ASMF

What is an ASMF? 

An Active Substance Master File (ASMF), or formerly known as European Drug Master File (EDMF) procedure, is a set of documents that protects the valuable confidential intellectual property of the manufacturer.

The main objective of the Active Substance Master File (ASMF) procedure, formerly known as the European Drug Master File (EDMF) procedure, is to allow valuable confidential intellectual property or ‘know-how’ of the manufacturer of the active substance (ASM) to be protected, while at the same time allowing the Applicant or Marketing Authorisation (MA) holder to take full responsibility for the medicinal product and the quality and quality control of the active substance. National Competent Authorities/EMA thus have access to the complete information that is necessary for an evaluation of the suitability of the use of the active substance in the medicinal product.

Final Guideline on Active Substance Master File Procedure – Revision 4 (PDF/358.28 KB)

Adopted

First published: 14/12/2018
Legal effective date: 17/06/2019
CHMP/QWP/227/02 Rev 4, EMEA/CVMP/134/02 Rev 4 Corr.https://www.ema.europa.eu/en/documents/report/final-guideline-active-substance-master-file-procedure-revision-4_en.pdfWhat is CEP and ASMF? 

The ASMF holder may have an ASMF as well as a Certificate of Suitability (CEP) issued by EDQM for a single active substance. Generally, it is however not acceptable that the Applicant/MA holder refers to an ASMF as well as to a CEP for a single active substance of a particular MAA/MAV. 
What is an ASMF in pharmaceutical industry? 

The main objective of the Active Substance Master File (ASMF) procedure, formerly known as the European Drug Master File (EDMF) procedure, is to allow valuable confidential intellectual property or ‘know-how’ of the manufacturer of the active substance (ASM) to be protected, while at the same time allowing the … 
What is the difference between Asmf and DMF? 

An Active Substance Master File (ASMF) is the currently recognised term in Europe, formerly known as European Drug Master File (EDMF) or a US-Drug Master file (US-DMF) in the United States.What is a EDQM CEP certificate? 

To obtain a Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP), applicants must send in electronic format the following documentation to the Certification of Substances Department (DCEP) of the EDQM: a completed application form which includes your invoicing details. 

Electronic Active Substance Master Files (eASMF)

ASMF Holders who are supplying substances to more than one Centrally Authorised Product (CAP) should submit their ASMF to the Agency once and not for each application.

The use of eCTD is mandatory for all for centralised procedure human ASMF submissions since 1 July 2016. The use of eCTD is mandatory for ASMFs used for DCP/MRP human procedures from 1 January 2018. Use of eCTD is mandatory for new national MAAs since 1 July 2018 and from 1 January 2019 for all other submission types. The relevant guidance should be followed and the technical eCTD validation criteria must be passed.

To ensure that the above is followed promptly, please refer to the human EMA Pre-authorisation guidance carefully and apply for an EMEA/ASMF/XXXXX number at your earliest convenience by submitting the EMEA/ASMF request form.

For veterinary medicines the accepted electronic format is VNeeS and NeeS and for ASMFs also exceptionally eCTD is allowed. More information can be found from the Veterinary Pre-submission guidance.

Please take a note of the voluntary EU ASMF Assessment worksharing. A different EU/ASMF request form should be submitted when requesting participation in the EU worksharing procedure.

It is very important to note that the above two initiatives are different.

• The EMA eASMF submission rules are mandatory since 1st September 2013 and are applicable to all Centralised applications.
• The EU Assessment worksharing initiative is valid for Centralised and Decentralised procedures.

A valid ASMF should have either an EMEA/ASMF number or an EU/ASMF number, depending on the intended use of the ASMF by its holder. When applying for EMEA or EU ASMF numbers, or submitting any documentation quoting these, please note that they are not inter-changeable. Only one ASMF number should be quoted.

It is mandatory to use XML delivery files for ASMF submissions using the eSubmission Gateway and the Web Client.

Related Documents

Archived documents

• EU Harmonised Technical Guidance for ASMF Submissions in eCTD format version 2.3(01.07.2020)Updated
• EMA Pre-authorisation guidance
• EMEA/ASMF number request template request form
• EU/ASMF number request template request form
• Letter of Access Template (Previously Annex 2), Template Administrative Information – (Previously Annex 3), Template Withdrawal of Access Letter –Should be filled in in accordance of the ASMF type (EU/ASMF/XXXXX or EMEA/ASMF/XXXXX)
• EU ASMF Assessment Worksharing
• Active Substance Master File Procedure Guidance – Human
• Active Substance Master File Guidance – Veterinary
• Example of ASMF in eCTD format

ACTIVE SUBSTANCE MASTER FILE (ASMF)

EMA Guideline on Active Substance Master File Procedure

EMA Additional guidance on documents relating to an Active Substance Master File

Templates for Active Substance Master File (ASMF) procedures

CMDh-CMDv Questions & Answers – Active Substance Master File (ASMF)

CMDh website for latest advice on ASMF procedures (Joint WG website including procedural guidance)

