Download what is now known as the Hatch-Waxman Act.

Cheaper Drugs Today And Better Drugs Tomorrow
History
The industry’s lobbying efforts were well-timed. In the late 1970s, the U.S. economy was
in recession and the Carter administration needed to create more jobs, the chair of the
House Health Subcommittee, Henry Waxman, began promoting the bill as an
opportunity to improve the country’s healthcare system.
To that end, he touted the social benefits that could result from restoring the patent
terms to certain pharmaceutical inventions and allowing companies to prepare to
market generic drugs before the corresponding pioneer patents expired.
Senator Orrin Hatch joined in, stating that enactment of the bill would be a groundbreaking compromise in the public interest in which the public receives the best of both
worlds—cheaper drugs today and better drugs tomorrow.
However, it was not until after the CAFC(court of appeals for federal circuits) handed
down the Roche decision when Congress was able to rally behind what is now known as
the Hatch-Waxman Act.
The Act can be divided into three main categories.
The first part relates to drug price competition.
Specifically, the legislation provides for an Abbreviated New Drug Application
(ANDA) to be implemented by the U.S. Food and Drug Administration (FDA).
Briefly, the ANDA provisions allow makers of generic drugs to apply for regulatory
approval of their drugs if




the drug hasn’t been patented,
the patent term of the subject drug has expired,
the patent will expire before the generic goes on the market, or
the patent is invalid or not infringed.
The second part of the Act relates to patent term restoration.
Briefly, this section provides that inventors of pioneer drugs may have their patent terms
extended by an amount of time equal to one-half of the FDA’s investigational new drug
period.
The maximum term of extension is five years, but the effective market exclusivity may not
exceed fourteen years.
The third part of the Act, relates to the research exemption to
patent infringement. Specifically, 35 U.S.C. § 271(e)(1) states,
“ It shall not be an act of infringement to make, use, offer to sell, or sell within the United
States or import into the United States a patented invention (other than a new animal
drug or veterinary biological product (as those terms are used in the Federal Food, Drug,
and Cosmetic Act and the Act of March 4, 1913) which is primarily manufactured using
recombinant DNA, recombinant RNA, hybridoma technology, or other processes involving
site specific genetic manipulation techniques) solely for uses reasonably
-related to the development and submission of information under a Federal law which regulates
the manufacture, use, or sale of drugs or veterinary biological products."
This part of the Act has been the subject of much controversy. In the context of Roche, it would
appear that the main reason :That Section 271(e)(1) was enacted was so that generic drug manufacturers could enter their
products into the marketplace as soon as the corresponding pioneer patents expire.
However, because of the ambiguous language of the statute and equally unclear legislative
history,
there has been considerable debate as to the scope of this statutory exemption as discussed
below.
Hatch-Waxman
Generic Manufacturers
• permitted to use safety and effectiveness data submitted by Brand companies
• need only demonstrate chemical and biological equivalence
• may begin testing before the patent on the proprietary drug expires
• first generic company to file an ANDA gets 180 days of “exclusivity
•Under Hatch-Waxman, the marketing approval process for
generic drug products is streamlined.

