EMA Releases Updated Final Guideline on Active Substance Master Files

Posted 13 July 2012 | By Alexander Gaffney, RAC 

A new final guideline published on 13 July 2012 by the European medicines Agency (EMA) updated the Active Substance Master File (ASMF) Procedure -its first upgrade since its formation in 2006.

The ASMF procedure, formerly known as the European Drug Master File (EDMF) procedure, is used to protect confidential intellectual property information while allowing regulatory agencies to access a more complete picture regarding how an active substance is manufactured. Both EMA and National Competent Authorities have complete access to the information.

Under the guideline, sponsors must submit to EMA "detailed, scientific information as indicated under the various headings" of the relevant parties. ASMF content should be presented using the Common Technical Document (CTD) format if they are for human medicines, but applicants of veterinary medicines can use either the CTD format or adhere to an alternate format contained within Annex 1 of the guideline.

Preserving Confidentiality

Any information the applicant wants to protect should be contained within the Restricted Part (RP) of the application, while all other scientific information should be included in the Applicant's Part (AP) of the application. "It is emphasized that the AP is still a confidential document that cannot be submitted by anyone to third parties without the written consent of the ASMF holder," explains EMA in the guideline.

This is not, however, to say that the AP can be empty while all other information is contained within the RP, says EMA.

"In all cases the AP should contain sufficient information to enable the Applicant/MA holder to take full responsibility for an evaluation of the suitability of the specification for the active substance to control the quality of this active substance for use in the manufacture of a specified medicinal product," explains EMA. "The RP would contain specific information not necessary to evaluate the suitability of a specification, such as the "detailed information on the individual steps of the manufacturing method and the quality control during the manufacture of the active substance."

The ASMF should contain both a table of contents and separate summaries for both the RP and the AP, which should be presented at Quality Overall Summaries (QOS) if the submission is in CTD format. EMA also explains that the ASMF procedure may be used in certain cases when there are no confidentiality issues, but may not be used for biological active substances.

Permission to Authorities

ASMF holders also need to give permission to the National Competent Authorities and EMA to assess the data in the ASMF specific to their particular application. This takes the form of a Letter of Access, and remains valid until it is explicitly withdrawn by the sponsor.

Sponsors should submit an ASMF to each National Competent Authority (and EMA) that they require approval from. In cases where a drug has more than one manufacturer, the applicant should compile all information into a single, identical section.

Every five years, Marketing Authorization holders will be required to declare the ASMF is up-to-date and conforms to current guidelines and regulations, and no changes have been made without approval from the National Competent Authorities or EMA.


Read more:

EMA - Guideline on Active Substance Master File Procedure


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