Nda ipr

(NEW DRUG APPLICATION)
R.MEENAKSHI
M Pharm (Pharm. Chemistry)
R.MEENAKSHI M.PHARM(Chemistry),2010 1

R.MEENAKSHI M.PHARM(Chemi2stry),2010
CONTENTS
 HISTORY
 INTRODUCTION
 APPLICATION FORM
 IND REVIEW PROCESS
 NDA REVIEW PROCES

HISTORY:
 The NDA has evolved when the FD&C act was passed in 1938,
NDAs were only required to contain information pertaining to the
investigational drug’s safety.
 In 1962, the Kefauver – Harris amendments to the FD&C act require
NDAs to contain evidence that a new drug was effective for its
intended use & that the established benefits of the drug outweighed
its known risks.
 The NDA was again the subject of change in 1985, when the FDA
completed a comprehensive revision of the regulations pertaining to
NDAs. This revision commonly called the NDA rewrite, modified
content requirements, it was mainly intended to restructure the ways
in which information & data are organized & presented in the NDA to
expedite FDA reviews.

INTRODUCTION:
The New Drug Application (NDA) is the vehicle through which drug
sponsors formally propose that the FDA approve a new pharmaceutical for sale
& marketing in United States.
 New chemical entity is an active ingredient that has never been approved by
regulatory authority of country for use in same type of product.

The goals of NDA are to provide enough information to permit FDA
reviewers to establish:
 Is the drug safe & effective in its proposed use, & do the benefits of
the drug outweigh the risks?
 Is the drug’s proposed labeling (package insert) appropriate, & what
should contain?
 Are the methods used in manufacturing (GMP) the drug & the
controls used to maintain the drug’s quality adequate to preserve the
drug’s identity, strength, quality & purity?
To legally gather the data on safety & effectiveness in the US,
the maker must first obtain an Investigational New Drug (IND)
designation from FDA.

 The Food and Drug Administration (FDA) regulates the development of novel
drugs. Both prescription and over-the-counter drugs are regulated by the
Center for Drug Evaluation and Research (CDER).
CDER has been established to ensure that drug products are safe and
effective. All new drug products must undergo a rigorous process of pre-clinical
and clinical evaluation..
 F or every 5000 compounds that enter pre-clinical testing, only five will continue
on to clinical trials in humans and only one will be approved for
marketing in the United States.
After each stage of development, the sponsor of the new product meets with
the FDA to determine next steps and establish end points for future trials.
Similar processes are required in other countries.

Preclinical Testing. A pharmaceutical or biotechnology company conducts
laboratory and animal studies to demonstrate biological activity of the compound
against the targeted disease, and the compound is evaluated for safety.
Investigational New Drug Application (IND)
 After completing preclinical testing, the company files an IND with the FDA to
begin to test the drug in humans.
 The IND becomes effective if the FDA does not disapprove it within 30 days. The
IND shows results of previous experiments and studies; how, where and by
whom the new studies will be conducted; the chemical structure of the
compound;
 how it is thought to work in the body; any toxic effects found in the animal
studies; and how the compound is manufactured.
 The IND must be reviewed and approved by the Institutional Review Board (IRB)
where the studies will be conducted,and progress reports on clinical trials must
be submitted to the FDA at least once annually.

New Drug Application (NDA). Following successful completion of all three
phases of human clinical trials, the company analyses all of the data and files an
NDA with the FDA if the data successfully demonstrate safety and effectiveness.
The NDA must contain all of the scientific information that the company has
gathered on the compound.
NDAs can exceed 100,000 pages or more. By legislation, the FDA is allowed six
months to review an NDA filing. In 2000, the average review time for approved
products was 16 months.
FDA Panel Review. Once CDER has reviewed the NDA, the product's sponsor
presents the data to a panel of experts.
The members of the panel may ask for clarification of specific data points, request
explanations for certain outcomes or events observed in the trial or pose questions
on potential issues that may occur if the product is approved for marketing.

The members of the panel then vote in favour of or against recommending
marketing approval.
While the FDA does not have to take the recommendation of the panel, it
usually does.
FDA Approval. Once the Review Panel has issued its recommendation, the
FDA makes the final decision on product approval.
Marketing of the drug is then permitted.

Letter codes describing review priority of the drug:
S – Standard review for drugs similar to currently available drugs.
P – Priority review for drugs that represent significant advances over
existing treatments
R.MEENAKSHI M.PHARM(Chemi1s0try),2010

NDA APPLICATION
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FORMAT OF APPLICATION:
3 copies of the application are required:
Archival copy
Review copy
Field copy
1. Archival copy:
It is a complete copy of the application.