Full name- Drug Price Competition and Patent Term Restoration Act

Enacted in 1984

Purpose of the act-dual balancing act

Effect on the pharmaceutical industry
Hatch-Waxman Act Today
Many top-selling prescription drugs in the US are currently the
subject of patent challenges by generic firms seeking to enter market under
the Hatch-Waxman Act:
— Singulair — asthma/allergy drug
— Lovenox — deep vein thrombosis / pulmonary embolism
— Abilify — schizophrenia, bipolar, and depression drug
DEFINITIONS:It is considered as the landmark legislation which established the modern system of
generic drugs in USA.
 Hatch-Waxman amendment of the federal food, drug and cosmetics act established
the process by which, would be marketers of generic drugs can file Abbreviated New
Drug Application (ANDA) to seek FDA approval of generic drugs.
Paragraph IV of the act, allows 180 day exclusivity to companies that are the "firstto-file" an ANDA against holders of patents for branded counterparts.
In simple words
“Hatch-Waxman act is the amendment to Federal, Food, Drug and Cosmetics act
which established the modern system of approval of generics through
Abbreviated New Drug Applications (ANDAs)”
Amongst the aims of the Hatch-Waxman Act of 1984 was that of encouraging
generic companies to challenge patents and gain early market entry. As explained
in an earlier article, the compensation for this was to be a 180-day exclusivity
period for the first generic company that was brave enough to file a Paragraph IV
application to register.
Market exclusivity
New chemical entities (NCE)
 505(b)(1) or New Drug Applications
Contains full reports of investigations of safety and effectiveness Five year exclusivity
 505(b)(2) Application
At least some of the information required for approval comes from studies not conducted by
or for the applicant
180 days Market Exclusivity
Section 505(j)(5)(B)(IV)
First to file
When does it start
Judgment trigger
Commercial marketing trigger
Salient Features Of The Act
Patent challenges and generic exclusivity
Patent term extension
Exemption to infringement
Prior to the Hatch and Waxman act the generic drug manufacturer had to do the
entire clinical trials.
 After the passage of Hatch and Waxman act the generic drug manufacturer had
to only prove bioequivalence of generic drug to the innovator drug by showing that
the generic drug is 80-125% bioequivalent to the innovator drug.
The time and cost involved for getting the generic drug into the market was
significantly reduced.
Low cost quality, safe and effective generic drugs were available to the patients.
Since 1984, over 10,000 generic drugs have entered the market, and generics
accounted for close to 50 percent of prescriptions filled (as on august 1, 2003).
Billions of dollars in health care costs are being saved annually.
Generic drug approval process isn’t less complicated as it involves patent and
exclusivity issues.
If any New Molecular Entity (NME) is approved.
It is granted a exclusivity period of 5 years, which could be extended to 3 more
years for supplements requiring clinical trials.
Patent Certifications
As per the Hatch and Waxman act, generic drug and 505 (b) (2) applicants should include
certifications in their applications for each patent listed in the “Orange Book” for the
innovator drug. This certification must state one of the following:
 (I) that the required patent information relating to such patent has not been filed (Para I
certification);
 (II) that such patent has expired (Para II certification);
 (III) that the patent will expire on a particular date (Para III certification); or
 (IV) that such patent is invalid or will not be infringed by the drug, for which approval is
being sought(Para IV certification).
A certification under paragraph I or II permits the ANDA to be approved immediately, if it is
otherwise eligible. A certification under paragraph III indicates that the ANDA may be
approved when the patent expires.
 A paragraph IV certification, however, begins a process in which the question of
whether the listed patent is valid or will be infringed by the proposed generic product may
be answered by the courts before the expiration of the patent.
 Under the current regulations, the ANDA applicant who files a paragraph IV
certification to a listed patent must notify the patent owner and the NDA holder for the
listed drug that it has filed an ANDA containing a patent challenge.
 Until the effective date of FDA’s final rule, all patents submitted and listed in the
Orange Book that are the subject of a paragraph IV certification require notice to the NDA
holder and patent owner.
 The notice must include a detailed statement of the factual and legal basis for the
ANDA applicant’s opinion that the patent is not valid or will not be infringed.
 The submission of an ANDA for a drug product claimed in a patent is an infringing act if
the generic product is intended to be marketed before expiration of the patent.
 Accordingly, the ANDA applicant who submits an application containing a paragraph IV
certification may be sued for patent infringement.
 If the NDA holder or patent owner files a patent infringement suit against the ANDA
applicant within 45 days of the receipt of notice, FDA may not give final approval to the
ANDA for at least 30 months from the date of that notice.
 This 30-month stay will delay approval of the generic drug product unless the court
reaches a decision earlier in the patent infringement case or otherwise orders a longer or
shorter period for the stay.
Key Terms of the Hatch-Waxman Amendments
Streamlined generic approval process
“Safe Harbor” for pre-approval activities
Patent term restoration to offset lengthy regulatory approval process
Non-patent exclusivity for innovators and generics
Framework for patent notification and litigation
• ANDA
– An abbreviated new drug application used to seek approval of a generic drug product.
• Paragraph IV Certification
– The brand-name company’s patents are invalid or not infringed by the ANDA.
• Orange Book
– The FDA’s listing of patents that claim brand-name drug products.
• 30-Month Stay
– A 30-month stay of FDA approval of an ANDA is invoked if a brand-name company
receives
notice of the generic applicant’s ANDA that contains a paragraph IV certification and
files suit
for patent infringement within 45-days of that notice.
•180-Day Marketing Exclusivity
– The first generic applicant to file an ANDA containing a paragraph IV certification is
awarded
180-days of marketing exclusivity, upon its commercial marketing or a court decision,
during
which the FDA may not approve a subsequent generic applicant’s ANDA for the same
drug
product.
Balancing Innovation with Affordability
“….the American people will save money, and yet receive the best medicine that
pharmaceutical science can provide.”
President Reagan, Sept. 24, 1984
“ MAJOR CERTIFICATIONS OF HWA“
 “That patent information on the drug has not been filed i.e. no patent information
appears in the orange book.
 That the patent has already expired.
 The date on which the patent will expire.
 That the patent is invalid or will not be infringed by the manufacture, use or sale of the
drug for which the ANDA is submitted”.
These certifications are termed as paragraph I, II, III, and IV certifications respectively.
Key Features of the Hatch-Waxman
Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy regulatory
approval process
• Non-patent exclusivity for innovators and generics
• Framework for patent notification and litigation
Requirements for generic approval
• Same active ingredient(s)
• Same route of administration
• Same dosage form
• Same strength
• Same conditions of use
Compared to reference listed drug (RLD) (brand name product)
Requirements for generic approval
1.
2.
3.
4.
5.
6.
7.
8.
NDA
Chemistry
Manufacturing
Controls
Labeling
Testing
Animal Studies
Clinical Studies
Bioavailability
1.
2.
3.
4.
5.
6.
ANDA
Chemistry
Manufacturing
Controls
Labeling
Testing
Bioequivalence
Key Features of the Hatch-Waxman
Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy
regulatory approval process
• Non-patent exclusivity for innovators and
generics
• Framework for patent notification and
litigation
“Safe Harbor” for pre-approval
activities
before the Act, a generic manufacturer who used a patented drug during the patent term for
the purpose of conducting tests to submit information to the FDA committed patent
infringement
35 U.S.C. § 271 (e)(1): It shall not be an act of infringement to make, use, offer to sell, or sell
within the United States or import into the United States a patented invention . . . solely for
uses reasonably related to the development and submission of information under a Federal
law which regulates the manufacture, use, or sale of drugs or veterinary biological products.
 Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005)

