DMF Drug Master File

 DRUG MASTER FILE
 Presented by :
 RUSHIKESH D MENDHE
 Roll no - 511
 Mpharm Ist Year
 (Department of Pharmaceutics)
 Content : :
 INTRODUCTION
 TYPES OF DMF
 DMF FORMAT & ASSEMBLY
 DELIVERY OF DMF TO FDA
 SUBMISSION OF DMF
 THE MECHANISM OF A DRUG MASTER FILE
 CTD & ELECTRONIC DMFS
 UPDATES TO DMF
 CLOSURE OF A DRUG MASTER FILE
 APPLICATION OF DMF
 REFERENCE
 INTRODUCTION :
 A Drug Master File (DMF) is a submission to the Food and Drug Administration (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.
 This guideline does not impose mandatory requirements.
 Objectives :
 Main Objective of the DMF is to support regulatory requirements
 To prove the quality, safety and efficacy of the medicinal product
 TYPES OF DMF :
 DMF FORMAT & ASSEMBLY :

 The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs
 Multiple volumes are numbered, and the paper must be standard paper size
 Paper length should not be less than 10 inches nor more than 12 inches.
 Each volume of a DMF should be not more than 2 inches thick
 DELIVERY OF DMF TO FDA :
 DMF should be submitted at following address :
 Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA

 SUBMISSION OF DMF :
 The DMF must be submitted in two copies, one with a blue cover and one with a red cover.
 Each page of each copy of the DMF should be dated and consecutively numbered.
 Each DMF submission should contain :
• A Transmittal letter
• Administrative information about the submission
• Other specific information
A. Transmittal Letter :
i) Original Submissions :
• Identification of submission: Original, the type of DMF as classified in Section III, and its subject.
• Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder, and all relevant document numbers.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.
ii) Ammendments :
• Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment.
• A description of the purpose of submission, e.g., update, revised formula, or revised process.
• Signature of the holder or the authorized representative.
• Typewritten name and title of the signer.

B. Administrative information about the submission:

1. DRUG MASTER FILE Presented by : RUSHIKESH D MENDHE Roll no - 511 Mpharm Ist Year (Department of Pharmaceutics) 1 Guided by : Dr. (Mrs.) PALLAVI M. CHAUDHARI Dr. D.Y Patil  College of  Pharmacy Akurdi ,Pune

2. Content : : INTRODUCTION TYPES OF DMF DMF FORMAT & ASSEMBLY DELIVERY OF DMF TO FDA SUBMISSION OF DMF THE MECHANISM OF A DRUG MASTER FILE CTD & ELECTRONIC DMFS UPDATES TO DMF CLOSURE OF A DRUG MASTER FILE APPLICATION OF DMF REFERENCE 2

3. INTRODUCTION : A Drug Master File (DMF) is a submission to the Food and Drug Administration (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. This guideline does not impose mandatory requirements. 3

4. Objectives : Main Objective of the DMF is to support regulatory requirements To prove the quality, safety and efficacy of the medicinal product  4

5. TYPES OF DMF : 5

6. 6

7. DMF FORMAT & ASSEMBLY : The DMF is submitted as Original and Duplicate jackets, collated, assembled, paginated, and jacketed, using covers obtained from the government printing office and a respecifically provided for the DMFs Multiple volumes are numbered, and the paper must be standard paper size Paper length should not be less than 10 inches nor more than 12 inches. Each volume of a DMF should be not more than 2 inches thick 7

8. DELIVERY OF DMF TO FDA : DMF should be submitted at following address : Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901 – B Ammendale Road Beltsville, MARYLAND 20705-1266 USA 8

9. SUBMISSION OF DMF : The DMF must be submitted in two copies, one with a blue cover and one with a red cover. Each page of each copy of the DMF should be dated and consecutively numbered. Each DMF submission should contain : A Transmittal letter Administrative information about the submission Other specific information 9

