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ANDA REGULATORY APPROVAL
PROCESS AND NDA APPROVAL

PROCESS

SUBMITTED TO : SUBMITTED BY :

DR. JAVED ALI , DR.SANJULA BABOOTA ASAD ALI

DEPARTMENT : Pharmaceutics IST SEMESTER (Pharmaceutics)

School Of Pharmaceutical School Of Pharmaceutical
Education and Research Education and Research

JAMIA HAMDARD JAMIA HAMDARD

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INTRODUCTION
WHAT IS ANDA AND ITS GOALS?
 An abbreviated new drug application (ANDA) contains data which is

submitted to FDA for the review and potential approval of a generic
drug product. Once approved, an applicant may manufacture and
market the generic drug product to provide a safe, effective, lower
cost alternative to the brand-name drug it references.

 A generic drug product is one that is comparable to an innovator drug
product in dosage form, strength, route of administration, quality,
performance characteristics, and intended use. All approved
products, both innovator and generic, are listed in FDA’s Approved
Drug Products with Therapeutic Equivalence Evaluations (Orange
Book).

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 Generic drug applications are termed “abbreviated” because
they are generally not required to include preclinical (animal)
and clinical (human) data to establish safety and effectiveness.
Instead, generic applicants must scientifically demonstrate that
their product performs in the same manner as the innovator
drug.

One way applicants demonstrate that a generic product
performs in the same way as the innovator drug is to measure
the time it takes the generic drug to reach the bloodstream in
healthy volunteers.

This demonstration of “bioequivalence” gives the rate of
absorption, or bioavailability, of the generic drug, which can
then be compared to that of the innovator drug. To be approved
by FDA, the generic version must deliver the same amount of
active ingredients into a patient’s bloodstream in the same
amount of time as the innovator drug.

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The act which is responsible for bringing generic drugs in the
market is the “HATCH WAXMAN ACT OF 1984 or the DRUG PRICE
CONTROL PATENT TERM RESTORTATION ACT of 1984”

The main objectives of this act include:

Redeem the drug approval delay: Earlier the innovators used to face a
lot of delay in the drug approval process for NDA which causes a lot of
financial losses for the brand drug manufacturers.
To bring a healthy competition and to avoid rise in the drug price:
Before the passage of this act there was no scope of the generic drug
manufacturers to enter the market until the patent term of the
innovator has expired because there were no provisions of challenging
the validity of the innovator’s patent , also there were not many
benefits expected by the generic drug manufacturers invest huge
capital to introduce another version of the same drug after its patent
expiry. This product monopoly kept competition away and the drug

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prices reaching high as demanded by the innovator.

Make life easier for the generic manufacturers: before the
passage of this act the generic drug manufacturers used to face
a lot of difficulties in doing all the pre-clinical and clinical
studies which is done by the brand name manufacturers to get
their generic approved, now they only have to perform the
BA/BE studies to show that the generic version of the brand
name drug is bioequivalent and is safe and effective.

ANDA APPROVAL PROCESS
An ANDA contains the data which is submitted to the “FDA’s
center for evaluation and research (CDER)” and “office of
generic drugs” for reviewing and approving the generic drug
product. Once the drug product will get approval the applicant
can now manufacture and market the generic drug product.

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The “Content and format of an abbreviated new drug
application”

1.Application form
2.Table of contents
3.Basis for abbreviated new drug application submission
4.Conditions of use
5.Active ingredients
6.“Route of administration, type of dosage form and strength”
7.Bioequivalence
8.Labeling
9.Chemistry, manufacturing and control
10.Patent certification

FORMAT OF ANDA:
Three copies of application are required, an archival copy, a review

copy and a field copy.
FDA will maintain guidance documents on the format and content of

applications to assist applicants in their preparation.
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FILING OF ANDA:
The generic manufacture should file one of the four possible patent certifications while
filing of an ANDA listed in the orange book,
Para 1 certification: in this there is no patent for the drug listed in the orange book.
Para 2 certification: the patent is listed in the orange book, but the patent has been
expired for the brand drug product.
Para 3 certification: in this the patent is listed and is valid but to market the generic
drug the applicant must get an approval once the patent expires.
Para 4 certification: the most critical of all, the generic applicant can either
challenges the validity of the brand name drug patent or claim it to be fake or invalid or
to affirms with the claims of the brand name patent.

Within 60 days after FDA receives an application, the agency will determine whether
the application may be filed.

The filing of an application means that FDA has made a threshold determination that
the application is sufficiently complete to permit a substantive review.

If FDA finds that none of the reasons for refusing to file the application apply, the
agency will file the application and notify the applicant in writing.

The date of filing will be the date 60 days after the date FDA received the application.
The date of filing begins the 180-day period described in section 505(c) of the act. This

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180-day period is called the “filing clock.”

Abbreviated New Drug Application (ANDA) Forms
and Submission Requirements
 The FDA aspires to assist applicants in developing abbreviated new drug

applications (ANDAs). To facilitate the development of an ANDA, agency
provides the following resources on ANDA forms and submission
requirements.

1) ANDA Forms
In order to submit a complete ANDA, applicants should review the forms
available on FDA website (https://www.fda.gov/) and prepare all that are
required for specific application.

a) Filing Review of ANDAs MAPP including filing checklist

b) Form FDA-356h: Application to Market a New Drug, Biologic, or Antibiotic
Drug for Human Use .

2) Electronic Submissions
The FDA no longer accepts paper ANDA submissions. All ANDA submissions MUST
be in eCTD format. eCTD submission sizes 10 GB or less must use the
FDA Electronic Submission Gateway (ESG). If an eCTD submission is greater

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than 10 GB, it may be submitted via physical media (DVD/USB Drive) to the
CDER Document Room or via ESG.

