Drug Master File

Views:
 
Category: Education
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

PowerPoint Presentation:

PREPARED BY: GUIDED BY: MR. HEM SHAH DR . RASHMIN B. PATEL M.PHARM SEM-II (Q.A) Assistant Professor ENROLLMENT NO: 03 ARCP DEPARTMENT OF QUALITY ASSURANCE A.R.COLLEGE OF PHARMACY,V.V.NAGAR. DRUG MASTER FILE

Contents:-:

Contents:- Introduction Definitions Types of DMF General information Submission to DMF Authorization to refer a DMF Review of drug master file Holder obligations Closure of drug master file Retirement of drug master file European DMF:- 1) Open part 2) Close part Difference between application and DMF Summary References 6/16/2012 ARCP, V.V.NAGAR 2

INTRODUCTION:

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. Objective: To support regulatory requirements and to prove the Quality, Safety and Efficacy of the medicinal product. 6/16/2012 ARCP, V.V.NAGAR 3

PowerPoint Presentation:

REMEMBER There is no legal or regulatory requirement to file a DMF. The information contained in DMF may be used to support an - Investigational New Drug Application (IND), - New Drug Application (NDA), - Abbreviated New Drug Application (ANDA) - An Export Application DMF is NOT a substitute for IND / NDA / ANDA or export application . 6/16/2012 ARCP, V.V.NAGAR 4

PowerPoint Presentation:

The Guideline discuss:- -types of DMF's -the information needed in each type -the format of submissions to a DMF -the obligations of the DMF holder. 6/16/2012 ARCP, V.V.NAGAR 5

BASIC TERMINOLOGIES :

BASIC TERMINOLOGIES 1 . Agency : The Food and Drug Administration. 2. Agent or Representative : Any person who is appointed by a DMF holder to serve as the contact for the holder. 6/16/2012 ARCP, V.V.NAGAR 6

PowerPoint Presentation:

3. Applicant/Customer/Authorised Party : Any person who submits an application or abbreviated application or an amendment or supplement to them to obtain FDA approval of a new drug or an antibiotic drug and any other person who owns an approved application. 4. Holder: A person who owns a DMF. 6/16/2012 ARCP, V.V.NAGAR 7

PowerPoint Presentation:

5. Drug product: A finished dosage form, for example, tablet, capsule, solution, etc. 6. Drug substance: An active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease. 6/16/2012 ARCP, V.V.NAGAR 8

PowerPoint Presentation:

7. Letter of authorization: A written statement by the holder or designated agent or representative permitting FDA to refer to information in the DMF in support of another person's submission. 8. Sponsor: A person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. 6/16/2012 ARCP, V.V.NAGAR 9

TYPES OF DRUG MASTER FILES:

TYPES OF DRUG MASTER FILES TYPE 1 Manufacturing Site, Facilities, Operating Procedures, and Personnel TYPE 2 Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product TYPE 3 Packaging Material TYPE 4 Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation TYPE 5 FDA-Accepted Reference Information 6/16/2012 ARCP, V.V.NAGAR 10

RATE OF DMF FILING AS OF MARCH 2011:

RATE OF DMF FILING AS OF MARCH 2011 6/16/2012 ARCP, V.V.NAGAR 11

Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel :

Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel Type I drug master files are no longer used . Once they were used to describe facilities. It 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, operational layout, equipment capabilities, processing and layout. The description of the site should include actual site address, and a map showing its location with respect to the nearest city. A diagram of major production and processing areas is helpful for understanding the operational layout. 6/16/2012 ARCP, V.V.NAGAR 12

Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product:- :

Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product :- Type II drug master files are required for drug substance, also referred to as active ingredients . A separate DMF is filed for each active ingredient . The DMF should include the brief description of the manufacturing facilities, the address, a contact, phone number and fax number. The manufacturing facility must be registered and the registration number should be listed. 6/16/2012 ARCP, V.V.NAGAR 13

1) Drug Substance Intermediates, Drug Substances, and Material Used in Their Preparation:- :

