nda

R.MEENAKSHI M Pharm (Pharm. Chemistry)

(NEW DRUG APPLICATION)

1

CONTENTSINTRODUCTION

HISTORY

NDA APPROVAL PROCESS

REVIEW PROCESS

ADVISORY COMMITTEE

CONFIDENTIALITY OF INFORMATION

AMILORIDE CASE POINT

REFERENCES2

R.MEENAKSHI M.PHARM(PHARMA CHEMISTRY)

3R.MEENAKSHI M.PHARM(PHARMA 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.


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.


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


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


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 Information8


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

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 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.


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.


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.


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.


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.


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.

Which is 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.

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


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.


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?


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.


NDA Review Process


An approval letter

An approvable letter

An non approvable letter

Three action letters


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


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


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. 37R.MEENAKSHI M.PHARM(PHARMA

CHEMISTRY)

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


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.


R.MEENAKSHI M.PHARM(PHARMA CHEMISTRY) 43

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