The document provides background information on the Hatch-Waxman Act, including: - It summarizes the key people involved in creating the Act - Henry Waxman and Orrin Hatch. - It outlines the history of drug regulation legislation leading up to the Hatch-Waxman Act of 1984. - It describes the objectives and key features of the Hatch-Waxman Act, which established an abbreviated approval pathway for generic drugs to help increase competition and lower drug costs.

1. Picture 2
ANDA
Hatch-Waxman Act: Global
Impact, Issues and
Challenges
Rajashri Ojha
Director, Raaj GPRAC

2. Introduction
The Hatch-Waxman Act also known
as Drug Price Competition and
Patent Term restoration Act, is an
act dealing with the approval of
generic drugs and associated
conditions for getting their
approval from the “Food and Drug
Administration(FDA),market
exclusivity, right of exclusivity,
patent term extension and
Orange Book Listing.”

3. Henry Arnold Waxman
Henry Arnold Waxman (born
September 12, 1939) is an
American politician. He has
represented California’s 30th
congressional district in the
U.S.

4. Orrin Grant Hatch
Orrin Grant Hatch (born
March 22,1934) is a
Republican United
States Senator from
Utah, serving since 1977.

5. History
Year Legislation Impact on Drug Regulation
1906 The Pure Food and Drug Act Established regulation of food and drugs in
the United States
1938 Federal Food, Drug, and Required new drugs to be demonstrated as safe
Cosmetic Act before marketing. Drug product marketed prior to
this act were not affected and became known as
"grandfather” or”pre-1938” drugs.
1962 Kefauver-Harris Drug Introduced efficacy concept into regulation. Drug
Amendments product marketed between 1938 and 1962
Amendments known as “DESI”drugs.
1984 Drug Price Competition and Expedited availibility of less costly generic
Patent Term restoration Act drugs & provided incentives for development
of new innovative medicines.

6. Necessity of Hatch-Waxman Act
 Absence of Generic drug
manufacturer
 Cumbersome regulatory procedure
 Patients were denied the option of
cheaper drugs

7. The Hatch Waxman Act (1984) simplified the
approval process for generic drugs
Started the generic drug industry
Provided for ANDAs (cheaper, faster)
Generic Drugs can be manufactured even while
originals are still under patent
FDA Orange Book
 Purpose: To make generic pharmaceutical firms aware
of patents protecting brand-name drugs
 All patents that claim a new drug, or some method of
using this drug are listed in the Orange Book
All new patent-protected drugs since Hatch-Waxman are
listed in the Orange Book

8. Objectives of Hatch-Waxman Act
Reducing the cost associated with
the approval of a generic drug
Allowing Early-Experimental Use
Motivating the generic drug
manufacturers

9. General Provision of the Act
 Maintaining list of patents which would be
infringed
 Only Bioavailability studies and not clinical trials
needed for approval
 Para I,II,III and IV certifications
 Data exclusivity period for NMEs
 Data exclusivity period for supplements
 Extension of the original patent term

10. Key Features -Hatch-Waxman Act
o Streamlined generic approval process
o “Safe Harbor” for pre-approval activities
o Patent term restoration to offset lengthy regulatory
approval process
o Non-patent exclusivity for innovators and generics
o Framework for patent notification and litigation

11. Hatch-Waxman Basics
Title I – Abbreviated New Drug Application
Title II - Patent Extension
Title III - Amendments to the Textile Fiber Product
Identification Act and Wool products Labeling Act of
1939

12. Drug Approval Process
a full, formal process –NDA (New Drug Application)
a more streamlined process that allows an applicant
to rely partially on existing safety and efficacy data
(Paper NDA)
a route designed to allow “copycat” drugs to be
rapidly approved (ANDA)

13. Generic Drugs
 Generic drug is a drug which is
produced and distributed without
patent protection. The generic drug
may still have a patent on the
formulation but not on the active
ingredient

14. Reference Listed Drug (RLD)
A reference listed drug (21 CFR 314.94(a)(3)) means
the listed drug identified by FDA as the drug product
upon which an applicant relies in seeking approval of
its ANDA.

