nda ipr

R.MEENAKSHI M.PHARM(Chemistry),2010 1

R.MEENAKSHI M Pharm (Pharm. Chemistry)

(NEW DRUG APPLICATION)

R.MEENAKSHI M.PHARM(Chemistry),20102

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..

For every 5000 compounds that enter pre-clinical testing, only five will continue on to clinical trials in humans and only one will be approved formarketing 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.


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.

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.


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


NDA APPLICATION

1.1. IndexIndex

2.2. SummarySummary

3.3. Chemistry, Manufacturing and ControlChemistry, Manufacturing and Control

4.4. Samples, Methods Validation Package and Samples, Methods Validation Package and LabelingLabeling

5.5. Non clinical Pharmacology and ToxicologyNon clinical Pharmacology and Toxicology

6.6. Human Pharmacokinetics and Human Pharmacokinetics and BioavailabilityBioavailability


• Microbiology ( for anti-microbial drugs only)Microbiology ( for anti-microbial drugs only)

• Clinical DataClinical Data

• Safety Update report ( typically submitted 120 days after the NDA’s Safety Update report ( typically submitted 120 days after the NDA’s submission )submission )

10.10. StatisticalStatistical

11.11. Case Report TabulationsCase Report Tabulations

12.12. Case Report FormsCase Report Forms

13.13. Patent InformationPatent Information

14.14. Patent Certification &Patent Certification &

15.15. Other InformationOther Information


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 PROCESSApplicant (Drug Sponsor)

IND

Sponsor Submits

New Data

Noti fy Sponsor

Safety Acceptable for Study to Proceed?

Safety Review

Reviews Complete

And Acceptable?

Clinical

Hold Decision

Study Ongoing*

No

Review by CEDR

No

Yes Yes

Yes

Medical Chemistry Pharmacology/

Toxicology

Statist ical

Complete Reviews

No Deficiencies

Sponsor Noti f ied

Of Deficiencies

No

*While Sponsor answers any def iciencies


NDA Review Process


THANK THANK YOUYOU

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