[Federal Register Volume 59, Number 190 (Monday, October 3, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-24052]


[[Page Unknown]]

[Federal Register: October 3, 1994]


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Part II





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Part 314




Abbreviated New Drug Application Regulations; Patent and Exclusivity 
Provisions; Final Rule
DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 314

[Docket No. 85N-0214]
RIN 0905-AB63

 
Abbreviated New Drug Application Regulations; Patent and 
Exclusivity Provisions

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing regulations 
on certain requirements governing the submission, review, and approval 
of abbreviated new drug applications (ANDA's). Specifically, these new 
regulations pertain to patent issues, certification and notice of 
certification of invalidity or noninfringement of a patent by ANDA 
applicants, effective date of approval of an application under the 
Federal Food, Drug, and Cosmetic Act (the act), and new drug product 
exclusivity. These regulations are intended to complete FDA's 
implementation of Title I of the Drug Price Competition and Patent Term 
Restoration Act of 1984.

EFFECTIVE DATE: November 2, 1994.

FOR FURTHER INFORMATION CONTACT: Sharon M. Sheehan, Center for Drug 
Evaluation and Research (HFD-600), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-0340.

SUPPLEMENTARY INFORMATION:

I. Background

    On September 24, 1984, the Drug Price Competition and Patent Term 
Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments) was 
enacted. The law consisted of two different titles. Title I authorized 
the approval of duplicate versions of approved drug products (other 
than those reviewed and approved under section 507 of the act (21 
U.S.C. 357)) under an ANDA procedure. Title II authorized the extension 
of patent terms for approved new drug products (including antibiotics 
and biological drug products), some medical devices, food additives, 
and color additives. Congress intended these provisions to provide a 
careful balance between promoting competition among brand-name and 
duplicate or ``generic'' drugs and encouraging research and innovation.
    Title I also amended section 505 of the act (21 U.S.C. 355) by 
requiring all New Drug Application (NDA) applicants and holders to 
provide certain patent information, requiring ANDA applicants to 
certify as to the status of patents claiming the drug product they 
intend to copy, providing for the submission and approval of 
applications for which the investigations relied on by the applicant to 
satisfy the ``full reports'' of safety and effectiveness requirements 
were not conducted by the applicant or for which the applicant had not 
obtained a right of reference or use from the person who conducted the 
investigations, establishing rules for disclosure of safety and 
effectiveness data submitted as part of an NDA, and providing specific 
time periods during which an NDA or an ANDA cannot be submitted or 
approved. The 1984 amendments also required FDA to promulgate new 
regulations implementing the statute. In the Federal Register of July 
10, 1989 (54 FR 28872), FDA published a proposed rule on Title I. In 
the Federal Register of April 28, 1992 (57 FR 17950), FDA published a 
final rule on some aspects of Title I, such as ANDA content and format, 
approval and nonapproval of an application, and suitability petitions. 
In that final rule, FDA stated that it was still examining issues 
concerning patents and market exclusivity, and would issue a final rule 
once it had completed its deliberations. This document now finalizes 
those provisions.
    In the Federal Register of March 7, 1988 (53 FR 7298), FDA 
published a final rule implementing Title II. That rule is codified at 
21 CFR part 60.

II. Highlights of the Final Rule

A. Patent Information, Certification, and Notice of Certification to 
Patent Owner and Certain Application Holders

    The statute prohibits the agency from making effective the approval 
of an ANDA or an application described by section 505(b)(2) of the act 
(referred to as a 505(b)(2) application) before all relevant product 
and use patents for the listed drug (a drug product listed in an 
approved drug product list published by the agency) have expired, 
except where the generic applicant asserts either that its product will 
not infringe the patent or that the patent is invalid. In the latter 
case, approval of the ANDA or the 505(b)(2) application may not be made 
effective until the patent owner and the NDA holder have been notified 
and have had an opportunity to litigate the issue of patent 
infringement or validity. To facilitate the patent protection 
provisions, the statute requires that applications submitted under 
section 505(b) of the act include the patent number and expiration date 
of all relevant patents that claim the drug (including product and 
formulation patents) in the application or use patents that claim a 
method of using the drug. The agency publishes this patent information 
in its approved drug product list (``Approved Drug Products With 
Therapeutic Equivalence Evaluations,'' also known as the ``Orange 
Book'') for each listed drug for which patent information has been 
submitted.
    A generic drug applicant submitting an ANDA that refers to a listed 
drug must include a certification as to the status of all patents 
applicable to the listed drug. Similarly, an applicant submitting a 
505(b)(2) application must make certifications with respect to patents 
claiming any listed drug or claiming a use for such listed drug. If a 
generic applicant certifies that a relevant patent expires on a 
specified date, the effective date of approval of the ANDA or 505(b)(2) 
application will be delayed until the expiration of the patent. Thus, 
for example, if the patent expired on January 1, 1995, the effective 
date of approval of the ANDA or 505(b)(2) application would be January 
1, 1995. The agency regards drug products with delayed effective dates 
as having tentative approvals; it does not consider the approval to be 
final until the effective date and the issuance of a final approval 
letter (see 57 FR 17950 at 17956). When a generic applicant certifies 
that any product or use patent is invalid or will not be infringed, the 
applicant must give notice of such certification to the patent owner 
and appropriate approved application holder for the listed drug. The 
generic applicant must include in the notice the factual and legal 
basis for the applicant's opinion that the patent is invalid or will 
not be infringed. Finally, a patent owner has 45 days from receipt of 
the notice of certification to file suit against the generic applicant 
to defend the patent. If the patent owner files suit within 45 days, 
the effective date of approval of the ANDA or 505(b)(2) application may 
be delayed up to 30 months pending resolution of the lawsuit.
    The final rule describes: (1) The requirements for the submission 
of patent information by an NDA holder or applicant, (2) the patent 
certification requirements applicable to generic applicants, and (3) 
the content of a patent certification notice. The final rule also 
specifies: (1) When and to whom the notice is to be sent, and (2) the 
effect of each type of patent certification on the effective date of 
approval of an application for a generic drug product.

B. Exclusivity

    Section 505(c)(3)(D) and (j)(4)(D) of the act protects certain 
listed drugs, or certain changes in listed drugs, from generic copying 
for specified periods by placing a moratorium on the submission, or by 
delaying the effective date of approval, of ANDA's and 505(b)(2) 
applications for those listed drugs. These so-called ``exclusivity 
provisions'' provide the following periods of protection from generic 
competition: (1) A 10-year period of exclusivity for new chemical 
entities approved during the period January 1, 1982, to September 24, 
1984, the date of enactment of the 1984 amendments; (2) a 5-year period 
of exclusivity for new chemical entities approved after September 24, 
1984; (3) a 3-year period of exclusivity for drugs that are not new 
chemical entities approved after September 24, 1984, if the applicant 
submitted an application containing reports of ``new clinical 
investigations (other than bioavailability studies) essential to 
approval and conducted or sponsored by the applicant''; (4) a 3-year 
period of exclusivity for certain changes made after September 24, 
1984, if the applicant submitted a supplement containing reports of 
``new clinical investigations (other than bioavailability studies) 
essential to approval and conducted or sponsored by the person 
submitting the application''; and (5) a 2-year period of exclusivity 
for drugs that are not new chemical entities, or for certain changes 
made to already approved drug products, approved during the period 
January 1, 1982, to September 24, 1984.
    The agency is codifying the provisions regarding 5- and 3-year 
exclusivity; FDA is not codifying the other exclusivity provision 
because they have expired. The final rule also defines certain terms 
used in the regulations, and clarifies the agency's interpretation of 
each of the provisions.