15. Generics usually cheaper than
innovator drugs
 No cost of identification and isolation of New Chemical
Entity
 No cost of research and development
 Minimum marketing cost because branded drug is
already approved as safe and effective

16. Generics works the same as
brand name drug

17. FDA Requirements for Approval
To gain FDA approval, a generic drug must:
 contain same active ingredients as the
innovator drug
 be identical in strenght,dosage form, and
route of administration
 have same use/indications
 have same batch requirements for
Identity,Safety,Purity and Quality
 follow strict standards of FDA’s GMPs

18. Generic product Development
FDA
Approval FDA Approval
NDA Submitted
FDA Review 2 ½ yrs
ANDA
1 ½ – 2 ½ yrs
Extensive Human Submitted FDA
3 yrs
Clinical Studies Review
Clinical Studies- 2 yrs
Formulation
Effectiveness ½ - 1 ½ yrs Bioavailability
Study
Clinical Studies- 1 yrs Safety & Efficacy
Safety Established by
Clinical trials of
Laboratory & Animal Studies 3 ½ yrs
Innovators
Branded Vs. Generic Product Development

19. A generic drug can be produced
for the drugs
 Where the patent has expired
 Which have never held patents
 In countries where a patent(s) is/are
not in force
 Where the generic companies certify
that the branded companies’ patent
are either invalid, enforceable or will
not be infringed

20. Drug approval Requirements
NDA ANDA
- Chemistry • Chemistry
" Manufacturing • Manufacturing
" Controls • Controls
" Labeling • Labeling
• Testing
" Testing
• Bioequivalence
" Animal Studies
" Clinical Studies
" Bioavailability

21. Comparison of Innovator and Generic Drug
S.N. PARAMETER INNOVATOR GENERIC
DRUG DRUG
1. Active ingredient Same Same
2. Safety & Efficacy Same Same
3. Quality & Strength Same Same
4. Performance & Standards Same Same
5. Costs & Prescription Highly expensive Less expensive
6. FDA inspection of yes yes
manufacturing facilities
7. FDA reviews reports of yes yes
adverse reaction
Cont….

22. Cont…
S.N. PARAMETER INNOVATOR GENERIC
DRUG DRUG
8. FDA reviews drug labeling yes No
9. Extensive research and yes No
development investments
10. Expensive marketing & yes No
advertising
11. Patent protection yes No
FDA review to show active
12. --- yes
ingredient is equivalent to
original
13. Product Development Time ~ 12 yrs 2~4 yrs

23. Authorized generics
The term Authorized generics refers to prescription
drugs that are produced by brand companies under a
new drug application (NDA) and marketed as generics
under private label.

24. Comparison - Authorized Generic
and Generics

25. Similarities between NDA Authorized
Generic and ANDA Generics
- Provide consumer saving , and
are approved by the FDA to be
marketed to the consuming
public.
- Highly regulated and undergo a
rigorous approval process
resulting in a safe and effective
treatment methodology.

26. Market entry of Authorized
generic
 Brand companies establish agreements with private
label marketing and distribution
 Brand companies can establish subsidiaries to
market Authorized generic of their own brands.
 Brand companies establish agreements with a
generic drug manufacturer to permit them to offer
the Authorized generic product until the generic
company gets its ANDA approval.

27. Advantage of Authorized Generics
provide consumers the highest brand quality at lower
generic prices
reduce the cost of prescription drugs more than the
reduction offered by the first generic entrant in the
market.
The availability of raw materials and production
capacity for Authorize generic reduces the possibility
of marketplace supply interruptions.

28. Orange Book
Approved Drug
Product with
Therapeutic
Equivalence
Evaluations

29. Definition
 The publication, “Approved Drug
Product with Therapeutic
Equivalence Evaluation” (the list,
commonly known as the Orange
Book)identifies drug products
approved on the basis of safety
and effectiveness by the FDA
under the Federal Food, Drug,
and Cosmetic Act.

30. Cont…..
Hatch-Waxman Act requires
that when a company submits
a new drug application(NDA)
to the FDA for approval,
patent information associated
with that pharmaceutical
should be listed in this book.

