Guidance

Handling of Active Substance Master Files and Certificates of Suitability

The MHRA accepts an Active Substance Master File and/or a Certificate of Suitability in both new national initial Marketing Authorisation Applications (MAA) and in Marketing Authorisation Variation (MAV) applications.

1. Overview

The MHRA accepts Active Substance Master Files (ASMFs) and Certificates of Suitability (CEPs). This document summarises the ASMF compilation and submission process.

2. Active Substance Master File (ASMF)

An ASMF should be prepared in accordance with the Committee for Medicinal Products for Human Use (CHMP) guideline on active substance master file procedure (CHMP/QWP/227/02 Rev 4).

Templates (letter of access; submission letter and administrative details form) included in the annexes to that guideline should continue to be used.

An applicant should submit the Applicant’s Part (AP) of the ASMF as part of the MA dossier, together with a letter of access issued by the ASMF holder.

When an ASMF procedure is to be used which relates to an ASMF that has not previously been submitted to the MHRA, the ASMF holder should submit a copy of the AP and Restricted Part (RP) to the MHRA. This should be accompanied by:

  • a completed submission letter and administrative details form
  • any relevant letter of access
  • the Quality Overall Summary for the AP and for the RP
  • a curriculum vitae for the Expert

The complete ASMF only needs to be submitted once to register the ASMF with the MHRA. The relevant documentation should be timed to arrive at approximately the same time as the MAA or MAV, so not more than one month before and not after the intended MAA/MAV submission date.

Changes to an ASMF should be handled in accordance with the CHMP guideline (CHMP/QWP/227/02 Rev 4). The ASMF holder needs to fulfil their responsibilities with respect to notifying each Applicant/MA holder and the MHRA, that changes are being proposed to the ASMF.

Submission of a new ASMF and any update to an ASMF should be made by the ASMF holder using the MHRA Submissions Portal.

The UK no longer participates in ASMF work sharing procedures with EU Member States. Any reference in the above guideline to the CTS ASMF assessment repository or to EU/ASMF/XXXXX  reference numbers has not been applicable to UK national applications since 1 January 2021.

Where an assessment of a new ASMF or an update to an ASMF has been conducted by another regulator such an assessment may be taken into consideration in subsequent MAA or MAV applications if they are submitted through the MHRA International Recognition Procedure (IRP) using one of the listed Reference Regulators (RRs). In that case the assessment report of the RR on both the applicant’s part and the restricted part is required to be submitted in support of application.  Please refer to MHRA guidance on the IRP: International Recognition Procedure - GOV.UK (www.gov.uk)

3. Certificates of Suitability (CEPs)

CEPs are not affected by the UK no longer being a Member State of EU as they are issued by the European Directorate for the Quality of Medicines and Healthcare (EDQM). This is a Directorate of the Council of Europe and a body that is independent of the EU. The UK remains a member of the Council of Europe and a signatory to the Convention on the Elaboration of a European Pharmacopoeia.

3.1 Marketing authorisation applicants

  • Should include appropriate information in the MAA or MAV application form.
  • Should include a copy of the current version of the relevant CEP in Modules 1 and 3.

The second of these actions relates to applications where there is:

  • a CEP for a chemical substance that is an active substance or excipient;
  • a CEP for a herbal drug or herbal drug preparation
  • a CEP for materials of animal or human origin that have been subject to an evaluation of the risk related to transmissible spongiform encephalopathies (TSE).

4. Further information

For further information, please email our Customer Services Centre at RIS.NA@mhra.gov.uk or call 020 3080 6000.

Updates to this page

Published 31 December 2020
Last updated 18 October 2024 + show all updates
  1. • Added section numbers and document overview • Updated all sections for clarity and territorial changes GB revised to UK • Added details of changes with respect to the Windsor framework following implementation and external references • Updated section 4 contact information

  2. First published.

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