This document discusses key provisions of the Hatch-Waxman Act, which established the modern system of regulating generic drugs in the US. It aims to balance the interests of branded drug companies, generic companies, and consumers. Some key points covered include: - It allows generic companies to submit abbreviated new drug applications without repeating clinical trials by proving bioequivalence. - It provides patent term extensions for branded drugs and 180-day exclusivity periods for first generic applicants challenging a patent. - It established a pathway for early experimental use of patented drugs and a 30-month stay on generic approvals if patents are challenged.

1. PREPARED BY:-(02) MANSI GANGWAR
SUBJECT:- REGULATORY AFFAIRS
BRANCH:- PHARMACEUTICS
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2.  Introduction
 Objective
 Significance
 General provision of hatch- Waxman act
 Provision with regard to paragraph IV filing
 Substantially complete ANDA
 Multiple ANDA submission
 Hatch-Waxman trade off
 New drug exclusivity
 Delay in generic entry
 Conclusion
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3.  The "DRUG PRICE COMPETITION AND PATENT TERM
RESTORATION ACT OF 1984," also known as the HATCH-WAXMAN
AMENDMENTS, established the approval pathway for generic drug
products, under which applicants can submit an abbreviated new drug
application (ANDA) under section 505(j) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act).
 In 1984, Two American politicians Orrin Grant Hatch & Henry Arnold
Waxman sponsored the Official act known as Hatch-Waxman Act.
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4.  In 1984 United States Federal law which encourages the manufacture
of generic drugs by the pharmaceutical industry and established the
modern system of government generic drug regulation in the United
States
 This act was needed to promote generic drug and innovators.
“AIM: To make available more low cost generic drugs”
4

5.  The main objectives of the HWA were as follows:
1) Reducing the cost associated with the approval of a generic drug:
 No need to do clinical trials, required from the generic drug
manufacturers was to prove that his generic version is
bioequivalent(80-125%) to the innovator drug.
2)Allowing Early-Experimental-Use: Before the Hatch-Waxman Act
even the experimental use of a patented drug was considered to be
infringement.
 This resulted in undue prolongation of patent protection for the
innovator drug as the approval of the generic version would take
another 2-3 years to enter the market.
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6.  Hence, it was an objective of the Hatch-Waxman Act to allow the early
experimental use of the patented drug and not to consider this pre-
patent-expiration use as infringement.
 3. Compensating the branded drugs manufacturers for the time
from the patent term because of the regulatory approval
 The branded drug manufacturers were allowed a Patent Term
Extension (maximum of 5 years) to compensate for the time lost in the
time-consuming regulatory approvals.
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7.  4.Motivating the generic drug manufacturers: The Hatch-Waxman
Act also established the concept of Market Exclusivity in the Federal
Food, Drugs and Cosmetic Act.
 Under this provision, exclusive marketing rights for 180 days were
granted to the generic drug manufacturer who was the first one to
file the application for marketing of the generic version of the
innovator drug.
 This provision provided incentive for the generic drug manufacturers
to file Abbreviated New Drug Application (ANDA) and promoted
healthy competition so that drugs could be available to public at
relatively lower prices once they go off-patent.
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8. “Hatch-Waxman act strives to strike a
balance between the interests of
branded drug manufacture, generic
drug manufactures and the consumer.”
8

9.  The Hatch-Waxman Act provides an expedited USFDA drug approval
program for speedy generic drugs entry in the market.
 It provides patent term extension for innovator drugs and Market
Exclusivity for the generic drugs manufacturer as an incentive for
continued innovation.
 The Hatch-Waxman Act added two provisions to the Federal Food,
Drug and Cosmetics Act namely Section 505(b)(2) and Section
505(j). Section 505(b)(2) was added with respect to New Drug
Application and Section 505 (j) was added with respect to ANDA.
 For filling ANDA, generic company must include a patent certification
as per section 505(j) (2) (A) of the Hatch Waxman act. This certification
has to make one of the following statement:- 9

10. 10
Para 1
• No patent information on the drug product that is the subject of the
ANDA has been submitted to FDA
Para 2
• That such patent has expired
Para 3
• The date on which such patient expires
Para 4
• That such patent is invalid or will not be infringed by the manufacture,
use, or sale of the drug product which the ANDA is submitted.