1) Drug Substance Intermediates, Drug Substances, and Material Used in Their Preparation:- Summarize all significant steps in the manufacturing and controls of the drug intermediate or substance including the critical steps and in process tests performed at those steps. The testing of all raw materials should be provided along with the in process controls, packaging, release, and stability testing. The impurity profile, particle size distribution, organic volatile impurities, and the residual solvent test results have become increasingly important. These tests should reference the current standards of the International Conference on Harmonization and The United States Pharmacopoeia, if not then it should be validated . 6/16/2012 ARCP, V.V.NAGAR 14

PowerPoint Presentation:

2) Drug product Manufacturing procedures and controls for finished dosage forms Submitted in an IND, NDA, ANDA, or Export Application. If cannot be submitted in an IND, NDA, ANDA, or Export Application. Submitted in a DMF. 6/16/2012 ARCP, V.V.NAGAR 15

PowerPoint Presentation:

FOLLOWING GENERAL POINTS INCLUDED IN TYPE II DMFS 1. Manufacturing Section 2. Quality Controls a. Input (Raw/Packaging Materials) b. Intermediates and In-process c. Finished Drug Substance 3. Validations 4. Stability data 5. Impurities 6. Packaging and labeling 6/16/2012 ARCP, V.V.NAGAR 16

PowerPoint Presentation:

MANUFACTURING SECTION IN DMFS (a) Data of inputs (Raw materials/Packaging materials) and Sources List all RMs and PMs with sources Identify Key Starting Materials (KSMs) Complex materials do not qualify as KSMs (b) Manufacturing Process details Synthetic scheme Process flow diagram Detailed Process write up 6/16/2012 ARCP, V.V.NAGAR 17

PowerPoint Presentation:

(2) QUALITY CONTROLS’ SECTION IN DMFS Objective: To ensure quality at every stage of processes. Gradual increase in checks as the process progresses. Specification and test methods. Complete analytical data of study batches. Sampling procedures adopted. Analytical Reference Standard (ARS). Test batches vs. ARS. 6/16/2012 ARCP, V.V.NAGAR 18

PowerPoint Presentation:

(3) ANALYTICAL VALIDATIONS Done accordance to reference guidelines: ICH Q 2A and B. Validation of In-house methods . Validation of Pharmacopoeial methods. 6/16/2012 ARCP, V.V.NAGAR 19

PowerPoint Presentation:

(4) IMPURIRIES’ SECTION Objective: To prove that quality obtained is by design of process, not by chance. Justification for limits applied. Assay/Impurities’ determination. Forced Degradation Studies. Three consecutive commercial scale batches. Accelerated studies. Long term studies. Study include all susceptible parameters. All validated methods. Labeled unidentified impurities. 6/16/2012 ARCP, V.V.NAGAR 20

PowerPoint Presentation:

(5) PACKING AND LABELING Detailed description of complete packing configuration. Food-grade certification of inner-most Packing Materials. Stability sample packing must be identical. Specification and Test methods for all Packing Materials. Specimen label must be submitted. Clear mention of recommended storage conditions. 6/16/2012 ARCP, V.V.NAGAR 21

:

TYPE III : Packaging Material Contents:- Its components and composition. Packaging material intended for which use. Names of the suppliers or fabricators of the components used in preparing the packaging material. Acceptance specifications. Toxicological data on these materials. 6/16/2012 ARCP, V.V.NAGAR 22

PowerPoint Presentation:

BUT REMEMBER THAT, Most of the type III DMF holders are ISO (International Organization of Standardization) certified , but the rules for ISO and those of CDER are not always the same. The needs of the applicant should also be considered. Responsibility for compatibility and safety of packaging components in finished drug product is the responsibility of the AUTHORISED PARTY(AP). It is not the responsibility of DMF HOLDER . 6/16/2012 ARCP, V.V.NAGAR 23

PowerPoint Presentation:

TYPE IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation Each additive should be identified by its method of manufacture, release specification, and testing methods. Toxicological data would be included. The official compendia and FDA regulation for color additives, direct food additives, indirect food additives, and food substances may be used as sources for release tests, specifications, and safety. 6/16/2012 ARCP, V.V.NAGAR 24

PowerPoint Presentation:

TYPE V : FDA Accepted Reference Information FDA discourages the use of Type V DMFs for miscellaneous information, duplicate information, or information that should be included in one of the other types of DMFs. 6/16/2012 ARCP, V.V.NAGAR 25

