Notice and Prefiling Considerations

• Author: Kenneth L. Dorsney
• Pages: 37-78

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chapter 3

Notice and Prefiling

Considerations

I. The NDA Owner’s Pre–Notice Letter Investigation

A. Timeline for Receiving the Notice Letter

If a Generic1 certifies under paragraph IV that a patent (or multiple pat-

ents) listed in the Orange Book is invalid or will not be infringed by the

Generic’s product,2 it must send a notice letter to the patent holder and

the owner of the new drug application (NDA) (which may be different

than the patent holder) no later than 20 days after the date postmarked

on the notice from the Food and Drug Administration (FDA) indicat-

ing the Abbreviated New Drug Application (ANDA) has been filed.3 The

Generic’s submission of an ANDA or paper NDA4 that seeks approval for

a drug or methods of using a drug protected by one or more patents is an

Rudolf E. Hutz, Reed Smith LLP; Jeffery B. Bove, Novak Druce Connolly Bove + Quigg

LLP; and Mary W. Bourke and Kristen Healey Cramer, Womble, Carlyle, Sandridge & Rice,

LLP. We wish to acknowledge the assistance of Dana K. Severance, Daniel M. Attaway, and

Chittam U. Thakore, Womble, Carlyle, Sandridge & Rice, LLP; and Karen Riesenburger

Poppel, Novak Druce Connolly Bove + Quigg LLP.

1. For purposes of this chapter we refer to the potential or actual ANDA applicant as the

“Generic.” We refer to the NDA holder and patent owner as the “NDA owner.”

2. 21 U.S.C. § 355(j)(2)(A)(vii)(IV).

3. 21 U.S.C. § 355(j)(2)(B)(ii)–(iii).

4. The Hatch-Waxman Act provides two different mechanisms for approval by a

Generic—sections 355(b) and (j). Section 355(j) is the more commonly used ANDA process

and is appropriate when the Generic seeks to market the same active pharmaceutical

ingredient (API) in the same form as the NDA owner. Section 355(b), commonly referred to

as a “paper NDA” is appropriate when the Generic seeks to market the same API, but in a

different form (for example, a different salt of the API). Both ANDAs and paper NDAs rely

on data from the original NDA, but paper NDAs generally require additional safety and

efficacy data before approval.

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CHAPTER 3

38

artificial act of patent infringement.5 Often, litigation is triggered when

the NDA owner receives notice that the Generic has filed a paragraph IV

certification as part of the ANDA or paper NDA. Receipt of the notice let-

ter triggers a 45-day period in which the NDA owner must file suit in a

district court to obtain the benefit of an automatic 30-month stay of final

approval of the ANDA.6 Given this short timeline, the NDA owner should

anticipate such notice letters and have a clear strategy in place long

before its patents and the products they embrace are challenged.

Many factors can affect the timing of receipt of a notice letter. Chief

among these are the expiration dates of the four regulatory exclusivities7

and the incentive for a Generic to be the first to file an ANDA.8 At a mini-

mum, a Generic will usually attempt to file an ANDA and certify under

paragraph IV to obtain approval of the ANDA before or coinciding with the

expiration of all regulatory exclusivities. Additionally, because the Hatch-

Waxman Act provides the first Generic filer with 180 days of generic

market exclusivity,9 this incentive is often a motivating factor behind the

timing of ANDA filings.10 An NDA owner with a successful new chemi-

cal entity (NCE) can anticipate receiving a notice letter four years after

the date the NDA was approved, or four and a half years if the NCE was

afforded pediatric exclusivity.11 For non-NCE drugs, such as drugs com-

prising an old compound that was discovered to treat a particular disease,

notice letters can be expected as soon as the Generic develops its version

of the drug and finalizes and files an ANDA.

In anticipation of receiving a paragraph IV notice letter, the NDA

owner should implement procedures to prepare for receipt and to sue

within 45 days of receipt of the notice letter to avoid forfeiting a statutory

30-month stay of final FDA approval of the Generic’s ANDA.12 Therefore,

5. 35 U.S.C. § 271(e)(2)(A).

6. 21 U.S.C. § 355(j)(5)(B)(iii).

7. See supra chapter 2.

8. Id.

9. 21 U.S.C. § 355(j)(5)(B)(iv).