III. Comments on the Proposed Rule

A. Section 314.50--Content and Format of an Application (21 CFR 314.50)

    The proposed rule contained several additions to the existing 
requirements in Sec. 314.50. The proposed additions focused on patent 
information and certifications and claimed exclusivity. Under proposed 
Sec. 314.50(i), for example, a 505(b)(2) applicant would be required to 
include in its application one of four possible certifications: (1) 
That patent information on the reference listed drug had not been 
submitted to FDA; (2) that the patent had expired; (3) the date on 
which the patent will expire; or (4) that the patent was invalid or 
would not be infringed by the manufacture, use, or sale of the proposed 
drug product.
    1. Two comments objected to the provision regarding use patents 
(patents that claim a use for the patented invention) under proposed 
Sec. 314.50(i). The comments explained that the provision would permit 
applicants to decide whether a use would infringe a patent and whether 
the patent owner should be notified. Both comments asked FDA to require 
applicants to send a certification of invalidity or noninfringement to 
all patent owners whose patents claim the active ingredient involved in 
the proposed drug product. One comment would also revise the provision 
to withhold approval of an application if the patent owner disagreed 
with the patent certification in order to give the patent owner an 
opportunity to initiate a lawsuit.
    The regulation corresponds to the statutory language at section 
505(b)(2)(B) of the act. The statute does not require a patent 
certification with respect to a use patent if the applicant is seeking 
approval for a drug product that does not claim a use protected by the 
patent. FDA also declines to revise the provision to have FDA withhold 
approval of an application under these circumstances. The statute 
provides express and specific grounds for delaying an effective date of 
approval (see section 505(c)(3) of the act). These do not include any 
express authority to delay an effective date of approval based on an 
inadequate notice, and the agency is not prepared to infer such 
authority. NDA holders are advised, however, to notify FDA of the 
patented uses that appear in the approved labeling for their products; 
this will enable the agency to provide some guidance to applicants 
required to submit either a patent certification under section 
505(b)(2)(A) or (j)(2)(A) of the act, or a statement under section 
505(b)(2)(B) or (j)(2)(A)(viii) of the act. These uses will be listed 
in the Orange Book.
    2. One comment noted that ``United States Office of Patent and 
Trademark'' in proposed Sec. 314.50(i)(1)(i) should be ``United States 
Patent and Trademark Office.''
    FDA agrees and has revised the provision accordingly.
    3. One comment asked FDA to give examples of patent certifications 
under proposed Sec. 314.50(i)(1)(i)(A)(1) to (i)(1)(i)(A)(3). As 
proposed, these provisions would require an applicant to certify that: 
(1) No patent information had been submitted to FDA, (2) the patent has 
expired, or (3) the patent would expire on a specific date.
    Generally, most applicants making paragraph I, II, or III patent 
certifications simply paraphrase the language used in 
Sec. 314.50(i)(1)(i)(A)(1) to (i)(1)(i)(A)(3) for each patent.
    4. The agency, on its own initiative, has amended 
Sec. 314.50(i)(1)(i)(A) to replace the reference to a patent that 
claims ``the drug or drugs'' with a patent that claims ``a drug (the 
drug product or drug substance that is a component of the drug 
product).'' The agency has made this amendment to clarify the types of 
patents for which a certification should be made.
    5. The agency, on its own initiative, has also amended 
Sec. 314.50(i)(1)(i)(A)(4) and Sec. 314.94(a)(12)(i)(A)(4) (21 CFR 
314.94(a)(12)(i)(A)(4)) to include a reference to unenforceable 
patents. As proposed, these provisions would have required applicants 
to certify that a patent is invalid or will not be infringed by the 
manufacture, use, or sale of the drug product that is the subject of 
the application. The agency has revised these certification statements 
to clarify how an applicant challenging a patent as unenforceable 
should word its paragraph IV certification. Although the agency 
realizes that courts have, in patent cases, distinguished invalid 
patents from unenforceable patents, the only court addressing the issue 
of unenforceable patents in the context of the provisions of section 
505 of the act interpreted the phrase ``invalid or not infringed'' to 
include an unenforceable patent. (See Merck v. Danbury Pharmacal, Inc., 
694 F.Supp. 1 (D. Del. 1988), aff'd, 873 F.2d 1418 (Fed. Cir. 1989) 
(applying section 505(j)(4)(B)(iii) of the act).) The agency agrees 
with the court's construction of the act. The alternative 
interpretation, precluding applicants challenging patents as 
unenforceable from filing certifications under paragraph IV, would be 
contrary to Congress' obvious intent in allowing patent challenges 
under section 505 of the act and would lead to absurd results. 
Subsequent to the Merck decision, the agency has accepted paragraph IV 
certifications from applicants challenging patents as unenforceable.
    The agency has also made corresponding changes to other provisions, 
such as the notice requirements in Secs. 314.52 and 314.95, to include 
certifications for ``unenforceable'' patents.
    6. Two comments disagreed with proposed Sec. 314.50(i)(1)(ii), 
which would require an applicant to state that, in its opinion and to 
the best of its knowledge, there are no patents that claim the drug or 
drugs on which investigations that the applicant relied upon in its 
application were conducted or that claim a use for the drug or drugs. 
One comment said applicants should only be required to certify that 
there are no listed patents. The other comment suggested deleting the 
provision and combining this patent certification with a paragraph I 
(no patent information submitted) certification.
    FDA believes the comments have misconstrued proposed 
Sec. 314.50(i)(1)(ii). The provision would require a ``no relevant 
patents'' certification if, ``in the opinion of the applicant and to 
the best of its knowledge,'' there are no patents described in the 
patent certification section (Sec. 314.50(i)(1)(i)). In other words, if 
an applicant made one of the four patent certifications under 
Sec. 314.50(i)(1)(i), the applicant would not make another 
certification under Sec. 314.50(i)(1)(ii).
    7. One comment strongly objected to proposed Sec. 314.50(i)(4). The 
provision would require section 505(b)(2) applicants whose applications 
were submitted after the late patent information is filed, or did not 
contain an appropriate patent certification at the time of the late 
submission, to submit a patent certification on such patents. The 
comment explained that section 505(d)(6) and 505(e)(4) of the act 
authorizes the agency, after providing an opportunity for a hearing, to 
refuse to approve an application or to withdraw approval of an NDA for 
failure to provide patent information. Thus, the comment argued that 
proposed Sec. 314.50(i)(4) conferred a benefit on NDA applicants by 
permitting late patent information submissions without applying the 
statutory requirements for timely submission.
    The agency has considered this and other comments which suggest 
regulatory approaches for handling patents that are filed outside the 
statutory time limits. Congress clearly intended to enforce timely 
submission of patent information. The statute requires that patent 
information be submitted with the application, by amendment prior to 
approval of the application, or within 30 days after the patent issues. 
(See 21 U.S.C. 355(b)(1) and (c)(2)). For the most extreme example of 
untimely patent filing--when a pioneer fails to file required patent 
information within 30 days of notice from the agency--Congress has 
provided the extreme remedy of withdrawal of approval of the new drug 
application. (See 21 U.S.C. 355(e)(4)). Congress did not directly 
address the question of patent filings that occur more than 30 days 
after issuance of the patent and for which the agency does not provide 
notice of the deficiency. The agency could treat these filings in a 
number of ways. The agency could refuse to publish in the list the 
untimely patent information. This approach has been rejected because it 
would provide no notice to subsequent 505(b)(2) or ANDA applicants that 
a patent exists that the NDA holder believes is applicable to the 
pioneer drug product. Absence of publication could lead an applicant to 
submit a 505(b)(2) application or an ANDA that it would not have 
submitted had the patent been listed. As a result, the applicant and 
the agency may expend resources unnecessarily. In addition, 505(b)(2) 
or ANDA applicants could thereby subject themselves and the NDA holder 
to unnecessary patent litigation.
    Prior to publication of the proposed rule, the agency was asked to 
consider regulatory language designed to allow a pioneer holder to 
