The document outlines the New Drug Application (NDA) process in the United States, detailing its significance, requirements, and the review procedure by the FDA. It explains the necessary documentation, classifications, and the role of NDA in ensuring the safety and efficacy of new pharmaceuticals before market approval. Additionally, it highlights the differences between NDA and Abbreviated New Drug Application (ANDA) for generic drugs.

1. 1
New Drug Application[NDA]
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016
Department of Pharmacy (Pharmaceutics) | Sagar Savale
6/19/2016 Sagar Kishor Savale

2. Introduction
Definition : The NDA application is the vehicle through which drug sponsors,
such as biotech and pharmaceutical companies, formally propose that the FDA
approve a new pharmaceutical for sale and marketing.
For decades, the regulation and control of new drugs in the United States has
been based on the New Drug Application (NDA).
26/19/2016 Sagar Kishor Savale

3. Since 1938, every new drug or therapy has been the subject of an approved NDA
before US commercialization.
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.
36/19/2016 Sagar Kishor Savale

4. Definitions
Drug: Drug are the substance intended to be used for or in the diagnosis,
treatment, mitigation, or prevention of any disease or disorder in human being or
animal.
New drug: Drug that has not been declared safe and effective by qualified expert
under the condition prescribed, recommended, or suggested in the and that may
be new chemical formula or an established drug prescribed for use in new way.
46/19/2016 Sagar Kishor Savale

5. 5
Drug
 All medicines for internal or external use of human beings or animals or
 All substances intended to be used for or in the diagnosis, treatment mitigation or
prevention of any disease or disorder in human and animal.
 Such substances (other than food) intended to affect the structure or any function of human
body.
 All substances intended for use as components of a drug including empty gelatin capsules.
 Such devices intended for internal or external use in the diagnosis, treatment, mitigation or
prevention of disease or disorder.
6/19/2016 Sagar Kishor Savale

6. 6
New drug
A new substance of chemical, biological, or biotechnological origin in bulk or
prepared dosage form used for diagnosis, treatment, mitigation or prevention of
any disease or disorder in human or animal which except during local clinical trial
has not been used in the country to any significant extent and during local clinical
trials has not been recognized in the country as effective and safe for the proposed
claims.
6/19/2016 Sagar Kishor Savale

7. 7
New Drug Application (NDA)
An application submitted by the manufacturer of a drug to the FDA - after clinical trials have
been completed - for a license to market the drug for a specified.
New Drug Application (NDA) is the vehicle in the United States through which drug sponsors
formally propose that the FDA approve a new.
Abbreviated New Drug Application (ANDA)
An application for a license to market a generic (or a duplicate) version of a drug that
has already been granted an approval under a full NDA (i.e. the drug has already met
the statutory standards for safety and effectiveness.
6/19/2016 Sagar Kishor Savale

8. OBJECTIVE OF NDA
Whether the drug's proposed labeling (package insert) is appropriate, and what it
should contain.
Whether the drug is safe and effective in its propose use, and whether the benefits
of the drug outweigh the risks .
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.
86/19/2016 Sagar Kishor Savale

9. NDA FORM
Form FDA-356h. Application to market a new drug, biological or an antibiotic drug for
human use.
Form FDA 3397. User fee cover sheet.
Form FDA 3331. New drug application field report.
Impurity in drug substances.
Required specification for FDAs IND, and ANDA drug master file binders.
Refusal to file.
96/19/2016 Sagar Kishor Savale

10. 10
FORMNO 356TH
6/19/2016 Sagar Kishor Savale

11. 11
Approval time
TOTAL APPROVAL
YEAR NO
AVG APPROVAL TIME
(MONTHS)
DECEMBER APPROVAL
1980 12 35 2
1981 27 31 7
1982 28 29 6
1983 14 29 2
1984 22 39 8
1985 30 32 16
1986 20 34 10
1987 21 32 15
1988 20 31 13
1989 23 33 10
1990 23 27.7 -
6/19/2016 Sagar Kishor Savale