31. Paragraph IV filing
 Patent is invalid or will not be infringed by
manufacture, use, or sale of the drug product for
which the ANDA is submitted

32. Contents of list
 Approved prescription drug product with
therapeutics equivalence evaluation
 Approved over-the-counter(OTC) drug product for
those drugs that may not be marketed without NDAs
or ANDAs
 Drug product with approval under section 505 of the
act
 A cumulative list of approved product that have
never been marketed

33. Therapeutic equivalence- related terms
 Pharmaceutical Equivalents
 Bioequivalent Drug Products
 Pharmaceutical Alternative
 Therapeutic Equivalents

34. Pharmaceutical Equivalents
 When drug products contains same active
ingredient(s), are of same dosage form, route of
administration and are identical in strength or
concentration.

35. Pharmaceutical Alternative
If drug products contain the same therapeutic moiety,
but are different salts, esters, or complexes of that
moiety, or are different dosage form or strengths.

36. Bioequivalent Drug Products
 This term describes pharmaceutical equivalent or
pharmaceutical alternative products that display
comparable bioavailability when studied under similar
experimental conditions.

37. Therapeutic Equivalents
If drug products are pharmaceutical equivalents and they
can be expected to have the same clinical effect and safety
profile when administered to patients under the
conditions specified in the labeling.

38. Therapeutics equivalence
evaluation code
 A code- drug product that FDA considers to be
therapeutically equivalent,i.e.drug product for which:
 no known bioequivalence problem,-
AA,AN,AO,AP,AT
 Meeting Bioequivalence requirements- AB
 B code - drug product considers not to be
therapeutic equivalent -
B*,BC,BD,BE,BN,BP,BR,BS,BT,BX

39. A code
AA product in conventional
dosage forms not presenting
bioequivalence problem
AB,AB1,AB2,AB3….
Products meeting necessary
bioequivalence requirements

40. Three code character
AB1, AB2, AB3……….
These codes are assigned only in
situations when more than one
reference listed drug of the same
strength has been designated.

41. Cont………..
 AN Solution and powders for aerosolization
 AO Injectable oil solution
 AP Injectable aqueous solution and, in certain
instances, intravenous non-aqueous
solution
 AT Topical products

42. B code
B* Drug products requiring further FDA
investigation and review to determine
therapeutic equivalence
BC Extended- release dosage form
BD Active ingredients and dosage form with
documented bioequivalence problems
BE Delayed-release oral dosage forms
BN Products in aerosol-nebulizer drug delivery
systems
BP Active ingredients and dosage forms with
potential bioequivalence problems

43. Cont………
BR Suppositories or enemas that deliver drugs for
systemic absorption
BS Product having drug standard deficiencies
BT topical products with bioequivalence issue
BX Drug products for which data are insufficient to
determine therapeutics equivalence

44. ANDA
“ ANDA” is the abbreviation for “abbreviated New
Drug Application” it contains data which when
submitted to FDA’s center for Drug Evaluation and
Research, Office of generic drugs, provides review
and approval of a generic drug product.

45. Address to send ANDA
Application
Office of Generic Drugs (HFD -600)
Center for Drug Evaluation and Research,
Food and Drug Administration
Metro Park North II,Room 150,
7500 Standish place, Rockville, MD 20855

46. ANDA Certifications
Paragraph I
Paragraph II
Paragraph III
Paragraph IV

47. ANDA Review Process
Major components of an ANDA review include:
Bioequivalence evaluation
Chemistry / microbiologic evaluation
Inspection of the manufacturing facility
Review of the proposed label

48. Bioequivalence requirements
An applicant submitting ANDA under section 505 (j)(2)
(c) of the act must demonstrate both pharmaceutical
equivalence and bioequivalence between generic drug
and innovator reference listed drug.