update, at any time, its patent information. This approach has been 
rejected because it would allow for manipulation of the patent filing 
system by the holder of the NDA and could result in delays in approval 
of otherwise approvable ANDA's. For example, if patents could be filed 
at any time after issuance, the holder of the NDA could delay the 
filing of a patent, and subsequent publication, until within 30 months 
prior to the expiration of the latest-expiring patent. Even if the ANDA 
applicant does not believe the patent is applicable to the pioneer 
drug, it will then be required either to file a paragraph III 
certification and wait until the patent expires, or to file a paragraph 
IV certification and therefore initiate the procedure set out at 
section 505(c)(3)(C) and (j)(4)(B). This procedure requires that the 
agency wait at least 30 months, unless a shorter or longer period is 
judicially ordered, before it makes effective approval of the 
application. Even if the NDA holder is unsuccessful in defending the 
late-filed patent, it will have extended its period of market monopoly 
in a manner inconsistent with the intent of Congress when it struck the 
balance between protecting the patent rights of innovators and 
encouraging prompt and efficient entry of generics onto the market. By 
requiring timely filing of patent information, the agency hopes to 
permit judicial resolution of patent disputes without unduly extending 
the innovator's period of patent protection.
    The approach adopted by the agency as best embodying the compromise 
adopted by Congress requires that if an NDA applicant submits required 
patent information on an approved drug product more than 30 days after 
issuance of the patent, FDA will publish the untimely information, but 
will not require ANDA and 505(b)(2) applicants with pending 
applications who have previously submitted a certification, i.e. those 
applicants who would be prejudiced by the late submission, to recertify 
to the new patent. Only applicants who initially submit ANDA's or 
505(b)(2) applications after the submission of the patent information 
or whose pending applications do not contain a valid certification at 
the time of submission would be required to submit a certification as 
to that patent. (See Secs. 314.50(i)(4) and 314.94(a)(12)(vi).) While 
this could result in two categories of ANDA's for a pioneer drug, those 
without certifications for the late-filed patent and those with 
certifications for that patent, this approach is the best means for 
discouraging manipulation of the patent filing scheme and providing 
optimum notice of applicable patents. Disputes over patent issues 
arising from this approach will be resolved by Federal courts.
    It is the agency's opinion that this remedy may also prove suitable 
in certain instances when an NDA holder fails to respond to an agency 
request for patent information within the statutory 30-day period. It 
is a less severe sanction than withdrawing the approval of the NDA, but 
nonetheless effectuates congressional intent to encourage timely filing 
and protect patent rights.
    8. One comment asked FDA to clarify supplemental patent 
certifications under proposed Sec. 314.50(i)(6)(i). The comment noted 
that the provision would have applicants submit new patent 
certifications if a patent were found valid and infringed, but does not 
instruct applicants what to do if a patent is found to be infringed, 
but also invalid.
    FDA has revised Secs. 314.50(i)(6)(i) and 314.94(a)(12)(vii)(A) to 
state that an applicant does not have to provide an amended patent 
certification if a court finds a patent to be invalid and infringed. 
FDA recognizes that courts have the discretion to focus on patent 
infringement issues and not decide patent validity. However, court 
decisions have also recognized the desirability of a court ruling on 
patent infringement even if the patent is held invalid. (See, e.g., 
Medtronic, Inc. v. Cardiac Pacemakers, Inc., 721 F.2d 1563 at 1583 
(Fed. Cir. 1983).) (``Though an invalid claim cannot give rise to 
liability for infringement, whether it is infringed is an entirely 
separate question capable of determination without regard to its 
validity. Because both validity and infringement involve construction 
of a claim, and because the construction must be the same in 
determining both, it is desirable to decide both questions at the same 
time.'') Moreover, in such instances, the Supreme Court has indicated 
that ``of the two questions, validity has the greater public 
importance.'' (See Sinclair & Carroll Co. v. Interchemical Corp., 325 
U.S. 327, 330 (1945).) Consequently, if a court finds a patent to be 
invalid and infringed, FDA will attach more importance to the finding 
of invalidity, and will not require an amended patent certification 
even if the patent is also found to be infringed.
    9. The agency, on its own initiative, has also revised 
Sec. 314.50(i)(6)(ii) regarding patent certifications when a patent is 
removed from the list of patents for any reason other than a 
declaration of invalidity. Section 314.50(i)(6)(ii), as proposed, would 
have required an applicant to certify that there are no patents that 
claim the drug or, if other relevant patents claim the drug, to submit 
a request to withdraw the paragraph IV (patent is invalid, 
unenforceable, or will not be infringed) certification. FDA has revised 
this section so that an applicant must certify that there are no 
patents that claim the drug or, if other relevant patents claim the 
drug, to provide an appropriate patent certification.
    10. On its own initiative, the agency has also revised 
Sec. 314.50(i)(6)(iii)(b) (now renumbered as 
Sec. 314.50(i)(6)(iii)(B)). As proposed, this provision would not 
require an applicant to amend a patent certification ``when information 
on an otherwise applicable patent is submitted after the 505(b)(2) 
application is approved, whether or not the approval of the abbreviated 
application is effective.'' Because an approval with a delayed 
effective date is tentative and is not final (see 57 FR 17950 at 
17956), the agency has revised Sec. 314.50(i)(6)(iii)(B) to require 
section 505(b)(2) applicants to amend their patent certifications until 
the effective date of approval.
    11. FDA received five comments on proposed Sec. 314.50(j) and the 
applicant's obligations when claiming marketing exclusivity for a 
product. One comment would change proposed Sec. 314.50(j) to have an 
applicant submit exclusivity information ``with'' its application 
rather than ``to'' its application.
    FDA agrees, in part, with the comment. In general, applicants 
should submit exclusivity information with their NDA's. If the NDA has 
been submitted, but has not been approved, the applicant should submit 
exclusivity information as an amendment.
    12. One comment would revise proposed Sec. 314.50(j)(3) to have an 
applicant state that, ``to the best of its knowledge or belief, a drug 
has not been approved.'' The comment said proposed Sec. 314.50(j)(3) 
would require applicants to ``prove a negative'' because they would 
have to show that ``no drug has previously been approved under section 
505(b) of the act containing any active moiety in the drug for which 
the applicant is seeking approval.''
    FDA agrees and has amended the rule accordingly.
    13. Proposed Sec. 314.50(j)(4)(i) contained a typographical error. 
As originally drafted, the provision interpreted ``new clinical 
investigations'' as a certification that, to the best of the 
applicant's knowledge, the clinical investigations included in the 
application ``meet the definitions of `new' and `clinical 
investigations' set forth in Sec. 314.108(a).'' Proposed section 
314.108(a), however, only defined ``new clinical investigation.'' The 
agency has corrected Sec. 314.50(j)(4)(i) to refer to ``new clinical 
investigation.'' The agency has also replaced the reference to ``the 
clinical investigations'' with ``each of the clinical investigations.'' 
This change is intended to clarify that each clinical investigation, as 
opposed to some clinical investigations, must meet the definition of a 
``new clinical investigation'' in Sec. 314.108. The agency has also 
made a minor grammatical change to Sec. 314.50(j)(4) to simplify its 
sentence structure.
    14. Proposed Sec. 314.50(j)(4)(ii) interpreted the phrase 
``essential to approval'' as:

    A list of all published studies or publicly available reports of 
clinical investigations known to the applicant through a literature 
search that are relevant to the conditions for which the applicant 
is seeking approval, a certification that the applicant has 
thoroughly searched the scientific literature and, to the best of 
the applicant's knowledge, the list is complete and accurate and, in 
the applicant's opinion, such published studies or publicly 
available reports do not provide a sufficient basis for the approval 
of the conditions for which the applicant is seeking approval 
without reference to the new clinical investigation(s) in the 
application, and an explanation as to why the studies or reports are 
insufficient.

