the hatch-waxman act and how it works: balancing incentives to innovate with the need for affordable...

The Hatch-Waxman Act and How it Works:

Balancing Incentives to Innovate with the Need for Affordable Drugs

Minnesota Intellectual Property Association

Biotech / Chem Law

June 4, 2009

Drug Price Competition and Patent Term Restoration Act

of 1984

Pub. L. No. 98-417Codified at 15 U.S.C. §§ 68b-68c, 70b (1994); 21 U.S.C. §§ 301 note, 355,

360cc (1994); 28 U.S.C. § 2201

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

Background

• 1962 Amendments to FDCA required proof of safety and efficacy

• Lengthy approval period for innovators = defacto shortening of patent term

• Onerous approval requirements for generics = “off-patent” drugs with no generic competition

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

Generic Market Share

Source: Gary Buehler presentation, FDA CDER; IMS Health 2009 study commissioned by GPhA

0

10

20

30

40

50

60

70

1984 2000 2008

%genericRx

Generic Market Share

In 2008, generic sales accounted for 69% of prescriptions written and 16% of all prescription dollars spent

Source: IMS Health 2009 study commissioned by GPhA

0

50

100

150

200

250

2007

brandsales$228b

genericsales$58.5b





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

NDA 1. Chemistry2. Manufacturing3. Controls4. Labeling5. Testing6. Animal Studies7. Clinical Studies8. Bioavailability

ANDA

1. Chemistry

2. Manufacturing

3. Controls

4. Labeling

5. Testing

6. Bioequivalence





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

Roche Products v. Bolar, 733 F.2d 858 (Fed. Cir. 1984)


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.”





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

Patent Term RestorationUnder 35 USC §156

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

Patent Term RestorationUnder 35 USC §156

NOT the same as Patent Term Adjustment under § 154 (delays in PTO review)

Extension is in addition to any adjustment under § 154





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)

Innovator Non-Patent Exclusivity

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





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 NoTE Code RLD Active Ingredient

Dosage Form;Route

StrengthProprietary

NameApplicant

021366 No ROSUVASTATIN CALCIUM

TABLET; ORAL 10MG CRESTOR IPR



021366 Yes ROSUVASTATIN CALCIUM




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

PatentExpiration

Drug Substance

Claim

Drug ProductClaim

Patent Use

Code

DelistRequested

021366 002 6316460 Aug 4, 2020 Y

021366 002 6858618 Dec 17, 2021

U-618

021366 002 RE37314 Jan 8, 2016 Y

Exclusivity Data

Appl No Prod NoExclusivity

CodeExclusivity Expiration

021366 002 NCE Aug 12, 2008

021366 002 I-573 Nov 6, 2011

021366 002 I-547 Nov 8, 2010

Generic applicant patent certifications

ANDA Certification

Paragraph I:

Paragraph II:

Paragraph III:

Paragraph IV:

Patent status

No Patent info in Orange Book

Patent expired

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

Submitting an ANDA with a PIV certification is an act of

infringement

35 USC § 271:

(a) direct infringement

(b) induced infringement

(c) contributory infringement

(e)(1) safe harbor


infringement

35 USC § 271 (e)(2): It shall be an act of infringement to submit –

(A) an [ANDA] Act for a drug claimed in a patent or the use of which is claimed in a patent . . .


infringement

“somewhat artificial” act of infringement that vests district courts with jurisdiction

– Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661 (1990)

Automatic Stay of FDA Approval

Initiation of Lawsuit means FDA cannot approve an ANDA until:

Final court ruling;

Patent expires; or

30 months from notification

Remedies for infringement§ 271(e) (4) For an act of infringement described in

paragraph (2) —

(A) court can set approval date as end of patent,

(B) grant injunctive relief;

(C) no damages unless there has been commercial manufacture, use, or sale .

The remedies prescribed by subparagraphs (A), (B), and (C) are the only remedies which may be granted by a court for an act of infringement described in paragraph (2), except that a court may award attorney fees under section 285.

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

Example timeline: rosuvastatin11/9/93

06/12/92

8/9/98

6/26/01

8/12/03

12/9/07

2/10/10

8/27/98

8/7/01

8/12/07

8/12/08

2/12/11

440 patent filing date

IND becomes effective

NDA filed

NDA approved - product marketing begins

infringement suits filed

trial scheduled

440 patent issues

reissue application

Re 314 patent issues

generic applicant first-to file date

NCE marketing exclusivity

expires

30 month automatic stay expires

6/12/12

1/8/16

Original patent expiration date

patent expiration date following extension

By Edward J. Pardon

the hatch-waxman act and how it works: balancing incentives to innovate with the need for affordable...

Documents

generic approval nda

generic competition

patent notification

patent drugs

litigation slide

gpha slide

patent term restoration

product slide