This document provides an overview of the non-clinical development process and global submission of Investigational New Drug Applications (IND), New Drug Applications (NDA), and Abbreviated New Drug Applications (ANDA). It discusses the purpose and requirements for IND, NDA, and ANDA submissions to regulatory agencies globally. Key points include the format and content of IND, NDA, and ANDA submissions, as well as criteria for IND applications and the review process by regulatory agencies. The goal is to obtain approval to conduct clinical trials for an investigational drug or market a new pharmaceutical product.

1. NON CLINICAL DEVELOPMENT:
GLOBAL SUBMISSION OF
IND,NDA & ANDA
PRESENTED BY:
LINGRAJ G C
1ST M.PHARM
DEPARTMENT OF PHARMACEUTICS
NATIONAL COLLEGE OF PHARMACY
SUBMITED TO:
Dr A. SHRINATH
DEPARTMENT OF PHARMACEUTICS
NATIONAL COLLEGE OF PHARMACY
1

2. CONTENT
• Introduction
• Global Submission of IND
• Global Submission of NDA
• Global Submission of ANDA
2

3. Introduction
 Non- Clinical development Phase primarily aims to
identify which candidate therapy has the greatest
probability of success, assess it’s safety & Build solid
scientific foundations before transition to the Clinical
development Phase.
 Also, during this phase candidate compound should
meet non medical objectives, including defining the
intellectual property rights & making enough
medicinal product available for clinical studies.
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4. GLOBAL SUBMISSION OF
IND
INTRODUCTION
 The investigational new drug application is the
result of a successful preclinical development
programme.
 IND is also a vehicle through which a sponsor
advances to next stage of drug development known as
clinical trials.
4

5. • There are 2 main categories
1. Commercial:-
• Permits sponsor to collect data on ‘clinical safety&
effectiveness’ needed for application for marketing in
the form of NDA.
2. Non-commercial (Research) :-
• Permits sponsor to use drug in research to obtain
‘advanced scientific knowledge’ of new drug .
• No plan to market the product .
5

6. Types of IND
1. Investigator INDs: It is submitted by Physician
who both initiates & conduct an investigation and
under whose immediate direction the investigational
drug is administered or dispensed.
2. Emergency Use INDs: It allows FDA to authorize
use of experimental drug in an emergency situation
that does not allow time for submission of an IND in
a normal way.
3. Treatment IND (Expanded access IND):
Submitted for experimental drugs showing promise
in clinical testing of serious conditions while final
work is conducted & FDA review takes place.
6

7. Criteria for IND
application
A clinical study is required for an IND if it is
intended to support a :
• New indication.
• Change in approved route of administration or dosage
level.
• Change in approved patient population (e.g. pediatric)
or a population at greater or increase in risk (elderly
,HIV positive , immuno compromised )
• Significant change in the promotion of an approved
drug. 7

8. FORMAT AND CONTENT OF IND
1) Cover sheet (Form FDA 1571).
2) A table of contents.
3) Introductory statement & General Investigational plan.
4) Investigator’s Brochure.
5) Protocols.
6) Chemistry , Manufacturing &Control information.
7) Pharmacology and toxicology information.
8) Previous human experience with investigational
product.
9) Additional Information
8

9. IND Application must contain information in
three broad areas:
a) Animal Pharmacology & Toxicology Studies:
Preclinical data to permit an assessment as to whether the
product is reasonably safe for initial testing in humans. If any
previous experience with the drug in humans.
b) Manufacturing Information:
Information regarding to the composition, manufacturer,
stability &controls used for manufacturing drug substance and
product.
c) Clinical Protocols and Investigator Information:
Detailed protocols proposed clinical studies to assess whether
initial phase trials will expose subjects to unnecessary risks.
Information and qualification of Clinical Investigators –
professionals . 9

10. IND FLOW CHART
10

11. • After pre-clinical investigations when the new molecule has
been screened for pharmacological activity and acute toxicity
potential in animals the sponsor requires permission from FDA
for its clinical trials in humans.
• The sponsor submits the application for conduct of human
clinical trials called Investigational New Drug (IND)
application to FDA.
• Once IND application is submitted , the sponsor must wait
for 30 days before initiating any clinical trial.
11