Three comments would revise proposed Sec. 314.50(j)(4)(ii) to have FDA 
declare whether a study is ``essential to approval'' before the 
applicant begins the study or at the applicant's request. Another 
comment would consider the agency's rejection of a suitability petition 
or ANDA as conclusive evidence that studies are ``essential to 
approval.''
    As stated elsewhere in this final rule, determining whether a study 
is essential for approval before a firm submits an application or even 
begins the study is not always feasible. Research goals and objectives 
often change during clinical investigations. Moreover, as stated in the 
preamble to the proposed rule, one cannot determine what studies will 
be essential to approval of an application by a review of protocols 
without knowing what drugs have been approved and what is in the 
published literature at the time the application is approved. If 
published reports of investigations, other than those conducted or 
sponsored by the applicant, are sufficient to approve a drug product, 
no additional studies would be essential to approval of that drug 
product as of the date of approval, and no exclusivity would be granted 
(see 54 FR 28872 at 28900 and 28901). Thus, it is far more practical 
for FDA to decide whether a study is essential for approval at the time 
the application is approved. FDA also believes that, if a pivotal study 
that could form the basis for approval were published by someone other 
than the applicant after submission but before approval of the 
application, there would be no exclusivity.
    The agency also declines to treat its rejection of a suitability 
petition or ANDA as conclusive evidence that studies are ``essential to 
approval.'' FDA may refuse to approve a suitability petition or ANDA 
for a variety of reasons. For example, under 21 CFR 314.93(e)(1)(ii), 
the agency may not approve a suitability petition that seeks to change 
an active ingredient if the drug product that is the subject of the 
petition is not a combination drug. Under 21 CFR 314.127(a), the agency 
may refuse to approve an ANDA if the methods used in, or the facilities 
and controls used for, the manufacture, processing, and packing of the 
drug product are inadequate to ensure and preserve its identity, 
strength, quality, and purity. Thus, the agency's refusal to approve a 
suitability petition or ANDA does not necessarily mean that studies 
conducted or sponsored by the applicant are ``essential to approval.''
    15. One comment also interpreted the terms ``scientific 
literature'' in proposed Sec. 314.50(j)(4)(ii) as literature existing 
at the time the application was submitted.
    FDA agrees that Sec. 314.50(j)(4)(ii) only requires applicants to 
provide a list of all published studies or publicly available reports 
of clinical investigations known to the applicant at the time the 
applicant submits the application.

B. Section 314.52--Notice of Certification of Invalidity or 
Noninfringement of a Patent

    Proposed Sec. 314.52 described the process whereby an applicant 
would provide notice of certification of invalidity or noninfringement 
of a patent. Proposed Sec. 314.52(a) would have required applicants to 
provide notice to each patent owner that is the subject of the 
certification and the holder of the approved application. Proposed 
Sec. 314.52(b) instructed applicants to provide notice after receipt of 
a letter from FDA stating that the application has been filed. Proposed 
Sec. 314.52(c)(6) specified the content of a notice, including a 
``detailed statement of the factual and legal basis of the applicant's 
opinion that the patent is not valid or will not be infringed.'' 
Proposed Sec. 314.52(d) would have required an applicant who amended 
its application to contain a patent certification to provide notice of 
certification of invalidity or noninfringement of a patent. Proposed 
Sec. 314.52(e) would have required applicants to document receipt of 
notice.
    16. FDA received two comments on proposed Sec. 314.52(a). One 
comment agreed with the provision, but stated that notice to the holder 
of the approved application should be considered only as informational 
``with no legal ramifications since the NDA holder has no patent rights 
by reason of its NDA.'' (Emphasis added in original.)
    The legal ramifications under patent law, if any, of this notice of 
certification of invalidity or noninfringement of a patent are beyond 
the scope of this rulemaking.
    17. One comment objected to proposed Sec. 314.52(a)(3). The comment 
explained that the provision would permit an applicant whose 
application did not cover any use claimed in a patent to refrain from 
making any patent certifications or providing any notice. The comment 
would require all applicants to provide notice of certification of 
invalidity or noninfringement of a patent to all patent owners whose 
patents claim the active ingredient that is the subject of the 
application.
    Under section 505(b)(2)(A) of the Act, an application must contain 
a certification with respect to each patent which claims the listed 
drug or which claims a use for such listed drug for which the 505(b)(2) 
applicant is seeking approval. One of these patent certifications is 
that the patent is invalid or will not be infringed by the manufacture, 
use, or sale of the new drug for which the application is submitted. 
(See section 505(b)(2)(A)(iv) of the Act). If an applicant makes a 
``paragraph IV'' certification, it must give notice to the patent owner 
and the NDA holder. (See section 505(b)(3)(A) of the Act.) If, however, 
the applicant is not seeking approval for a use that is covered by a 
use patent, the statute does not require a ``paragraph IV'' 
certification or notice to that patent owner and NDA holder. (See 
section 505(b)(2)(B) and (b)(2)(A) of the Act.)
    Thus, Sec. 314.52(a) is consistent with the statute, and FDA 
declines to revise it as suggested by the comment.
    18. FDA received three comments on proposed Sec. 314.52(c) 
regarding the content of a notice of certification of invalidity or 
noninfringement of a patent. Two comments favored extremely detailed 
statements of the factual and legal basis of the applicant's opinion 
that the patent is not valid or will not be infringed. These comments 
would require the applicant to list all components used in the proposed 
drug product, the proportions of each component, and list all grounds 
supporting its opinion that the patent is invalid or will not be 
infringed. One comment opposed disclosure of the proposed drug 
product's formulation and also objected to the use of a ``designated 
intermediary'' in proposed Sec. 314.52(c)(6)(iii).
    In general, the statute requires a notice of certification of 
invalidity or noninfringement of a patent to state that an application 
has been submitted and to include ``a detailed statement of the factual 
and legal basis of the applicant's opinion that the patent is not valid 
or will not be infringed.'' (See section 505(b)(3)(B) and 
355(j)(2)(B)(ii).) The proposed rule listed the type of information FDA 
considered necessary to enable patent owners to decide whether to sue 
for patent infringement. The list at proposed Secs. 314.52(c) and 
314.95(c) generated substantial debate, as reflected in the comments, 
as to the details to be included in a notice. The agency is neither 
prepared nor required to become involved in issues concerning 
sufficiency of notice for purposes of enforcing patent law. Therefore, 
FDA has revised both Secs. 314.52(c) and 314.95(c) so that the detailed 
statement of the factual and legal basis behind the applicant's opinion 
that the patent is invalid, unenforceable, or will not be infringed 
must include: (1) For each claim of the patent alleged not to be 
infringed, a full and detailed explanation why the claim is not 
infringed; and (2) for each claim of a patent alleged to be invalid or 
unenforceable, a full and detailed explanation of the grounds 
supporting the allegation. These provisions, as revised, paraphrase the 
statutory language. The sufficiency of the notice, for purposes of 
patent enforcement, is an issue to be resolved by the applicant and the 
patent owner or the holder of the approved application.
    The agency has also revised Secs. 314.52(c)(6) and 314.95(c)(6) by 
removing paragraphs (c)(6)(iii) entirely. FDA is making this change due 
to the numbers of comments that objected to the use of a ``designated 
intermediary'' and the ``referee'' concept in proposed Secs. 314.52 and 
314.95.
    19. One comment would amend proposed Sec. 314.52(e) pertaining to 
documentation of receipt of notice of certification of invalidity or 
noninfringement of a patent. The comment would include a signed receipt 
or delivery manifest as documentation of notice.
    Section 314.52(e) clearly states that documentation of notice may 
be a copy of the return receipt or ``other similar evidence of the date 
the notification was received.'' The provision also states that FDA 
will accept as adequate documentation of the date of receipt a return 
receipt or ``a letter acknowledging receipt by the person provided the 
notice.'' Thus, Sec. 314.52(e) does not limit an applicant to a 
particular form of documentation of notice. Applicants are required, 
however, to obtain agreement from FDA in advance if they intend to use 
a form of documentation other than return receipt.
    20. The agency has also revised Sec. 314.52(f) to state that the 
45-day period provided for in section 505(c)(3)(C) of the Act will 
begin on the day following the date of receipt of the notice by the 
patent owner or its representative and by the approved application 
holder. The reasons for this change are described in comment 62 below.
    The agency, on its own initiative, has also revised Sec. 314.52(f) 
to state that the agency may begin the 45-day period on a later date if 
the applicant has amended its application to state that a later date 
should be used. This could occur, for example, where the applicant has 
amended its notice to the patent owner to provide more information 
regarding the applicant's notice of invalidity or noninfringement. This 
revision is also consistent with the corresponding provision for 
ANDA's.

