Drug Master File (DMF)-USA

Facilitator:

Dr.N.Vishal Kumar Guptha

Asst Professor,

Dept of Pharmaceutics,

J.S.S.C.P, Mysuru.

Submitted by:LakshmiKanth Reddy.P

1st M.PharmaDept of Pharmaceutical analysis

J.S.S.C.P, Mysuru

4/26/2015 1

What is drug master file ?

• Drug Master File (DMF) is a document prepared by a pharmaceutical manufacturer and submitted to the appropriate regulatory authority in the intended drug market.

• However, the document provides the regulatory authority with confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

• Typically, a DMF is filed when two or more firms work in partnership on developing or manufacturing a drug product.4/26/2015 2

• The DMF filing allows a firm to protect its intellectual property from its partner while complying with regulatory requirements for disclosure of processing details.

• API manufacturers with a large number of DMFs are often considered more reliable in terms of quality, regulatory standing, and ability to meet Current Good Manufacturing Process (cGMP) requirements.

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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

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What does the DMF contains?

• Drug Master File (DMF) is a document

containing complete information on an

Active Pharmaceutical Ingredient (API) or

finished drug dosage form.

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• The DMF contains factual and complete information on a drug product's chemistry, manufacture, stability, purity, impurity profile, packaging, and the cGMP status of any human drug product.

DMF CONTAINS

Chemistry

Manufacture

Stability cGMP

Packaging

ImpurityProfile

Purity

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DRUG MASTER FILE - USA

• In the United States, DMFs are submitted to

the Food and Drug Administration (FDA).

• The Main Objective of the DMF is to support

regulatory requirements and to prove the

quality, safety and efficacy of the medicinal

product for obtaining an Investigational New

Drug Application (IND), New Drug Application

(NDA), An Abbreviated New Drug Application

(ANDA), another DMF, Or an Export

Application.

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Types of DRUG MASTER FILE:

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 Information4/26/2015 8

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 lay out, area, map equipment capabilities - model, make, capacity operational layout - QA, QC, R&D

A diagram of major production and processing areas is helpful for understanding the operational layout.

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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

• 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.

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•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

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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.

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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.

• Toxicological data on these materials

would be included under this type of

DMF, if not otherwise available by cross

reference to another document.

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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.

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4/26/2015 15

Description DMF Type No of DMFs

Manufacturing site, facilities, operating procedures, and personnel

I 1,826

Drug substance, drug substance intermediate, and materialsused in the preparation, or Drug Product

II 15,230

Packaging Material III 4,511

Excipient, Color, Flavor, Essence or material used in theirpreparation

IV 1,749

FDA Accepted reference information V 355

Blanks Blanks 1,969

GRAND TOTAL 25,640

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type 18%

type 266%

type 39%

type 48%

type 59%

SUBMISSIONS REQUIRMENTS TO

DRUG MASTER FILES

• Each DMF submission should contain a transmittal letter, administrative information about the submission, and the specific information to be included in the DMF.

• 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.

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A. Transmittal Letters

• Original Submissions

• Amendments

B. Administrative Information

• Original Submissions

• Amendments

Cont…!!!

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A. Transmittal Letters (The following should be included)

• Original Submissions

a. Identification of submission: Original, the type of DMF 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. Typewritten name and title of the signer.

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• 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.

Transmittal Letters (The following should be included)

Cont…

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B. Administrative Information (The following should be included)

• 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.

B. The specific responsibilities of each person listed in any of the categories in Section a.

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.

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Administrative Information (The following should be included)

• 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.

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.

Cont..!!

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Steps for Filing A DMF:

1. Set the document margins at 3/4 inch for the left (at least) and 1/2 inch for the right.

2. Print the transmittal page, administrative information and DMF information on standard letter-size paper. If a larger sheet of paper is required for a diagram or schematic, fold the sheet and attach it to a letter-sized page in a manner that will allow for the page to be opened and refolded. At a maximum, each volume of a DMF should be no more than 2 inches thick.

3. Number multiple volumes for one submission according to the total number of volumes (if more than one). (For example, 1 of 3, 2 of 3, etc.)

4. Sign all documents requiring signature (only if you are the DMF holder or authorized representative).

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Cont…

5. Copy and collate the document; FDA requires you submit both.

6. Punch documents with a standard hole-punch.

7. Cover each original and copy of each volume with a document jacket. Prepare the submission for shipping and mail to:

Drug Master File Staff

Food and Drug Administration

5901-B Ammendale Rd.

Beltsville, MD 20705-1266

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In General:

To submit the data

First select type of DMF I.e. type I to IV DMF

A holder must first submit A LETTER OF

INTENT to the drug master file staff

FDA then will contact the holder to discuss

the proposed subbmission.4/26/2015 25

Transfer of Ownership

To transfer ownership of a DMF to another party, the holder should so notify FDA and authorized persons in writing. The letter should include the following:

– Name of transferee

– Address of transferee

– 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 and 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.

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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 request should include a statement of holder's obligations.

• 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.

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Reference:

1. Guideline for Drug Master Files, Centre for Drug Evaluation and Research, Food and Drug Administration, Department of Health and Human Services, Office of Drug Evaluation I (HFD-100), 5600 Fishers Lane, Rockville, Maryland 20857, September 1989.

2. Guidelines for drug master files, United States, Food and Drug Administration, Retrieved 2009-09-19. DMF search engine. FDA: Guideline for drug master file

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THANK YOU…!!!!4/26/2015 29

http://www.registrarcorp.com/fda-drugs/master-files/registration.jsp?lang=en

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