Types of Drug Master Files (DMFs)
Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation; or Drug Product
The Generic Drug User Fee Amendments (GDUFA) include provisions for DMF fees, a completeness assessment, and communications with DMF holders for Type II DMFs for drug substances (active pharmaceutical ingredients (APIs)) used to support ANDAs. These provisions do not apply to other types of DMFs or to Type II DMFs used to exclusively support NDAs or INDs. For more information about GDUFA as it relates to Type II DMFs, see:
- DMF enhancements under GDUFA II
- Completeness Assessments for Type II API DMFs Under GDUFA (guidance for industry)
A completeness assessment is a series of questions that must be satisfied for a DMF to be made publicly available on FDA’s website. It does not replace the full scientific review to determine the adequacy of a DMF to support an ANDA regulatory action. Send inquiries concerning the status of a DMF that is being reviewed for a completeness assessment to DMFOGD@fda.hhs.gov. - List of Type II DMFs Available for Reference
A list of DMFs that have passed the completeness assessment and are available for reference by ANDAs under GDUFA. - List of Drug Master Files (DMFs)
For submissions of sterility assurance information, see:
- MAPP 5040.1 Product Quality Microbiology Information in the Common Technical Document—Quality (CTD-Q)
- Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products (guidance for industry)
Additional Resources
- Q1A(R2) Stability Testing of New Drug Substances and Products (ICH guidance for industry)
- Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (ICH guidance for industry; see also Q7 Questions and Answers)
- Q11 Development and Manufacture of Drug Substances (ICH guidance for industry; see also Q11 Questions and Answers)
Type III Packaging Material
FDA does not require that packaging information be submitted in a DMF. NDA, ANDA, or BLA applicants or IND sponsors who receive information from the manufacturer of a packaging component or material of construction may include that information directly in the application. If, however, the manufacturer does not wish to share information with the applicant or sponsor (i.e., because it is considered proprietary), it may be placed in a Type III DMF and incorporated into the application by a manufacturer’s letter authorizing reference to the DMF.
For submission requirements related to Type III DMFs, see guidance for industry Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (Rev.6). Revision 7 of this guidance has been issued as a draft for public comment and includes a proposed exemption for Type III DMFs. When final, this guidance will represent FDA’s current thinking on this topic.
For submissions of sterility assurance information, see:
- MAPP 5040.1 Product Quality Microbiology Information in the Common Technical Document—Quality (CTD-Q)
- Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products (guidance for industry)
Additional Resource
- Container Closure Systems for Packaging Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Documentation (guidance for industry; see also Questions and Answers)
Type IV Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation
Each additive should be identified and characterized by its method of manufacture, release specifications, and testing methods.
Additional Resource
- Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients (guidance for industry)
Type V FDA-Accepted Reference Information
For submissions of sterility assurance information, see:
- MAPP 5040.1 Product Quality Microbiology Information in the Common Technical Document—Quality (CTD-Q)
- Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products (guidance for industry)
Additional Resources
- Use of a Drug Master File for Shared System REMS Submissions (draft guidance for industry)
- Type V DMFs for CDER-Led Combination Products Using Device Constituent Parts With Electronics or Software (draft guidance for industry)