Nda

(NEW DRUG APPLICATION)
R.MEENAKSHI
M Pharm (Pharm. Chemistry)
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CONTENTS
INTRODUCTION
HISTORY
NDA APPROVAL PROCESS
REVIEW PROCESS
ADVISORY COMMITTEE
CONFIDENTIALITY OF INFORMATION
AMILORIDE CASE POINT
REFERENCES
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R.MEENAKSHI M.PHARM(PHARMA
CHEMISTRY)

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CHEMISTRY)

What are new drugs?
A drug that contains as its active ingredient a new chemical
entity would be considered to be a new drug.
All definitions for a new drug appear in the Code Of
Federal Regulations for a new drug entity.
A drug’s recommended new use or change in
recommended dosage, dosage form or route of
administration also can be considered to be a new drug.
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HISTORY
When the Federal Food, drug and cosmetic act of 1938 was
passed, a new era of drug product development began.
 The act required the assurance of safety and stated minimum
requirements for manufacturing and quality control.
 It provided only 60 days for review by FDA before the distribution
of any new drug product.
 The 1962 kefauver-Harris Amendments to the act required
greatly increased information concerning the safety ,
effectiveness,quality,sale,use,manufacturing and controls of the
drug products.
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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.
 NDA must be submitted complete in proper form and with
all critical data
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All NDA’S must contain the following information
 Index
 Summary
 Chemistry, Manufacturing and Control
 Samples, Methods Validation Package and
Labeling
 Non clinical Pharmacology and Toxicology
 Human Pharmacokinetics and
Bioavailability
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 Microbiology ( for anti-microbial drugs only)
 Clinical Data
 Safety Update report ( typically submitted 120 days after the
NDA’s submission )
 Statistical
 Case Report Tabulations
 Case Report Forms
 Patent Information
 Patent Certification &
 Other Information 8
CHEMISTRY)

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.
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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
 Clinical – clinical microbiology documents
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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.
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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 drug products proposed indications for use.
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 Whether the submission is an original submission or
resubmission to an application.
 Whether the applicant proposes to market the drug
product as a prescription or an OTC product.
 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.
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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.
 concluding discussion that represents benefit & risk
considerations related to the drug.
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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)
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 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.
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Clinical data section:
PHASE 1: Used to describe the human pharmacology of the
drug and preferred route of administration.
PHASE 2: 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.
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Statistical section:
 This section concerning the description & analysis of each
controlled clinical study, & the documentation & supporting
statistical analyses used in evaluating the controlled clinical
studies.
 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.
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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.
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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.
Which is described in the application to determine whether
the drug substance & the drug product meet the
specifications given in the application
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 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
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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.
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Case report forms:
 Copies of individual case report forms for each patient
who died during a clinical study.
 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.
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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
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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
The FDA is required to review an application within 180
days of filing.
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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?
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Review priority classification
Under food drug and administration modernisation act
(FDAMA) depending on the anticipated therapeutic or
diagnostic value of submitted NDA, its review might receive
priority (p) or standard (s) classification.
Both original NDA’s and effective supplements receive a
review priority classification.
During the NDA evaluation there is no guidelines or
rules that require open communication between FDA and
sponser.
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NDA Review
Process
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R.MEENAKSHI M.PHARM(PHARMA CHEMISTRY)

Three action letters
An approval letter
An approvable letter
An non approvable letter
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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
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Supplements are required if there is a proposed change in
drug or its labelling.
The changes cannot be put into effect until supplemental
NDA has been approved by FDA
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The Regulation provides certain changes that can be made
without the approval of a supplemental application.
They are…
A different container size or closure system for solid oral
dosage forms
Change in a description of a drug that does not involve a
change in a dosage strength or form
 An editorial or minor change in labelling
Deletion of a colour ingredient
Addition of reasonable expiration data based on FDA
approval protocol. R.MEENAKSHI M.PHARM(PHARMA 37
CHEMISTRY)

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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
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However, amiloride was introduced in several European
countries & Asian countries.
Its excellent tolerance & usefulness, especially when used in
combination with hydro chlorthiazide, led finally to its
approval by FDA in 1981.
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Nda

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