The document discusses the process for submitting a New Drug Application (NDA) to the FDA for approval of a new pharmaceutical. It explains that an NDA contains extensive information on the drug's safety and efficacy established during clinical trials. The FDA assembles review teams to evaluate the NDA across several technical sections including chemistry, non-clinical studies, clinical data, and labeling. The review process involves determining if the application is complete and classifying it for either priority or standard review, with priority given to drugs that would significantly improve treatment options.

1. INVESTIGATIONAL NEW DRUG
APPLICATION
Y.KEERTHI
MPHARM
PHARMACOLOGY 1ST YR
2ND SEM
G.PULLA REDDY
INSTITUTE OF
PHARMACY

2. INTRODUCTION
• The NDA application is a regulatory mechanism through which
drug sponsors formally propose that the FDA approve a new
pharmaceutical for sale and marketing
• Usually, six different teams are responsible for reviewing an
NDA. The teams are organized by technical reviewing
responsibilities:
1. Clinical Pharmacology/toxicology
2. Chemistry,Statistics, Biopharmaceutical and
3. Microbiology

3. NEW DRUGS???
•A new drug is that which contains a new chemical entity as its
active ingredient
•A drug’s recommended new use or change in recommended
dosage, dosage form or route of administration also can be
considered as a new drug

4. The FDA has established guidelines for formatting,
assembling, and submitting the NDA. Failure to follow these
guidelines can result in deficiencies that could
•Delay review,
•Require an amended application, or
•Result in a refusal to File.

5. NDA APPROVAL PROCESS
• The information of drug’s safety and efficacy collected
during the animal and human trials during the IND
process becomes part of NDA application
• FDA requires drug sponsors to submit multiple copies of
NDA
1. Archival copy
2. Review copy
3. Field copy

7. The review copy is divided into six technical sections
•Chemistry, manufacturing and controls(CMC)
•Non clinical pharmacology and toxicology’
•Human pharmacokinetics and bioavailability
•Microbiology
•Clinical data
•Statistical data

8. APPLICATION FORM
The applicant shall submit a completed & signed
application form that contains:
•The name and address of the applicant
•The date of the application
•The application number if previously issued
•The name of the product including its established,
proprietary, code and chemical names
•The dosage form and strength
•Route of administration

9. •The identification numbers of all IND applications that are
referenced in the application
•The drug products proposed indications for use
•Whether the submission is an original submission or re-submission
to an applicant
•Whether the applicant proposes the drug product as
prescription or an OTC product
•The applicant, or the applicant’s attorney, agent or other
authorized official shall sign the application

10. NDA CONTENTS
•Index
•Application summary
•Chemistry, manufacturing and controls(CMC)
•Non clinical pharmacology and toxicology
•Human pharmacokinetics and bioavailability
•Microbiology
•Clinical data
•Safety update reports( typically submitted 120days after
the NDA’s submission)

11. •Statistical
•Case report tabulations
•Case report forms
•Labeling
•Patent forms
•Patent information
•Patent certification &
•Other information

13. INDEX
•For each element of the application , the index must identify the
page and volume number
•Each review section must contain an index specific to that review
section

14. SUMMARY
The summary must present the most information about the drug
product and conclusions to be drawn from this information, a
•Factual summary of safety and effectiveness data
•An annotated copy of the proposed labeling
•A discussion of the product’s benefits and risks
•A description of foreign marketing history of drug
•A summary of technical section

15. CHEMISTRY MANUFACTURING AND
CONTROLS INFORMATION
The first technical section (CMC)of NDA include:
•The composition
•Manufacturing
•Specifications of the drug substance and the drug product
The three main elements
•Chemistry, manufacturing and controls information
•Samples
•Methods of validation package

16. NON CLINICAL PHARMACOLOGY
AND TOXICOLOGY
• The second technical section of NDA provides a
description of all animal and in vitro studies with
the drug
• Provide individual study reports including:
1. Pharmacology
2. Toxicology
3. ADME studies

17. HUMAN PHARMACOKINETICS AND
BIOAVAILABILITY
• This technical section includes data from phase 1 safety and
tolerance studies in healthy volunteers and ADME studies
• This technical section must include individual study reports
from 5 types of biopharmaceutic studies:
1. Pilot or background studies
2. Bioavailability/Bioequivalence
3. Pharmacokinetic studies
4. In vivo studies
5. In vitro studies

18. MICROBIOLOGY
This sections requires the following technical information
and data:
•A complete description of the biochemical basis of drug’s
action on microbial physiology
•The drug’s anti microbial spectrum
•Describe any known mechanisms of resistance to the drug
•Clinical microbiology laboratory methods

