# Presentation: 722248

## FDA/Industry Container Closure Guidance Training SessionOctober 26, 1999

**TYPE III DRUG MASTER FILES **
**James D. Vidra, Ph.D.**
**CDER**

## Outline

- Location of packaging information
- Types of DMFs
- Purpose of a Type III DMF
- Review of a Type III DMF
- Contents of a Type III DMF
- Table 3
- Letters of authorization (LOA)
- Obligations of a Type III DMF holder
- Summary

## Location of Packaging Information

- The container closure system should be identified and described within the application
- Information on packaging components or materials may be located either within the application or in a Type III DMF

## Types of DMFs

- I	Manufacturing facilities
- II	Drug substance or drug product manufacturers
- III	Packaging materials
- IV	Excipients, colorants, etc.
- V	FDA-accepted reference information

## Purpose of a Type III DMF

- Provide confidential detailed packaging material information in support of an application (IND, NDA, ANDA, BLA)
- Permitted under 21 CFR 314.420
- Cannot substitute for an application

## Review of Type III DMFs

- A letter of authorization (LOA) is required
- Information is reviewed to support the approval of an application, another DMF or a supplement or amendment to any of these
- DMF may provide information on one or more packaging components in its entirety

## Review (cont’d)

- DMF deficiencies are sent to the DMF holder only*
- Applicant is notified that DMF is deficient*
- *CDER Guideline for Drug Master File, September 1989

## Examples

_**Location: DMF**_** **
**Individual containers**
**Pressurized containers**
**Bulk containers**
**Cap Closures**
**Liners**
**Innerseals**
**Resins / Elastomers**
**Valve Closure System**

_**Location: Application**_
**Complete container closure system**

## Contents of a Type III DMF*

**Description of intended use**
**Components / composition**
**Acceptance specifications**
**Release specifications for finished material or component****	****	**
**Provide the supplier / fabricator name & address**
**Data supporting acceptability **
**Toxicological data if appropriate**
***CDER Guideline for Drug Master File, September 1989**

## Information re: a Container Closure System (Guidance for Industry : Container Closure Systems for Packaging Human Drugs and Biologics, May 1999)

**Information re: a Container Closure System (Guidance for Industry : Container Closure Systems for Packaging Human Drugs and Biologics, May 1999)**

## Examples of Schematics 

**Drawings of a bottle**
**Diagrams of multiple layered materials**
**Tamper- & child-resistant closures**
**Metered dose valves**

## Example: Relationship between Application & DMFs

## Letters of Authorization

- FDA to refer to specific DMF information in support of a third party’s application
- A copy must be provided in the application
- Duplicate copies should be included in the DMF

## Example of an LOA

- Drug Master File Staff				Date
- Food And Drug Administration
- 12229 Wilkins Ave.
- Rockville, Maryland  20852
- 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 #XXXX 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,
- 				John Doe
- 				Director, Regulatory Affairs

## DMF Holder Obligations

- Notify applicants of any pertinent changes (21 CFR 314.420 (c))
- Annual update should contain:
- List of companies/persons authorized reference to DMF (21CFR314.420(d))
- All amendments incorporated since the previous update
- Foreign DMF holders are encouraged to engage a U.S. Agent
- Notify all transfer of ownerships

## Summary

- Location of packaging information
- Types, purpose, review, and contents of a Type III DMF
- Table 3
- Letters of authorization
- Obligations of a Type III DMF holder