This document discusses new drug applications (NDAs) and abbreviated new drug applications (ANDAs) submitted to the US Food and Drug Administration (FDA). It begins with an overview of the drug development process, then describes the goal and contents of an NDA, including clinical data from trials and information on safety, efficacy, and manufacturing. It also classifies types of NDAs. The document then discusses ANDAs for generic drugs, noting they do not require new clinical trials but must demonstrate bioequivalence to the brand drug. It covers patent certification requirements for ANDAs. In conclusion, the key differences between NDAs and ANDAs are summarized, with ANDAs taking less time and money but

1. BY DR ANTHONY
CRASTO
1

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4. 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.
4

5. *DRUG DEVELOPMENT
Development of a new
therapeutic drug is a complex,
lengthy and expensive process
costs nearly 900 million
dollars and an average of 15
years.

6. Basic
Biomedical
Research
Clinical
Science
and
Knowledge
Goal:
Improved
Health
Translation from
basic science to
human studies
Translation of
new knowledge
into clinical practice

7. DRUG DEVELOPMENT PROCESS

8. 8

9. 9
*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

10. 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)
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Already Marketed Drug Product - No Previously Approved NDA

11. *The Federal Food, Drug, and Cosmetic Act is
the basic food and drug law of the U.S The law
is intended to assure consumers that foods are
pure and wholesome, safe to eat, and
produced under sanitary conditions; that drugs
and devices are safe and effective for their
intended uses; that cosmetics are safe and
made from appropriate ingredients; and that
all labeling and packaging is truthful,
informative, and not deceptive.

12. * Code Of Federal Regulations (CFR)
oThe final regulations published in the Federal Register (daily published
record of proposed rules, final rules, meeting notices, etc.) are collected
in the CFR.
o The CFR is divided into 50 titles that represent broad areas subject to
Federal regulations.
o The FDA's portion of the CFR interprets the
The Federal Food, Drug, and Cosmetic Act and related statutes.
Section 21 of the CFR contains most regulations pertaining to food and
drugs.
21CFR Part 312 Investigational New Drug Application
21CFR Part 314
INDA and NDA Applications for FDA Approval to
Market a New Drug (New Drug Approval)
21CFR Part 316 Orphan Drugs
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory
[Animal] Studies
21CFR Part 50 Protection of Human Subjects
21CFR Part 56 Institutional Review Boards
21CFR Part 201 Drug Labeling
21CFR Part 54 Financial Disclosure by Clinical Investigators

13. *CDER's Manual of Policies and Procedures (MaPPs)
MaPPS are approved instructions for internal practices
and procedures followed by CDER staff to help
standardize the new drug review process and other
activities.

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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

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29. *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.
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30. 30
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

31. 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
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32. 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
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33. 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
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34. 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
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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

36. 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.
36

37. 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)
37
Item 20: Other/pediatric use

38. 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
38

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40. 40

41. “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
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42. *To reduce the price of the drug.
*To reduce the time development.
*Increase the bioavailability of the drug in comparison to
references list drug
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50. 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
50

51. Described in section 505(j)(2)(A)(vii) of the Act.
I Patent Not Submitted to FDA –
Approval effective after OGD scientific determination
51
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

52. 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
52

53. 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
53

54. Orphan drug refers to a product that treats a rare disease -
affecting fewer than 200,000 Americans
54
7 years exclusivity
 Granted on approval of designated orphan drug
 OGD works with the Office of Orphan Products

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56. NDA ANDA
Applicable for new drug Applicable for generic drug
Take longer time ( 12-15
Compare to NAD less time
years)
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
56

57. *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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58. Something about IND
58

59. IND (Investigational New Drug
Application)
 FDA's role in the development of a new drug begins
when the drug's sponsor has screened the new
molecule for pharmacological activity and acute toxicity
potential in animals, wants to test its diagnostic or
therapeutic potential in humans
 The molecule changes in legal status under the Federal
Food, Drug, and Cosmetic Act and becomes a new drug
subject to specific requirements of the drug regulatory
system
 Drug is to be the subjected to an approved marketing
application before it is transported or distributed across
state lines
 IND- notice of claimed investigational exemption for a
new drug must be filed with regulatory body

60. CCLLAASSSSIIFFIICCAATTIIOONN OOFF IINNDD
Commercial
o Permits sponsor to collect data on clinical safety and
effectiveness needed for application for marketing in
the form of NDA
Research (non-commercial)
o Permits the sponsor to use drug in research to obtain
advanced scientific knowledge of new drug
oNo plan to market the product

62. In three broad areas:
Animal Pharmacology and Toxicology Studies –
oAn assessment as to whether the product is
reasonably safe for initial testing in humans
oAny previous experience with the drug in
humans
Manufacturing Information
ocomposition, manufacturer, stability, and
controls used for manufacturing the drug
Clinical Protocols and Investigator Information
oCommitments to obtain informed consent from
the research subjects, to obtain review of the
study by an institutional review board (IRB), and
to adhere to the investigational new drug
regulations.

63. Once the IND is submitted, the sponsor must wait 3300 ddaayyss
before initiating any clinical
trials. During this time, FDA
has an opportunity to review the
IND for safety to assure that
research subjects will not be
subjected to unreasonable risk
63

64. Safety Reporting Requirements for INDs and BE/BA Studies
CGMP for Phase 1 Investigational Drugs
Exploratory IND Studies
Content and Format of Investigational New Drug Applications (INDs) for
Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic,
Biotechnology-Derived Products
Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including
Well-Characterized, Therapeutic, Biotechnology-Derived Products
Bioavailability and Bioequivalence Studies for Orally Administered Drug
Products
IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products
for the Treatment of Cancer
Guideline for Drug Master Files
A Drug Master File (DMF) is a submission to the Food and Drug Administration
(FDA) that may be used to provide confidential detailed information about
facilities, processes, or articles used in the manufacturing, processing,
packaging, and storing of one or more human drugs.
Required Specifications for FDA's IND, NDA, and ANDA Drug Master File
Binders
Immunotoxicology Evaluation of Investigational New Drugs

65. To take full advantage of Chemical Web content, it is essential
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66. DR ANTHONY CRASTO
amcrasto@gmail.com
http://newdrugapprovals.org/