REGULATORY REQUIREMENT
FOR PRODUCT APPROVAL

Therapies obtaining NDA, ANDA for generic drugs ways and

means of US registration for foreign drugs

Presented by: Submitted to:

Dipak Kumar Gupta Dr. Sanjula Baboota

M.Pharm(1st sem) Dept. of pharmaceutics

JAMIA HAMDARD

FDA OR USFDA

Definition

The United States Food and Drug Administration
is an agency within the U.S. Established for
Public Health and Service.

WAYS AND MEANS OF US REGISTRATION OF
FOREIGN DRUGS

• For decades, the regulation and control of new drugs in the
United States has been based on the New Drug Application
(NDA). 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.

• Source: https://www.fda.gov

INTRODUCTION

The FDA is led by the Commissioner of Food and Drugs,

who is appointed by the president and confirmed by the

Senate.

The Commissioner reports to the Secretary of Health and

Human Services.

The agency is headquartered in White Oak, Maryland

In 2008, the FDA started opening offices in foreign

countries, including China, India, Costa Rica, Belgium and

the United Kingdom.

What does FDA do?

FDA is responsible for:

Protecting the public health by assuring the safety, effectiveness

and security of human and veterinary drugs, vaccines and other

biological products, medical devices, nation’s food supply,

cosmetics, dietary supplements, and products that give off

radiation.

Regulation tobacco products.

Advancing the public health by helping to speed product

innovations.

Helping the public get the accurate, science-based information

they need to use medicines and foods to improve their health.

Organization

The FDA organization comprises of several offices and centers:

• Office of commissioner of food and drugs

• Center for biologics evaluation and research (CBER)

• Center for devices and radiological health (CDRH)

• Center for drug evaluation & research (CDER)

• Center for food safety

• Center for tobacco products

• Center for veterinary medicine

• Office of regulatory affairs

• National Center for toxicological research

Mission

The food and Drug Modernization Act states that the FDA

has 4 roles :

 To promote health by reviewing research and approving

new products.

To ensure foods and drugs are safe and properly labelled.

To work with other nation to “reduce the burden of

regulation”.

To cooperate with scientific experts and consumers to

effectively carry out these obligations.

Parts of US FDA

1. Center for Drug Evaluation and Research (CDER)

2. Code of Federal Regulation (CFR)

3. Investigational New Drug Application (INDA)

4. New Drug Application (NDA)

5. Abbreviated New Drug Application (ANDA)

Center for Drug Evaluation and Research
(CDER)

CDER’s Responsibility

 To ensure the availability of safe and effective

prescription, non-prescription and generic drugs

to the American people.

INVESTIGATIONAL NEW DRUG
APPLICATION (INDA)

• After successful performance of pre-clinical studies, the

investigator has to apply to FDA for permission to

administer unapproved drug product to human beings.

• Once the IND is submitted the sponsor must wait 30 days

before initiating any clinical trials

• During this time FDA will review the IND for safety to assure

that research subjects will not be subjected to unreasonable

risk.

NEW DRUG APPLICATION (NDA)

NDA is critical component of drug approval process

which required to submit to USFDA before drug

commercialization.

The data gathered during the animal studies &

human clinical trials of an investigational new

drug(IND) become a part of the NDA.

GOAL OF NDA

To provide enough information to permit FDA reviewer
to reach:

Safety

Efficiency

Quality for pharmaceutical production

Appropriate labeling

Methods used in manufacturing

NDA IS APPLICABLE TO:

New molecular entity

New salt of previously approved drugs

New formulation of previously approved drug

New combinations

New indication for already marketed drugs

NDA FORMS

FORM NO. CONTENT

Form FDA-356 h Application to market a new drug,
biologics ,an antibiotic drug for
human use

Form FDA-358 h Instructions

Form FDA-3397 User fee cover sheet

Form FDA-3331 New Drug Application Field Report

ASSEMBLING APPLICATION FOR
SUBMISSION:

FDA requires drug sponsors to submit multiple copies of the
NDA:

The Archival copy

The Review copy

The Field copy

DEFINITIONS:

1) The Archival copy:

 It contains all sections of the NDA

 Including the cover sheet

 4 copies of the labeling section

 3 additional copies of CMC(chemistry, manufacture,
control) & method of validation package

 Should also contain case reports tabulation & case
report forms.