Training presentations on Active Substance Master File (ASMF) work sharing procedure:

• ASMF worksharing – Introduction to the procedure (October 2018)
• Requesting an EU_ASMF repository number (October 2018)
• Submitting an initial worksharing ASMF (October 2018)
• Determining the parent procedure (October 2018)
• Assessment report template (October 2018)
• Sharing assessment reports (October 2018)
• Submitting a variation to an ASMF (October 2018)
• Use of an approved ASMF in a new procedure (October 2018)

An Active Substance Master File (ASMF), or formerly known as European Drug Master File (EDMF) procedure, is a set of documents that protects the valuable confidential intellectual property of the manufacturer. The purpose of an ASMF is to provide the Health Authorities (HAs) with complete information of the active substance used in a drug product to evaluate its suitability for the product. It also allows the Marketing Authorization Holder (MAH) of the product to take the responsibility for the quality of the active substance used in the product.

ASMF Content

An ASMF must contain all the scientific information related to the active substance. The information of an ASMF is divided into two parts:

1. Applicant Part (AP) – Contains information considered as non-confidential by the MAH
2. Restricted Part – Contains confidential information

ASMF Usage

An ASMF is submitted only to support a Marketing Authorisation Application (MAA) or Marketing Authorisation Variation (MAV). It is used for the following active substances:

1. Active substances that are new
2. Already existing active substances, which are excluded from the European Pharmacopoeia (Ph.  Eur.)
3. Pharmacopoeial active substances, which are included in the (Ph. Eur.)

An ASMF holder is required to submit the following to the MAH holder:

• A copy of AP’s latest version
• A copy of the summary/detailed version of AP’s latest version
• A copy of the letter of access, which has not been previously submitted for the same product

A single active substance can have both, an ASMF as well as a Certificate of Suitability (CEP). However, the MAH cannot refer to both the documents for a single active substance. In case, the information present in a CEP is insufficient, only then both the documents can be referred.

////////////////// Active substance master file, ASMF, letter of access, submission letter

Advertisement

How to submit an Active Substance Master File?

How to submit an Active Substance Master File?

The Active Substance Master File (ASMF) describes the quality of an API and is an essential document for the marketing authorisation of medicinal products. The procedure to submit an ASMF has been recently updated and described extensively in a new EMA Q&A document. Read more about the newest provisions.

How to submit an Active Substance Master File?

As part of the authorisation procedure for a medicinal product, applicants have to provide detailed information about the quality of the API. Generally, the applicant doesn’t manufacture the API himself but receives it from an API manufacturer and has to submit  the quality-related information regarding the API directly to the authority (see Directive 2001/83/EC, Annex I) in a separate document: the “Active Substance Master File” (ASMF, former name: “European Drug Master file”). An ASMF is always composed of two parts: the “open” part (applicant’s part) which doesn’t contain any confidential information and is known by the applicant – and the “closed” part which is much more detailed and represents the manufacturer’s know-how with regard to the manufacture of the API and its analytics. For the competent authority, this closed part of the ASMF represents the basis for the assessment of the API’s quality and safety in the context of the proceeding of the marketing authorisation application.Although this procedure has been established for several years now, there are time and again uncertainties regarding certain points. In the Question and Answer document entitled “Pre-authorisation Procedural Advice for Users of the Centralised Procedure” (EMA/339324/2007) which has been recently revised and published in December 2013, the EMA covers the topic extensively under Question No 24 “How shall I submit an Active Substance Master File”. The answer to this question is treated in 7 pages which were also revised in December 2013 and are thus up-to-date. There are in total 9 sub-chapters dealing with the following issues: 24.1. What data should be submitted by the ASMF holder? 24.2. What data should be submitted by the applicant or MAH? 24.3. What is the EMEA/ASMF reference number? 24.4. Who should request an EMEA ASMF reference number? 24.5. When and how to request an EMEA ASMF reference number? 24.6. EMEA ASMF or EU ASMF reference number? 24.7. Which format and submission channel should be used for submitting ASMFs? 24.8. How to proceed if the ASMF was previously submitted in paper format? 24.9. How to proceed if there is an existing eCTD life-cycle for the ASMF? The issues dealt with within the sub-chapters indicate how urgent the update of the Question and Answer document was. Indeed, there are now two numbering systems for ASMFs: EU’s ASMF reference number and EMEA’s ASMF reference number. Whereas EU’s ASMF number is used for centralised, decentrialised as well as national authorisation procedures, an EMEA’s reference number has to be applied for in case of new applications or variation applications which are submitted after the 1st September 2013 (possibly in addition to an already existing EU ASMF number). This is a requirement from the “Guideline on Active Substance Master File Procedure” dated 1st October 2012. The Question and Answer document should now help avoiding confusion with regard to applications, the two numbering systems and life-cycle management. Further clarifications concern the framework of the ASMF procedure. The API has to be “well defined” in an ASMF. Biological APIs used in vaccines or cell therapeutic medicines or APIs obtained from blood are not “well defined” chemical entities in this sense and thus the ASMF procedure is not applicable to them.