12. • Clinical trials in humans can begin only after IND is reviewed
by the FDA and a local institutional review board (IRB).
• IRBs approve clinical trial protocol, informed consent of all
participants and appropriate steps to prevent subjects from
harm.
• If the FDA accepts the IND request within 30 days of
submission, clinical testing of the new molecule on human
may begin by the investigator.
12

13. • . At this point, the molecule under the legal status of
FDA becomes a new drug subject to specific
requirements of drug regulatory system.
• If at any time during clinical testing, the data furnished
to FDA indicate the IP to be toxic under the criterion of
FDA’s Benefit/Risk ratio, FDA can terminate clinical
trial and its actions are not subject to any judicial
review.
13

14. Application submission:-
• Most of INDs are paper submission. While only
12%INDs submitted electronically,28% of IND
Amendments are submitted electronically a result of
maintaining a growing number of INDs submitted
electronically to date.
14

15. TIMELINE:
• 30 days after FDA receives the application , unless
FDA notifies the sponsor that the investigations
described in the application are subject to a clinical
hold.
• Any earlier notification issued with approval clinical
investigations in IND may begins.
15

16. GLOBAL SUBMISSION OF NDA
• Vehicle through which drug sponsors formally
propose that the regulatory body (FDA) approve a
new pharmaceutical for sale & marketing.
• The data gathered during the ‘animal studies’ &
‘Human clinical trials’ of an Investigational new
product become part of NDA.
16

17. The goal of NDA are to provide enough information to
permit FDA reviewers to establish the following :
• Safety & Effectiveness of drug ?
• Proper labelling ?
• Are the methods used for manufacturing (GMP) the
Drug & Controls used to maintain the drug’s quality
adequate to preserve the drug’s identity, strength,
quality &purity ?
17

18. Classification of NDA
• Centre for drug evaluation and Research(CDER) classifies new
drug applications according to the type of drug being submitted
and its intended use:
a . New molecular entity
b. New salt of previously approved drug
c. New formulation of previously approved drug
d. New combination of two or more drugs
e. Already marketed drug product- Duplication (i.e., new
manufacturer)
f. New indication (claim) for already marketed drug (includes
switching marketing status from prescription to OTC)
g. Already marketed drug product ( no previously approved
NDA)
18

19. • The following letter codes describe the review
priority of drug:
• S- Standard review : For drugs similar to currently
available drugs.
• P- Priority review : For drugs that represent
significant advances over existing treatments.
19

20. Format and Contents of NDA
As outlined in Form no.-FDA-356th , Application to
Market a New drug for Human use .NDA consists of
many different sections:
• Index
• Labelling
• Application Summary
• CMC (chemistry, manufacturing & controls
• Non clinical- (Animal) Pharmacology & Toxicology
• Human pharmacokinetics & Bioavailability.
• Microbiology (for antimicrobial drugs only)
• Clinical data
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21. • Safety Update Report
• Statistics
• Case report Tabulations
• Case report forms
• Patent information
• Patent certification
• Other information.
Format:
It involves 3 copies;
1. Archival Copy
2. Review Copy
3. Field Copy
21

22. 1.ARCHIVAL COPY
• It is a complete copy of an application for submission.
• It should include a cover letter to:
i. Confirm any agreements or understanding between
FDA& applicant.
ii. Identify a contact person regarding the application.
iii. Identify the reviewing division of FDA
iv. Convey any other important information about
application .
22

23. 2.REVIEW COPY
• Divided into 6 technical sections shown with specific
colour:
• Chemistry, manufacturing & controls(CMC)
• Non clinical pharmacology & toxicology
• Human pharmacokinetics & Bioavailability-
• Microbiology (if required )
• Clinical data –
• Statistical
23

24. 3.FIELD COPY
• Separately bound copy of the Quality Section
• It is directly send to appropriate field office .
24

25. NDA CONTENTS
Index : - Comprehensive table of contents -
Show the location of every section in archival NDA
by volume & page number
Labelling : -Draft labelling used on Product
container, Cartons or packages, proposed package
insert.
Application Summary : An abbreviated version of
entire application.
Involves few elements of application that all
reviewers review.
Gives a clear idea of Drug &its application.
25