19. CLINICAL DATA SECTION
PHASE 1: Used to describe the human pharmacology of the
drug and preferred route of administration
PHASE2 : Involves dosing of a limited number of patients for
treatment or prevention of disease of interest
It evaluates the effectiveness of the drug
PHASE 3: Drug is assessed for its safety, effectiveness and most
desirable dosage for the disease to be treated and the results
are corrected and verified in large number of patients

20. STATISTICAL SECTION
This technical section presents the descriptions of statistical
analyses
•All controlled clinical trial reports
•Integrated efficacy and safety summaries
•Integrated summary of risks and benefits

21. SAMPLES
•The samples should be in sufficient quantity to permit FDA to
perform 3 times each test
•To determine whether the drug substance & the drug product
meet the specifications given in the application
•The drug substance used in the drug product from which the
samples of the drug product were taken
•Reference standard & blanks

22. LABELING
•Container labels
•Package insert, and
• Any patient information leaflet

23. CASE REPORT FORMS AND
TABULATIONS
Tabulations for each patient:
•Every Phase I clinical pharmacology study.
•Well-controlled Phase II
•Well controlled Phase III efficacy study
•It also must include tabulations of safety data from all
clinical studies.

24. CASE REPORT FORMS
Criteria for including complete CRFs
Included for all patients that :
• Died during a clinical study
• Were dropped during the clinical trial due to adverse
event (AE)
1. regardless of whether the AE was considered to be related
to the study drug,
2. Regardless of whether patient was receiving a placebo or
comparative drug.
Patients that do not meet the above criteria- CRFs must be
provided at the request of the FDA only

25. PATENT INFORMATION
•If the FDA considers it acceptable it will then determine
application completeness
•If complete, the FDA considers the application “filed” and
begin the review process within 60 days
•The purpose of NDA from FDA perspective is to ensure that
new drug meet the criteria to be safe and effective

26. REVIEW PRIORITY
CLASSIFICATION
•Under food and drug administration modernization act
(FDAMA) depending on the anticipated therapeutic or
diagnostic value of submitted NDA, its review might receive
priority (p) or standard (s) classification
During the NDA evaluation there is no guidelines or rules
that require open communication between FDA and sponser

27. PRIORITY REVIEW: The drug product if approved would be a
significant improvement compared with marketed products in
treatment, diagnosis or prevention of a disease
IMPROVEMENT CAN BE DEMONSTRATED BY:
•Evidence of increased effectiveness in treatment or diagnosis of
disease
•Elimination or substantial reduction of a treatment limiting
drug reaction
•Documented enhancement of patient compliance
•Evidence of safety and effectiveness of a new substance

28. STANDARD REVIEW: All non priority applications will be
considered standard applications i.e., application for drugs
similar to those on the market are considered standard
The target date for completing all aspects of a review and
the FDA taking action :
•On the standard application (approve/not approve) is 10
months
•And on priority application is 6months (approve/not
approve) after date it was filed

30. at the end of that the FDA is required to respond with an action
letter
THREE ACTION LETTERS
•An approval letter
•An approvable letter
•An non approvable letter

31. APPROVAL LETTER: It signifies that all substantive
requirements for approval are met with and that the sponsor
company can begin marketing the drug as of the date on letter
APPROVABLE LETTER: It signifies that application substantially
complies with requirements but has minor deficiencies that must
be addressed before an approval letter is sent
Within 10 days of receipt sponsor must respond

32. NON APPROVABLE LETTER
It signifies that FDA has a major concern with the application
and will not approve the proposed drug product for marketing
as submitted

33. ADVISORY COMMITTEES
•It is an extremely important step in the approval process
•It represents the best opportunity that the applicant has to
address the agency and the public about the evidence of
safety and effectiveness and the importance of the drug to the
public health

34. CONFIDETIALITY OF INFORMATION
•In general, no data or information submitted to FDA as part of
an IND or NDA will be made public prior to FDA approval or
disapproval of the NDA
•Even the existence of IND or NDA will be kept confidential by
FDA if it has not been disclosed by sponsor

35. •Upon approval, FDA issues a summary of the basis for the agency
approval of the product, which describes the safety and
effectiveness data on which the agency relied
•In general, FDA will release the full data and information on
safety and effectiveness after drug becomes subject to generic
competition

36. REFERENCES
1. http://www.authorstream.com/Presentation/tusharpremin-
276870-new-drug-application-phase-trials-clinical-studies-preclinical-
science-technology-ppt-powerpoint/
2. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/3. www.troutmansanders.com/.../New%20Drug
%20Application%20Checklist...