2. Review copy:
Include the information needed by each review
discipline for its evaluation.
 Quality
 Non clinical
 Clinical – safety & efficacy documents for
clinical reviewer
 Clinical – safety & efficacy documents for
statistical reviewer
 Clinical – clinical pharmacology &
pharmacokinetics documents and
 Clinical – clinical microbiology documents

3. Field copy:
Separately bound copy of the quality section. It is directly
send to the appropriate field office.
FDA will maintain guidance documents on the format & content
of applications to assist applicants in their preparation.

Application form:
The applicant shall submit a completed & signed application
form that contains:
 The name 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 & chemical names,
 The dosage form & strength, The route of administration,
 The identification numbers of all IND applications that are
referenced in the application,
 The identification numbers of all drug master files & other
applications under this part that are referenced in the application,&
 The drug products proposed indications for use.

 Whether the submission is an original submission, a resubmission, or a
supplement to an application.
 Whether the applicant proposes to market the drug product as a
prescription or an OTC product.
 A check list identifying what enclosures required under this section the
applicant is submitting.
 The applicant, or the applicant’s attorney, agent or other authorised official
shall sign the application.
b) Index:
A comprehensive index by volume number & page number to the
summary, the technical sections, & the supporting information.

c) Summary: statement identifying the pharmacologic class of the drug & a
discussion of the scientific rationale for the drug, its intended use, & the
potential clinical benefits of the drug.
 brief description of the marketing history.
 chemistry, manufacturing, & controls section of the application.
 non-clinical pharmacology & toxicology section of the application.
 human pharmacokinetics & bioavailability section of the application.
 microbiology section of the application (for anti infective drugs only)
 clinical data section of the application, including the results of statistical
analysis of the clinical trials.
 concluding discussion that represents benefit & risk considerations related to
the drug

d) Technical sections:
 chemistry, manufacturing, & controls section: Describing the composition,
manufacture, & specification of the drug substance & the drug product.
 Non clinical pharmacology & toxicology section:
 Human pharmacokinetics & bioavailability section:
 Microbiology section (If the drug is anti-infective):
• A description of the biochemical basis of the drug action on microbial
physiology.
• A description of the antimicrobial spectra of the drug – to demonstrate
concentrations of the drug required for effective use
• A description of any known mechanisms of resistance to the drug.
• A description of clinical microbiology laboratory methods needed for effective
use of drug.

5. Clinical data section:
6. Statistical section:
i. This section concerning the description & analysis of each controlled clinical
study, & the documentation & supporting statistical analyses used in
evaluating the controlled clinical studies.
ii. A copy concerning a summary of information about the safety of the drug
product, & the documentation & supporting statistical analyses used in
evaluating the safety information.
7. Pediatric use section:
Includes the integrated summary of the information that is relevant to the
safety & effectiveness & benefits & risks of the drug in pediatric populations
for the claimed indications.

e) Samples & labeling:
Upon the request from FDA, the applicant shall submit the samples.
 The samples should be in sufficient quantity to permit FDA to perform 3 times
each test described in the application to determine whether the drug
substance & the drug product meet the specifications given in the application:
 The drug product proposed for marketing
 The drug substance used in the drug product from which the samples of the
drug product were taken
 Reference standards & blanks
 Samples of the finished market package, if requested by FDA

f) Case report forms & tabulations:
Case report tabulations:
Tabulations of the data from each adequate & well controlled study phase 2 &
phase 3 studies,
Tabulations of the data from the earliest clinical pharmacology studies phase 1
studies
Tabulations of the safety data from other clinical studies.
Case report forms:
Copies of individual case report forms for each patient who died during a clinical
study or
who did not complete the study because of an adverse event whether believed to
be drug related or not, including patients receiving reference drugs or
placebo.

g) Other:
 The applicant ordinarily is not required to resubmit information
previously submitted, but may incorporate the information by
reference.
 The applicant shall submit and accurate & complete English
translation of each part of the application that is not in English.
h) Patent information:

IND REVIEW PROCESS
Applicant (Drug Sponsor)
IND
Medical Chemistry Pharmacology/
Sponsor Submits
New Data
Clinical
Hold
Decision
Toxicology
Yes Yes
Notify Sponsor
Safety Review
Review by CEDR
Safety Acceptable for
Study to Proceed?
Reviews Complete
And Acceptable?
No
No
Study Ongoing*
Yes
R.MEENAKSHI 24 M.PHARM(Chemistry),2010
Statistical
Complete Reviews
No
Deficiencies
Sponsor
Notified
Of Deficiencies
No
*While Sponsor answers
any deficiencies

NDA Review Process

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