C. Section 314.53--Submission of Patent Information

    Proposed Sec. 314.53 contained general requirements for the 
submission of patent information by NDA applicants and NDA holders. For 
example, proposed Sec. 314.53(b) would have required an NDA applicant 
to submit information on each patent that claims the drug or drug 
product for which the applicant is seeking approval or a method of 
using the drug that is the subject of the NDA or amendment or 
supplement and with respect to which a claim of patent infringement 
could reasonably be asserted if a person not licensed by the owner of 
the patent engaged in the manufacture, use, or sale of the drug 
product. Proposed Sec. 314.53(c) described general reporting 
requirements, such as information on the type of patent and the name of 
the patent owner, and also required applicants to submit 
``certifications'' with respect to formulation or composition patents 
(proposed Sec. 314.53(c)(2)) and method of use patents (proposed 
Sec. 314.53(c)(3)).
    21. One comment addressed patent information and amendments of 
patent information under proposed Secs. 314.50(h) and 314.53. These 
provisions would require each application under section 505(b) of the 
act to contain specific information about each patent that claimed the 
drug product or a method of using the drug product. The provisions also 
would require applicants to amend patent information or patent 
certifications and would permit the agency to disclose patent 
information. The comment said FDA should only publish patent 
information filed by NDA applicants at the time FDA approves the NDA.
    A drug product does not necessarily have a patent by the time FDA 
approves the NDA. The statute expressly recognizes that a patent might 
issue after NDA approval, and, under such circumstances, instructs the 
NDA holder to file patent information within 30 days of the patent's 
issue date. Once FDA receives this information, the agency is obliged 
to publish it (see section 505(c)(2) of the act). Patent information 
might also change after NDA approval. For example, the patent term 
restoration provisions at 35 U.S.C. 156 give patent holders the 
opportunity to extend patent terms. The extended patent term may be as 
long as 5 years. However, patent owners cannot apply for patent term 
extension until FDA approves the product for marketing (see 35 U.S.C. 
156(d)(1)). Thus, patent term restoration (also known as ``patent term 
extension'') always occurs after NDA approval, and patent owners who 
obtain such extensions usually notify FDA of the new patent expiration 
date. The new expiration date will be important to ANDA applicants 
because section 505(j)(2)(A)(vii) of the act requires ANDA applicants 
to submit patent certifications. Consequently, FDA does not accept the 
comment's suggestion.
    22. One comment would amend proposed Sec. 314.53 to establish a 
mechanism ``for review of submitted patent information to determine, at 
least on a very general basis, applicability to the particular NDA in 
question.''
    FDA declines to adopt the comment. As stated elsewhere in this 
final rule, FDA does not have the expertise to review patent 
information. The agency believes that its scarce resources would be 
better utilized in reviewing applications rather than reviewing patent 
claims.
    23. FDA, on its own initiative, has amended Sec. 314.53(b) by 
replacing the phrase, ``such patents consist of drug (ingredient) 
patents'' with ``such patents consist of drug substance (ingredient) 
patents.'' The final rule also replaces the phrase ``For patents that 
claim a drug or drug product'' with ``For patents that claim a drug 
substance or drug product.'' These changes are intended to clarify the 
type of patents involved.
    24. One comment would amend proposed Sec. 314.53(b) by requiring an 
applicant to declare that it holds each patent or is the exclusive 
licensee of the patent owner or is authorized to submit patent 
information on behalf of the patent owner. The comment would also 
prohibit an applicant from submitting patent information and would 
prohibit the agency from listing any patent information if the 
applicant did not make any of these declarations.
    The agency declines to amend the provision. Under Sec. 314.53(c), 
the applicant must provide the name of the patent owner or, if the 
patent owner or applicant does not reside or have a place of business 
within the United States, the name of an agent or representative who 
resides or maintains a place of business within the United States and 
is authorized to receive notice of patent certification. Requiring an 
applicant to declare that it is the patent owner or exclusive licensee 
or is authorized to submit patent information would go beyond the 
statutory language at section 505(b)(1) of the act and would not serve 
any statutory purpose.
    FDA also declines to amend the rule to prohibit the applicant from 
submitting patent information or to prohibit the agency from listing 
patent information without a declaration of ownership or license. Such 
an amendment would be contrary to section 505(b)(1) of the act and may 
result in less published patent information, thereby causing applicants 
to question the accuracy and validity of any patent information listed 
by FDA.
    25. FDA received two comments that objected to proposed 
Sec. 314.53(b) and (c) regarding the submission of patent information 
by NDA applicants. Both comments claimed that the 1984 amendments only 
require NDA applicants to provide patent numbers and patent expiration 
dates.
    FDA disagrees with the comments. Section 505(b)(1) of the act 
requires an applicant to file ``the patent number and the expiration 
date of any patent which claims the drug for which the applicant 
submitted the application * * * and with respect to which a claim of 
patent infringement could reasonably be asserted if a person not 
licensed by the owner engaged in the manufacture, use, or sale of the 
drug.'' The requirement in Sec. 314.53(b) and (c) that applicants 
provide information on the type of patent and the name of the patent 
owner or authorized representative is consistent with the purpose of 
section 505(b)(1) of the act.
    26. One comment objected to proposed Sec. 314.53(c)(2) and (c)(3). 
Proposed Sec. 314.53(c)(2) would have required an applicant to provide 
a patent certification for each formulation or composition patent in 
addition to certain, general patent information. Proposed 
Sec. 314.53(c)(3) would have required applicants to provide similar 
certifications for method of use patents. The comment said that a 
patent may contain formulation, composition, and method of use claims. 
The comment suggested deleting the proposed rule's classification of 
patents and replacing it with a general certification that the patents 
listed by the applicant contain claims with respect to which the 
applicant could reasonably assert a claim of infringement against a 
person engaged in the unlicensed manufacture, use, or sale of the drug 
for which the application was submitted.
    FDA acknowledges that a patent may contain a variety of claims, and 
has revised proposed Sec. 314.53(c)(2) by creating a single 
certification statement. The new certification statement would have an 
applicant state that, ``The undersigned declares that Patent No. 
________ covers the formulation, composition, and/or method of use of 
(name of drug product). This product is (currently approved under 
section 505 of the Federal Food, Drug, and Cosmetic Act) [or] (the 
subject of this application for which approval is being sought): 
________________.'' However, because section 505(b)(1) of the act 
specifically requires applicants to ``file with the application the 
