Notice and Pre-Filing Considerations

• Author: Kenneth Dorsney
• Pages: 33-74

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chapter 3

Notice and Pre-Filing

Considerations1

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

A. Timeline for Receiving the Notice Letter

If a Generic2 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,3 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 twenty days after the date postmarked

on the notice from the Federal Drug Administration (FDA) indicating the

abbreviated new drug application (ANDA) has been filed.4 The Generic’s

submission of an ANDA or paper NDA5 that seeks approval for a drug or

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

act of patent infringement.6 Often, litigation is triggered when the NDA

1. Rudolf E. Hutz, Jeffery B. Bove, Mary W. Bourke, & Kristen Healey Cramer, Connolly

Bove Lodge & Hutz, LLP. We wish to acknowledge the assistance and contributions of R.

James Balls, Dana K. Severance, and Daniel M. Attaway, Connolly Bove Lodge & Hutz, LLP.

2. 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.”

3. 21 U.S.C. § 355(j)(2)(A)(vii)(IV).

4. Id. § 355(j)(2)(B)(ii).

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

Generic: Section 355(b), (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.

6. 35 U.S.C. § 271(e)(2)(A).

CHAPTER 3

34

owner receives notice that the Generic has filed a Paragraph IV certifica-

tion as part of the ANDA or paper NDA. Receipt of the notice letter trig-

gers a forty-five-day period in which the NDA owner must file suit in a

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

final approval of the ANDA.7 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 exclusivi-

ties8 and the incentive for a Generic to be the first to file an ANDA.9 At

a minimum, 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,10 this incentive is often a motivating factor

behind the timing of ANDA filings.11 An NDA owner with a successful new

chemical 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.12 For non-NCE drugs, such as drugs

comprising 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

forty-five days of receipt of the notice letter to avoid forfeiting a statutory

thirty-month stay of final FDA approval of the Generic’s ANDA.13 There-

fore, it is important that the NDA owner implement an internal system

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

7. 21 U.S.C. § 355(j)(5)(B)(iii).

8. See Chapter 2, Section II.A.2.

9. See Chapter 2, Section II.B.4.

10. 21 U.S.C. § 355(j)(5)(B)(iv).

11. 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 AND 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. S15584 (daily ed., Nov.

25, 2003) (“and the exclusivity is available to more than one generic applicant, if they all

challenge patents on the same day”) (statement of Sen. Kennedy); 21 U.S.C. § 355(j)(5)(D)

(III) (if all first applicants forfeit exclusivity, “no applicant shall be eligible”).

12. 21 U.S.C. § 355(j)(5)(f)(ii).

13. 21 C.F.R. § 355(c)(3)(c).

I. The NDA Owner’s Pre-Notice Letter Investigation 35

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. Pre-Suit 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

forty-five-day window to file a patent infringement suit post-notice letter

simply is not enough time to thoroughly investigate issues and implement

remedial action when necessary.

The FDA obligates the NDA owner to verify the propriety of the patents

listed in the Orange Book.14 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.15 If a patent covering a drug issues while the NDA

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

patent.16 If the patent is granted after FDA approval of the drug, the NDA

owner must list it within thirty days of patent grant.17 The FDA will list a

patent submitted after the thirty-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.18

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

listed patent, but the FDA will do nothing more than request that the NDA

14. Id. § 314.53(b); 59 Fed. Reg. 50,338, 50,345 (Oct. 3, 1994).

15. 21 U.S.C. § 355(b)(1)(G).

16. 21 C.F.R. § 314.53(d)(1).

17. 21 U.S.C. § 355(c)(2).

18. 21 C.F.R. §§ 314.94(a)(12)(VI), 314.50(i)(4); see also Am. Bioscience, Inc. v.

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

19. 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.”).