12. 12
Introduction of NDA and ANDA
NDA and ANDA is application is send to FDA for approval of new drug and abbreviated (
generic) new drug.
 When new drug application is submitted to food and drug administration it must be carefully
prepared , comprehensive , readable and well indexed.
 The guideline issued by FDA has to follow Should follow D & C Act.
 Code of federal regulation title 21 section 314 ( 21 CFR 314) is provided a brief description
for NDA and ANDA
 Experience : It is generally planned 3 years ago.
6/19/2016 Sagar Kishor Savale

13. 13
Requirement
Requirement for NDA
Format requirement
A) No of copies - Before 1985- 3 copies & now only 2 copies.
Archival copy
Review copy
1) Archival copy
- Reference copy for FDA ( i.e. retained by FDA )
- Locate information not contained in review copy
2) Review copy
- Divided in to five or six section containing technical
and scientific information separately bound
- It contains copy of cover letter, application form,
overall summary, index, specific review section
6/19/2016 Sagar Kishor Savale

14. 14
B) Assembling the application
1) Folder
- Color folder
Eg. archival copy - blue
chemistry section – red
- Name of applicant and name of drug product
- NDA no. if known
2) Paper size and binding
- Page 8.5 – 11 inches
- Bound at left side
- Use both side
- Accurately no.
3) Pagination – page no of both copy should have same
6/19/2016 Sagar Kishor Savale

15. 15
4) Volume size and identification
- Not more than 2 inches thick
- Should have name of applicant, drug and
- NDA no.
5) Packing carton
- Box size 14 -12- 9.5 inches
6/19/2016 Sagar Kishor Savale

16. 16
Basic requirements
Archival copy contains
- Application form (FDA 356th) It contains
- basic identification information
- as per form items no. 1 and 2 should bound together
- 3 to 12 submitted separately
- 13 and 14 separately
- Index -
6/19/2016 Sagar Kishor Savale

17. 17
Summary requirement
1) Labeling : -Proposed label
- It is also called mini summary
2) Pharmacological class
Intended use
Potential clinical benefit
3) Foreign marketing history
- List of country who approved same drug
- List of country who withdrawn same drug
6/19/2016 Sagar Kishor Savale

18. 18
4) Chemistry, mfg., control
A) Drug substance
Names:- name, synonym, code designation, brand name, identification no. and
chemical name.
Physical and chemical properties: MP, BP, mol wt., solubility, mol. Formula structural
formula, PH, isomer, polymorphs.
Stability
Manufacture- Name and method.
6/19/2016 Sagar Kishor Savale

19. 19
B) Drug product
a) Composition
b) Dosage form
c) Manufacture
d) Specification
e) Analytical method
f) Container
g) Closure
h) Stability
i) Investigational formulation
6/19/2016 Sagar Kishor Savale

20. 20
5) Nonclinical pharmacology and toxicology summary
A) Pharmacological studies
B) Acute toxicity studies
C) Multi dose toxicity studies
D) Mutagenicity studies
E) Reproduction studies
F) ADME studies
6) Human pharmacokinetic summary
7) Microbial summary
- Microbial spectra
- Mechanism of action
6/19/2016 Sagar Kishor Savale

21. 21
8) Clinical data summary and result
A) Clinical pharmacology
B) Overview of clinical studies
C) Controlled clinical studies
D) Uncontrolled clinical studies
E) Other studies and information
F) Safety summary
a) Extent of exposure
b) Adverse event
c) Clinical laboratory data
e) Over dose
f) drug abuse
6/19/2016 Sagar Kishor Savale

22. Guidance Documents for NDA
Submitting documentation for the stability of human drugs and biologics.
Format and content of human pharmacokinetics and bioavailability section of an
application.
Providing clinical evidence of effectiveness for human drug and biological product.
226/19/2016 Sagar Kishor Savale

23. 23
9) Discussion of benefit to risk relationship and proposed post marketing studies.
10) Bioavailability summary
NDA technical section requirement
1) Chemistry, manufacturing, and control
A) Drug substance
B) Product
2) Non clinical pharmacology and toxicology
3) Human pharmacokinetics
4) Bioavailability section
6/19/2016 Sagar Kishor Savale

