By: DEBANGSHU S. ROY MBA P.M. Hamdard University

ABBREVIATED NEWDRUG APPLICATION

FILING

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An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's CDER, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product.

Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the public.

All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

ANDA

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INNOVATOR VS GENERICS

S.N. PARAMETERS INNOVATOR DRUG GENERIC DRUG1. Active ingredients Same Same 2. Safety & efficacy Same Same 3. Quality & strength Same Same 4. Performance and standards Same Same 5. Costs/prescription Highly expensive Less expensive 6. FDA inspection of manufacturing facilities Yes Yes 7. FDA reviews reports of adverse reactions Yes Yes 8. FDA reviews drug labeling Yes No 9. Extensive research and development investments Yes No 10. Expensive marketing & advertising Yes No 11. Patent protection Yes No 12. FDA review to show active ingredient is equivalent to original NA Yes 13. Product Development Time ~ 12 yrs 2- 4 yrs

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Generic Drug Approval

In 1970 FDA established the ANDA as a mechanism for the review and approval of generic versions.

Before 1978, generic product applicants were required to submit complete safety and efficacy through clinical trials.

Post 1978, applicants were required to submit published reports of such trials documenting safety and efficacy.

Neither of these approaches was considered satisfactory and so originated Hatch Waxman Act on 1984.

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Indispensability GroundsFor Generics

Contain the same active ingredients as the innovator drug (inactive ingredients may vary).

Must be identical in strength, dosage form, and route of administration.

Must have same use/indications.

Must be bioequivalent.

Must have same batch requirements for Identity, Safety & Purity.

Must follow strict standards of FDA's GMPs.

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Commonly known as “Drug Price Competition & Patent Term Restoration Act” of 1984.

“The Hatch-Waxman Act is an act dealing with the approval of generic drugs and associated conditions for getting their approval from FDA, market exclusivity, rights of exclusivity, patent term extension and Orange Book Listing.”Necessitated By :

1. Absence of Generic drug manufacturing. 2. Cumbersome regulatory procedures. 3. Patients were denied the option of cheaper drugs.

Hatch-Waxman Act

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1. Maintaining list of patents which would be infringed.

2. Only Bioavailability studies and not clinical trials needed for approval.

3. Para I, II, III and IV certifications.

4. Data exclusivity period for New Molecular Entities.

5. Extension of the original patent term.

6. The “Bolar” Provision.

General Provisions of the Act

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Recent additions to the Hatch-Waxman Act

Under the “Medicare Prescription Drug and Modernization Act”, 2003:

1.Non-extension of the 30-month period.

2.Time limit for informing patent owner.

3.Provision for allowing declaratory judgment.

4.Benefit of exclusivity for several ANDAs filed on same day allowed.

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ANDA CERTIFICATION

CLAUSES

PARAGRAP

H I

PARAGRAPH II

PARAGRAPH III

PARAGRAPH IV

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PARA-I

Required patent information has not been filed.

FDA may approve generics

immediately, one or more applicants

may enter.

PARA-II

Patent has expired

FDA may approve generics

immediately, one or more applicants

may enter.

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PARA-III

Patent not expired, will be expired on

a specific date.

FDA may approved ANDA effective on

the date of expiration, one or

more applicant may enter.

PARA-IV

Patent is invalid or non infringed by

generic applicant.

Generic applicant file notice to

patent holder.

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PARA IV CERTTIFICATION

After 45 days Patent Holder doesn’t sue

applicant ► FDA may approve ANDA.

ANDA Applicant granted approval.

After 45 days Patent Holder sues the Applicant ► 30months stay granted

to Patent Holder.

30 Months stay

expired

For the first Applicant the EMR of

180 day

s starts

with court’s decision

.

Subsequen

t approvals for

EMRs

are granted

after

expiry of

first applicant’s 180 days.

30 Months stay not expired.

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30 Months stay not expired

If judgement’s in favour of Patent Holder ► FDA can not approve ANDA

untill patent expiry.

No entry occurs untill Patent

Expiry.

Judgement favouring ANDA ► EMR of 180 days begins for first

applicant.

