Title: FDA Expectations Type III DMFs
1FDA Expectations Type III
DMFs Drug Master File Workshop March 26,
2002 Arlington, Virginia Frank O. Holcombe, Jr.,
Ph.D. Associate Director
for Chemistry Office of Generic Drugs, OPS/CDER
2Drug Master File What is a DMF? Described at 21
CFR 314.420 A mechanism for providing
information relevant to drug applications but
separate from a drug application. How is it
used? As a source of information
supplementing that found in the drug
application.
3Drug Master File Types of DMF A DMF type is
determined by the subject matter covered in the
submission Type II - Drug Substances,
Intermediates, Starting Materials Type III -
Packaging Materials Type IV - Excipients Type
V - Other
4Drug Master File Qualitative Difference Between
DMF Types Type II - Complete Information may
be Found in NDA DMF not Needed May be
Related Firms Type III - Application Unlikely
to Contain Sufficient Information Probably
Unrelated Firms
5Type III Drug Master File Type III DMFs -
Encompass the Large and Diverse World of
Container Closure Systems Variety of
Materials Variety of End Product Wide Range
of Complexity of Components Manufacturing
Processes
6Packaging Materials Container - Polymer
(plastic), Glass, Metal Polymers - resins,
additives Fabrication - additives, colorants
Closure - Polymers, Elastomers Liners -
Paper, Polymer Seals - Wax, Polymer Delivery
Control Components - Springs, Tubes,
Gaskets Labeling - Adhesives, Solvents
7Packaging Materials Container Closure System
Not Considered in Isolation Part of Drug
Component, Drug Product Universe Solids/Liqu
ids/Solvents Complex Formulations Complex
ing Agents Integral Part of Health Care
8Packaging Materials Drug Product Approval
Based on a Determination that a Drug Product
is Safe and Effective Determination
Includes Evaluation of Container Closure System
as Related to Effect on Quality Attributes of
Drug Product Role of Container Closure System
is to Protect Drug Product from Change
9Type III Drug Master File Final Evaluation of
Packaging Materials is in the Context of Drug
Product Acceptability (DMF is not
approved) Drug Master File is Source of
Information Not Submitted in the Drug
Application Examples - Information
considered Proprietary Formulation/Material
Composition Vendor Supplied Materials
10Packaging Materials Guidance - Container
Closure Systems for Packaging Human Drugs and
Biologics Section III - Qualification
Quality Control of Packaging
Components Necessary Topics include Descripti
on Suitability Quality Control Stability
11Packaging Materials Defines Requirements in
Terms of Suitability of Packaging for Intended
Use Sufficient Information is Necessary to
Demonstrate Adequacy in Areas of -
Protection Compatibility Safety Performan
ce
12Packaging Materials Component Descriptions Which
are Not Useful Liner LDPE or Wax-Coated
Insufficient Information to Review Film
Multisource and/or equivalent - Not
Communicated to Customer Formula/Compositio
n List of Codes or Trade Names - Difficult to
Identify Container Equivalent Material (HDPE) -
Must Still be Shown to Meet Criteria Defined
for Equivalent Material.
13Type III Drug Master File Guidance
Perspective - Location of Information, DMF or
Application Unimportant, because DMF is only
an Adjunct to Application Likely
Availability Suggests Material and Fabrication
be Associated with DMF Product Related Use
with Application Overlap in Areas of
Description and Finished Component
Acceptance
14Type III Drug Master File Guidance
Perspective Reluctant to Prescribe Location
other than in General Terms Proprietary
Information Business Relationships Control
Inference Regulatory Allowance of DMF
15Type III Drug Master File Guidance
Perspective Does (Section V. B.) Describe Items
that Have Been Submitted in DMFs Information
Related to Description Suitability Quality
Control of the Packaging Component/Material
16Type III Drug Master File Expectations -
Information is in Submitted Documents -
Information is Sufficient to Allow
Identification of Potential Issues -
Information is Sufficient to Determine that
Potential Issues were Addressed
17Type III Drug Master File Expectations Standards
- References are Specific - Compliance to the
Standard Is Demonstrated - References are
Current Trade Names - Traceable Vendor Supplied
Materials - Data Sheets Submitted - LOA if
DMF Exists
18Type III Drug Master File Expectations Changes
DMF Holder Responsible for Notifying
Customers Applicant Responsible for
Determination of Appropriate Filing to Drug
Application
19Type III Drug Master File Goal - Review
Environment Having - Easily Understood Roadmap
of Product - Seamless Documentation -
Description of All Materials and Components
Used - Suitability - Quality Systems Used
20Type III Drug Master File Goal Review Outcome
Facilitated by DMF Holder and Drug Applicant
Understanding and Collaboration for
Submission of Necessary Information leading
to Predictable Review Increased Regulatory
Surety about DMF Continuing Drug Approval
Process