50. ANDA Patent Certification Options
Paragraph I Paragraph II Paragraph III Paragraph IV
(required patent (Patent has not expired (patent is invalid or not
information (Patent has but will expire on a infringed by generic
has not been filed) expired) particular date) applicant)
FDA may FDA may FDA may approve ANDA Generic applicant
approve approve effective on the that the provides notice to
ANDA ANDA patent expires; one or patent holder & NDA
immediately, immediately, more applicant may enter filer; entry of first filer
one or more one or more
generic applicant generic may or /may not occur
may enter applicant may
enter

51. Paragraph IV Certification
45 days 45 days
Patent holder does not sue; the FDA Patent holder sues generic applicant within 45
may approve ANDA assuming other days; trigger of automatic 30-month stay
regulatory conditions are fulfilled
Generic applicant may
enter 30 – month stay not 30 – month stay expired; the FDA may
expired be able to approve ANDA
If court rules in If court rules in Patent
brand-name generic applicant’s expires,FDA can For the first generic Subsequent
company’s favor, favor, the FDA can approve applicant the 180-days generic applicants
the FDA can not approve ANDA & ANDA;180-days exclusivity period may only
approve ANDA 180-days exclusivity exclusivity does begins upon marketing be approved after
until patent expires period begins not extend beyond or court decision, the first generic
patent expiration whichever comes first applicant’s 180
days have expired
First generic applicant may enter;
No entry occurs until subsequent generic applicants may One or more generic applicants may
patent expiration only be approved after the first enter
generic applicants 180 days have
expired.

52. Notice Letter
Generic applicant who files a paragraph IV
certification must notify the patent and NDA holder
with a detailed statement
Patent/NDA holder has 45 days to sue
Generic applicant can file a declaratory judgment
action if not sued

53. Generic Entry Legal
stay(prohibition)
Innovator company has 45 days from generic
notification to file suit
FDA suspends generic approval until:
final judicial ruling
patent expires
30 months from generic notification date
Innovator may list additional patents prior to ANDA
approval and trigger new 30-month stay

54. Contents of ANDA
1. Application Form 356h
2. Application copies
3. Cover letter
4. Table of contents
5. Tabs
6. Pagination
7. Field copies – Additional information

55. Application Copies
I. Archival copy
II. Review copy
III. Field copy

56. Cover Letter
1) Purpose of application
2) Type of submission (ANDA,amendments,supplements,annual
report, or resubmission)
3) Name , title, signature and address of the applicant
4) Proprietary name and established name of the drug product
5) Number of volume submitted
6) Commitment to resolution of any issues identified in the
methods validation process after approval
7) Statement that the application or a portion of the submission is
in electronic format
8) Clearly identify submission that contain sterility assurance
data

57. Common Technical Document
(CTD)
Common Technical Document ( CTD)annexure I.docx
 Module 1: Administrative Information or Regional
 Module 2: summary
Quality overall summary, drug substance and
drug product information, clinical BE
summary
 Module 3: Quality CMC information
(3.2.S), (3.2.P) and (3.2.R)
 Module 4: Not applicable to ANDA submission
 Module 5: clinical study report

58. Labeling
Section 505(j)(2)(A)(v) of the Act
states that an abbreviated
application for a new drug must
contain:
“information to show that the labeling proposed
for the new drug is the same as the labeling
approved for the listed drug except for
changes required because of differences
approved under a petition or because the new
drug and the listed drug are produced or
distributed by different manufacturers”

59. The Pharmaceutical Patent
A patent an exclusive rights
granted by a state (national
government) to an inventor
or their assignee for a
limited period of time in
exchange for a public
disclosure of an invention.

60. Types of Infringement
 Direct Infringement – If a person makes, uses, or
sells the patented invention.
 Indirect Infringement – If a person actively
encourages another to make, use, or sell the
patent invention.
 Contributory Infringement – If a person
knowingly sells or supplies an items for which
the only use is in connection with a patented
invention.

61. Duration of patent
most industrialized foreign countries - 20 years.

62. Exclusivity
Exclusivity is a statutory provision and is granted to an
NDA&ANDA applicant if statutory requirement are
met.

