Overview of API Drug Master File

A Drug Master File (DMF) is one of the essential documents submitted to regulatory authorities to support drug approvals. It contains detailed technical information about the Active Pharmaceutical Ingredient (API).

Two Parts of API DMF

Open Part (Applicant’s Part):

• Contains general, non-confidential information about the API.
• Shared with the applicant to support the drug product dossier.

Closed Part (Restricted Part):

• Contains confidential and proprietary information especially related to manufacturing.
• Submitted directly to the regulatory authority by the API manufacturer via LOA.

What is LOA?

A Letter of Access (LOA) is a formal agreement in which the manufacturer agrees to provide the restricted part of the DMF to the regulatory ministry whenever requested.

Sections of the DMF (As per ICH CTD Format)

3.2.S – Drug Substance

3.2.S.1 General Information

3.2.S.1.1 Nomenclature: INN, chemical name and CAS.

3.2.S.1.2 Structure: Chemical structure, molecular weight

3.2.S.1.3 General Properties: Solubility, pKa, melting point

3.2.S.2 Manufacture

3.2.S.2.1 Manufacturer(s): Names and addresses

3.2.S.2.2 Manufacturing Process & Controls: Flow chart & narrative

3.2.S.2.3 Control of Materials: Raw materials & specifications

3.2.S.2.4 Controls of Critical Steps: In-process controls

3.2.S.2.5 Process Validation: Protocols & outcomes

Note: This section includes confidential data forming part of the Closed Part.

3.2.S.3 Characterization

3.2.S.3.1 Structure Elucidation: IR, NMR, MS data

3.2.S.3.2 Impurities: Organic, inorganic & residual

3.2.S.4 Control of Drug Substance

3.2.S.4.1 Specification

3.2.S.4.2 Analytical Procedures

3.2.S.4.3 Validation of Analytical Methods

3.2.S.4.4 Batch Analyses (COAs)

3.2.S.4.5 Justification of Specification

3.2.S.5 Reference Standards or Materials

Characterization and COAs for reference/primary standards and impurities

3.2.S.6 Container Closure System

Packaging specifications, COAs for primary/secondary/tertiary containers, primary labels.

3.2.S.7 Stability

Accelerated & long-term stability data, stress testing

3.2.S.7.1 Stability Summary and Conclusions

3.2.S.7.2 Post-approval Stability Protocol and Commitment

3.2.S.7.3 Stability Data

Note: For Europe it’s called ASMF or EDMF having open and restricted part while for USA it’s called DMF having 5 types. DMF and ASMF both purpose is same but technically written differently. You can’t submit ASMF in USA or DMF in Europe.

Read also:

• Frequently Asked Questions on DMF Filing
• Differences in Filing for Drug Master File in US, Canada and Europe
• Key Considerations for API Source Change in Formulation

Resource Person: Dr. Nirma Tasleem Rao (Rph)