2)REVIEW COPY:

Includes the cover letter, form FDA-356h, the

administrative sections ,comprehensive NDA index,

individual table of contents, the labeling section &

the application summary.

Intended for reviewers in the corresponding

technical disciplines.

3)THE FIELD COPY:

It required since 1993 for use by FDA inspectors

during pre approval facilities inspections.

It includes cover letter, form FDA 356h, the

administrative sections, individual table of contents,

the labeling section, the application summary, CMC

& method of validation package.

NDA CONTENT:
Overall NDA index

Section 2 Labeling

Section 3 Application summary

Section 4 Chemistry, manufacturing and control (CMC)

Section 5 Non clinical pharmacology & toxicology

Section 6 Human pharmacokinetics & bioavailability

Section 7 Microbiology

Section 8 Clinical data

Section 9 Safety data

Section 10 statistical data

NDA CONTENTS:
Section 11 Case report tabulation

Section 12 Case report form

Section 13 Patient information

Section 14 Patient certification

Section 15 Establishment description

Section 16 Debarment certification

Section 17 Filed copy certification

Section 18 User free cover sheet(form FDA-3397)

Section 19 financial disclosure

Section 20 Other/pediatric use

FAST TRACK APPROVAL

Drugs For

Serious diseases

Fill an unmet medical need

Must be requested by the drug company

FDA -60 Days Review Decision

ACCELERATED APPROVAL

• In 1992 FDA instituted the Accelerated Approval
regulation

• Based on a surrogate endpoint, not on clinical outcome

A surrogate endpoint is a marker- a laboratory
measurement, or physical sign- that is used in clinical
trials as an indirect or substitute measurement that
represents a clinically meaningful outcome, such as
survival or symptom improvement.

PRIORITY REVIEW

• A priority review designation is given to drugs that offer

major advances in treatment.

• The goal for completing a priority review is six months.

• It can given for drugs use to serious/non-serious

diseases.

Abbreviated new drug application
(ANDA)

Generic drug application are called “abbreviated” once

approved, an applicant may manufacture and market the

generic drug product to provide a safe, effective, low cost.

INTRODUCTION

• The generic drug is a safe, effective and economical
substitute of a brand name drug product.

• The act which surrounds the generic drug approval
process of the USFDA is the “Hatch Waxman Act of 1984”
which we also identify by the “Drug price control and
Patent Term Restoration Act of 1984” which led to a
plethora of generic drugs entering into the market.

• Early before the passage of the act the pharmaceutical
market was ruled by the brand name drug manufacturers
which we also call as the innovators.

• The generic drug manufacturers seldom used to compete
with them and invest their funds for the already existing
brands in the market.

Generic Drug

 Generic drug products must be bioequivalent with
respect to the Brand/Reference drug in terms of,

Active Pharmaceutical Ingredient(API)

Route of drug administration

Dosage form

Strength

Indication/Direction to use

Safety

ANDA Approval Process

NDA Vs ANDA Review Process

NDA Requirements ANDA Requirements

1. Chemistry 1. Chemistry
2. Manufacturing 2. Manufacturing
3. Controls 3. Controls
4. Labelling 4. Labelling
5. Testing 5. Testing
6. Animal Studies 6. Bioequivalence
7. Clinical Studies
8. Bioavailability

CONCLUSION

NDA ANDA

Applicable for new drugs Applicable for generic drugs

Take longer time (12-15 years) Compare to NDA less time taken (1-2
years)

More expenditure of money Comparatively less

Cost of drugs are more Cost of drugs are less

Nonclinical studies and clinical Nonclinical studies and clinical
investigations are essential investigations are nonessential except

bioavailability and bioequivalence

REFERENCES

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

2)https://www.fda.gov/downloads/drugs/guidancecomplia
nceregulatoryinformation/guidances/ucm077097.pdf

3)https://www.fda.gov/drugs/developmentapprovalproces
s/howdrugsaredevelopedandapproved/approvalapplication
s/newdrugapplicationnda/default.htm