【正文】 Files in the US ? Comparison of US DMF, European ASMF and CEP ? RDPAC Proposal for DMF in China 2 Drug Master Files in the US ? What a DMF is and is not ? Types of DMFs ? Electronic filing and CTDQ ? Administrative information ? Technical information by type of DMF ? Review process ? Technical amendment process ? Interaction between FDA and DMF holder during DMF review ? Issues of concerns for drug manufacturers ? Remarks 3 What a Drug Master File is and is not ? A Drug Master File (DMF) is a submission to FDA that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs ? The submission of a DMF is not required by law or regulation. A DMF is submitted solely at the discretion of the holder. ? A DMF usually covers manufacturing information not considered releasable via a Freedom of Information Act (FOIA) request ? There are no “Open” and “Closed” parts of a DMF 4 What a Drug Master File is and is not (cont’d) ? The information contained in the DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA), Abbreviated New Drug Application (ANDA), another DMF, Export Application, or amendments and supplements to any of these ? A DMF is not a substitute for an IND, NDA, ANDA, or Export Application ? Technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application ? DMF is not approved or disapproved – FDA will determine if its technical content is acceptable or deficient in support of the related application – If deficient, a letter is sent. If acceptable , no letter is sent. 5 Types of DMFs* ? Type II: Drug substance, drug product, intermediates, and material used in their manufacture ? Type III: Packaging material ? Type IV: Excipients, colorant, flavor, essence, or material used in their preparation ? Type V: Other reference information accepted by FDA – ., sterile manufacturing facilities, biotech contract facilities, clinical, toxicology * Type I for manufacturing facility was eliminated in January 2021. 6 Active vs Inactive DMFs as of January 11, 2021 (Total 23,453) 9,789 Active 42% Inactive 58% 13,664 Number of DMFs ? As of January 11, 2021, there were 23,453 DMFs in the Center for Drug Evaluation and Research (CDER) ? The percentage of active vs. inactive* DMFs has remained constant over the past 3 years * An inactive DMF is one that has been withdrawn by the holder or closed by the FDA because of overdue for update 7 Number of Active DMFs by Type 70% 20% Types of Active DMFs as of January 11, 2021 (Total 9,789) Type V 8 FDA References on DMF ? Regulation: 21CFR ? Guidance ? DMF list and submission information ents/DrugMasterFilesDMFs/ – List of DMFs。 updated quarterly – Additional information about DMF submissions ? Manual of Policy and Procedure (MaPP) p – Cover Form for the Technical Review of DMF – Chemistry Reviews of DMFs for Drug Substances/Intermediates ? Questions or ments are sent by Email to 9 Electronic Filing and CTDQ ? Paper DMFs continue to be acceptable – CTDQ format is not required, but acceptable ? Electronic DMFs are accepted, but not required – CTDQ format is required for electronic DMFs ? DMFs originally submitted in paper can be resubmitted as electronic DMFs. The entire DMF must be resubmitted. ? Once a DMF has been submitted in electronic form, no paper documents (including Letters of Authorization, or LOAs) may be submitted ? Module 1 is required for all eCTD submissions, as it contains the necessary administrative information to identify the DMF 10 Administrative Information ? Name and address of DMF holder and contact person and/or agent ? Names and addresses of manufacturing and testing facilities ? Letter of Authorization (LOA) – An LOA allows FDA, and only FDA, to “access,” ., “read,” the DMF – The holder must submit an LOA to the DMF, and send a copy to the applicant – The applicant includes copy of LOA in their application. This is the only mechanism to trigger review of the DMF – The DMF will be reviewed only when