The document discusses the European Drug Master File (EDMF), which was established in 1989-1991 and later revised in 2005. The EDMF, also known as an Active Substance Master File (ASMF), contains confidential manufacturing information that is divided into an applicant's part and a restricted part. The applicant's part is provided to marketing authorization applicants, while both parts are submitted to health authorities. The EDMF system aims to protect proprietary information while providing sufficient data to support drug approvals and ensure product quality.

1. EUROPEAN DRUG MASTER FILE

3. EU DMF (EDMF or ASMF)
• Established in 1989-1991
• Revised in 2005 and became ASMF (Active Substance Master File)
after implementation of CTD in EU
• Applicable only to active substances
• Has been divided into 2 parts
• Applicant Part (Open)
• ASM Restricted Part (Closed / Confidential)

4. European Master File
• The DMF contains information which includes valuable know-how
which should be kept confidential and submitted to the authorities
only. Therefore, it should be divided into 2 parts – an applicant’s part
and an ASM Restricted Part. The applicant’s part of a DMF is provided
by the ASM (Active Substance Manufacturer) to the applicant directly
and becomes part of the application for marketing authorization.
Both the applicant’s part and the ASM Restricted Part of the DMF are
submitted to the authorities.
• Applicant’s part of a DMF – opening part

5. • The applicant must be supplied by the ASM with sufficient
information to be able to take responsibility for an evaluation of the
suitability of the active substance specification to control the quality
of the substance. This normally includes a brief outline of the
manufacturing method, information on potential impurities
originating from the manufacturing method, from the isolation
procedure (natural products) or from degradation and, where
applicable, information on the toxicity of specific impurities.
• ASM Restricted Part of DMF – closing part
• Detailed information on the individual steps of the manufacturing
method such as reaction conditions, temperature, validation and
evaluation data for certain critical steps of the manufacturing
method, etc. and on quality control during manufacture may contain
valuable know-how. Such information may therefore be supplied to
the authorities only.

6. Use of DMFs
• Supporting documents for the registration / approval of drug
products
• In the Chemistry, Manufacturing and Controls (CMC) sections of the
drug submission, the DMF documents the drugs identity, purity,
strength and quality.
• Protect Proprietary and Confidential Information

7. Procedure – Part(1)
• ASMF can only be submitted in relation with a MAA
• is developed to keep intellectual property of ASM confidential.
• Can also be used when no confidentiality issue between MAH and
ASM
• MAA: either CEP or ASMFshould be submitted

8. CEP: Certificate of suitability to the monog of
Er Ph
• applicable to p'ceutical substances only
• through CEP mfgr is able to provide proof that the quality of
substance is suitably controlled by the relevant monograph.
• to apply for CEP mfgr will submit a detailed dossier which may
contain confidential data.
• CEP files that by applying the relevant monograph of Er Ph it is
possible to check whether or not the quality of substance is suitable
for use
• this procedure is intended to be used for substances for which a
monograph has been adopted by Er Ph commission.

9. Steps:
• Submission of dossier
• Acknowledgement of receipt
• Designation of assessors
• Assessment
• Notification of Decision
• Follow up to the certification of suitability

10. ASMF/EDMF
• Applicable to pharmaceutical substances
• content: AP, RP
• Ap contains the information that the ASMF holder regards as non
confidential to applicant where as RP contains the information that
asmf regards as confidential

11. AP
• AP should contain sufficient information to enable the applicant / MA
holder to take full responsibility for an evaluation of suitability of the
specifications for the active substance to control the quality of this
active substance for use in manufacture of specified medicinal
product.

12. Restricted (confidential) Part
• Manufacture
• Detailed description
• Control of Materials
• Control of critical steps and intermediates
• Process Validation
• Manufacturing Process Development
• Impurities: for those impurities which do not need to be controlled in
the final active substance and which are related to detailed
description of the manufacturing process.
• Justification of specification: for information related to detailed
description of manufacturing process, control of materials and
process validation.

13. Restricted (confidential) Part (2)
• Exceptions
• Validation data of sterilisation process may be required in Applicant’s
part when no further sterilisation process of the final product (GMP
certification to be added)

14. Procedure – part 2
• ASMF holders → Applicant/MA Holder
• Copy of latest version of the AP
• Copy of QOS (quality overall summary)
• Letter of access: where this letter has not been submitted earlier for
the product concerned. letter of access is "Permission of ASMF holder
to competent Authorities to access the data in the ASMF in relation
to a specific application" (Annex 2).

16. Procedure – part (3)
• ASMF holder should submit EDMF to Competent Authorities
• The ASMF (applicant + restricted part) either only once or for each
MA application (depends on national requirements)
• Letter of access where this letter has not been submitted earlier by
MAholder / applicant himself or by the EDMF holder for the product
concerned.
• where the same active substance is used in a no. of applications for
different products in one or more member states, the EDMF holder
should submit identical documentation to every competent
authority.

17. EU ASMF Structure: CTD
• In EU, ASMF must be submitted in different sections in CTD modules
• Module 1: Contains administrative and prescribing information
(administrative information is only required for an ASMF)
• Module 2: Contains common overall summaries (QOS) of an
“Applicant’s part” (open part) and “Restricted part” (close part). It is
nothing but summary of the information provided in module 3.
• Module 3: Contains all Quality information. It contains applicant’s
part and restricted part. Applicant’s Part contains information
required for marketing authorization. The Restricted Part contains
information that is extremely confidential for the ASMF holder and
can share with the health authority only.