Transcript anda certification clauses

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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INNOVATOR VS GENERICS
S.N. PARAMETERS
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Active ingredients
Safety & efficacy
Quality & strength
Performance and standards
Costs/prescription
FDA inspection of
manufacturing facilities
FDA reviews reports of
adverse reactions
FDA reviews drug labeling
Extensive research and
development investments
Expensive marketing &
advertising
Patent protection
FDA review to show active
ingredient is equivalent to original
Product Development Time
INNOVATOR DRUG GENERIC DRUG
Same
Same
Same
Same
Highly expensive
Same
Same
Same
Same
Less expensive
Yes
Yes
Yes
Yes
Yes
No
Yes
No
Yes
Yes
No
No
NA
~ 12 yrs
Yes
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 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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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 HatchWaxman 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
PARAGRAPH I
PARAGRAPH
II
PARAGRAPH
III
PARAGRAPH
IV
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PARA-I
PARA-II
Required patent
information has not
been filed.
Patent has expired
FDA may approve
generics immediately,
one or more
applicants may enter.
FDA may approve
generics immediately,
one or more
applicants may enter.
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PARA-III
PARA-IV
Patent not expired, will
be expired on a specific
date.
Patent is invalid or non
infringed by generic
applicant.
FDA may approved ANDA
effective on the date of
expiration, one or more
applicant may enter.
Generic applicant file
notice to patent holder.
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PARA IV CERTTIFICATION
After 45 days Patent
Holder sues the
Applicant ► 30months
stay granted to Patent
Holder.
After 45 days Patent
Holder doesn’t sue
applicant ► FDA may
approve ANDA.
ANDA Applicant granted
approval.
30 Months stay expired
For the first Applicant
the EMR of 180 days
starts with court’s
decision.
30 Months stay not
expired.
Subsequent approvals
for EMRs are granted
after expiry of first
applicant’s 180 days.
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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.
Judgement favouring
ANDA ► EMR of 180
days begins for first
applicant.
No entry occurs untill
Patent Expiry.
First Applicant enters,
subsequent applicants
enter only after expiry of
EMR for the First
Applicant.
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ANDA REVIEW PROCESS
APPLICANT
ANDA
ACCEPTABLE &
COMPLETE
REFUSE TO FILELETTER ISSUED
NO
YES
CHEMISTRY/MICRO
REVIEW
B.E. REVIEW
REQUEST FOR PLANT
INSPECTION
B.E. REVIEW
ACCEPTABLE
LABELING REVIEW
YES
CHEMISTRY/LABELING
REVIEW ACCEPTABLE
NO
NO
PREAPPROVAL INSPECTION
ACCEPTENCE
B.E. DEFICIENCY
LETTER
YES
NO
NOT APPLICABLE
LETTER
APPROVAL DEFERRED PENDING
SATISFACTORY RESULTS
ANDA APPROVED
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The CTD Triangle
Regional
Admin.
Information
MODULE 1
Quality
Overall
summary
Quality
MODULE 3
Non Clinical Clinical
overview Overview
Non Clinical
Clinical
Summary
Summary
Non Clinical
Report
MODULE 4
Clinical
Report
MODULE 5
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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 Vs ANDA Review
Process
NDA REQUIREMENT
ANDA REQUIREMENT
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First-Time Generic Drug
Approvals - July 2011
Generic Drug
Name
FONDAPARINUX SODIUM
INJECTION
Generic
Brand Name
Manufacturer
Approval Date
DR. REDDY'S
LABORATORIES LIMITED
7/11/2011
ARIXTRA INJECTION
ALFUZOSIN
HYDROCHLORIDE
EXTENDED-RELEASE
TABLETS
TEVA
UROXATRAL EXTENDEDPHARMACEUTICALS USA RELEASE TABLETS
7/18/2011
ALFUZOSIN
HYDROCHLORIDE
EXTENDED-RELEASE
TABLETS
SUN PHARMA GLOBAL
FZE
UROXATRAL EXTENDEDRELEASE 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
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