This document provides an overview of New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs). NDAs are required for new drugs and include extensive clinical trial data to prove safety and efficacy. The review process takes 12-15 years and is more expensive. ANDAs are for generic drugs and do not require new clinical trials, only proof of bioequivalence. The review process takes 1-2 years and is less expensive. Both application types provide information on chemistry, manufacturing, labeling, and clinical data in a standardized format.

1. New Drug Application(NDA)
Vs
Abbreviated new drug application
(ANDA)
1
Prepared by
Dr. Jigar Vyas
Professor
Sigma Institute of Pharmacy

2. Contents
1.New Drug Application(NDA)
a) Introduction.
b) Goal of NDA
c) Classification of NDA
d) New drug development review
e) The NDA in CTD Format
2. Abbreviated new drug application(ANDA)
a) Introduction
b) Goal of ANDA
c )Patent certification condition
3. Conclusion.
4. References.
2

3. New Drug Application
 Introduction
Critical component for drug approval process
which required to submit to USFDA before drug
commercialization.
The data gathered during the animal studies and
human clinical trials of an Investigational New Drug
(IND) become part of the NDA.
 Goal
The NDA provide enough information to permit
FDA reviewer to reach safety, efficacy and quality for
pharmaceutical production
3

4. NDA Classifications
 New Molecular Entity
 New Salt of Previously Approved Drug (not a new molecular entity)
 New Formulation of Previously Approved Drug (not a new salt OR a
new molecular entity)
 New Combination of Two or More Drugs
 Already Marketed Drug Product - Duplication (i.e., new
manufacturer)
 New Indication (claim) for Already Marketed Drug (includes switch
in marketing status from prescription to OTC)
 Already Marketed Drug Product - No Previously Approved NDA
4

5. New Drug Development and Review Process
Steps from Test Tube to New Drug Application Review
5

6. Phases of clinical testing
Phase Number of
patients
Length Purpose Percent
successfully
completing
Phase1 20-100 Several months Mainly safety
67
Phase2 Up to several
hundred
Several months
to two years
Some short-term
safety but mainly
effectiveness
45
Phase3 Several hundred
to several
thousand
1-4 years Safety,
effectiveness,
dosage
5-10
6

7. 7

8. 8

9. NDA Review Process
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10. NDA 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: Labeling
It must include all draft labeling that is intended for use on
the product container, cartons or packages, including the
proposed package insert.
10

11. Section 3: Application summary
 Proposed annotated package insert
 Pharmacology class, scientific rational, intended use, and
potential clinical benefits
 Foreign marketing history
 Chemistry, Manufacturing and control summary
 Nonclinical pharmacology and toxicology summary
 Human pharmacokinetics and bioavailability summary
 Microbiology summary
 Clinical data summary and results of statistical analysis
 Discussion of benefit/risk relationship
11

12. Section 4: Chemistry, manufacturing and controls
 Chemistry, manufacturing and control information
 Samples
 Methods validation package
Section 5: Nonclinical pharmacology and toxicology
 Provide individual study reports, including pharmacology,
toxicology, ADME studies.
 Effects related to the therapeutic indication, such as the
pharmacodynamic ED50 in dose- ranging studies and the
mechanism of act ion (if know n)
 Interactions with other drugs (or cross-reference the location of
the information in any of the above subsection 12

13. Section 6: Human Pharmacokinetics and bioavailability
 includes data from Phase I safety and tolerance studies in
healthy volunteers. Element in the section tabulated
summary of studies showing all in vivo biopharmaceutics
studies performed.
Summary of analytical method used in in vivo
biopharmaceutic study
Pilot or background studies
Bioavailibility or bioequivalence studies
Pharmacokinetic studies
In vitro studies 13

14. Section 7: Microbiology
Includes for anti infective drug products.
requires the following technical information and data:-
A complete description of the biochemical basis of the
drug action on microbial physiology
The drugs antimicrobial spectrum
Describe any known mechanism of resistance to the drug
and provide information/data of any known epidemiologic
studies demonstrating prevalence to resistance factor
Clinical microbiology laboratory methods
14

15. Section 8: Clinical data
Includes.
List of investigators and list of INDs and NDAs
Background or overview of clinical investigations
Clinical pharmacology
Controlled clinical trials
Uncontrolled clinical trials
Other studies and information
Integrated summary of effectiveness data
Integrated summary of safety information
Drug abuse and overdose information
Integrated summary of benefits and risks of drug 15

16. Section 9: Safety data
Statements in draft labeling
Contraindications
Warnings
Precautions
Adverse events
Section 10: Statistical data
All controlled clinical trial reports
Integrated efficacy and safety summaries
Integrated summary of risks and benefits
16