patent number and the expiration date of any patent which claims the 
drug for which the applicant submitted the application or which claims 
a method of using such drug,'' and because FDA lacks patent law 
expertise, the agency strongly encourages applicants to identify, to 
the best of their ability, the type of patent covering the drug or drug 
product. This information will help FDA determine which claims cover 
the drug or drug product and which claims cover a method of use.
    27. One comment said FDA should not list formulation patents. 
Proposed Sec. 314.53(c)(2) would require applicants under section 
505(b) of the act to provide information on formulation or composition 
patents, and FDA would publish this information under Sec. 314.53(e). 
The comment said this would increase the number of generic drug 
applications by avoiding difficult questions of exclusivity for 
``patentably distinct formulations'' and noted that patent owners can 
always resort to patent law to halt possible patent infringement.
    FDA disagrees with the comment. The statute expressly requires 
applicants to file ``the patent number and the expiration date of any 
patent which claims the drug for which the applicant submitted the 
application * * *'' (section 505(b)(1) of the act). Thus, if the 
formulation patent claimed the drug product in the application, the 
applicant must file information on that patent.
    28. One comment would revise proposed Sec. 314.53(c)(2)(i), 
(c)(3)(i), and (c)(4) to refer to a ``declaration'' rather than 
``certification.'' The comment explained that the 1984 amendments used 
the word ``certification'' with respect to patent information to be 
submitted by applicants under section 505(b)(2)(A) and (j)(2)(A)(vii) 
of the act, so use of the word ``certification'' in proposed 
Sec. 314.53(c) would be confusing.
    The agency agrees and has revised these and other sections of the 
rule accordingly.
    29. One comment would delete proposed Sec. 314.53(c)(2)(ii) and 
(c)(3)(ii). The comment said that the provision for the correction of 
patent information at proposed Sec. 314.53(f) would ensure that patent 
information is correct.
    The provisions cited by the comment serve different purposes. As 
revised, Sec. 314.53(c)(2)(ii) requires an applicant to provide patent 
information about a product within 30 days after the date of approval; 
these provisions contemplate the possibility that the patents 
pertaining to a product's formulation, composition, and uses may change 
between the time the application is initially submitted and the time 
the application is approved (see 54 FR 28872 at 28909). Although 
Sec. 314.53(f) enables any person to dispute the accuracy or relevance 
of the patent information submitted to FDA, it is the responsibility of 
the applicant, not the general public or the applicant's competitors, 
to ensure that the information provided by the applicant is accurate. 
These provisions for amending patent information are necessary for 
maintaining an accurate list of patent information and useful for 
applicants who must comply with the patent certification requirements. 
Therefore, FDA declines to adopt the comment.
    30. FDA received two comments on proposed Sec. 314.53(c)(4) (now 
renumbered as Sec. 314.53(c)(3)), which would enable an applicant to 
claim that there are no relevant patents that claim the drug product or 
a method of using the drug product. One comment supported the 
provision; the other recommended deleting it entirely, stating that the 
only party that would be injured by the failure to list a patent is the 
NDA applicant.
    FDA declines to delete the provision as suggested. The agency 
disagrees with the assertion that the NDA applicant would be the only 
party injured by the failure to list a patent. The patent holder may be 
a person other than the NDA applicant and may be injured if the 
patented invention is made, sold, or used without the patent owner's 
knowledge or consent. Failure to list a patent may also result in 
injury to other applicants who devote resources towards submitting 
applications for duplicate products without realizing that those 
products may be covered by the patent.
    31. FDA, on its own initiative, has reorganized Sec. 314.53(d) to 
clarify further when and where patent information should be submitted. 
As revised, Sec. 314.53(d)(1) pertains to patent information 
requirements for original applications. New Sec. 314.53(d)(2), formerly 
Sec. 314.53(d)(2)(ii), applies to patent information requirements for 
supplements, and a new Sec. 314.53(d)(3), formerly 
Sec. 314.53(d)(2)(i), applies to patent information submitted after an 
application has been approved. The agency has renumbered the remaining 
paragraphs accordingly.
    32. Proposed Sec. 314.53(d) instructed applicants when and where to 
submit patent information in an original application and in a 
supplement and would require an applicant to provide patent information 
within 30 days if a patent issues for a drug, drug product, or method 
of use after the application had been approved. Three comments asked 
FDA to extend the 30-day period in proposed Sec. 314.53(d) to 60 days.
    FDA declines to accept the comment. The 30-day period is consistent 
with section 505(c)(2) of the act and permits the agency to include the 
latest patent information in supplements to the Orange Book. If FDA 
provided for a longer time period, the Orange Book and its supplements 
might be less likely to contain current patent information for each 
product, and potential applicants might be misled by outdated patent 
information. FDA has, on its own initiative, clarified 
Sec. 314.53(d)(1) and (d)(3) to mention the 30-day deadline.
    33. Proposed Sec. 314.53(d)(2)(ii) (now renumbered as 
Sec. 314.53(d)(2)) would require an applicant to submit patent 
information for a patent that claims the drug, drug product, or a 
method of using the product if the applicant sought approval of 
certain, listed changes through a supplemental application. One comment 
would revise proposed Sec. 314.53(d)(2)(ii) to require an applicant to 
provide a patent declaration for each supplement. The comment explained 
that this would ``eliminate the risk that the four types of supplements 
described in the proposal do not comprise the entire universe of 
supplements that may affect the patent information filed with the 
FDA.'' The comment would also require an NDA applicant to submit 
information on patents that claim the formulation or composition each 
time the NDA applicant submits a supplement to revise the formulation 
or composition.
    FDA disagrees with the comment. Section 505(b)(1) of the act 
requires an applicant to submit information on each patent that claims 
the drug or a method of using a drug product for which a claim of 
patent infringement could reasonably be asserted if a person not 
licensed by the owner engaged in the manufacture, use, or sale of the 
drug. The supplements listed in new Sec. 314.53(d)(2)(i)--supplements 
to change a formulation, to add a new indication or other condition of 
use, to change the strength, or to make any other patented change 
regarding the drug, drug product, or any method of use--are those that 
concern the drug product or a method of using the drug product. 
Additionally, new Sec. 314.53(d)(2)(i)(D) provides for the submission 
of patent information for any other type of patented change. Requiring 
an applicant to provide patent information for all supplements, even if 
the supplement did not involve a change to the drug product or a method 
of using the product (i.e., a change in the site of manufacturing), 
would increase the workload on applicants and the agency without a 
