This is a presentation to the MassBio membership providing an overview of the legal and regulatory framework that governs the introduction of generic drugs in the United States.

1. THE FRAMEWORK FOR GENERIC DRUG REGULATION
IN THE UNITED STATES
As presented to the MassBio on March 25, 2016
Lana Gladstein
Nutter McClennen & Fish, LLP

2. Agenda
• Introductions
• FDCA and Hatch-Waxman Act
• Overview of Hatch-Waxman requirements
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3. Generic Drugs – Big Picture
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Source: 7th Annual Generic Drugs Savings Report, 2015
http://www.gphaonline.org/media/wysiwyg/PDF/GPhA_Savings_Report_2015.pdf

4. Food Drug and Cosmetic Act (FDCA)
 The Food Drug and Cosmetic Act (Sec. 505), 21 USC §355
 Governs regulatory approval of “any new drug.”
 Includes the 1984 Drug Price Competition and Patent Term Restoration Act, aka
the Hatch-Waxman Act, which was enacted to encourage innovation of new
drugs and to “get generic drugs into the hands of patients at reasonable
prices—fast.” In re Barr Labs, Inc., 930 F.2d 72, 76 (D.C. Cir. 1991).
 A “drug” includes any article “intended for use in the diagnosis, cure, mitigation,
treatment or prevention of disease in man or other animals” – 21 USC § 321(g)
 articles are chemically made;
 but, recombinant drugs that are well characterized and whose mechanisms are well
understood, can be approved as drugs (e.g., insulin).
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5. NDA and ANDA
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NDA (New Drug Application) - 21 U.S.C. §355(b)(1)
 Requires clinical trial data of safety and efficacy.
 Enjoys data and marketing exclusivities which preclude approval of generics and 505(b)(2)
applicants, but not other NDA applicants.
ANDA (Abbreviated New Drug Application) - 21 U.S.C. §355(j)
 Requires the use of the same active ingredient, same route of administration, same dosage form,
and strength as the Reference Listed Drug (of an approved NDA).
 Requires submission of bioequivalence studies only.
 No data exclusivity, but a first approved ANDA gets 180 days marketing exclusivity.

6. Hatch-Waxman Act: ANDA Approval
Framework
A generic product must have:
same active ingredient
same route of administration
same dosage form
same strength as the Reference Listed Drug (RLD)
same labeling as the RLD (except for trademarks and any use
exceptions) and
be bioequivalent to the RLD (i.e., same pharmacokinetic profile).
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7. Hatch-Waxman Act: Patent Certifications
Requires the ANDA applicant to certify regarding each patent listed in the
Orange Book (OB):
 Paragraph I – no patent is listed in the OB.
 Paragraph II – the patent has already expired.
 Paragraph III – the generic will not market until the patent expires.
 Paragraph IV – the patent is invalid, unenforceable, or will not be
infringed.
 Section viii (applies to method claims only) – the ANDA label will “carve
out” all references to a particular patented use.
Note: in the context of H-W litigation, a generic can counterclaim to delist
an improperly listed OB patent. 21 U.S.C. §355 (j)(5)(C)(ii)(I)
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8. Hatch-Waxman Act – Patent Litigation
ANDA with a Para. IV certification = artificial act of patent infringement.
Para. IV certification must contain a detailed statement of reasons why the patent
is invalid or not infringed and include an offer of confidential access to the ANDA.
Para. IV certification must be provided to the NDA holder (and patent owner)
within 20 days of FDA’s acceptance of the ANDA.
NDA holder has 45 days from Para. IV notice to file suit to get a 30-month stay of
FDA approval of the ANDA.
The stay ends at 30 months or upon a final decision by a court, whichever is first.
If first-to-file ANDA applicant wins litigation, it gets 180 days of marketing
exclusivity (i.e., the FDA cannot approve another generic for 180 days, but the
brand can launch own “authorized generic”).
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9. Hatch-Waxman Act – Hallmarks of
Patent Litigation
Bench trial, unless and until the generic launches at risk;
No damages (injunctive relief only), unless the generic launches at risk;
Brand-generic settlements are subject to FTC scrutiny and approval:
• Reverse-payment settlements are disfavored and may have antitrust
liability. FTC v. Actavis, Inc., 133 S. Ct. 2223, 2225–26 (2013) (holding that
under the Hatch-Waxman Act, the parties entering into reverse payment
settlements may have antitrust liability if the payments are designed to
delay competition between a brand and generic company).
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10. Thank you
© 2016 Nutter McClennen & Fish LLP
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Lana Gladstein
Partner
lgladstein@nutter.com
617-439-2161