# Handling of Active Substance Master Files and Certificates of Suitability Source: https://www.keypedia.com/records/uk_mhra_guidance/uk-mhra/12805e13-238e-4b52-afd5-eff8e5f51908 Type: Detailed Guide Published: December 31, 2020 Updated: October 18, 2024 > This guidance from the UK Medicines and Healthcare products Regulatory Agency (MHRA) outlines the requirements for submitting Active Substance Master Files (ASMFs) and Certificates of Suitability (CEPs) for medicinal products. Following the UK’s departure from the European Union, the MHRA has established independent procedures, though it continues to follow the CHMP/QWP/227/02 Rev 4 guideline for ASMF compilation. Key requirements include the submission of the Applicant’s Part and the Restricted Part of the ASMF through the MHRA Submissions Portal. Submissions must be timed to coincide with Marketing Authorisation Applications (MAA) or Variations (MAV), ideally no more than one month prior to the application. The UK no longer participates in EU work-sharing or uses EU reference numbers. However, the MHRA may consider assessments from other recognized regulators under the International Recognition Procedure (IRP), provided the full assessment report is submitted. Regarding Certificates of Suitability, the process remains unchanged as they are issued by the European Directorate for the Quality of Medicines and Healthcare (EDQM), of which the UK remains a member. Applicants must include current CEP copies in Modules 1 and 3 of their dossiers. ASMF holders are responsible for notifying both the MHRA and the marketing authorisation holders of any proposed changes to the files. These protocols ensure that active substances meet safety and quality standards within the UK regulatory framework. --- ## Content 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.