Handling of Active Substance Master Files and Certificates of Suitability in the UK

Overview

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK accepts Active Substance Master Files (ASMFs) and Certificates of Suitability (CEPs) as supporting quality data in both new national initial Marketing Authorisation Applications (MAAs) and Marketing Authorisation Variations (MAVs). This guidance outlines the expectations for preparation, submission and management of these files under the UK regulatory framework.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Active Substance Master File (ASMF)

An Active Substance Master File (ASMF) should be compiled in accordance with established international practice, notably the CHMP guideline on active substance master file procedure (CHMP/QWP/227/02 Rev 4). The ASMF is normally submitted in two parts:

• The Applicant’s Part (AP), which is included in the marketing authorisation dossier;
• The Restricted Part (RP), which is submitted confidentially to the MHRA by the ASMF holder with a letter of access allowing the MHRA to assess the restricted information.
  Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

The complete ASMF only needs to be submitted once to register it with the MHRA. To align timing with the MAA or MAV submission, the ASMF documentation should arrive not more than one month before and not after the intended submission date.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Changes to an ASMF should follow the same CHMP guideline procedures, and the ASMF holder must notify both the Applicant/MA holder and the MHRA of any proposed updates.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Certificates of Suitability (CEPs)

A Certificate of Suitability (CEP) certifies that the quality of an active substance is suitably controlled by the relevant European Pharmacopoeia monograph. CEPs issued by the European Directorate for the Quality of Medicines & Healthcare (EDQM) can also be submitted to the MHRA to support a UK MAA or MAV in lieu of full active substance data.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

CEPs remain valid irrespective of Brexit because the EDQM is part of the Council of Europe, not the EU; the UK remains a signatory to the European Pharmacopoeia Convention. This means CEPs continue to be accepted in UK applications post-EU exit.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Submission Logistics and Practical Notes

• The Applicant’s Part (AP) should accompany the MAA dossier with a letter of access from the ASMF holder, permitting the MHRA to assess confidential details in the Restricted Part (RP).
• The complete ASMF is usually submitted via the MHRA Submissions Portal, following MHRA portal requirements.
• ASMF updates and new submissions should be coordinated so they arrive in an appropriate timeframe relative to the corresponding MAA or MAV.
  Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Key Responsibilities

• The ASMF holder is responsible for compiling the complete ASMF, submitting the Restricted Part with confidentiality, and informing relevant parties of changes.
• The Applicant/MA holder must include the Applicant’s Part of the ASMF in the marketing application with the appropriate access documentation.
• A CEP holder provides the certificate and any required assurances regarding monograph compliance to support the application.
  Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)

Conclusion

The MHRA’s handling of Active Substance Master Files (ASMFs) and Certificates of Suitability (CEPs) ensures that high-level quality data for active substances can support UK marketing authorisation submissions in a way that protects confidential manufacturing information while meeting regulatory requirements.
Source: Handling of Active Substance Master Files and Certificates of Suitability (gov.uk) (gov.uk)