Abbreviated New Drug Application

[ANDA]

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 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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 ANDA
❑“A drug product that is comparable to a brand/reference listed drug product in dosage
form, strength, route of administration, quality and performance characteristics, and
intended use”.
❑ It termed "abbreviated" because they generally not required to include preclinical
(animal) and clinical (human) data to establish safety and effectiveness.

Basic Generic Drug Requirements are:

❖ Same active ingredient(s)
❖ Same route of administration
❖ Same dosage form
❖ Same strength
❖ Same conditions of use
❖ Inactive ingredients already approved in a similar NDA

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 Goal of ANDA

❑To reduce the price of the drug.

❑To reduce the time development.

❑Increase the bioavailability of the drug in comparison to

references list drug.

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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 Ground 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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 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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 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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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

PARAGR PARAGR
PARAGR PARAGR
APH III APH IV
APH I APH II

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PARA-I PARA-II
Required patent
information Patent has expired
has not been
filed.

FDA may approve FDA may approve

generics generics
immediately, one immediately, one
or more applicants or more applicants
may enter. may enter.

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PARA-III PARA-IV
Patent not expired, Patent is invalid or
will be expired on non infringed by
a specific date. generic applicant.

FDA may approved

ANDA effective on
Generic applicant file
the date of
notice to patent
expiration, one or
holder.
more applicant may
enter.

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 PARA IV
CERTTIFICATION

After 45 days Patent

After 45 days Holder sues the
Patent Holder Applicant ►
doesn’t sue 30months stay
applicant ► FDA granted to Patent
may approve Holder.
ANDA.

ANDA Applicant
30 Months stay
granted 30 Months stay
expired
approval. not expired.

For the first Subsequent

Applicant the approvals for
EMR of 180 days EMRs are granted
starts with after expiry of first
applicant’s 180 13
court’s decision. days.
 30 Months stay not
expired

If judgement’s in
favour of Patent Judgement favouring
Holder ► FDA can ANDA ► EMR of 180
not approve ANDA days begins for first
untill patent expiry. applicant.

First Applicant
enters, subsequent
No entry occurs applicants enter only
untill Patent Expiry. after expiry of EMR
for the First
Applicant.
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 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 1516

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 MODULES IN A CTD

MODULE I: Administrative and Prescribing

Information
[Link] of Contents.

[Link] data of Administrative Documents entailing:

⮚Patent Information on patented product.
⮚Patent Certifications.
⮚Debarment certification.

[Link] information like Package and container labels,

packaging inserts, patient leaflets, etc.

[Link] Comparison between Innovator and Generic

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drug.
 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

4. Table of Content.

5. Body of Data

6. 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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 ANDA CONTENTS

CTD MODULES ANDA REQUIREMENT

Module 2
Common Technical Document yes
Summaries
Module 3
Quality yes

Module 4
Nonclinical Study Reports no
(Animal studies)
Module 5
Clinical Study Reports yes
(BA/BE studies)
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 BROAD OUTLINE FOR ANDA

Product must meet appropriate standards of

❑ Identity,
❑ Strength,
❑ Quality and
❑ Purity
Efficacy and safety should be equivalent to branded
product already established

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Information required for filing ANDA

• Product’s formulation
• Manufacturer’s procedure
• Control procedure
• Testing
• Facilities
• Dissolution profile
• Labeling

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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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[Link] on the PDF and Documents should be included as
same.

[Link] or Passwords should not be included.

[Link] Indexes should be included.

[Link] Signatures may be added, Procedures are being

employed for archival of the same.

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First-Time Generic Drug Approvals - July
2011
Generic Drug Name Generic Brand Name Approval Date
Manufacturer
FONDAPARINUX ARIXTRA 7/11/2011
DR.

REDDY'S

SODIUM LABORATORIES
INJECTION
LIMITED
INJECTION
ALFUZOSIN TEVA UROXATRAL 7/18/2011
HYDROCHLORID EXTENDED-
PHARMACEUTIC
E EXTENDED- ALS USA RELEASE
RELEASE TABLETS
TABLETS
ALFUZOSIN SUN PHARMA UROXATRAL 7/18/2011
HYDROCHLORID GLOBAL EXTENDED- 25
 Patent Certification condition for ANDA
Described in section 505(j)(2)(A)(vii) of the Act.
▪ I Patent Not Submitted to FDA –
Approval effective after OGD scientific determination
▪ II Patent Expired –
Approval effective after OGD scientific determination
▪ III Patent Expiration Date (honored) –
Tentative approval after OGD scientific determination, final
approval when patent expires
▪ IV Patent Challenge –
Tentative approval after OGD science determination, final
approval when challenge won
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 Paragraph IV certification

According to section 505(j)(2)(B)(i), 2157 CFR

• The ANDA applicant must provide appropriate notice of a
paragraph IV certification to each owner of the patent that is
the subject of the certification and to the holder of the
approved NDA to which the ANDA refers

And by Section 505(j)(5)(B)(iv)

• An incentive for generic manufacturers to file paragraph IV
certifications and to challenge listed patents as invalid, or not
infringed, by providing for a 180-day period of marketing
exclusivity

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 Patent Challenge Successful – Award of 180-
Day Exclusivity Period
⮚ Awarded to first ANDA holder to file a complete application
with patent challenge

⮚ Protection from other generic competition – blocks approval of

subsequent ANDAs

⮚ Protection triggered by:

First commercial marketing
Forfeiture provisions

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 Orphan Drug Exclusivity (ODE)

⮚ Orphan drug refers to a product that treats a rare

disease - affecting fewer than 200,000 Americans

⮚ 7 years exclusivity

⮚ Granted on approval of designated orphan drug

⮚ OGD works with the Office of Orphan Products

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Difference between NDA &ANDA

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 DETAILS NDA ANDA IND

[Link],manufacturing,
yes Yes Yes
and controls

[Link] pharmacology
Yes No Yes
and toxicology (Animal data)

3. Human pharmacokinetics
Yes Yes No
and bioavailability

4. Microbiology Yes Yes No

Yes
[Link] data Yes No
(BABE studies)

[Link] Yes Yes Yes

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