26. CMC: First technical section of NDA
Includes information on Composition,
manufacturing and specifications of drug substance &
drug product.
Non clinical pharmacology & toxicology:
Provides a description of all animal & in vitro
studies with drug.
Provide individual study reports, including
pharmacology, toxicology & ADME studies.
Human pharmacokinetics& Bioavailability :
Includes data from phase I safety & tolerance studies
in healthy volunteers &ADME studies.
PK parameter , giving value of Cmax , AUC, tmax ,
Ke , Vd 26

27. Microbiology: Required for anti-infective drug
product. Used in case of involvement of antimicrobial
drugs.
Clinical Data: Largest document & complex section
• List of investigators& list of INDs and NDAs
• Background/overview of clinical investigations
• Clinical pharmacology
• Controlled & Uncontrolled clinical trials
• Other studies & information.
Safety update reports: Safety updates should be
submitted 4 months after initial application, following
the receipt of an approval letter & any other time that
FDA requests.
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28. Statistics: Description & documentation of Statistical
analyses performed to evaluation of controlled
clinical trials &other safety information.
Case Report Form Tabulations:Complete
tabulations for each patient from every well
controlled phase II &phase III and from every phase I
clinical pharmacology studies & also Safety data .
Case Report Forms(CRFs): Complete CRFs of each
patient who died during a clinical study & patients
who were dropped from study.
Others:Patent information &certification,
Establishment description, Debarment & Field copy
certification, User fee cover sheet , Financial
disclosure.
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29. NDA CHART
29

30. TIMELINE
Review time frames:
• Within 180 days of receipt of an application, FDA
will review approval , approvable or not approval
letter ,this period is called the ‘review clock’
• Applicant may withdraw at this period & later
resubmit it .
• The time period may be extended by mutual
agreement between FDA & applicant .
30

31. Filling timeline frames:
• Within 60 days after FDA receives , a determination
is made whether application may be filed.
• This determines whether sufficient information is
provided to proceed with in depth review.
• If FDA files the application ,applicant will be notified
in written .the date of filling will be the date 60 days
after FDA received application.
• The date of filling begins the 180 days period of
review ,if FDA refuses it then applicant can meet with
FDA & discuss.
31

32. ABBREVIATED NEW DRUG APPLICATION
(ANDA)
• An ANDA contains data submitted to U.S food & drug
administration (FDA’s CDER) ,office of generic drugs
request for review and ultimate approval of a generic
drug.
• Once ANDA is approved ,an applicant may
manufacture &market the generic drug product to
provide a Safe, Effective, Low cost alternative to
public.
• A generic drug product is one compared with innovator
drug product in Dosage form, Strength, Route of
administration, Quality, Performance characteristics
&intended use. 32

33. • All approved products, both innovator & generic are
listed in Orange Book.
• Use of bioequivalence as the base for approving
generic drug products was established by the "Drug
Price Competition and Patent Term Restoration Act of
1984," also known as the HATCH-WAXMAN ACT.
• It is because of this Act that there is the availability of
less costly generic drugs into the market without
conducting costly and duplicative clinical trials.
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34. FORMAT & CONTENT OFANDA
a .Application summary
b. Chemistry, Manufacturing and controls section
c. Non clinical pharmacology and toxicology section
d. Human pharmacokinetics & bioavailability section
e. Clinical and statically section
f. Microbiology section
The patent certification involved in ANDA that
includes: 34

35. Paragraph I
- That the
patent
information has
not been
submitted to
FDA.
Paragraph
II
- That the
patent has
expired
Paragraph III
- That the
patent will
expire (on date
of marketing)
Paragraph IV
- Patent is invalid,
unenforceable or
will not be
infringed by
manufacture, use or
sale of generic drug.
35

36. • Bioequivalence:
A generic drug is considered to be Bioequivalent to
Branded Drug if,
 The rate & extent of absorption do not show a
significant difference from listed drug or
 Extent of absorption does not show a significant
difference in rate is intentional or not medically
significant.
NON
EQUIVALENT
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38. REFERENCES:
• www.ijdra.com
• www.fda.gov
• www.researchgate.net
• fdocuments.in
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