significant benefit.
    The suggestion that FDA require an applicant to submit information 
on patents that claim the formulation or composition each time the NDA 
applicant submits a supplement to revise the formulation or composition 
is apparently based on a misreading of proposed 
Sec. 314.53(d)(2)(ii)(A) (now renumbered as Sec. 314.53(d)(2)(i)(A)). 
This section already requires an applicant to provide such information. 
Thus, the comment's suggestion is unnecessary.
    34. One comment would revise proposed Sec. 314.53(d)(2)(ii)(D) (now 
renumbered as Sec. 314.53(d)(2)(i)(D)) to require the submission of 
patent information if the applicant submits a supplement to make any 
other patented change ``except patented manufacturing processes.''
    The suggested revision is unnecessary because Sec. 314.53(b) 
clearly states that, ``Process patents are not covered by [Sec. 314.53] 
and information on process patents may not be submitted to FDA.''
    35. One comment would delete proposed Sec. 314.53(d)(2)(v) (now 
renumbered as Sec. 314.53(d)(2)(iv)), which would require an applicant 
to comply with the requirements for amending formulation, composition, 
or method of use patent information. The comment said applicants are 
already required to comply with such requirements.
    FDA disagrees with the comment. Section 314.53(d)(2)(iv) requires 
applicants to amend the patent information to account for changes 
proposed in supplemental applications whereas Sec. 314.53(c)(2)(ii) and 
(d)(2)(ii) require an applicant to amend patent information when there 
have been changes in status, or there is other new information 
regarding the relevant patents.
    36. Proposed Sec. 314.53(d)(3) (now renumbered as 
Sec. 314.53(d)(4)) would require an applicant to submit two copies of 
each submission of patent information. One copy would go to the 
archival copy of the application and the other copy would go to the 
chemistry, manufacturing, and controls section of the review copy. One 
comment would delete the phrase ``of the review copy'' from proposed 
Sec. 314.53(d)(3) on the grounds that the phrase appeared to be a 
typographical error.
    FDA believes that the comment misreads proposed Sec. 314.53(d)(3). 
An applicant is required to submit an archival copy and a review copy 
of an application consisting of several separately bound technical 
sections. New Sec. 314.53(d)(4) requires an applicant to provide two 
copies of each submission of patent information. One copy will go to 
the archival copy of the NDA; the other will go to the chemistry, 
manufacturing, and controls technical section of the review copy of the 
NDA.
    37. FDA, on its own initiative, has amended Sec. 314.53(e) 
regarding public disclosure of patent information. As originally 
proposed, Sec. 314.53(e) stated that, for each use patent, FDA would 
publish the ``approved indications or other conditions of use covered 
by a patent and any unapproved indications or condition of use to which 
the applicant certified.'' The agency is deleting the reference to 
``any unapproved indications or condition of use'' to be consistent 
with the patent information requirements in Sec. 314.53(c).
    38. FDA received two comments on proposed Sec. 314.53(f) regarding 
corrections of patent information errors. The proposed provision would 
require a person disputing the accuracy or relevance of patent 
information submitted to and published by FDA to first notify the 
agency in writing stating the grounds for the disagreement. The agency 
would then ask the NDA holder to confirm whether the patent information 
was correct, but would not change the patent information listed in the 
Orange Book unless the NDA holder withdrew or amended that information. 
If the NDA holder did not change the patent information, a 505(b)(2) 
applicant or ANDA applicant would be required to make a certification 
for the listed patent despite any disagreement as to its correctness.
    Both comments said that FDA should ensure that patent information 
submitted to the agency is complete and applies to a particular NDA. 
One comment would also amend the rule to have FDA confirm, upon request 
from any person, the accuracy or relevance of the patent information 
submitted to the agency. One comment said the agency should not provide 
applicants the grounds for a disagreement on the accuracy or relevance 
of patent information.
    As stated elsewhere in this rule, FDA does not have the resources 
or the expertise to review patent information for its accuracy and 
relevance to an NDA. Therefore, the agency declines the comment's 
requests to ensure that patent information is complete and relevant to 
an NDA and to confirm, upon request, the validity of patent information 
submitted to the agency. The agency believes that the declaration 
requirements under Sec. 314.53(c), as well as an applicant's potential 
liability if it submits an untrue statement of material fact, will help 
ensure that accurate patent information is submitted.
    FDA also declines to amend the rule to prevent the agency from 
providing applicants the grounds for a disagreement on the accuracy or 
relevance of patent information. Absent such information, a patent 
owner will be unable to evaluate the disagreement or to explain whether 
the patent information is correct.
    39. One comment noted that proposed Sec. 314.53(f) does not require 
applicants to correct patent listings. The comment would revise the 
provision to permit applicants to ``make otherwise pertinent 
certifications while a listing dispute is pending.'' The comment would 
also require FDA to notify the NDA holder of the disagreement within 15 
days of notification and require patent owners or NDA holders to 
respond to a disagreement on patent information or to withdraw or amend 
the patent information within 30 days. The comment would then require 
FDA to immediately send the NDA holder's response to the party that 
began the disagreement and inform the party whether the patent would 
remain listed.
    As originally proposed, Sec. 314.53(f) expressly required an 
applicant to make ``an appropriate certification for each listed 
patent'' notwithstanding any disagreement as to the correctness of the 
listed patent information. If, as FDA assumes, the proposed reference 
to ``otherwise pertinent certifications'' means ``appropriate 
certifications,'' the proposal is unnecessary. If the proposed 
reference is to negate any responsibility to file an appropriate 
certification for a patent that is subject to a dispute over listing, 
FDA rejects the proposal. Until the dispute is resolved, the patent is 
listed within the meaning of the act. FDA also declines to amend the 
rule to impose deadlines for resolving patent disagreements. The agency 
believes that such deadlines would be impractical, considering the 
agency's lack of expertise in patent matters and the volume of 
applications FDA receives, and agency resources would be better spent 
on reviewing applications rather than exchanging disputed patent 
information among parties as proposed by the comment. The agency also 
notes that it has not had any significant problems with the informal 
procedures described in proposed Sec. 314.53(f) as most NDA holders 
have amended or corrected their patent information after FDA has 
informed them of a dispute.
    The agency has, however, revised Sec. 314.53(f) to provide a new 
address for the submission of written statements disputing the 
relevance or accuracy of patent information. Such statements should now 
be directed to the Drug Information Services Branch in the Division of 
Drug Information Resources. This change reflects current FDA 
operations.

