC revokes the waiver, or
• the NIBSC alerts the manufacturer to product-specific safety or quality concerns.  In this event, the NIBSC and the manufacturer will agree an immediate mechanism to allow the NIBSC to perform an appropriate level of quality review prior to placing batches on the NI market.

3.  Independent batch release from 1 January 2025

This section provides information on what to expect following the 1 January 2025.  From this date, medicines within the scope of the EU’s Centralised Procedure will no longer be authorised as PLGBs, but as UK-wide PLs. For further details, please read the UK-wide licensing guidance.

Biological medicines in scope of this guidance will fall under Category 1, as defined in section 4 of the UK-wide licensing guidance, and from 1 January 2025, the same control testing (batch release) procedure will apply across the whole of the UK for biological medicines. The following arrangements will apply for independent batch release:

• All batches for sale or supply in the UK (Great Britain and Northern Ireland) will require NIBSC certification, except for batches that were manufactured and certified by a country with whom the UK has a relevant Mutual Recognition Agreement (MRA) (see footnote [2]).
• EU Official Control Authority Batch Release (OCABR) certificates issued after 31 December 2024 will no longer be automatically accepted for batches for Northern Ireland. However, evidence of previously obtained OCABR batch certification (see footnote [3]) may still be considered for all UK batches. Please contact us at ControlTesting@mhra.gov.uk to discuss specific arrangements for your product.
• The waiver process outlined in section 2.3 above for batches for Northern Ireland whose OCABR certificates were issued in a different EEA State to that in which the batch was manufactured will be revoked on 1 January 2025. Please get in touch with us at ControlTesting@mhra.gov.uk if you think your product may fall under Category 2 as defined in section 4 of the UK-wide licensing guidance.
• Unless special MRA arrangements apply (see footnote [2]), you will need to send samples and documentation to NIBSC for all batches to be used in the UK.
• Please submit samples and manufacturing protocol documentation as soon as available and (if applicable) evidence of previously obtained OCABR batch certification as soon as you have it (see footnote [3]).
• At least seven working days prior to placing a batch on the market, you must provide the MHRA with a UK Marketing Information Form and a copy of the relevant certificate (if applicable) to the email address on the MIF. This applies to all batches for the UK (Northern Ireland and Great Britain). Further information on the MIF process can be obtained from MarketingInformationForm@mhra.gov.uk.
• The statutory fees will continue to apply.
• Products supplied from Northern Ireland to Great Britain will no longer require confirmation that a NIBSC certificate is available before supplying a Great Britain wholesaler or other authorised person in Great Britain.
• All batches placed on the UK market under a Parallel Import licence will require a NIBSC certificate.

What you can expect from us

The NIBSC will continue to apply a risk-based approach to decide when to perform laboratory testing in addition to protocol review. The NIBSC will also endeavour to meet current batch release turnaround times and continue to offer parallel testing, which is optional and in most cases means submitting samples ahead of documentation to meet your anticipated release date.

4.  Additional information

The NIBSC will continue to certify batches destined for non-EU/EEA/UK countries.

For European Batch release, NIBSC can continue to offer batch release testing in liaison with a European OMCL via a subcontract arrangement. Please contact NIBSC on ControlTesting@mhra.gov.uk for further information.

View instructions for the shipping of samples to NIBSC for independent batch release testing.

5.  Contacts

For further information, please email ControlTesting@mhra.gov.uk. Alternatively, contact your Trade Association.

Footnotes:

[1] Subject to the UK providing written guarantees to the European Commission as provided for in Article 8 of EU Regulation 2023/1182 and following the entry into force and application procedure provided for in Article 14.

[2] The list of states with a Mutual Recognition Agreement in relation to independent batch release testing of biological medicines is:

• Switzerland
• Israel

Both Mutual Recognition Agreements include provisions allowing for the re-examination of batches by the NIBSC where there are public health concerns. The Mutual Recognition Agreement for Israel covers vaccines only.

[3] NIBSC will review OCABR certificates issued by EU/EEA OCABR laboratories when deciding whether to rely on a paper assessment or to carry out laboratory testing of batches. NIBSC applies a risk-based approach to assign products that are not covered by Mutual Recognition Agreements ^[1] into evaluation groups:

• Evaluation group 1: NIBSC performs a protocol review and laboratory testing of batch samples.
• Evaluation group 2: NIBSC performs a protocol review and does not perform laboratory testing if a valid OCABR batch certificate has been provided.

The approach is flexible and products can be moved between evaluation groups. Please contact ControlTesting@mhra.gov.uk to discuss arrangements for specific products.

The list of EEA states is:

Austria, Belgium, Bulgaria, Croatia, Republic of Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden.