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Regulatory Focus™ > News Articles > 2019 > 10 > FDA Revises 1989 Guidance on Drug Master Files

FDA Revises 1989 Guidance on Drug Master Files

Posted 18 October 2019 | By Zachary Brennan 

FDA Revises 1989 Guidance on Drug Master Files

The revised draft guidance from the US Food and Drug Administration (FDA) on drug master files (DMFs) deals with submissions on confidential information about facilities, manufacturing, processing, packaging and storing drugs.

FDA said Friday that the update includes new procedures for DMFs referenced in abbreviated new drug applications (ANDAs), more detailed instructions on submitting original DMFs versus amendments, reference to the electronic submission requirements under section 745A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that apply to certain DMFs, clarification and reorganization of material associated with Type III and Type IV DMFs and a change in FDA's contact person for the guidance.

The 22-page draft, updated from September 1989, also discusses the four types of DMFs (Type I DMFs were discontinued in 2000):
  • Type II, which is for drug substance, drug substance intermediate and materials used in their preparation or drug product
  • Type III is for packaging material
  • Type IV is for excipient, colorant, flavor, essence or material used in their preparation
  • Type V is for FDA-accepted reference information
The guidance also features information on the format and delivery of DMFs, submitting original DMFs in eCTD format, submission recommendations by DMF type and FDA processing and review policies. The agency also touches on the differences between DMFs for BLAs and DMFs for applications under the FD&C Act.

A footnote on the second page says, “Although FDA’s approach to the use of master files in BLAs under the PHS Act largely parallels its approach to the use of DMFs in applications under the FD&C Act, there is a significant difference: a BLA holder is generally expected to have knowledge of and control over the manufacturing process for the biological product for which it has a license. For biological products in BLAs under the PHS Act, FDA has, as a scientific matter, generally not permitted applicants to incorporate information about drug substance, drug substance intermediate, or drug product by reference to a master file; rather, FDA generally expects such information to be submitted directly to the BLA.”

In June, FDA proposed a new rule to allow certain biologics, originally approved under a new drug application (NDA), to continue relying on DMFs for certain information even after the NDA is deemed to be a license for a biological product on 23 March 2020.

The agency also further extended the implementation date for Type III DMF submissions in eCTD format to 5 May 2020.

Drug Master Files Guidance for Industry

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