The document discusses guidelines for Active Substance Master Files (ASMF) and European Drug Master Files (EDMF) in the European Union. Some key points: - An ASMF/EDMF contains quality and quality control information for an active pharmaceutical ingredient. It has two parts - an applicant part given to marketing authorization applicants, and a restricted part for regulatory authorities. - The ASMF procedure can be used for new active substances, existing substances not in pharmacopeias, and pharmacopeial substances. It cannot be used for biological substances. - Marketing authorization applicants must include specified information from the ASMF in their application dossier and have access to the current active substance manufacturer. ASMF

1. ACTIVE SUBSTANCE MASTER
FILE
(ASMF)
EUROPEON DRUG MASTER
FILE (EDMF)
EMA GUIDELINE FOR MEDICINAL
PRODUCT
CHMP/QWP/227/02 REV.04/CORR*
SANDEEP BANSAL
(Drug Regulatory Affairs)

2. ASMF OR EDMF
• ASMF mean the Active Substance Master
File.
• EDMF means the European Drug Master
File.
• It contains all the data of Quality and
Quality control of the Active Substance
(API).

3. CONTENTS OF THE ASMF
• ASMF Should contain detailed scientific
information as indicated under the various
headings to applicant for Marketing Authorization
(MA) for Medicinal Products in the member
states of the European Union (EU).
• ASMF linked to human medicinal products should
be presented in the Format of “CTD” as
mentioned in Annexure 1, Directive 2001/83/EC
as amended.

4. Continued…..
• ASMF should be physically divided into two
separate parts, namely:
1. Applicant Part (AP)
2. Restricted Part (RP)
• Applicant Part contains the non-confidential
information to the applicant/MA holder.
• Restricted Part contains the Confidential
information directly to the Regulatory
Authority.

5. Continued..
• ASMF should contains the Table of Contents
(TOC) and Separate Summarize for both AP &
the RP.
• In cases, where the ASMF is provided in the
CTD format both summarizes should be
presented as a “Quality Overall Summary
(QOS)”.

6. USE OF THE ACTIVE SUBSTANCE
MASTER FILE (ASMF)
• ASMF can only be submitted in support of an
Marketing Authorization Application (MAA) &
Marketing Authorization Variation (MAV).
• The ASMF Procedure can be used for the
following active substances:
1. New Active Substance
2. Existing Active Substance (Not mentioned in
the EU Pharmacopeia).
3. Pharmacopeial Active Substance.

7. ASMF POINTS
• The ASMF procedure can not be used for the
Biological Active Substance.
• The ASMF holder may have an ASMF as well as a
“Certificate of Suitability (CEP)” issued by
European Directive Quality Management (EDQM)
for a single active substance.
• The ASMF holder should give permission to the
EMA/other Regulatory Authorities to assess the
data in the ASMF in relation to a specific
MAA/MAV in the form of a Letter of Access (LOA),
See Annexure 2.

8. Continued..
• The ASMF holder should submit to the
Applicant/MA holder:
1. A copy of Latest version of Applicant Part
(AP).
2. A copy of the Quality Overall Summary
(QOS).
3. A copy of Letter of Access (LOA).

9. CONTENTS OF MA DOSSIER WHEN THE
ASMF PROCEDURE IS USED
• The MA holder should have all the access of the current
manufacturer of the active substance.
• In order to ensure that they are capable of taking full
responsibility for the quality of the Active Substance Should
be mentioned in the dossier.
• The Specification used by the Applicant /MA holder to
control the correct quality of Active Substance should be
mention in the dossier.
• Should mention the same analytical method as mentioned
in the specification test.
• Should mention the Batch analyses Report (COA).
• MA holder should include a copy of the AP in MA Dossier.

10. CHANGES AND UPDATES TO THE ASMF
• ASMF holder should keep the content of their ASMF’s
updated with respect to the actual synthesis/Mfg.
process.
• ASMF holders shall not modify the contents of their
ASMF (e.g. manufacturing process or specifications)
without informing each Applicant/MA holder and each
National Competent Authority/EMA.
• This obligation remains valid until the Letter of Access
has been withdrawn by the ASMF holder, see Annex 4.
• ASMF holders should provide the updated ASMF to all
interested parties with reference to the revised version
number.

11. Continued..
• Any change to the ASMF should be reported by every MA
holder to the relevant National Competent Authority/EMA
by means of an appropriate variation procedure. A
Submission Letter should be provided (Annex 3).
• At the occasion of the 5-year renewal of a medicinal
product, MA holders are required to declare that the
quality of the product, in respect of the methods of
preparation and control, has been regularly updated by
variation procedure to take account of technical and
scientific progress, and that the product conforms with
current CHMP/CVMP quality guidelines. They will also
declare that no changes have been made to the product
particulars other than those approved by the Competent
Authority/EMA.

12. ANNEXURES