Transcript Document

FDA Provisions
GUIDELINE FOR DRUG MASTER
FILES
GUIDELINE FOR DRUG MASTER FILES
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This guideline is intended to provide DMF holders
with procedures acceptable to the agency for
preparing and submitting a DMF
The guideline discusses
types of DMF's,
the information needed in each type,
the format of submissions to a DMF,
the administrative procedures governing review of
DMF's, and
the obligations of the DMF holder.
GUIDELINE FOR DRUG MASTER FILES
DMF's are generally created to allow a party
other than the holder of the DMF to
reference material without disclosing to
that party the contents of the file.
Open part
Closed part
Definitions
Agency means the FDA
Agent or representative means any person who is
appointed by a DMF holder to serve as the contact
for the holder
Applicant means 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
Holder means a person who owns a DMF
Letter of authorization means 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
Generic Drug
 A generic drug is identical, or bioequivalent to a
brand name drug in dosage form, safety, strength,
route of administration, quality, performance
characteristics and intended use.
 A generic is similar in its therapeutic properties to a
branded formulation and comes into the market
when the latter goes off patent.
Generic Market
The opening up of the generics market presents
attractive opportunities for Indian bulk drug
manufacturers
The advantage of targeting the US market is the
price realisation for generics. The price is much
higher compared to what companies would get in
the domestic market.
Indian manufacturers have filed a higher number of
Drug Master Files (DMF) with the US FDA in
recent times
DMF (Drug Master File)
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
A DMF filing is required for companies to supply
bulk drugs to the US market
DMF (Drug Master File)
Technical contents of a DMF are reviewed in
connection with the review of an IND, NDA,
ANDA, or an Export Application.
The information contained in the DMF may be used
to support an Investigational New Drug Application
(IND), a New Drug Application (NDA), an
Abbreviated New Drug Application (ANDA),
another DMF, an Export Application, or
amendments and supplements to any of these
A DMF is NOT a substitute for an IND, NDA,
ANDA, or Export Application
DMF filings
About 10 Indian companies have made more than
10 DMF filings up to the second quarter of 2003
DMF filings
Cipla
53
Ranbaxy
48
Dr Reddy’s
44
Wockhardt
32
IPCA
19
Unichem
19
Neuland
16
Cadila
15
Lupin
14
Shasun
12
Types of DMF filings
Type I Manufacturing Site, Facilities, Operating
Procedures, and Personnel (Plant information)
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 Information
(other clinical toxicological and sterile
manufacturing information)
Abbreviations
“A” = Active
“I” = Inactive
“N” = Not an assigned number
“P” = DMF Pending Filing Review
Submissions to the Drug Master Files
Each DMF submission should contain a
 transmittal letter
 administrative information about the
submission
 the specific information to be included in the
DMF (technical information)
The DMF must be in the English language
Transmittal Letters
 Original Submissions
 Amendments
Administrative Information
 Original Submissions
 Amendments
Type II Drug substance, drug substance
intermediate, and Material Used in Their
Preparation, or Drug Product
A Type II DMF should, in general, be
limited to a single drug intermediate, drug
substance, drug product, or type of material
used in their preparation.
Summary of all significant steps in the
manufacturing and controls of the drug
intermediate or substance.
Content of a DMF
Company profile
Letter of submission/transmittal
Batch formula
BPR
Key RM/FP/Intermediates
Quality data
Stability data
Specifications and test methods
Analytical method validation
General information and
suggestions
Stability- Stability study design, data,
interpretation, and other information should be
submitted, when applicable
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
Letter of Authorisation to the FDA
The DMF will be reviewed only when it is
referenced in an application
Before FDA can review DMF information
in support of an application, the DMF
holder must submit in duplicate to the DMF
a letter of authorization permitting FDA to
reference the DMF.
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.
If FDA reviewers find deficiencies in the information
provided in a DMF, a letter describing the deficiencies
is sent to the DMF holder. At the same time, FDA will
notify the person who relies on the information in the
deficient DMF that additional information is needed in
the supporting DMF.
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