11. 11
ANDA APPROVALS

12.  An ANDA certified under paragraphs I or II is approved immediately
after meeting all applicable regulatory and scientific (efficacy, safety and
bioequivalence) requirements.
 This means that the generic drugs manufacturer may get immediate
approval for manufacturing the generic versions of the branded drugs
upon filing an ANDA
 If, the patent information on the branded drug has not been filed by the
branded drug manufacturer or if the patent for the branded drug has
expired.
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13.  A Para III filing is made when the ANDA applicant does not have any
plans to sell the generic drug until the original drug is off patent.
 In case of Para III the application is processed for approval, however
its approval status depends upon the product’s patent expiry.
 ANDA approval under Para III certification is made effective from
the date of patent expiration.
 An ANDA applicant filing a Paragraph IV certification must notify the
proprietor of the patent.
 The patent holder may bring a patent infringement suit within 45
days of receiving such notification.
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14.  If the patent owner timely brings a patent infringement charge against
the ANDA applicant, then the USFDA suspends the approval of the
ANDA until:
 The date of the court’s decision that the listed drug patent is either
invalid or not infringed;
 The date on which the listed drug patent expires, if the court finds the
listed drug’s patent is infringed; or
The date that is 30 months from the date the owner of the listed
drug’s patent received notice of the filing of a Para IV certification.
(Subject to modification by the court).
This means that for 30 months from the date of receipt of notice of
Para VI filing, no ANDA can be approved.
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15.  In other words, once the branded drug company indicates its intent
to begin a patent infringement suit against the generic company as a
result of the paragraph IV filing,
 the USFDA is prohibited from approving the drug in question for
thirty months or until such time that the patent is found to be invalid
or not infringed.
 If, prior to the expiration of thirty months, the court holds that the
patent is invalid or would not be infringed, then the USFDA approves
the ANDA when that decision occurs.
 Conversely, if the court holds that the patent is valid and would be
infringed by the product proposed in the ANDA prior to the
expiration of thirty months, then the USFDA does not approve the
ANDA until the patent expires.
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16. 16

17. 17
PARA IV CERTIFICATION
After 45 days patent holder sues
the applicant 30 months stay
granted to patent holder
30 months stay
expired
30 months stay not
expired
After 45 days patent holder
doesn’t sue applicant FDA may
approve ANDA
ANDA applicant granted
approval

18. 18
30 months stay
expired
For the first applicant
the Exclusive
Marketing Right of
180 days start with
court’s decision
Subsequent
approvals for
Exclusive Marketing
Rights are granted
after expiry of first
applicant’s 180 days
30 months stay
not expired
If judgement’s in
favour of patent
holder FDA can
not approve
ANDA until patent
enquiry
No entry
occurs until
patent expiry
Judgement favouring
ANDA Exclusive
Marketing Right of 180
days begin for first
applicant
First applicant enters
subsequent only after
expiry of Exclusive
Marketing Right for
the first applicant