17. Section 11: Case report tabulation
 include complete tabulation for each patient from every
adequately are well controlled phase II and Phase III
efficacy, clinical pharmacology study. It also 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.
17

18. Application itself consists of a cover letter and a completed form
FDA-356h along with several other supporting items as
appropriate
Item 13: Patent information
Item 14: Patent certification
Item 15: Establishment description
Item 16: Debarment certification
Item 17: Field copy certification
Item 18: User fee cover sheet (Form FDA-3397)
Item 19: Financial disclosure (Form FDA 3454, form FDA-3455)
Item 20: Other/pediatric use
18

19. The NDA in CTD Format
Module 1 is not part of the CTD because it is not harmonized
CTD NDA: 314.50
Module 1 a) Application form
c)2.1 Annotated text of proposed
labeling
e)Samples and Labeling
h)Patent information
i) Patent certification
j)Claimed exclusivity
Module 2 c)Summaries
d)5.7 Abuse potential
Module 3 d)1 CMC
Module 4 d)2 Nonclinical pharm/tox
Module d)3 Human PK
d)4 Microbiology
d)5 Clinical data
d)6 Statistical section
f) CRF and CRT 19

20. ANDA
“A drug product that is comparable to a brand/reference listed
drug product in dosage form, strength, route of administration,
quality and performance characteristics, and intended use”
It termed "abbreviated" because they generally not
required to include preclinical (animal) and clinical (human)
data to establish safety and effectiveness.
Basic Generic Drug Requirements are:--
 Same active ingredient(s)
 Same route of administration
 Same dosage form
 Same strength
 Same conditions of use
 Inactive ingredients already approved in a similar NDA 20

21. Goal of ANDA
 To reduce the price of the drug.
 To reduce the time development.
 Increase the bioavailability of the drug in comparison
to references list drug.
21

22. ANDA Review process
22

23. NDA vs. ANDA Review Process
NDA Requirement ANDA Requirement
23

24. What is Bioequivalence?
A generic drug is considered to be bioequivalent to the brand
name drug if:
 The rate and extent of absorption do not show a significant
difference from listed drug, or
The extent of absorption does not show a significant
difference and any difference in rate is intentional or not
medically significant
24

25. Patent Certification condition for
ANDA
Described in section 505(j)(2)(A)(vii) of the Act.
 I Patent Not Submitted to FDA –
Approval effective after OGD scientific determination
 II Patent Expired –
Approval effective after OGD scientific determination
 III Patent Expiration Date (honored) –
Tentative approval after OGD scientific determination, final
approval when patent expires
 IV Patent Challenge –
Tentative approval after OGD science determination, final
approval when challenge won
25

26. Paragraph IV certification
According to section 505(j)(2)(B)(i), 2157 CFR
 The ANDA applicant must provide appropriate notice of a
paragraph IV certification to each owner of the patent that
is the subject of the certification and to the holder of the
approved NDA to which the ANDA refers
And by Section 505(j)(5)(B)(iv)
 An incentive for generic manufacturers to file paragraph IV
certifications and to challenge listed patents as invalid, or
not infringed, by providing for a 180-day period of
marketing exclusivity
26

27. Patent Challenge Successful – Award
of 180-Day Exclusivity Period
Awarded to first ANDA holder to file a complete
application with patent challenge
Protection from other generic competition – blocks
approval of subsequent ANDAs
Protection triggered by:
First commercial marketing
Forfeiture provisions
27

28. Orphan Drug Exclusivity (ODE)
Orphan drug refers to a product that treats a rare disease -
affecting fewer than 200,000 Americans
7 years exclusivity
 Granted on approval of designated orphan drug
 OGD works with the Office of Orphan Products
28

29. ANDA approval status
29

30. CONCLUSION
NDA
ANDA
Applicable for new drug Applicable for generic drug
Take longer time ( 12-15
years)
Compare to NAD 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
investigations are essential
Nonclinical studies and clinical
investigations are nonessential
except bioavailability and
bioequivalence
30

31. REFERENCES
 Douglas J. Pisano, David S. Manlus –FDA Regulatory Affairs, A
guide for Prescription Drugs, Medical Devices and Biologics-
New drug Application –Second edition-Marcel Dekker,inc- page
no 69-108.
 Richard A. Guarino- New Drug Approval process-1)The New
Drug Application, Content, Format 2) Abbreviated $
Supplementary New Drug Application- Fourth edition-Marcel
Dekker,inc- page no 113-183.
 Loyd V. Allen Jr, Nicholas G. Popovich, Howard C. Ansel’s
Pharmaceutical Dosage Forms and delivers systems- New
Drug Development and Approval Process-8th edition- B.I.
publication- Page no 25-65.
 http://www.fda.gov/cder/guidance/index.htm.
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