First Applicant enters, subsequent applicants enter only after expiry

of EMR for the First Applicant.

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APPLICANT

ANDA

ACCEPTABLE &COMPLETE

REFUSE TO FILE- LETTER ISSUED

B.E. REVIEW

REQUEST FOR PLANT INSPECTION

CHEMISTRY/MICRO REVIEW

LABELING REVIEW

NOT APPLICABLE LETTER

ANDA APPROVED

B.E. DEFICIENCY LETTER

APPROVAL DEFERRED PENDING SATISFACTORY RESULTS

PREAPPROVAL INSPECTION ACCEPTENCE

B.E. REVIEW ACCEPTABLE CHEMISTRY/LABELING REVIEW ACCEPTABLE

YES

YES

YES

NO

NO

NO

NO

ANDA REVIEW PROCESS

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MODULE 1

MODULE 3 MODULE 4 MODULE 5

MO

DU

LE

2

Regional Admin.

Information

Quality

Overall

summary

Non Clinical overvie

wNon Clinical Summary

Clinical

Overview

Clinical Summary

Quality Non Clinical Report

Clinical Report

Not

part of

CTD

CTD

The CTD Triangle

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MODULES IN A CTD

MODULE I: Administrative and Prescribing Information

1.Table of Contents.

2.Includes data of Administrative Documents entailing:Patent Information on patented product.Patent Certifications.Debarment certification.

3. Prescribing information like Package and container labels, packaging inserts, patient leaflets, etc.

4. Labelling Comparison between Innovator and Generic drug.

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MODULE II: SUMMARIES AND OVERVIEWS

1. Table of Contents.

2. Introduction to Summary Documents.

3. Overviews and Summaries: Module II should contain documents like: M4Q: The CTD- quality M4S: The CTD- safety M4E: The CTD- efficacy MODULE III: information on product quality

1. Table of Content.

2. Body of Data.

3. Literature Reference.

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MODULE IV: NON CLINICAL STUDY REPORTS

Not required in ANDA Filing.

MODULE V: CLINICAL STUDY REPORTS

1. Table of Contents.

2. Study Reports including Case Report Forms and Case Report Tabulations.

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RECOMMENDATIONS FOR e-CTD

1. PDF Files with version 3.0 of Acrobat Reader

2. Use of Embedded fonts in the Portable Document Format

3. A Print area of 8.5 inches by 11 inches and margin of 1 inches is ensured on sides.

4. Scanned Documents should be avoided as Source Documents.

5. Hypertexts can be indicated by Blue-Texts or by rectangles using thin lines.

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6. Numbering on the PDF and Documents should be included as same.

7. Security or Passwords should not be included.

8. Full Indexes should be included.

9. Electronic Signatures may be added, Procedures are being employed for archival of the same.

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BIOEQUIVALENCE

A Generic drug is considered to be bioequivalent to Brand drug if:

Rate & extent of absorption do not show a significant difference from RLD.

Two drugs are said to be Bioequivalent if their Bioavailability after administration in same dose are similar to a degree that there effects, with respect to safety & efficacy can be expected to be the same.

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NDA REQUIREMENT ANDA REQUIREMENT

NDA Vs ANDA Review Process

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First-Time Generic Drug Approvals - July 2011

Generic Drug Name

Generic Manufacturer

Brand Name Approval Date

FONDAPARINUX SODIUM INJECTION

DR. REDDY'S LABORATORIES LIMITED

ARIXTRA INJECTION

7/11/2011 

ALFUZOSIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS

TEVA PHARMACEUTICALS USA

UROXATRAL EXTENDED-RELEASE TABLETS

7/18/2011 

ALFUZOSIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS

SUN PHARMA GLOBAL FZE

UROXATRAL EXTENDED-RELEASE TABLETS

7/18/2011 

PARICALCITOL INJECTION

SANDOZ CANADA, INC.

ZEMPLAR INJECTION

7/27/2011 

METRONIDAZOLE GEL

TOLMAR INC. METROGEL 7/22/2011 

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THANK YOU