Difference european drug master file & us drug master file

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1. GUIDED BY:- Mrs. FALGUNI TANDEL Assist. Prof. PREPARED BY:- DINESH KUMAR M.Pharm.:-2 nd SEM. QA. I ST Shift Enroll. No.:- 132330804003 DIFFERENCE: EUROPEAN DRUG MASTER FILE & US DRUG MASTER FILE

2. TABLE OF CONTENTS :- INTRODUCTION UNITED STATE DMF TYPE OF USDMF FORMAT OF USDMF REVIEW OF USDMF SUBMISSIONS TO DRUG MASTER FILES EUROPEAN DMF CONTENT OF THE ACTIVE SUBSTANCE MASTER FILE USE OF THE ACTIVE SUBSTANCE MASTER FILE PROCEDURE ADVANTAGE OF DMF REFERENCES

3. INTRODUCTION:- DMF is a document prepared by a pharmaceutical manufacturer and submitted to the appropriate regulatory authority in the intended drug market. DMF is a document containing complete information on an API / drug substance, intermediate of drug substance, packaging material, excipient or drug product. The DMF contains complete information on quality aspect such as chemistry, manufacture, purity, impurity profile, packaging, stability etc.

4. UNITED STATE DMF:- In the United States, DMFs are submitted to the Food and Drug Administration (FDA). OBJECTIVE :- To support regulatory requirements. To prove the quality, safety and efficacy of the medicinal product for obtaining an Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA),and an Export Application.

5. TYPE OF USDMF:- In US there are five types of DMF's: Type I Manufacturing Site, Facilities, Operating Procedures, and Personnel Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product Type III Packaging Material Type IV Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation Type V FDA Accepted Reference Information

6. Type I Manufacturing Site, Facilities, Operating Procedures, and Personnel Its is recommended for a person outside of the United States to assist FDA in conducting on site inspections of their manufacturing facilities. The DMF should describe the manufacturing site, equipment capabilities, and operational layout. The site should include actual site address, and a map showing its location with respect to the nearest city.

7. Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product It should be limited to a single drug intermediate, drug substance, drug product, or type of material used in their preparation. It Summarize all significant steps in the manufacturing and controls of the drug intermediate or substance. Type III Packaging Material Each packaging material should be identified by the intended use, components, composition, and controls for its release.

8. Data supporting the acceptability of the packaging material for its intended use should also be submitted. 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. Type V FDA Accepted Reference Information It consists miscellaneous information, duplicate information, or information that should be included in one of the other types of DMF's.

9. FORMAT OF DMF:- Different countries have different requirement for format and submission of DMF. The United States Food and Drug Administration require two copies of each Type DMF in the CTD format, but not in CTD module form. FDA requires continuous document in the CTD format. There are no different sections as an "Applicant's Part" or "Restricted Part" such as Europe.

10. REVIEW OF DMF:- After receiving DMF is reviewed for administrative content. This may take 2-3 weeks. If DMF is ok with administrative content then acknowledgement letter will be issued, and notice has been sent to holder of the DMF. If DMF is not ok with administrative point of view, the holder will be notified with letter of deficiency.

11. SUBMISSIONS TO DRUG MASTER FILES:- A. Transmittal Letters:- The following should be included: A.1. Original Submissions:- a. Identification of submission: the type of DMF as classified in Section III, and its subject. b. 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.

12. A. 2. Amendments a. Identification of submission: Amendment, the DMF number, type of DMF, and the subject of the amendment. b. A description of the purpose of submission, e.g., update, revised formula, or revised process. c. Signature of the holder or the authorized representative. d. Type written name and title of the signer.

13. B. Administrative Information:- Administrative information should include the following: B.1. Original Submissions:- a. Names and addresses of the following: (1) DMF holder. (2) Corporate headquarters. (3) Manufacturing/processing facility. (4) Contact for FDA correspondence. (5) Agent(s), if any.

14. b. The specific responsibilities of each person listed in any of the categories in Section a. c. Statement of commitment.

15. B.2. Amendments:- a. Name of DMF holder. b. DMF number. c. Name and address for correspondence. d. Affected section and/or page numbers of the DMF.

16. e. The name and address of each person whose IND, NDA, ANDA, DMF, or Export Application relies on the subject of the amendment for support. f. The number of each IND, NDA, ANDA, DMF, and Export Application that relies on the subject of the amendment for support, if known. g. Particular items within the IND, NDA, ANDA, DMF, and Export Application that are affected, if known.

17. EUROPEAN DMF:- Commonly known as the European Drug Master File (EDMF). ASMF is the older name of EDMF. The content and the format for drug master file used in United States differs from that used in European Countries to obtain market authorization (MA). OBJECTIVE:- To support regulatory requirements of a medicinal product to prove its quality, safety and efficacy. This helps to obtain a Marketing Authorization grant .

18. CONTENT OF THE ACTIVE SUBSTANCE MASTER FILE:- The overall content of the EDMF should contain detailed scientific information to Applicants for Marketing Authorizations for Medicinal Products in the Member States of the European Union. EDMFs linked to human medicinal products should be presented in the form of the Common Technical Document (CTD). EDMFs for veterinary medicinal products may also be presented in CTD form after consultation with the Competent Authorities/EMEA.

19. The scientific information in the EDMF should be physically divided into two separate parts, namely the Applicants Part (AP) and the Restricted Part (RP). The AP contains the information that the EDMF holder regards as non-confidential to the Applicant/MA holder. That can be submitted by anyone to third parties without the written consent of the EDMF holder. In all cases the AP should contain sufficient information.

20. The RP contains the information that the EDMF holder regard as confidential. The RP may contain the remaining detailed information on the individual steps of the manufacturing method (reaction conditions, temperature, validation and evaluation data of critical steps).

21. Use of the Active Substance Master File Procedure:- The ASMF procedure can be used for the following active substances (except biological active substances) A. New active substances. B. Existing active substances not included in the European Pharmacopoeia. Pharmacopoeial active substances included in the Pharmacopoeia Europe. The ASMF procedure cannot be used for biological active substances.

22. The ASMF holder should submit to the Applicant/MA holder:- a copy of the latest version of the AP. a copy of the QOS on the latest version of the AP. a copy of the Letter of Access where this letter has not been submitted earlier for the product concerned.

23. ADVANTAGE OF DMF:- DMF maintain confidentiality of proprietary information (e.g. manufacturing procedure) for the holder. Number of applicants can refer the information. Finished product manufacturing companies consider API manufacturer having DMF number / CEP (certificate of suitability) more reliable in terms of quality and regulatory stand.

24. REFERENCES:- http://en.wikipedia.org/wiki/Drug_Master_File http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129994.pdf http://www.tga.gov.au/pdf/euguide/qwp22702rev1.pdf http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm122886.htm http://pharmatreasures.blogspot.in/2011/10/drug-master-file-dmf.html