The document details the process and regulations surrounding abbreviated new drug applications (ANDA) for the approval of generic drugs by the FDA, emphasizing their equivalence to innovator drugs in terms of active ingredients, safety, and efficacy, but with reduced costs. It outlines the Hatch-Waxman Act, which streamlined the approval process and facilitated the introduction of generic drugs in the U.S. market by reducing the need for extensive clinical trials. Additionally, it discusses the bioequivalence of generic drugs and the structural requirements for submission, including content and modules for electronic submissions.

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

2. ANDA
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).
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3. INNOVATOR VS GENERICS
S.N. PARAMETERS INNOVATOR DRUG GENERIC DRUG
1. 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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4. 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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5. Indispensability Grounds
For 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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6. Hatch-Waxman Act
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.
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7. General Provisions of the Act
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.
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8. 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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9. ANDA CERTIFICATION CLAUSES
PARAGRAPH PARAGRAPH
PARAGRAPH I PARAGRAPH IV
II III
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10. PARA-I PARA-II
Required patent
information has not been Patent has expired
filed.
FDA may approve FDA may approve
generics generics
immediately, one or more immediately, one or more
applicants may enter. applicants may enter.
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11. PARA-III PARA-IV
Patent not expired, will Patent is invalid or non
be expired on a specific infringed by generic
date. applicant.
FDA may approved ANDA
effective on the date of Generic applicant file
expiration, one or more notice to patent holder.
applicant may enter.
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12. PARA IV CERTTIFICATION
After 45 days Patent
After 45 days Patent
Holder sues the
Holder doesn’t sue
Applicant 30months
applicant FDA may
stay granted to Patent
approve ANDA.
Holder.
ANDA Applicant granted
30 Months stay expired 30 Months stay not
approval.
expired.
For the first Applicant Subsequent approvals
the EMR of 180 days for EMRs are granted
starts with court’s after expiry of first
decision. applicant’s 180 days.
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13. 30 Months stay not
expired
If judgement’s in favour Judgement favouring
of Patent Holder FDA ANDA EMR of 180
can not approve ANDA days begins for first
untill patent expiry. applicant.
First Applicant enters,
subsequent applicants
No entry occurs untill
enter only after expiry of
Patent Expiry.
EMR for the First
Applicant.
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14. ANDA REVIEW PROCESS
APPLICANT
ANDA
ACCEPTABLE & REFUSE TO FILE-
COMPLETE NO LETTER ISSUED
YES
B.E. REVIEW CHEMISTRY/MICRO
REVIEW
REQUEST FOR PLANT
INSPECTION LABELING REVIEW
CHEMISTRY/LABELING
B.E. REVIEW ACCEPTABLE
YES REVIEW ACCEPTABLE
NO
NO
PREAPPROVAL INSPECTION NOT APPLICABLE
ACCEPTENCE
NO LETTER
B.E. DEFICIENCY LETTER
YES APPROVAL DEFERRED PENDING
SATISFACTORY RESULTS
ANDA APPROVED
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15. The CTD Triangle
Regional
Admin.
Information
MODULE 1
Non Clinical Clinical
Quality overview Overview
Overall Non Clinical Clinical
summary Summary Summary
Quality Non Clinical Clinical
Report Report
MODULE 3 MODULE 4 MODULE 5
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16. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. NDA Vs ANDA Review Process
NDA REQUIREMENT ANDA REQUIREMENT
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23. First-Time Generic Drug
Approvals - July 2011
Generic Drug Generic Brand Name Approval Date
Name Manufacturer
FONDAPARINUX SODIUM DR. REDDY'S ARIXTRA INJECTION 7/11/2011
INJECTION LABORATORIES LIMITED
ALFUZOSIN TEVA UROXATRAL EXTENDED- 7/18/2011
HYDROCHLORIDE PHARMACEUTICALS USA RELEASE TABLETS
EXTENDED-RELEASE
TABLETS
ALFUZOSIN SUN PHARMA GLOBAL UROXATRAL EXTENDED- 7/18/2011
HYDROCHLORIDE FZE RELEASE TABLETS
EXTENDED-RELEASE
TABLETS
PARICALCITOL SANDOZ CANADA, INC. ZEMPLAR INJECTION 7/27/2011
INJECTION
METRONIDAZOLE GEL TOLMAR INC. METROGEL 7/22/2011
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40. THANK YOU
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