24. 24
5) Microbiology
A) Mechanism of action
B) Pharmacokinetics
C) Antimicrobial activity
D) Enzyme hydrolysis rate
E) Assessment of resistance
F) In vivo animal studies
G) In vitro studies during clinical trial
H) Published literature
I) Miscellaneous studies
6/19/2016 Sagar Kishor Savale

25. 25
6) Clinical data section
- adverse dose- response information
- drug -drug interaction
- drug disease interaction
Other NDA requirement
A) Safety updates
B) Sample : 4 samples
C) Method validation
D) Label : Draft labeling -4 copies
Final print labeling -12 copies
E) Case report
6/19/2016 Sagar Kishor Savale

26. 26
NDA and ANDA Requirements
Brand Name Drug Generic Drug
NDA Requirements ANDA Requirements
1. Chemistry 1. Chemistry
2. Manufacturing 2. Manufacturing
3. Controls 3. Controls
4. Labeling 4. Labeling
5. Testing 5. Testing
6. Animal Studies
7. Clinical Studies 6. Bioequivalence
8. Bioavailability
6/19/2016 Sagar Kishor Savale

27. 27
NDA Classifications
1. New Molecular Entity
2. New Salt of Previously Approved Drug (not a new molecular entity)
3. New Formulation of Previously Approved Drug (not a new salt OR a new
molecular entity)
4. New Combination of Two or More Drugs
5. Already Marketed Drug Product - Duplication (i.e., new manufacturer)
6. New Indication (claim) for Already Marketed Drug (includes switching
marketing status from prescription to OTC)
7. Already Marketed Drug Product - No Previously Approved NDA
6/19/2016 Sagar Kishor Savale

28. Specification for FDAs DMF binders
• Polyethylene binder:
Front- 248× 292 mm
Back- 248× 305 mm
Ink Colour must be BLACK
286/19/2016 Sagar Kishor Savale

29. • Paper binder
Front 267×292mm
Back 267× 305mm
Ink must be BLACK , Marron Colour binder ink must be WHITE
296/19/2016 Sagar Kishor Savale

30. FORM COLOUR DOCUMENT
FDA form 2226 Blue NDA archival binder
FDA form 2675 Red IND archival binder
FDA form 3316 Red Drug master file binder
FDA form 3316a Blue Drug master file binder
archival binder
306/19/2016 Sagar Kishor Savale

31. FORM COLOUR DOCUMENT
FDA Form 2626a Red NDA chemistry binder
FDA Form 2626b Yellow NDA pharmacology binder
FDA Form 2626c Orange NDA pharmacokinetic binder
FDA Form 2626d White NDA microbiology binder
FDA Form 2626e Tan NDA clinical data binder
FDA Form 2626f Green NDA statistics binder
FDA Form 2626h Marron NDA field submission chemistry
binder
FDA Form 2675a Green IND chemistry binder
316/19/2016 Sagar Kishor Savale

32. Assembling application for submission
32
FDA
Archival copy Review copy
6/19/2016 Sagar Kishor Savale

33. Archival copy
 Reference copy for FDA ( i.e. retained by FDA ) .
 Locate information not contained in review copy.
 It must bound in blue cover
Review copy
 Divided in to five or six section containing technical and scientific information separately
bound.
 It contains copy of cover letter, application form, overall summary, index, specific review
section.
336/19/2016 Sagar Kishor Savale

34. NDA Contents
• The NDA have as many as 15 different section in addition to the Form FDA 356h
itself.
• The specific content of NDA will depend on the nature of the drug product and
the information available at the time of submission the application.
346/19/2016 Sagar Kishor Savale

35. NDA content
35
section 1
Section 2
Section 3
Section 4
Chemistry , manufacturing and control
Section 5 Nonclinical pharmacology and toxicology
Index
summary
Sample and labeling
6/19/2016 Sagar Kishor Savale

36. NDA Contents
36
Section 6
Section 7
Section 8
Section 9
Section 10
Human pharmacokinetics and bioavailability
Clinical microbiology
Clinical data
Safety update report
statistics
6/19/2016 Sagar Kishor Savale

