The document provides an overview of the New Drug Application (NDA) process. It discusses that an NDA is required for approval to market a new drug in the US. The goals of an NDA are to demonstrate a drug's safety, efficacy, appropriate labeling, and quality manufacturing. An NDA contains extensive data from non-clinical and clinical trials. It follows a common technical document format and is reviewed by the FDA to determine if the drug's benefits outweigh the risks for approval.

1. A SEMINAR ON
New Drug
Application
By
MANSI NARENDRASINH CHAUHAN
M.Pharm

2. Product Development & Technology Transfer
Topic: New Drug Application
Presented by
MANSI NARENDRASINH CHAUHAN
M.Pharm
Pharmaceutical Quality Assurance
Guided by
Dr. Sachin Narkhede &
Mrs. Neha Vadgama
Smt. BNB Swaminarayan Pharmacy College Salvav-Vapi

3. CONTENTS
~ What is NDA: Introduction & Goals
~ When we will go for NDA
~ NDA Forms
~ Contents of NDA
~ Data required to be submitted
~ The NDA in CTD Format
~ Submission of NDA
~ Review & Approval of NDA
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4. What is NDA:
Introduction
• 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.
• In 1985, the FDA revised its
regulations governing NDAs in a
number of ways designed to speedup
the review process.
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5. Goals of
NDA
• The goals of the NDAs are to provide enough
information to permit FDA reviewer to
reach the following key decisions:
• Whether the drug is safe and effective in its
proposed uses, and whether the benefits of
the drug outweigh the risks.
• Whether the drug's proposed labeling
(package insert) is appropriate, and what it
should contain.
• Whether the 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.
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6. When will we go for NDA?
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7. 5

8. NDA Forms &
Electronic
Submission
• Form FDA-356h. Application to Market a
New Drug, Biologic, or An Antibiotic Drug
For Human Use
• This form is to be submitted with each
original NDA & every supplement thereof.
• Form FDA-3397. User Fee Cover Sheet
• Form FDA-3331. New Drug Application Field
Report
• Guidance Documents for Electronic
Submissions: CDER, eCTD, FDA(ESG),
FAERs, SPL.
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9. contents
of NDA
• The documentation required in an NDA is
supposed to tell the drug's whole story,
including what happened during the clinical
tests, what the ingredients of the drug are,
the results of the animal studies, how the
drug behaves in the body, and how it is
manufactured, processed and packaged.
• An NDA is a document comprising of 20
sections of data analyses on animal and
human studies, the drug’s pharmacology,
toxicology and dosage, and its
manufacturing process.
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10. • SECTION- 1 Index
• SECTION- 2 Labelling
• SECTION- 3 Application summary
• SECTION- 4 CMC chemistry, manufacturing, &
controls
• SECTION- 5 Nonclinical, pharmacology & toxicology
• SECTION- 6 Human pharmacokinetics &
bioavailability
• SECTION- 7 Clinical microbiology
• SECTION- 8 Clinical data
• SECTION- 9 Safety update reports
• SECTION- 10 statistics
NDA
CONTENTS
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11. • SECTION- 11 Case report tabulation
• SECTION- 12 Case report forms (CRFs)
• SECTION- 13 Patent information
• SECTION- 14 Patent certification
• SECTION- 15 Establishment description
• SECTION- 16 Debarment certificate
• SECTION- 17 Field copy certification
• SECTION- 18 user fee coversheet
• SECTION- 19 Financial disclosure
• SECTION- 20 other
NDA
CONTENTS
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12. Contents
Section 1: Overall NDA index
• The NDA index is a comprehensive table of contents that
enables the reviewers to find specific information in this
massive document quickly.
Section 2: Labelling
• It must include all draft labelling that is intended for use on
the product container, cartons or packages, including the
proposed package insert.
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13. Section 3: Application summary
• This is an abbreviated version of the entire application it should
contain:
• Proposed annotated package insert
• Pharmacological class, scientific rational, intended use & potential
clinical benefits
• Foreign marketing history
• Chemistry, Manufacturing, Controls summary
• Nonclinical pharmacological & toxicology summary
• Human pharmacokinetics & bioavailability summary
• Microbiology summary
• Clinical data summary & results of statistical analysis
• Discussion of benefit/risk relationship
Contents
1
1

14. Section 4: chemistry, manufacturing & controls
The first technical section of NDA it includes three main
elements:
• Chemistry, manufacturing & controls information.
• Samples (submitted only upon FDA’s request).
• Method validation package.
Section 5: Nonclinical pharmacology & toxicology
• Provide individual study reports, including pharmacology,
toxicology, ADME studies.
• Effects related to the therapeutic indication, such as the
pharmacodynamic ED50 dose-ranging studies and the
mechanism of action.
• Interaction with other drugs.
Contents
1
2

15. Section 6: Human pharmacokinetics & bioavailability
It includes data from phase I safety & tolerance studies in
healthy volunteers.
• Summary of analytical method used in in-vivo
biopharmaceutical study.
• Pilot or background studies
• Bioavailability or bioequivalence studies
• Pharmacokinetic
• In-vitro studies
Contents
1
3

16. Section 7: Microbiology
It includes information for anti-infective drug products &
requires the following technical information & data:
• A complete description of the biochemical basis of the
drug action on microbial physiology.
• The drug’s antimicrobial spectrum.
• Describing any known mechanism of resistance to the
drug & provide information/data of any known
epidemiologic studies demonstrating prevalence to
resistance factor.
• Clinical microbiology laboratory factor.
Contents
1
4