10. A. Transmittal Letter : i) Original Submissions : Identification of submission: Original, the type of DMF as classified in Section III, and its subject. Identification of the applications, if known, that the DMF is intended to support, including the name and address of each sponsor, applicant, or holder, and all relevant document numbers. Signature of the holder or the authorized representative. Typewritten name and title of the signer. ii) Ammendments : Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment. A description of the purpose of submission, e.g., update, revised formula, or revised process. Signature of the holder or the authorized representative. Typewritten name and title of the signer. 10

11. B. Administrative information about the submission: i) Original Submissions : Names and addresses of the following: - DMF holder. - Corporate headquarters. - Manufacturing/processing facility. - Contact for FDA correspondence. - Agent(s), if any. The specific responsibilities of each person listed in any of the categories in Section a. Statement of commitment. A signed statement by the holder certifying that the DMF is current and that the DMF holder will comply with the statements made in it.   11

12. ii) Amendments Name of DMF holder. DMF number. Name and address for correspondence. Affected section and/or page numbers of the DMF. The name and address of each person whose IND, NDA, ANDA, DMF, or Export Application relies on the subject of the amendment for support. The number of each IND, NDA, ANDA, DMF, and Export Application that relies on the subject of the amendment for support, if known. Particular items within the IND, NDA, ANDA, DMF, and Export Application that are affected, if known. 12

13. The Mechanism of a Drug Master File: A DMF goes through two stages : First, FDA assesses whether all parts of the DMF are included and in the correct order. Once FDA determines that the eDMF is acceptable, it will then undergo an administrative review as discussed above. If the DMF is not acceptable, the holder will be informed. The holder must then satisfactorily respond to any deficiencies for the DMF 13

14. If the DMF passes the administrative review and is found to be acceptable, Office of Pharmaceutical Quality (OPQ) sends an Acknowledgement Letter for review of the technical content. However, if the DMF is not acceptable from an administrative point of view, OPQ sends an Administrative Filing Issues (AFI) letter. The required time for this could be from 2-3 weeks. 14

15. CTD & Electronic DMFs : The CTD(Common Technical Documents) is organized into five modules, those are: Module 1 : References regional information such as forms, cover letter, labeling , and investigational brochures Module 2 : Quality Overall Summary Module 3 : Quality Module 4 : Non-clinical information Module 5 : Clinical information Once a DMF has been submitted in electronic form no paper documnts to be submitted. 15

16. UPDATES TO DMF : DMF are to update by annually, the updates shall be reported as “Annual Report”, and the annual report date will be from on the anniversary date of the original submission. Failure to submit an Annual report to the DMF in past three years, FDA will send “Overdue Notification Letters” (ONLs) to DMF holder. If a DMF holder does not respond to this letter within 90 days with the submission of an Annual Report, the DMF may be closed by the FDA. 16

17. CLOSURE OF A DRUG MASTER FILE : A holder who wishes to close a DMF should submit a request to the Drug Master File Staff stating the reason for the closure. The Agency may close a DMF that does not contain an annual update of persons authorized to incorporate information in the DMF by reference and a list of changes made since the previous annual report. The holder will be notified of FDA's intent to close the DMF. 17

18. Application of DMF : The DMF can be referenced by drug manufacturers in support of their NDAs, ANDAs and clinical trial applications Maintain confidentiality of proprietary information (e.g., Manufacturing procedure) for the holder Permit review of information by reviewers in the Center for Drug Evaluation and Research( CDER) to support applications submitted by one or more applicants 18

19. REFERENCE : Yehaskel Albert, An Overview of Drug Master Files, Pharmaceut Regulatory Affairs 2018, Vol 7,Issue-1; 190 – 198 S. Anusha, N.V.N. Mounica , V. Sharmila, S. Sravika , M. V. Nagabhushanam,Reddy Nagarjuna, ‘Processing And Submission Of Drug Master File’, World Journal of Pharmacy and Pharmaceutical Sciences, Volume 6, Issue 3, 356-366 Official site of FDA - https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs 19