What is type 4 DMF? DMF (Drug Master file) word is common to all in pharmaceutical field. This phenomena of DMF is origin of US FDA. DMF’s are submissions to US FDA which contains, confidential detailed information about facilities, processes, material used in manufacturing, processing, packaging and storing of human drug products. Advantage of DMF process is, Allow parties to use as reference material without disclosing confidential material content. They are not required by statue organisation FDA neither approves or disapproves, FDA uses as review material in the application submissions of NDA’s, ANDA’s, IND’s, and BLAs. DMF is systematic structured document and its structure is guide for people who prepares and submits the same. Various information is available of web pages for, List of DMF’s, Types of DMFs, Submission resources, Templates and related information. US FDA is also preparing FAQ also on DMF. Contact email is dmfquestion@fds.hhs.gov Physical media submission is only accepted if volume is more than 10GB. DMF for 3938 is used for submission of DMF. If one is not familiar with this preparation then it is highly recommended to hire US FDA consulting firm with relevant experience for proper documentation and submission. Our main topic is What is type 4 DMF? So let us understand various types of DMF’s. Type I DMF: This contains manufacturing site facilities, operating procedure and personnel. This will make FDA person understand about sites outside of USA. Site information will have detailed layout, Equipment available. Document also gives physical address of site along with map. Type II DMF: This contains information on single drug substance, drug substance intermediate, Material used in the preparation of drug substance, Holder describes all steps involved in the manufacturing. This information contains chemistry, manufacturing, and controls used, along with analytical data for methods validation. Type III DMF: This contains information on packaging material. Description of each material information on its use and composition. It is also required to submit data of suppliers a well as data to support the acceptability of packaging material. Type IV DMF: This contains information on drug product other content like excipients, colourant, flavouring agent. All these additives must be described as per their manufacturing methos, testing methods and specification. It is also required to submit toxicological data related to these materials. Type V DMF: This contains FDA accepted referenced information. This Type V is to be used when all four types are not relevant. TYPE V should not be used to duplicate the information given in other four types. Type IV DMF is document about excipient manufacturer to submit confidential information that may be needed by agency in reviewing NDA (New drug application) for drug product which contains that
excipient. NDA holders are required to submit DMF reference letter from excipient manufacturer. FDA authority thus accesses DMF information and reviews them for NDA application. Guideline suggests following, 1 Introduction 2. Definitions of various terms used in document like agency, holder, sponsor, drug product, drug substance, environment. Each DMF submission should contain transmittal letter. DMF must be in English only. If this is in other language then certified translator is required. Each page of document must be dated and consequently numbered. Transmittal letter should have information about original submission. Identification of an applicant, name addresses of each sponsor signature of holder or authorised representative. Amendment’s detail. Description of the purpose of amendment. Signature of holder or an authorised representative. DMF type IV must also contain commitment of holder to state that holder has commitment that unit and facilities will be operated as per applicable environmental laws. Stability: Study design data interpretation. Original and duplicate copies shall be submitted. Standard paper size of 8.5 by 11 inches is preferred. Some document can be much bigger like floor plan drawing. Left margin of at least0.75 inch should be left out this is for making hole and for binding purpose. Delivery address: Drug master file staff, Food and drug administration, 5901 B Ammendale road, Beltsville, MD 20705-1266. Required delivery charges must be paid in advance. Letter of authorisation to FDA. This is to permit FDA to refer the DMF. Copy to applicant, sponsor or another holder. The letter of authorisation is also sent to affected applicant, sponsor or another holder. Original DMF document is first reviewed for its content and format for meeting its minimum requirement, if it does then FDA assigns DMF number and acknowledge the same. Notice is required to all affected parties, sponsor and another holder for any changes made. Update: holder should update the list in the annual update. Updated list should contain holder’s name, DMF number and date of update. Any person whose authorisation has been withdrawn in previous year, should be captured under suitable caption. If list is unchanged then it must mention that list is current. An appointment of an agent: Holder should submit signed letter of appointment to the DMF giving name address and scope of responsibility. Transfer of ownership: The holder should notify to FDA and authorised person in writing. The new holder should submit a letter of acceptance.
Closure of DMF: Holder who wants to close the DMF, should submit request to DMF staff stating reason for closure. There should also be a statement that holder’s obligation as detailed in section have been fulfilled.