Notice and Prefiling Considerations

AuthorKenneth L. Dorsney
chapter 3
Notice and Prefiling
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.
dor54588_03_ch03_037-078.indd 37 5/5/16 5:28 PM
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,
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.
(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
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).
dor54588_03_ch03_037-078.indd 38 5/5/16 5:28 PM
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).
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.”).
dor54588_03_ch03_037-078.indd 39 5/5/16 5:28 PM

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