10. In the race to be first to file, it is not uncommon for more than one Generic to file

an ANDA on the same day, in which case the Generics will share the 180-day exclusivity.

FOOD & DRUG ADMIN.

,

GUIDANCE FOR INDUSTRY, 180-DAY EXCLUSIVITY WHEN MULTIPLE ANDAS

ARE SUBMITTED ON THE SAME DAY

(July 2003); 21 U.S.C. § 355(j)(5)(B)(iv)(II)(bb) (defining

“first applicant” to mean “an applicant that, on the first day on which a substantially

complete application containing a [paragraph IV certification] is submitted for approval of

a drug, submits a substantially complete application that contains and lawfully maintains

a [paragraph IV certification] for the drug.”); see also 149

CONG. REC.

31,783 (2003) (Senator

Kennedy) (“and the exclusivity is available to more than one generic applicant, if they all

challenge patents on the same day”); 21 U.S.C. § 355(j)(5)(D)(iii) (if all first applicants forfeit

exclusivity, “no applicant shall be eligible”).

11. 21 U.S.C. § 355(j)(5)(F)(ii).

12. 21 U.S.C. § 355(c)(3)(c).

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I. The NDA Owner’s Pre–Notice Letter Investigation 39

it is important that the NDA owner implement an internal system for

quickly identifying, routing, and processing notice letters. NDA owners

should alert employees when to expect a notice letter, train employees to

identify and date stamp notice letters, and instruct them to immediately

forward notice letters to legal counsel.

B. Presuit Due Diligence and Review of Orange Book Listings

NDA owners should review patent portfolios and develop strategies to list

and enforce Orange Book patents long before receipt of a notice letter. The

45-day window to file a patent infringement suit post–notice letter simply

is not enough time to thoroughly investigate issues and implement reme-

dial action when necessary.

The FDA obligates the NDA owner to verify the propriety of the pat-

ents listed in the Orange Book.13 When it files its NDA, the NDA owner

must submit a list of certain patents that cover its drug, which the FDA

then lists in the Orange Book.14 If a patent covering a drug issues while

the NDA is pending, the NDA holder has 30 days to notify the FDA of the

new patent.15 If the patent is granted after FDA approval of the drug, the

NDA owner must list it within 30 days of patent grant.16 The FDA will list

a patent submitted after the 30-day period has lapsed, but delaying the

listing of a patent may preclude the patent holder from invoking certain

benefits under the Hatch-Waxman Act.17

The FDA generally does not concern itself with patent matters and

leaves it to the courts to resolve validity and infringement disputes. The

FDA will not investigate whether a patent is properly listed in the Orange

Book.18 A Generic may write to the FDA challenging the propriety of a

13. 21 C.F.R. § 314.53(b); 59 Fed. Reg. 50,338, 50,345 (Oct. 3, 1994).

14. 21 U.S.C. § 355(b)(1)(G).

15. 21 C.F.R. § 314.53(d)(1).

16. 21 U.S.C. § 355(c)(2).

17. 21 C.F.R. § 314.94(a)(12)(vi); 21 C.F.R. § 314.50 (i)(4); see also Am. Bioscience, Inc.,

v. Thompson, 269 F.3d 1077 (D.C. Cir. 2001).

18. Apotex, Inc. v. Thompson, 347 F.3d 1335, 1347 (Fed. Cir. 2003) (“Instead, [the NDA

holder and the FDA] contend that the FDA has only a ministerial role in the listing process,

and that it is the responsibility of the NDA holder to determine whether a patent claims the

drug or a method of using the drug that is the subject of the NDA for purposes of Orange

Book listing. The FDA has adopted a regulation, 21 C.F.R. § 314.53(f), which implements

its view of the allocation of statutory responsibilities. Under the regulation, if any person

disputes an Orange Book listing, that person must notify the FDA. The agency will then ask

the NDA holder to confirm the correctness of the patent information, but the FDA will not

modify the Orange Book information unless the NDA holder submits a change. Thus, the

regulation codifies the FDA’s position that its duties with respect to Orange Book listings

are purely ministerial.”). See also Am. Bioscience, 269 F.3d. at 1084 (“As we noted, and the

parties agree, the FDA has a longstanding policy not to get involved in patent disputes. It

administers the Hatch-Waxman Amendments in a ministerial fashion simply following the

intent of the parties that list patents.”).

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