PowerPoint Presentation:

To submit the data which is not covered in type I to IV DMF A holder must first submit a letter of intent to the drug master file staff FDA will then contact the holder to discuss the proposed submission 6/16/2012 ARCP, V.V.NAGAR 26

PowerPoint Presentation:

General Information and Suggestions a). Environmental Assessment Type II, Type III, and Type IV DMF's should contain a commitment by the firm that its facilities will be operated in compliance with applicable environmental laws. b). Stability Stability study design, data, interpretation, and other information should be submitted, when applicable, as outlined in the " Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics. " 6/16/2012 ARCP, V.V.NAGAR 27

PowerPoint Presentation:

C) Format, Assembly, and Delivery An original and duplicate are to be submitted for all DMF submissions. The original and duplicate copies must be collated, fully assembled, and individually jacketed. Each volume of a DMF should in general, be not more than 2 inches thick. For multi volumes submissions, number each volume. 6/16/2012 ARCP, V.V.NAGAR 28

PowerPoint Presentation:

U.S. standard paper size (8-1/2 by 11 inches) is preferred. Paper length should not be less than 10 inches nor more than 12 inches. However, it may occasionally be necessary to use individual pages larger than standard paper size to present a floor plan, synthesis diagram, batch formula, or manufacturing instructions 6/16/2012 ARCP, V.V.NAGAR 29

PowerPoint Presentation:

6/16/2012 ARCP, V.V.NAGAR 30

PowerPoint Presentation:

D). Delivery to FDA . Drug Master File submissions and correspondence should be addressed as follows: Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901-B Ammendale Road Beltsville, MARYLAND 20705-1266 USA. 6/16/2012 ARCP, V.V.NAGAR 31

PowerPoint Presentation:

SUBMISSIONS TO DRUG MASTER FILES : Each DMF submission should contain a transmittal letter, administrative information about the submission, and other specific information. The DMF must be in the English language . Whenever a submission contains information in another language, an accurate certified English translation must also be included. Each page of each copy of the DMF should be dated and consecutively numbered. An updated table of contents should be included with each submission. 6/16/2012 ARCP, V.V.NAGAR 32

PowerPoint Presentation:

A. Transmittal Letters: The following should be included: A.1. Original Submissions A. Identification of submission: Original, 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. C. Signature of the holder or the authorized representative. D. Type written name and title of the signer. 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. Typewritten name and title of the signer . 6/16/2012 ARCP, V.V.NAGAR 33

PowerPoint Presentation:

B. Administrative Information B.1. Original Submissions A. Names and addresses of the following: DMF holder. Corporate headquarters. Manufacturing/processing facility. Contact for FDA correspondence. Agent(s), if any. B. The specific responsibilities of each person listed above. C. 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. 6/16/2012 ARCP, V.V.NAGAR 34

PowerPoint Presentation:

B.2. 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. 6/16/2012 ARCP, V.V.NAGAR 35

V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE :

V. AUTHORIZATION TO REFER TO A DRUG MASTER FILE A. Letter of Authorization ( LoA ) to FDA: The letter of authorization should include the following: The date. Name of DMF holder. DMF number. Name of person(s) authorized to incorporate information in the DMF by reference. Specific product(s) covered by the DMF. 6/16/2012 ARCP, V.V.NAGAR 36

PowerPoint Presentation:

Section numbers and/or page numbers to be referenced. Statement of commitment that the DMF is current and that the DMF holder will comply with the statements made in it. Signature of authorizing official. Typed name and title of official authorizing reference to the DMF. 6/16/2012 ARCP, V.V.NAGAR 37

PowerPoint Presentation:

LETTER OF AUTHORIZATION (LOA) US FDA Send a letter to remind holder obligations DMF HOLDER 1 copy of LOA to the APPLICANT Send 2 copies of LOA to the FDA The applicant submits THIS copy of LOA in their Application. 6/16/2012 ARCP, V.V.NAGAR 38

PowerPoint Presentation:

General Format for LOA. Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901-B Ammendale Road Beltsville MD 20705-1266 Re: DMF #XXXXX, Type III Hairless Cap Liner Dear Sir or Madam: By copy of this letter, DRUG HOLDER “X” is authorizing APPLICANT ABC to incorporate by reference into their NDA/ANDA/IND/SUPPLEMENTAL NDA our DMF #XXXXX, DATE, Section WXYZ, Pages 105-115. We hereby authorize your office to review the aforementioned specific information in DMF #XXX in considering the application filed by APPLICANT ABC. The component/material furnished will be manufactured in accordance with DMF #XXXX and in compliance with CGMPs. This DMF holder states that DMF #XXXXX is current and will comply with all statements made within it. Sincerely, XYZ . 6/16/2012 ARCP, V.V.NAGAR 39

PowerPoint Presentation:

B. Copy to Applicant, Sponsor, or Other Holder The holder should also send a copy of the letter of authorization to the affected applicant, sponsor, or other holder who is authorized to incorporate by reference the specific information contained in the DMF. 6/16/2012 ARCP, V.V.NAGAR 40

DRUG MASTER FILE REVIEW:- :

DRUG MASTER FILE REVIEW:- A DMF IS NEVER APPROVED OR DISAPPROVED . The agency will review information in a DMF only when an IND sponsor, an applicant for an NDA, ANDA, or Export Application, or another DMF holder incorporates material in the DMF by reference. As noted, the incorporation by reference must be accompanied by a copy of the DMF holder's letter of authorization. 6/16/2012 ARCP, V.V.NAGAR 41

PowerPoint Presentation:

REVIEWER When reviewer receives an application (IND/NDA/ANDA) that references DMF Requests the DMF from the CDR (central document room) After getting DMF, the Reviewer starts the review procedure If Reviewer found any deficiency in the content of DMF, The APPLICANT is also notified but, the nature of the deficiencies is not communicated to the applicant. The DETAILED DEFICIENCIES are communicated to the holder. HOLDER should submit the REQUESTED INFORMATION to the DMF in response to the agency's deficiency letter along with transmittal letter having subject matter. 6/16/2012 ARCP, V.V.NAGAR 42

HOLDER OBLIGATIONS :

HOLDER OBLIGATIONS Notice Required for Changes to a Drug Master File . H older must notify each affected applicant or sponsor who has referenced its DMF of any pertinent change in the DMF (21 CFR 314. 420(c)). B. Listing of Persons Authorized To Refer to a Drug Master File The updated list should contain the holder's name, DMF number, and the date of the update. 6/16/2012 ARCP, V.V.NAGAR 43

PowerPoint Presentation:

Any person whose authorization has been withdrawn during the previous year should be identified under a suitable caption. If the list is unchanged on the anniversary date , the DMF holder should also submit a statement that the list is current. C. Annual Update The holder should provide an annual report on the anniversary date of the original submission. If the subject matter of the DMF is unchanged, the DMF holder should provide a statement that the subject matter of the DMF is current. 6/16/2012 ARCP, V.V.NAGAR 44

PowerPoint Presentation:

Failure to update can cause delays in FDA review of a pending IND, NDA, ANDA or any amendment or supplement to such application; and FDA can initiate procedures for closure of the DMF. D. Appointment of an Agent When an agent is appointed, the holder should submit a signed letter of appointment to the DMF giving the agent's name, address, and scope of responsibility (administrative and/or scientific). E. Transfer of Ownership The letter should include the following: - Name of transferee - Address of transferee 6/16/2012 ARCP, V.V.NAGAR 45

PowerPoint Presentation:

Name of responsible official of transferee - Effective date of transfer - Signature of the transferring official - Typewritten name and title of the transferring official. The new holder should submit: - A letter of acceptance of the transfer - An update of the information contained in the DMF, where appropriate. - Any change relating to the new ownership (e.g., plant location and methods) should be included. 6/16/2012 ARCP, V.V.NAGAR 46

CLOSURE OF A DRUG MASTER FILE :

CLOSURE OF A DRUG MASTER FILE A holder 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 6/16/2012 ARCP, V.V.NAGAR 47

DMF RETIREMENT PROCEDURE:- :

DMF RETIREMENT PROCEDURE:- If a DMF has had no activity (amendment or annual report) in three years FDA will initiate retirement procedure Note: LOA does not count for activity. FDA sends overdue notice to holder and/or agent using most recent address. If no response in 90 days, one copy of DMF is sent to Federal Records Center (FRC) and the other is destroyed. 6/16/2012 ARCP, V.V.NAGAR 48

