Regulatory requirement for
product approval: API
Submitted to: Submitted by:
Dr. Anupam Sarma Name- Mary Boruah
Sandipan Das
Assistant Professor M.Pharm.1st semester (Pharmaceutics)
Dept. of Pharmaceutics
GCU
Contents-
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Introduction
NDA
NDA Review
DMF
INTRODUCTION
• Active pharmaceutical ingredients (API) are the constituents which gives medical products are their
pharmacological activity. For this reason the quality and the stability of APIs are crucial factors in the
overall quality, safety and efficacy of medicinal products.
• Regulatory guidelines is an organization’s adherence to law’s, regulations guidelines and specifications
relevant to its business.
• In order to obtain a marketing authorization for a drug product the applicant has to show evidence of
efficacy, safety and quality of the drug product.
• No matter what specific system has been established in any country or region, the information normally
contained in a DMF, NDA, or ANDA is usually expected for regulatory submissions around the world.
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4 Regulatory issues that may occur are- Filings, compendia and GMP.
Filings- The various issues are that regulatory filings can have a long-term impact
upon firms because of the inspectional reviews that take place at the manufacturing
sites producing APIs.
Compendia-API standards of quality are frequently included in publications called
Compendia.
GMP- While there are no regulations covering GMP for APIs in the United States,
FDA does expect GMP compliance with Q7A (In November 2000, the International
Conference on Harmonization issued Q7A, which is a guidance addressing API GMP).
NEW DRUG APPLICATION (NDA)
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API materials that are the active for new drugs are covered by NDA documentation.
Innovator companies would use their IND or NDA filings to provide the expected details
covering an API, while all others would establish and submit a DMF with the FDA.
Since 1938, every new drug has been the subject of an approved NDA before U.S.
commercialization.
The NDA application is the vehicle through which drug sponsors formally propose that the
FDA approve a new pharmaceutical for sale and marketing in the U.S.
The data gathered during the animal studies and human clinical trials of an Investigational
New Drug (IND) become part of the NDA.
After the successful completion of clinical research, if the drug candidate proven satisfactory to be
6 safe and effective for its intended use, then drug sponsor can submit New Drug Application(NDA)
to respective regulatory authority in order to get marketing license and start commercial production.
To submit New Drug Application(NDA) filing, drug sponsor must provide all the Research data
which are obtained from preclinical to phase 3 clinical trial along with following documents–
Proposed labelling
Safety updates
Drug abuse information
Patent information
Location where the clinical trial studies have been conducted
Compliance Report of preclinical study
Directions for use
NDA Review
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After NDA received by the regulatory agency, it undergoes a technical screening.
This evaluation ensures that sufficient data and information have been submitted in each area
that justify NDA filing.
At the conclusion of the review of NDA, there are 3 possible outcomes that can send to drug
sponsor:
1.Not approvable- it display list of deficiencies and explain the cause of rejection.
2.Approvable–minor changes are suggested for the marketing approval
3.Approved for marketing.
It will take 6–12months after NDA submission to get approval letter for marketing
Drug Master File
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Definition: Drug master files (DMFs) are submissions to FDA used to provide
confidential, detailed information about facilities, processes or articles used in
the manufacturing, processing, Packaging and storing of human drug products.
They are not required by regulation.
DMF support Investigational New Drug Application (INDA), New Drug
Application (NDA) and Abbreviated New Drug Application (ANDA)
Types of DMF
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Originally Five Types:
Type I Plant information
Type II Drug substance, drug product, intermediates and material used in their
manufacturing.
Type III Packaging
Type IV Excipients.
Type V Other information which is generally not covered by type I to type IV
drug master files. (Usually clinical, toxicity data are covered.)
Type I
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Manufacturing site, facilities, operating procedures and personnel (no longer
accepted by FDA).
Points included-
Manufacturing site
Equipment capabilities
Operational layout
Actual site address
A map showing its location with respect to the nearest city
Corporate headquarters
As per Jan. 12, 2000 FR notice : Elimination of Type I DMFs done by July 10, 2000.
Type II
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Drug substances, drug substance intermediates and material used in their
preparation, or drug product.
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.
Summarize all significant steps in the manufacturing and controls of the drug
intermediates or substance.
Type III
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Contents:-
Packaging material intended for which use.
Its components and composition.
Names of the suppliers or fabricators of the components used in preparing the packaging material.
Acceptance specifications.
Toxicological data on these materials.
The 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.
Type IV
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Excipient, colorant, flavour, 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.
Type V
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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
FDA WILL THEN
TO SUBMIT DATA A HOLDER MUST CONTACT THE
WHICH IS NOT FIRST SUBMIT A HOLDER TO
COVERED IN LETTER OF INTENT DISCUSS
TYPE I TO TYPE IV TO THE DRUG
MASTER FILE STAFF PROPOSED
DMF
SUBMISSION.
Contents of DMF submission
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There are certain requirements for each DMF submissions such as;
Transmittal (cover) letter
Administrative information about the submission and
Technical information or specific information
Aside from the user's fee form, no other forms should be filled out or submitted along with
a DMF submission.
Each page of each copy of the DMF should be dated and consecutively numbered.
Transmittal Letter
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Original Submissions and Amendments
It should cover:
Identification of submission. (Original /supportive to original DMF / Amendment)
Type of DMF and subject (update, revised formula, or revised process)
The name and address of each sponsor, applicant, or holder, and all relevant document
numbers.
Signature of the holder or the authorized representative.
Typewritten name and title of the signer
Administrative information
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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
Reference-
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1. Berry. I.R.,& Martin. R. P.(2019) The Pharmaceutical Regulatory Process 2 nd
edition, Active Pharmaceutical Ingredient, 381-384
2. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-
master-files-guidelines
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THANK YOU