statutory text “provides a wide berth for the use of patented drugs in activities related to the
federal regulatory process”

use of patented compounds in preclinical studies is protected . . . as long as there is a
reasonable basis for believing that the experiments will produce “the types of information
that are relevant to an IND or NDA.”
Key Features of the Hatch-Waxman
Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy
regulatory approval process
• Non-patent exclusivity for innovators and
generics
• Framework for patent notification and
litigation
Patent Term Restoration

Formula Under 35 USC §156:
 50% of the time spent in initial clinical trials (IND); PLUS

 100% of the time spent in new drug application (NDA) approval process
Other Requirements:






No more than 5 years or up to 14 years from date of FDA approval
Patent not expired
No previous extension under this provision
First permitted commercial marketing or use
NOT the same as Patent Term Adjustment under § 154 (delays in PTO review)
Extension is in addition to any adjustment under § 154
Key Features of the Hatch-Waxman
Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy
regulatory approval process
• Non-patent exclusivity for innovators and
generics
• Framework for patent notification and
litigation
Innovator Non-Patent Exclusivity

Exclusivity Regardless of Existence of Patent

NCE (New Chemical Entity): 5 years
 New active ingredient, new molecules, new salts
 FDA can’t even accept a generic application for 5 years (4 years if a PIV challenge)
 Effectively 7 ½ years if there is a PIV challenge after 4 years

New product/new use /supplemental exclusivity: 3 years
 (new clinical studies to support a new indication, formulation, salt, dosage
regimen, etc.; enantiomers)
Exclusivity Regardless of Existence of Patent


Orphan Drug: 7 years
 If FDA approval is for disease affecting less than 200,000 U.S. citizens

Pediatric use: 6 months in addition to existing exclusivity or patent term
 If pediatric study is undertaken in response to FDA written request
Key Features of the Hatch-Waxman
Act
• Streamlined generic approval process
• “Safe Harbor” for pre-approval activities
• Patent term restoration to offset lengthy
regulatory approval process
• Non-patent exclusivity for innovators and
generics
• Framework for patent notification and
litigation
Framework for patent notification and
litigation

NDA holder must notify FDA of any patent that claims a drug or method of using a drug
and with respect to which a claim of infringement can reasonably be asserted