37. NDA Contents
37
Section 11
Section 13
Section 12
Section 14
Case report tabulation
Case report form
Patent information
Patent certification
Section 15 other
6/19/2016 Sagar Kishor Savale

38. 38
THE TWO TRANSLATIONAL BLOCKS
Basic
Biomedical
Research
Clinical
Science
and
Knowledge
Goal:
Improved
Health
Translation from
basic science to
human studies
Translation of
new knowledge
into clinical practice
6/19/2016 Sagar Kishor Savale

39. 39
DRUG DEVELOPMENT PROCESS
6/19/2016 Sagar Kishor Savale

40. 40
NDA review
Usually six different teams responsible for reviewing NDA includes
1. Chemistry
2. Clinical
3. Pharmacology/ toxicology
4. Statistics
5. Biopharmaceutical
6. Microbiology
6/19/2016 Sagar Kishor Savale

41. 41
New Drug Development and Review Process
Steps from Test Tube to New Drug Application Review
416/19/2016 Sagar Kishor Savale

42. 42
Phases of clinical testing
Phase Number of
patients
Length Purpose Percent
successfully
completing
Phase 1 20-100 Several months Mainly safety
67
Phase 2 Up to several
hundred
Several months
to two years
Some short-
term safety but
mainly
effectiveness
45
Phase 3 Several hundred
to several
thousand
1-4 years Safety,
effectiveness,
dosage
5-10
6/19/2016 Sagar Kishor Savale

43. 436/19/2016 Sagar Kishor Savale

44. 44
NDA Review Process
446/19/2016 Sagar Kishor Savale

45. FDA –Approval process
456/19/2016 Sagar Kishor Savale

46. Fast track approval
 Drug for
Serious disease.
Fill an unmet need.
Must be requested by the drug company .
FDA 60 days review decision.
466/19/2016 Sagar Kishor Savale

47. Accelerated approval
In 1992 FDA instituted the accelerated approval regulation.
Based on surrogate endpoint, not on clinical outcome.
A surrogate endpoint is a marker- a laboratory measurement, or physical sign
that is used in clinical trial as an indirect or substitute measurement that
represent a clinically meaningful outcome, such as survival or symptom
improvement.
476/19/2016 Sagar Kishor Savale

48. Priority review
A priority review designation is given to drug that offer major advances in
treatment.
The goal for completing a priority review is 6 month.
It can given for drug used in serious/non serious disease.
486/19/2016 Sagar Kishor Savale

49. 49
Common Technical Documents
MODULE-1: Administrative Information
MODULE- 2: Quality Overall Summary
MODULE-3: Quality
MODULE-4: Non- Clinical Studies
MODULE-5: Clinical Studies
6/19/2016 Sagar Kishor Savale

50. 6/19/2016 Sagar Kishor Savale 50
MODULE 1
MODULE 3 MODULE 4 MODULE 5
Regional
Admin.
Information
Quality
Overall
summa
ry
Non
Clinical
overviewNon Clinical
Summary
Clinica
l
Overvi
ew
Clinical
Summary
Quality
Non
Clinical
Report
Clinical
Report
The CTD Triangle
50

51. 6/19/2016 Sagar Kishor Savale 51

52. 52
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 526/19/2016 Sagar Kishor Savale

53. Difference between NDA & ANDA
NDA ANDA
Applicable for new drug Applicable for generic drug
Money requirement is high Less money compare to NDA
12 to 15 year required 1 to 2 year required
Cost of drug is high Cost of drug is less
Non clinical and clinical study are essential. Bioavailability and bioequivalence study
essential
536/19/2016 Sagar Kishor Savale

54. REFERENCE
www.hhs.gov
www.fda.com
www.usfda.com
www.slideshere.com
www.mpssociety.org
www.jpsr.pharmainfo.in
 Richard A. Guarino , (1993) New drug Approval process, Marcel Dekker, 2nd edition, p.no
256-319
 Ram .I. Mahato pharmaceutical dosage form and drug delivery CRC press pharmacy edu.
series p.no 7
546/19/2016 Sagar Kishor Savale

55. 556/19/2016 Sagar Kishor Savale