APPROVAL OF ANDA

FDA will approve an application and issue the applicant an
approval letter on the basis of draft labeling if the only
deficiencies in the application concern editorial or similar
minor deficiencies in the draft labeling.

Such approval will be conditioned upon the applicant
incorporating the specified labeling changes exactly as
directed, and upon the applicant submitting to FDA a copy of
the final printed labeling prior to marketing.

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Flow chart for approval process of ANDA

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WHAT IS NDA?
NEW DRUG APPLICATION

The New Drug Application (NDA) is the formal final
step taken by a drug sponsor, which involves
applying to the Food and Drug Administration (FDA)
to get approval required to market a new drug in
the U.S. An NDA is a comprehensive document with
20 sections that includes data and analyses on
animal and human studies, the drug’s
pharmacology, toxicology and dosage, and the
process to manufacture it.

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Safety and Effectiveness of a new drug in its proposed
use(s)

Whether the drug’s proposed labeling (package insert)
is appropriate

Methods used in manufacturing the drug and the
controls used to maintain the drug’s quality are adequate
to preserve the drug’s identity, strength, quality, and
purity

The benefits of the drug outweigh the risks

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NDA FORMS & ELECTRONIC
SUBMISSIONS

 Form FDA- 356h- Application to market a New
drug, biologic or an antibiotic drug for human use.

 Form FDA- 3397- User fee cover sheet

 Form FDA- 3331- New drug application field
report

Guidance documents for electronic submissions

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Form FDA- 356h PREVIEW

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 The specific contents of the NDA will depend on the Nature of the drug product and
the information available at the time of submission the application .

 The NDA may have as many as 20 different sections in addition to the Form FDA-356h
itself.

INDEX

LABELLING
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APPLICATION SUMMARY

Chemistry, Manufacturing and
controls(CMC)

Non clinical pharmacology and
toxicology

Human Pharmacokinetics and
bioavailability

Clinical Microbiology

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Clinical Data

Safety Update Reports

Statistics

Case Report tabulations

Case Report Forms(CRFs)

Patent Certification

Patent Information 20

Establishment description

Debarment Certificate

Field Copy Certification

User Fee Coversheet

Financial Disclosure

Other 21

THE THE
THE FIELD

ARCHIVAL COPY REVIEW
COPY COPY

FDA 22

ARCHIVAL COARPYCH IVAL COPY
•The cover letter
•Form FDA- 356h
•The Administrative sections
•Comprehensive NDA index
•Four copies of labeling section
•Three copies of CMC, Methods validation package
•Case report tabulations & Case report forms

FDA
REVIEW COPY

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REVIEW OF NDA

FDA

PRIORITY REVIEW STANDARD REVIEW

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REVIEW OF NDA
Under food drug and administration modernisation act (FDAMA) depending
on the anticipated therapeutic or diagnostic value of submitted NDA, its
review might receive priority (p) or standard (s) classification.

PRIORITY REVIEW- The drug product if approved there would be a significant
improvement compared with marketed products in treatment, or diagnosis
or prevention.
IMPROVEMENT can be demonstrated by :

Evidence of increased effectiveness in treatment or diagnosis or disease.

Elimination or substantial reduction of a treatment limiting drug reaction.

Documented enhancement of patient compliance.

Evidence of safety and effectiveness of a new drug substance. 25

STANDARD REVIEW : All non priority applications will be
considered standard applications i.e. application for drugs
similar to those in the market are considered standard.

The target date for completing all aspects of review and the
FDA taking an action-

For standard application is 10 months.

And fior priority application is 6 months after the date it was
filed.

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REVIEW OF NDA

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At the end of that, the FDA is required to respond with
an action letter.

THREE ACTION LETTERS

An approval letter
An approvable letter
A non approvable letter

1). APPROVAL LETTER – It signifies that all substantive
requirements for approval are met with and that the
sponsor company can begin marketing the drug as of the
date on letter.

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2). APPROVABLE LETTER- It signifies that application
substantially complies with requirements but has minor
deficiencies that must be addressed before an approval
letter is sent,
sponsor must respond within 10 days

3).NON APPROVABLE LETTER- It signifies that FDA has a
major concern with the application and will not
approve the proposed drug product for marketing as
submitted

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SUPPLEMENT NDA
 Once the NDA is approved , any significant change in manufacturing

, control, packing or other physical properties of the drug or any
change in the labelling can be done by using supplement NDA.

 The changes cannot be put into effect until supplemental NDA has
been approved by FDA.

The Regulation provides certain changes that can be made without the
approval of a supplemental application. They are…

 A different container size or closure system for solid oral dosage
forms

 Change in a description of a drug that does not involve a change in a
dosage strength or form

 An editorial or minor change in labelling

 Deletion of a colour ingredient

 Addition of reasonable expiration data based on FDA approval
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protocol.

CONFIDENTIALITY OF INFORMATION

 In general , no data or information submitted to
FDA as part of an IND or NDA will be made public
prior to FDA approval or disapproval of the NDA.

Even the existence of IND or NDA will be kept
confidential by FDA if it has not been disclosed
by sponsor.

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1) https://www.fda.gov/

2) Notes provided by DR. Sanjula baboota on regulatory
requirement for product approval.

3)https://www.fda.gov/downloads/drugs/guidancecompli
anceregulatoryinformation/guidances/ucm077097.pdf

4)https://www.fda.gov/Drugs/DevelopmentApprovalProc
ess/HowDrugsareDevelopedandApproved/ApprovalApplica
tions/NewDrugApplicationNDA/default.htm

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