63. Term of Exclusivity
 Orphan Drug - 7 years
 New Chemical Entity - 5 years
 Pediatric Exclusivity - 6 months
 Patent Challenge - 180 days
 Others Exclusivity - 3 yrs

64. Patent and Exclusivity regulation in
C.F.R. (Code of Federal Regulation)
 21 C.F.R. 314.52 Notice of certification of invalidity or
non infringement of a patent
 21 C.F.R. 314.53 Submission of patent information
 21 C.F.R. 314.107 Effective date of approval of a 505 (b)(2)
application or abbreviated new drug
application under section 505(j) of
the act.
 21 C.F.R. 314.108 New drug product exclusivity
 21 C.F.R. 316.31 Scope of orphan- drug exclusive
approval
 21 C.F.R. 316.34 FDA recognition of exclusive approval

65. Patent and Exclusivity
Patent Exclusivity
-by patent and trademark office -by FDA upon approval of a drug
-continue along the development grants exclusivity and can run
lifeline of a drug and can encompass a concurrently with a patent or not.
wide range of claims.
May expired before drug approval, granted upon approval of a drug
issued after drug approval, and product if statutory provision are met.
anywhere in between.

66. Reward to the 1st ANDA Filer
First ANDA filer with Paragraph IV
 180 day exclusivity period
 No other ANDA approval for subsequent generics for
180 days
 Measured from the earlier date of marketing or court
decision

67. 180-days clock
180 –day clock begins the earlier of
3. The day that the generic is
commercially marketed or
4. The day of a court decision finding that
the brand –name patent is either
invalid or not infringed by the generic.

68. Multiple Exclusivity
Shared exclusivity-
When more than applicant submit an ANDA for the
same product on the same day

69. Benefits of Exclusivity
 The 180-day generic drug exclusivity
 Strong financial incentive for an ANDA applicant

70. Section 505 of the Act
(1)section 505(b)(1)
(2) section 505(b)(2)
(3) section 505(j)

71. Section 505(b) (2)
A 505(b) (2) application is a new drug application
(NDA)
submitted under section 505(b)(1)
approved under section 505(c) of the Act.
Cont…

72. Cont…..
“A 505(b) (2) application is one for which one or more of
the investigations relied upon by the applicant for
approval "were not conducted by or for the applicant
and for which the applicant has not obtained a right of
reference or use from the person by or for whom the
investigations were conducted" (21 U.S.C. 355(b) (2)”

73. Type of information useful in 505 (b) (2)
Application
 Published literature
 Agency’s finding of safety
and effectiveness for an
approved drug

74. Benefits of 505(b) (2) Application
First ,that distinguishes from the Abbreviated New
Drug Application (ANDA)
 Second, an approved 505(b)(2) product, receive an
"AB" substitutability rating in the Orange Book.

75. ANDA Suitability Petitions
Suitability petition submitted to the Agency seeking
permission to file an abbreviated new drug application
for a change from a listed drug in dosage form,
strength, route of administration, or active ingredient
in a combination product.

76. Type of changes which can be included
in ANDA Suitability Petition
A different route of administration
A different dosage form
A different strength
A different active ingredient in a combination product
in which the other active ingredients match those of
the RLD

77. Loopholes in the Hatch-Waxman act
Thirty-Month Stay Period
Authorized Generics
Citizen Petitions
Reverse Payment Agreements

78. Thirty-Month Stay Period
The 30-month stay results from the filing of an
infringement suit by the original patentee within 45
days of the prospective generic manufacturer filing a
Paragraph IV Certification.

79. Citizen Petitions
A citizen petition submitted to the Agency seeking
permission to file an abbreviated new drug application
for a change from a listed drug in dosage form,
strength, route of administration, or active ingredient
in a combination product.
This loophole utilized by the pioneer pharmaceutical
companies to delay the arrival of generic on the
market is the citizen petition mechanism.