19.  The first generic applicant to file a Paragraph IV certification is awarded
a 180-day market exclusivity period by the USFDA.
 Who challenges a listed patent by filling a paragraph IV certification and
there by runs the risk of having to defend a patent infringement suit
 The statue provides that the first applicant to file a substantially
complete ANDA containing a para IV certification to a listed patent will
be eligible for a 180-day period of exclusivity beginning either from the
date it begins commercial marketing to the generic drug product.
 FOR EXAMPLE :- 180 day exclusivity was granted to Ranbaxy and
Watson laboratories for marketing generic version of Lipitor.
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20. The 180-day market exclusivity period ordinarily begins on the earlier
of two dates:
The day the approved generic drug is first commercially marketed; or
The day a court decision holds that the patent which is the subject of
the certification is invalid or not infringed.
 A successful defense of a patent infringement suit is not necessary to
obtain this exclusivity period
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21.  Under the proposed rule, only the applicant submitting the first
“Substantially complete ANDA” with a paragraph IV certification with
respect to patent in the Orange book for the listed drug would be
eligible for exclusivity.
 To be “Substantially complete” it is proposed that the application must
contain all of the information required like bioequivalence, etc.
 If a new bioequivalence study is required to obtain approval of the
ANDA then the application would be considered not substantially
complete and the applicant would not be eligible for exclusivity.
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22.  Another way to lose exclusivity is to withdraw paragraph IV
certification either voluntarily or as a result of a settlement or defeat in
patent litigation by first applicant.
 Now in such case if first applicant again submit paragraph IV certificate
and there are no subsequent applicants for 180 days exclusivity then
first applicant would be eligible for exclusivity.
 If there is other applicant that has submitted a paragraph IV
certification for the same drug product neither the first applicant nor
the any subsequent applicant would be eligible 180 day exclusivity.
 The FDA has provided an exception in its proposed rule with respect
to loss of exclusivity due to an ANDA being not substantially complete.
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23.  Multiple generic applicants submit ANDA’s with paragraph IV
certification to the same patents on the same day;
 The agency explained that when, on the same day, more than one
applicant submits an ANDA for the same drug containing a para IV
certification to a listed patent, and no such certificate was submitted
previously, all the applicants will share exclusivity.
 Exclusivity will be triggered for all first applicants for a specific listed
patent when one of them begins to market its product
(or on the date of any court decision finding that patent invalid,
unenforceable, or not infringed, if earlier)
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25. 25
BRAND -30 MONTHS STAY
 Automatic injunction
 Notice of generic
competition
BRANDS GENERICS
GENERIC- 180 DAY EXCLUSIVITY
 1st successful Para IV filer A big head
start on others

26.  180-day market exclusivity for first successful challenger to Orange Book
patent
 Allows generics to challenge Orange Book patents without risk of damages
 “Safe Harbor” rule allows generics to perform bioequivalence and other
testing relating to regulatory approval without risk of patent infringement
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“Dr Reddy’s was the first Indian company to get the 180-day
exclusivity for marketing fluoxetine 40 mg capsule in august
2001”

27. Orange Book provides public notice of patents
 Allows for resolution of patent disputes prior to generic entry
 30-month stay of FDA approval of generic drugs
 Patent Term Restoration
 Allows for Several Market Exclusivities:
Data Exclusivity
 5 years for New Chemical Entity (NCE) Drug
 3 years for non-NCE Drug
 Orphan Drug (7 years)
 Pediatric (PEDS) (6 months) 27

28. (A)Non-patent Exclusivities
provide legal opportunities to extend the period free of
competition called non-patent exclusivity provisions
(1) Orphan drug exclusivity, which is granted to drugs:
(Drugs for a rare or unusual diseases are often treated as orphan drug)
 a) That treat a disease or condition that affects less than 200,000 people in
the US; or
 b) For which it is unlikely that US sales of the drug will recoup its
development costs.
 This exclusivity period is seven years, but only applies to use in treating the
specific rare disease or condition
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29.  This is granted if the FDA has not previously approved the “active
drug moiety” (active moiety is defined as any ion or molecule which
is attributed to the drug physiological or pharmacological action)
 New Chemical Entity exclusivity bars a generic drug company from
filing an application for approval of a generic drug five years from
the first approval of the relevant NDA.
 However, a generic drug company may file an ANDA with a
Paragraph IV certification four years after the first NDA approval
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30.  This applies when new clinical studies lead to new or changed
formulations, dosing regimens or patient population.
 The applicant is entitled to this exclusivity if an application or
supplement contains reports of new clinical investigations conducted or
sponsored by the applicant that were essential for approval.
 This exclusivity, sometimes called data exclusivity, prohibits the FDA
from approving a generic drug application for the new dosage form or
use for three years after the first NDA approval.
 However, it does not otherwise bar approval of generic drug
applications
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31.  This applies if the FDA requested that the NDA holder conduct studies
with the drug in pediatric populations.
 Paediatric exclusivity adds six months of exclusivity to any marketing
or patent exclusivity
 The paediatric studies are conducted on a drug which already has
NDA approval and in response to a request from FDA to conduct such
a study and the report of which has to be submitted to FDA.
 Even if the study fails or the results are unsuccessful the exclusivity is
independent of it.
 The exclusivity is granted to all of the applicants dosages or
formulation and indications for the drug with an existing marketing
exclusivity or a patent with the same active ingredient.
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32. 32
Types Term
New chemical entity exclusivity 5 years
New clinical study exclusivity 3 years
Orphan drug exclusivity 7 years
Paediatric exclusivity 6 months
180 day generic market exclusivity 180 days

