New FDA Guidance on Completeness Assessements for Type II API Drug Master Files

Since 1st October 2012, special regulations have been applying to the US Type II Drug Master Files. This year in February, the FDA published a new Guidance for Industry. Read here what the DMF holder has to consider when submitting data about the API Drug Master File.,15339,S-WKS_n.html

Since the coming into force of the “Generic Drug User Fee Act” (GDUFA) on 1st October 2012, special regulations have been applying to the submission to the FDA of a Drug Master Files for a pharmaceutical API (Type II DMF). The DMF holder must pay a one-time fee when authorising the reference of his/ her DMF in an application for a generic drug (Abbreviated New Drug Application, ANDA). Moreover, the DMF will undergo a completeness assessment through the FDA.

This year in February, the FDA published a Guidance for Industry entitled “Completeness Assessments for Type II API DMFs under GDUFA” which provides DMF holders with comprehensive information regarding the application for a Type II DMF. The document describes the criteria according to which the FDA performs a completeness assessment and which data are expected.

This completeness assessment does not replace the full scientific assessment to be executed at a later time. It serves to find out whether the data contained in the DMF are sufficient for the ANDA. In a completeness assessment, the following elements are examined:

  • Is the DMF active?
  • Has the fee been paid?
  • Has the DMF been previously reviewed?
  • Does the DMF pertain to a single API?
  • Does the DMF contain certain administrative information?
  • Does the DMF contain all the information necessary to enable a scientific review?
  • Is the DMF written in English?

The Guidance contains a checklist (Appendix 1) listing the criteria according to which the FDA performs the assessment. For the DMF holder, this list is helpful to check the completeness of his/ her data before submitting them to the FDA.

One essential element underlined in this Guidance is to pay the DMF fee in due time (at least 6 months prior to the submission of an ANDA). The FDA won’t continue to process the DMF as long as the fee hasn’t been paid. If the applicant of an ANDA references in his dossier a DMF for which a fee is due, the FDA will inform him. If the fee hasn’t been paid within 20 days after notification, the FDA will stop the further processing of the application.

When submitting a DMF, the form “FDA 3794″ (Generic Drug User Fee Cover Sheet) should be attached. It contains the minimum information required by the FDA to determine whether the DMF holder has satisfied his fee obligations.

After the successful completeness assessment of a DMF, a number will be attributed and posted on a publicly available API DMF list. The FDA has compiled all important information regarding DMFs Type I-V on the Drug Master File webpage. Here, you can also find the list of all active DMFs.

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Drug Master File Procedures in the EU, the US and Japan 22-23 October 2015, Hamburg, Germany

Drug Master File Procedures in the EU, the US and Japan

22-23 October 2015, Hamburg, Germany


Marieke van Dalen, Aspen Oss B.V, The Netherlands

Dr Hiltrud Horn, Horn Pharmaceutical Consulting, Germany

Dr Usfeya A Muazzam, Bonn, Germany
Dr Boris Pimentel, DSM-Nutritional Products AG, Switzerland
Dr Wilhelm Schlumbohm, Berlin, Germany



Learning Objectives

This education course is intended to provide guidance on the procedures for the European ASMF, the US-DMF and the Japanese DMF. You will get to know
how to describe manufacturing processes
how to compile data for drug substance stability, impurities and residual solvents
which are the important points to consider for US-DMFs
which are the requirements for Japanese DMFs
how to handle changes in European, US and Japanese DMFs

Participants will have the opportunity to take part in one of two parallel workshops about
Description of the manufacturing process or How to compile data for Impurities and Residual Solvents


Documentation of the drug substance quality is an integral part of any marketing authorisation application. In Europe the most common document for this purpose is the Active Substance Master File (ASMF) as long as the applicant has no Certificate of Suitability of the pharmacopoeial monograph (CEP). The European ASMF procedure differs significantly from the US-DMF procedure and for strategic reasons it is very important to take these differences into account. Moreover there are particular requirements for DMFs in Japan. For global acting companies it is a big challenge to handle the different procedures of compiling, submitting, changing and maintaining Drug Master Files in an efficient way.

Target Group

The education course is designed for all persons involved in the compilation of pharmaceutical dossiers for marketing authorisations especially for Drug Master Files who want to become familiar with the different DMF procedures. Furthermore, the course will be of interest to personnel from Quality Units of the pharmaceutical and the API industry.


The European Active Substance Master File procedure – An Introduction
Chemical pharmaceutical documentation for active substance(s) –
Regulatory requirements in EU, USA
Types of active substances – types of documentation
CTD Module 3, CEP and ASMF (former DMF)
CEP for a substance for TSE risk assessment

Drug Master File Procedures in the US
Types of Drug Master Files
Submissions to DMFs
Closure of a DMF
US vs EU DMF – differences in the procedure

How to document drug substance stability
Stability Guidelines
Stability Testing of new drug substances and drug products
Storage Conditions
Bracketing and Matrixing Designs
Stability data from new drug dosage forms
How to document evaluation of stability data
Optimising the submission

Residual solvents and Impurities: synthesis derived Impurities, Metals and genotoxic Impurities
Impact of the new guidelines ICH Q3D and ICH M7
Sources of Impurities
Setting and justification of specifications
Residual solvents, solvent classes
Content and scope of data – documentation requirements
Frequent mistakes

Handling Changes in European Drug Master Files
Why is there a need for changes
Types of changes
How to communicate with the customers and how to get feed back
Differences between ASMF and CEP
How to maintain an ASMF
Keeping track of the customers’ stand in relation to a specific change

Handling Changes in US Drug Master Files
Post approval activities
Reporting requirements to the FDA (CBE 0, CBE 30, Annual Report)
Post approval commitments and post approval reporting requirements
Risk evaluation and mitigation strategies (REMS)
Major re-organisation of a US-DMF
Holder obligations

Requirements of the Drug Master File Procedure in Japan
Regulatory procedures in Japan
points to consider when dealing with Japanese authorities
Regulatory documentation standards
Master File registration procedure
Master File review by Japanese authority

Changes and Maintenance of Japanese Drug Master Files
Change procedures and communication with the Japanese authority
Types of changes
Notification of changes

Non-ECA Members: EUR 1.790,–
ECA Members: EUR 1.590,–
EU GMP Inspectorates: EUR 895,–
APIC Members (does not include ECA membership): EUR 1.690,–
(All prices excl. VAT)
If you have any questions, please contact us:

Tel.: +49 (0)6221 / 84 44 0 E-Mail:–the-US-and-Japan_9255_n.html