80. Authorized Generics
a practice employed by pioneer
pharmaceutical companies to bring
their own “generics” to market,
currently escapes coverage under the
Hatch-Waxman Act .
Competition from authorized generics
substantially cuts into the share of
profits

81. Reverse Payment Agreements
More recently, brand name drug manufacturers have
begun entering into reverse payment agreements with
generic drug makers, under which the brand company
pays a substantial amount of money to the generic
company to either not file an ANDA application or, if
it has already filed the application, to stay out of the
market for some period of time

82. FDA Proposal for Legislative Changes
On October 21, 2002, President Bush announced that
the Food and Drug Administration would propose new
rules associated with the 30-month stay and the
requirements for listing patents in the Orange Book.
several bills were introduced in the 107th Congress
that would make changes to the Hatch-Waxman Act of
which S. 812 passed the Senate. It has been
reintroduced in the 108th Congress.

83. Bills
 Medicare Rx Drug Benefit and Discount Act of 2002
 Greater Access to Affordable Pharmaceuticals Act
(GAAP) (108th Congress)
 Consumer Access to Prescription Drugs Improvement
Act
 Medicare Prescription Drug, Improvement, and
Modernization Act of 2003 (“the Medicare Act”)
{Hatch-Waxman Reform Provision [section 1101],
December 3,2003

84. Greater Access to Pharmaceuticals Act
This act would amend the Hatch-Waxman Act to
excise the automatic 30-month stay associated with
patents listed in the Orange Book. Instead, the NDA
holder must obtain a preliminary injunction against
the generic firm to prevent manufacture and
marketing of the product during prosecution of the
patent infringement suit.

85. Medicare Rx Drug Benefit and
Discount Act of 2002
Medicare prescription issues permits the 180- day
market exclusivity period to begin on the day of a
court decision from which no appeal can or has been
taken. The bill establishes conditions under which the
first ANDA applicant must forfeit the 180-day
exclusivity provided by the Food and Drug
Administration.

86. Greater Access to Affordable
Pharmaceuticals Act (GAAP) (108th
Congress)
It would limit the ability of brand name drug
manufacturers to prevent generic competition by
triggering multiple 30-month stays on the same drugs.
The bill would generally allow only one stay per drug
to be granted.
Generic companies would have the right to assure that
their drugs are not in violation of any patent before
going to market.

87. Consumer Access to Prescription
Drugs Improvement Act
It would allow for only one 30-month stay for those
patents listed in the Orange Book as of the date of
passage of the bill. The automatic stay is to be
eliminated for all new drugs and associated patents
listed in the Orange Book.
Prospectively, NDA-holders must request a
preliminary injunction from the court in order to
prevent the FDA from approving the generic version
filed under a paragraph IV certification.

88. Medicare Prescription Drug, Improvement, and
Modernization Act of 2003
 Non-extension of the 30-month period
 The 180-Day Exclusivity Provision
 Certain Conditions Result in Forfeiture of the 180-Day
Exclusivity Period
 provision for Counterclaim for Delisting patents
 Provision regarding timing of notice of Paragraph IV
certifications
 Provision for allowing declaratory judgment
 Benefit of exclusivity for several ANDAs filed on same day
allowed
 FTC Review Provision

89. The Outcome of the Act
The Rising Generic Industry

90. Generic Pathway Under the Act
Abbreviated New Drug Application (ANDA)
No independent clinical trial for safety and
efficacy
Reliance on clinical data of innovator drug
Bioequivalence to innovator drug
No infringement for generic clinical testing
prior to patent expiration
Certifications to patents of innovator drug
listed in Orange Book

91. Controversial Strategies
Multiple 30-month stays
Listing patents in Orange Book after ANDA is filed
No mechanism to de-list patent from the Orange
Book
Settlement agreement between generic and brand-
name to postpone the triggering of 180-day
exclusivity period

92. Hatch-Waxman Summary
Innovator gets:
Patent term extension/restoration
Guaranteed marketing exclusivity
period
Automatic 30 month stay of FDA
approval if litigation
Generic Gets:
Streamlined approval process
First-to-file 180-day marketing
exclusivity
Safe harbor and possibility of definitive
decision prior to launch

93. Conclusion
The enactment of act was the major up
thrust in the history of American and
Global generic pharmaceutical industry.
Its main purpose was to encourage
generic competition thereby providing
cheap and economic medicines to
public. The main provision of this act is
180 days exclusivity to first filer, 30
month stay and patent listing.