PowerPoint Presentation:

EUROPEAN DRUG MASTER FILE 6/16/2012 ARCP, V.V.NAGAR 49

PROCEDURE FOR ACTIVE SUBSTANCES :

PROCEDURE FOR ACTIVE SUBSTANCES An Active Substance Manufacturer (ASM) RESTRICTED PART OF DMF APPLICANT’S PART OF DMF OPEN PART CLOSED PART Content of Drug Master File 6/16/2012 ARCP, V.V.NAGAR 50

PowerPoint Presentation:

APPLICANT’S PART OF DMF OPEN PART ( AVAILABLE TO APPLICANT) Active substance manufacturer Supplies information to the applicant This information includes: outline of the manufacturing method impurities originating from the manufacturing method, isolation procedure and degradation information on the toxicity of specific impurities 6/16/2012 ARCP, V.V.NAGAR 51

PowerPoint Presentation:

The applicant’s part of a DMF is provided by the ASM to the applicant directly and becomes part of the application for marketing authorization. The applicant’s part of the DMF is still a confidential document which cannot be submitted to third parties without the written agreement of the ASM. 6/16/2012 ARCP, V.V.NAGAR 52

PowerPoint Presentation:

ASM RESTRICTED PART OF DMF CLOSED PART ( NOT AVAILABLE TO THE APPLICANT) IT INCLUDES: Detailed information about… Individual steps of the manufacturing method such as reaction conditions, temperature , etc. Validation and evaluation data for certain critical steps of the manufacturing method, etc 6/16/2012 ARCP, V.V.NAGAR 53

PowerPoint Presentation:

6/16/2012 ARCP, V.V.NAGAR 54

PowerPoint Presentation:

APPLICATIONS DRUG MASTER FILES 1. comes under the regulatory states and must be filed. 1. Not mandatory and don’t come under reg. requirements . 2. Each application and its supplement are entered into a common database. 2. DMF are entered into database according to their types. 3. Submitted to a particular review division 3. Submitted to CDER 4. Assignment to a reviewer and each submission has a due date. 4. No assignment too reviewer, no due dates. 5. Review procedure is different than DMF . If anniversary date of annual update is missed, FDA will send a reminder. 5. DMFs are review only when referenced by application . If anniversary date of annual update is missed, FDA will not send reminder. 6/16/2012 ARCP, V.V.NAGAR 55

PowerPoint Presentation:

CHANGES IN DMF SYSTEM :- Over the past decade, there have been some changes in the DMF system to help make it work better. However some things remain the same. Changes in the DMF System and Procedures (Internal changes):- Creation of Review Cover Form Creation of Type II Review Format Implementation of Re-review Policy Creation of Central Review File Revision of Database View Changes in the DMF System and Procedures (External changes):- Elimination of Type I DMFs Post-Approval Changes Guidance and Creation of DMF List Website Creation of DMF QUESTION Establish Position of DMF Expert 6/16/2012 ARCP, V.V.NAGAR 56

PowerPoint Presentation:

UNCHANGED THINGS OF DMF:- No review of DMF on receipt of it. Review only when referenced in application. All of the DMF is still confidential. DMFs are neither approved nor disapproved. The holder still has the responsibility to notify customer of changes. 6/16/2012 ARCP, V.V.NAGAR 57

SUMMARY:- :

SUMMARY:- The DMF system presents challenges for both the industry and the FDA. Some of the changes have made the system smother (for both industry and FDA) Problems can be minimized: if holders and applicants Understand their responsibilities Adhere to the regulations Follow the recommendations in the Guidance. Communicate with each other 6/16/2012 ARCP, V.V.NAGAR 58

References:-:

References:- www.fda.gov www.fda.gov/cder/guidance/dmf.html www.emea.eu.int/htms/vet http://www.fda.gov/cder/Offices/ONDQA/presentations/shaw.pdf 6/16/2012 ARCP, V.V.NAGAR 59

PowerPoint Presentation:

60 6/16/2012 ARCP, V.V.NAGAR

authorStream Live Help