FDA publishes in “Orange Book”
Active Ingredient Search Results from "OB_Rx" table for query on “Rosuvastatin."
Appl No
TE Code
RL
D
Active Ingredient
Dosage Form;
Route
021366
No
ROSUVASTATIN
CALCIUM
TABLET; ORAL
021366
No
ROSUVASTATIN
CALCIUM
TABLET; ORAL
021366
Yes
ROSUVASTATIN
CALCIUM
TABLET; ORAL
021366
No
ROSUVASTATIN
CALCIUM
TABLET; ORAL
Strength
Proprietary
Name
10MG
CRESTOR
IPR
20MG
CRESTOR
IPR
40MG
CRESTOR
IPR
5MG
CRESTOR
IPR
Applicant
Patent and Exclusivity Search Results from query on Appl No 021366 Product 002
in the OB_Rx list.
Patent Data
Appl
No
Prod
No
Patent
No
Patent
Expiration
021366
002
6316460
Aug 4, 2020
021366
002
6858618
Dec 17, 2021
021366
002
RE37314
Jan 8, 2016
Drug
Substance
Claim
Drug
Product
Claim
Patent
Use
Code
Y
U-618
Y
Exclusivity Data
Appl No
Prod No
Exclusivity Code
Exclusivity Expiration
021366
002
NCE
Aug 12, 2008
021366
002
I-573
Nov 6, 2011
021366
002
I-547
Nov 8, 2010
Delist
Requested
Generic applicant patent certifications
ANDA Certification
Paragraph I:
Patent status
No Patent info in Orange Book
Patent expired
Paragraph II:
Paragraph III:
Paragraph IV:
No product launch until patent
expires
Patent is
invalid,unenforceable, or will
not be infringed by the
manufacture, use, or sale of
the drug product for which the
ANDA is submitted
Generic exclusivity
First ANDA filer with Para. IV certification gets:
 180 days of exclusivity against other generics
 Starts with first marketing or final appeals court decision
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
ADDITIONAL INFORMATION ON THE HATCH WAXMAN ACT
Some additional information about the HWA as given below:
The 30-month stay is permitted only once, in case of those patents listed in the Orange
Book, when an ANDA is filed under paragraph IV certification. Modifications to the 30-month
stay are allowed based on district court judgments.
The generic drug manufacturers filing ANDA under paragraph IV are required to submit full
and complete information over and above what is necessary under current law and must
notify the patent owner within 20 days.
If the patent owner does not file infringement proceeding within 45 days of notification
issued by ANDA applicant, the applicant may request for a declaratory judgment and thus
avoid being sued. Even if the applicant is sued, applicant may file a counter claim requiring
patent owner to make changes in the Orange Book listings.
This favors the patent holder, because he does not have to pay any damages for not
modifying the Orange Book listing in time and there is apparently no time limit for making
such modifications.
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
A patent can be extended only once
Patent must claim the active ingredient of the approved product
One extension per regulatory review period
Extension only applicable to the approved product, not all the claims of the
patent
Conclusions :• Hatch-Waxman Amendments have been successful in encouraging generic entry.
• The 30-month stay and the 180-day marketing exclusivity provisions should be amended to ensure that
the provisions are not gamed to delay or deter generic entry.
• The HWA provides an expedited USFDA drug approval program for speedy generic entry and Market
Exclusivity as an incentive for continues innovation.
• Pre-HWA those seeking to market a generic version of a branded drug also had to carry out their own
safety and efficacy studies much like the branded drug companies.
• Post-HWA for getting the generic approval the generic drug companies are not required to conduct the
costly and time consuming clinical trials and tests.
• The generic drug companies are allowed to rely on the clinical studies done by the
branded drug manufacturer.
• Unlike the pre-HWA era, undue patent extension may be avoided as the generic versions may be made
available as soon as the patent term of the patented product is over.
Paragraph IV filings are generally associated with litigations as the patent owner tries to
maintain its monopoly by bringing in picture the de facto preliminary injunction of 30
months by commencing an infringement suit against the generic drug manufacturer who
applies for the generic version of the patented drug.
The HWA also has provision for the generic drug manufacturer to invalidate the patent for
branded drugs or at least prove that his generic version will not infringe the patent in
question.
The HWA also allows for a patent term extension of a maximum of 5 years for the branded
drug manufacturer to compensate for the time lost during the NDA approval by the
USFDA.
ADVANTAGES OF HATCH – WAXMAN ACT 1984
•Authorized generics contravene the purposes of the Hatch-Waxman legislatively
supervised, negotiated compromise. They “disrupt the ‘bounty’ system established by
the Hatch-Waxman Act.’”
•The “loophole” in the Hatch-Waxman scheme that permits introduction of authorized
generics during the 180-day exclusivity period, diverts a significant portion of sales that
would be realized by a successful generic challenger to the authorized generic and its
branded sponsor.
•Authorized generics negatively affect the incentive given to generic manufactures to
challenge drug patents.
• Authorized generics may help consumers by lowering short-term prices.
•Authorized generics should “be banned as a strategic response to impending Paragraph IV
entry, but should be allowed in their absence or after 180-day exclusivity expiration.
•The Hatch-Waxman Act should be amended to prohibit the introduction of an authorized
generic equivalent to a branded product, either directly or indirectly, by an NDA holder,
during the 180-day Hatch-Waxman exclusivity period.
1. en.wikipedia.org/wiki/Drug_Price_Competition_and_Patent_Term_Restoration_Act
2. www.fda.gov/newsevents/testimony/ucm115033.htm
3. www.brinkshofer.com/resource_center/85-the-hatch-waxman-act-research-exempt-frompatent-infringement