17. Section 8: Clinical data
• List of investigators and list of INDs & NDAs
• Background or overview of clinical investigations
• Clinical pharmacology
• Controlled & uncontrolled clinical trial
• Other studies & information
• Integrated summary of safety & effectiveness data
• Integrated summary of benefits & risks of drug
• Drug abuse and overdose information
Contents
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18. Section 9: Safety data
• Statements in draft labelling
• Contraindications
• Warnings
• Precautions
• Adverse effects
Section 10: Statistical data
• All controlled clinical trial reports
• Integrated efficacy and safety summaries
• Integrated summary of risks & benefits
Contents
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19. Section 11: Case report tabulation
• Include complete tabulation for each patient
from every adequacy are well controlled phase II
& phase III efficacy, Clinical pharmacology
study. It also contains tabulation of safety data
from all clinical studies.
Section 12: Case report forms
• Include the complete CRF for each patient who
died during a clinical study or adverse event,
regardless of whether the AE is considered to be
related to the study drug, even if the patient was
receiving a placebo or comparative drug.
Contents
1
7

20. 1) Introduction
2) Chemical & pharmaceutical information
3) Animal pharmacology
4) Animal toxicology
5) Human/clinical pharmacology (phase I)
6) Therapeutic exploratory trials (phase II)
7) Therapeutic confirmatory trials (phase III)
8) Special studies
9) Regulatory status in other countries
Data required
to be
submitted
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8

21. • The agreement to assemble all the Quality, Safety
and Efficacy information in a common format
called CTD - Common Technical Document. it
has revolutionized the regulatory review
processes, led to harmonized electronic
submission that, in turn, enabled implementation
of good review practices.
• For industries, it has eliminated the need to
reformat the information for submission to the
different ICH regulatory authorities.
• In July 2003, the CTD became the mandatory
format for new drug applications in the EU and
Japan, and the strongly recommended format of
choice for NDAs submitted to FDA, United
States.
The NDA in
CTD Format
1
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22. • The CTD is organized into five modules.
Module 1 Regional administrative information.
Modules 2 Quality overall summary contains the CTD
summaries and should begin with a general
introduction to the drug, including its pharmacological
class, mode of action and proposed clinical use.
• Module 2 should also provide the non-clinical
overview and the clinical overview, as well as the
non-clinical written summaries and the tabulated
summaries, and the clinical summary.
Module 3 Quality As a foundation for the
aforementioned material, module 3 contains
information on quality topics.
CTD
Modules
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23. Module 4 Nonclinical Study Reports The document
primarily addresses the organization of the information to
be presented in registration applications for new
pharmaceuticals.
Module 4Q: Quality Harmonized structure and format for
presenting CMC information in a registration dossier. The
table of contents includes sections on Drug Substance &
Drug Product. A new section on Pharmaceutical
Development.
Module 4S: Safety Structure and format of the nonclinical
summaries, more extensive summaries &discussion of the
nonclinical information on pharmacology,
pharmacokinetics and toxicology.
Module 4E: Efficacy structure and format of the clinical
data, including summaries & detailed study reports. ICH
M4E(R1) Guideline on Enhancing the Format & Structure
of Benefit-Risk Information.
Module 5 Clinical Study Reports
CTD
Modules
2
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24. 2
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25. Archival copy is a complete copy of an
application submission. The FDA reviewers &
officials use it as a reference source for locating the
information not available in the section of the
review copy. It contains:
• The cover letter
• Form FDA-356H
• The administrative sections
• Comprehensive NDA index
• Four copies of labelling sections
• Three copies of CMC, method validation package
• Case report tabulation, case report forms
Submission of
NDA: Archival
copy
2
3

26. Review copy of an application is divided into 5
or 6 sections bearing technical & scientific
information required by FDA reviewers. It
contains:
• The cover letter
• Form FDA-356H
• The administrative sections
• Comprehensive NDA index
• The labelling sections
• The Application summary
The applicants should use colored folders for
binding the specific sections of the review copy.
Submission of
NDA: Review
copy
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27. Archival copy Light blue FD2626
Chemistry manufacturing control
section
Red FD2626a
Non clinical pharmacology &
toxicology section
Yellow FD2626b
Human pharmacokinetic &
bioavailability section
Orange FD2626c
Microbiology section White FD2626d
Clinical data section Light brown FD2626e
Statistical section Green FD2626f
Field copy Maroon FD2626h
Documents Folder colour Form number
2
5

28. • Though FDA reviewers are involved with a drug's
development throughout the IND stage, the official
review time is the length of time it takes to review a
new drug application
• Once a new drug application is filed, FDA review
team, medical doctors, chemists, statisticians,
microbiologists, pharmacologists, and other experts
evaluates whether the studies submitted show that the
drug is safe and effective for its proposed use.
• The review team analyzes study results and looks for
possible issues with the application, Each reviewer
prepares a written evaluation containing conclusions
and recommendations about the application.
• These evaluations are then considered by team
leaders, division directors, and office directors,
depending on the type of application.
Review &
approval of
NDA
26

29. 2
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31. References
• Leon Lachman, Herbert A. Liberman, Joseph L. Kaing.
(1987). Third edition. The theory and practice of
industrial pharmacy. Varghese publishing house.
• Ilango K. D., Shukla V. K., Lakade S. H. (2020).
Industrial pharmacy II. Thakur publication PVT. LTD.
• https://www.fda.gov.htm
• https://www.fda.gov/drugs/types-applications/new-
drug-application-nda .htm
• https://www.ich.org/page/ctd.htm
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