33.  An NDA holder must provide the FDA with the patent number and
expiration date of any patent that claims either:
 a) The drug, including the active ingredient and the formulation for
the active ingredient.
 b) A method of using the drug, but not other inventions such as:
metabolites;
synthetic intermediates; or
methods of making the drug.
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34. 34
 The orange book is a resource which
identifies drug product approved on the
basis of safety and effectiveness by the
FDA and related patent and exclusivity
information
 The orange book is available on the
internet and is updated monthly.

35. Reverse payment agreements
Sham litigations
Sham citizens petitions
Walker process
Product hopping
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36.  Both parties decide it is in their mutual best interests to settle via a
significant payment from the patent owner/branded to the
generic to keep the generic drug off the market.
 The generic may make more money than by rushing to market the
drug.
 The branded may also make more money by paying the generic to
defer marketing the drug for a certain period of time.
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37.  Brand sues generic for patent infringement.
 Court finds for generic, often trigers, and holds patent invalid or
unenforceable.
 Hatch-Waxman 30-month stay allows brand to win even if they
lose.
 Plaintiffs must prove brand’s infringement suit is objectively and
subjectively baseless.
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38.  Companies can petition FDA to not approve an ANDA
Should be based on safety or formulation concerns
 Citizen’s Petitions delay approval of ANDAs
 Ripe for abuse, and often abused
 Delay itself is the goal
 Same standard as Sham Litigation
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39.  Delay sometimes allows brands to introduce new versions of the
product.
 Changes are often minimal but can defeat generic competition.
 Brands actively convert the market – Free samples – Pulling the
“old” product from the market.
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40.  Sometime there is unnecessary delay in entry of generic drug into the
market.
 This can happen because of delay in approval of ANDA by FDA or
because of some kind of settlement between first generic (first ANDA
approver) and innovator.
 Thus as per rule until first generic finishes 180 day exclusitivity period no
other generic manufacturer can be granted 180 exclusitivity period.
 As a result innovator and first generic enjoys undue advantage.
 To counter this FDA has involved new concept called “Triggering
period”
 Under this concept the commencement of the 180-day exclusivity period
for the first applicant is either the first commercial marketing of the first
applicant’s product, or a decision of a court holding the patent invalid,
not infringed, or unenforceable, whichever is earlier.
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41.  The Hatch Waxman Act
i. extended the life of the pharmaceutical patents up to 14 years from
the time the NDA is approved by the FDA ,
ii. provided additional market exclusivity for the new uses or new
formulations,
iii. allowed potential generic manufacturers to conduct work related to
marketing approval of the drug without the charge of patent
infringement,
iv. permitted generic manufacturers to use safety and effectiveness
research performed by the brand name pharmaceutical companies,
v. introduced the concept of bioequivalence to obtain the approval of
generic drug, and simplified generic drug approval process by
introducing ANDA, and
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42. vii. encouraged patent challenges by providing 180-day market
exclusivity for the first generic manufacturer who files ANDA,
viii. Hatch Waxman Act led to the birth of generic industry,
ix. It also gave protection to innovators in terms of 30 month stay,
market exclusivities and patent term extensions,
x. But, the brand companies are taking advantage of the loopholes of
HWA in the form of authorized generics and reverse payment
agreements,
xi. Brand companies are also involved in sham litigations to take
advantage of 30 month stay provision,
xii. Maintaining the balance between these two important contributors
to health care will be essential in meeting the goals of affordable
health care and innovative research.
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