D. Section 314.54--Procedure for Submission of an Application Requiring 
Investigations for Approval of a New Indication for, or Other Change 
From, a Listed Drug

    Proposed Sec. 314.54(a)(1)(vii) would require an applicant seeking 
approval of a drug product that represents a modification of a listed 
drug, to provide certain information regarding marketing exclusivity if 
the applicant believed the modification would be entitled to such 
exclusivity.
    The agency received no comments on this provision and has finalized 
it without change.

E. Section 314.70--Supplements and Other Changes to an Approved 
Application

    Proposed Sec. 314.70(e) (now renumbered as Sec. 314.70(f)) would 
require applicants submitting a supplement to an approved application 
to provide certain marketing exclusivity information if the applicant 
intended to seek market exclusivity.
    The agency received no comments on this provision and has finalized 
it without change.

F. Section 314.94--Content and Format of an Abbreviated Application (21 
CFR 314.94)

    Proposed Sec. 314.94(a)(12) contained the patent certification 
requirements for ANDA's. For example, under proposed 
Sec. 314.94(a)(12)(i), an ANDA applicant would provide a patent 
certification with respect to each patent that claims the reference 
listed drug or that claims a use of the reference listed drug for which 
the ANDA applicant is seeking approval. Proposed Sec. 314.94(a)(12)(ii) 
would permit an ANDA applicant to certify that there are no relevant 
patents that claim the listed drug or a method of use of the listed 
drug. Proposed Sec. 314.94(a)(12)(iii) would permit an ANDA applicant 
to state that the use for which the applicant is seeking approval is 
not covered by a patent claiming a use for the listed drug.
    40. One comment claimed that proposed Sec. 314.94(a)(12)(i)(A) was 
inconsistent with the statute because the statute only requires ANDA 
applicants to make certifications for listed patents rather than 
patents issued by the United States Patent and Trademark Office. Two 
comments added that the suggestion regarding patent searches that FDA 
made in the preamble to the proposed rule was irrational and legally 
insupportable. One company, however, agreed that ANDA applicants should 
submit patent certifications with respect to all patents, including 
those that had not been submitted to FDA for listing.
    The rule simply paraphrases the statutory language in section 
505(j)(2)(A)(vii) of the act. The rule does not require ANDA applicants 
to conduct patent searches. If the applicant believes that no patent 
exists, the applicant is to submit a patent certification under 
Sec. 314.94(a)(12)(ii) that no relevant patents exist. If the applicant 
believes that a patent exists but that the patent owner has not filed 
patent information at FDA, the ANDA applicant would certify that, ``in 
its opinion and to the best of its knowledge,'' no patent information 
has been submitted (i.e., make a paragraph I certification). FDA, 
however, believes it would be prudent for applicants to conduct patent 
searches if possible. A patent search could reveal the existence of an 
unlisted, but valid, patent and thus prevent an unnecessary expenditure 
of resources by applicants and FDA on a product that might not be 
marketable. A patent search might also enable ANDA applicants to avoid 
unnecessary patent infringement litigation.
    41. One comment suggested that FDA publish all patent information, 
including descriptions of the patents and patent numbers, in the Orange 
Book.
    The Orange Book already contains an addendum listing both patent 
and exclusivity information. This section provides patent numbers and 
patent expiration dates as well as exclusivity codes and expiration 
dates. In addition, for a use patent, FDA includes in the Orange Book a 
code identifying the indication covered by the patent. As for patent 
descriptions, FDA lacks the expertise to review and summarize patents 
and individual patent claims and does not believe that expanding the 
Orange Book to include patent descriptions would be an efficient use of 
FDA resources. However, persons who wish to obtain a synopsis of a 
particular patent can consult the Official Gazette for Patents, which 
is published by the United States Patent and Trademark Office. The 
Official Gazette for Patents contains short descriptions of patents and 
is publicly available.
    42. One comment asserted that FDA should list patents that claim 
drug products for which the patent owner is not seeking or has not 
obtained approval. The comment explained that the statute requires NDA 
holders and applicants to submit information on ``any patent which 
claims the drug for which the applicant submitted the application'' 
(section 505(b)(1) of the act). The comment, citing Sec. 314.50(d)(1), 
claimed that ``drug'' means the active ingredient while ``drug 
product'' denotes a marketed product composed of active and inactive 
ingredients. Thus, because section 505(b)(1) of the act uses the term 
``drug,'' the comment continued, any patent that claims the active 
ingredient is a patent that claims the drug for which the applicant 
submitted the application and should be listed.
    FDA disagrees with the comment's interpretation of section 
505(b)(1) of the act. The statutory provision states that patent 
information is to be filed on patents that claim the drug ``for which 
the applicant submitted the application.'' Similarly, the House Report 
accompanying the Drug Price Competition and Patent Term Restoration Act 
indicates that the patent information to be filed ``includes the patent 
number and the expiration date of any patent which claims the drug in 
the NDA or which claims a method of using such drug with respect to 
which a claim of patent infringement could reasonably be asserted * * 
*.'' H. Rept. 857, 98th Cong., 2d sess. 31-32 (1984) (emphasis added). 
Thus, both the statute and its legislative history reveal that Congress 
intended the term ``drug'' to mean ``drug product'' rather than 
``active ingredient'' because NDA's are granted only for drug products 
and not for active ingredients. FDA's interpretation of this provision 
has been upheld by a United States magistrate in Pfizer v. FDA, No. HM-
88-1019, slip op. at 10-13 (D. Md. October 2, 1989) and adopted by a 
Federal district court (see Pfizer, Inc. v. Food and Drug 
Administration, 753 F.Supp. 171 (D. Md. 1990)).
    43. Several comments sought clarification regarding the interaction 
between proposed Sec. 314.94(a)(12)(i)(A)(4) and Sec. 314.94(a)(12)(v), 
180-day exclusivity periods under section 505(j)(4)(B)(iv) of the act, 
and licensees.
    Because patent licensees are subject to 180-day exclusivity that 
has been granted to another applicant, the only instance in which 
proposed Sec. 314.94(a)(12)(v) would apply would be where a patent 
licensee would seek to have an effective approval of its ANDA or 
505(b)(2) application within 45 days of its receipt or filing (because 
the patent holder has 45 days to file a lawsuit against an ANDA 
applicant making a paragraph IV certification). Because the agency does 
not anticipate approving an ANDA or 505(b)(2) application in 45 days, 
FDA, on its own initiative, removed the provisions in 
Sec. 314.94(a)(12)(v) and Sec. 314.107(b)(1)(iv) related to consent by 
a patent owner to an immediate effective date of approval for a 
licensee.
    44. Two comments disagreed with proposed Sec. 314.94(a)(12)(ii), 
which would require ANDA applicants to certify that there are no 
relevant patents that claim the listed drug referred to in the ANDA. 
One comment said that ANDA applicants should only be required to 
certify that no listed patents claim the listed drug referred to in the 
ANDA. The second comment suggested deleting the provision and revising 
proposed Sec. 314.94(a)(12)(i)(A)(1) so ANDA applicants would certify 
that no patent information had been filed.
    FDA declines to accept the comments. As stated in the preamble to 
the proposed rule, an applicant makes a patent certification under 
Sec. 314.94(a)(12)(ii) if ``in the applicant's opinion and to the best 
of its knowledge, no relevant patents claim the listed drug or a method 
of using the listed drug'' (54 FR 28872 at 28885). The applicant makes 
the patent certifications under Sec. 314.94(a)(12)(i) when it is aware 
of or believes that a patent covers the listed drug. (Id.) FDA believes 
that Sec. 314.94(a)(12)(ii) will enable FDA to ensure that each 
applicant has complied with the patent certification requirements.
    45. One comment asked FDA to define ``relevant'' for proposed 
Sec. 314.94(a)(12)(ii). The word ``relevant'' refers to those patents 
defined by section 505(j)(2)(A)(vii) of the act for which a patent 
certification would be required, i.e., patents that claim the listed 
drug, or drug substance component thereof, referred to in the ANDA or 
that claim a use of the listed drug or drug substance for which the 
ANDA applicant seeks approval and for which patent information is 
required to be filed under section 505 (b) and (c) of the act and 
Sec. 314.53.
    Although patents that are held to be invalid or unenforceable in a 
judicial decision may be removed from the list by FDA, a patent that 
has been declared invalid or unenforceable in a lawsuit resulting in 
180-day exclusivity will be deemed relevant under 
Sec. 314.94(a)(12)(ii) and will not be removed from the list until the 
end of the 180-day exclusivity period. This will ensure that 180-day 
exclusivity cannot be avoided by changing a patent certification.
    46. Several comments objected to proposed Sec. 314.94(a)(12)(iii), 
which would require ANDA applicants to provide a patent statement if 
the listed patent is for a method of use and that applicant does not 
intend to claim any of the patented uses. The comments recommended that 
such ANDA applicants certify, under Sec. 314.94(a)(12)(i)(A)(4), that 
the listed use patent would not be infringed, thereby giving the patent 
owner notice of possible patent infringement. One comment asked how 
proposed Sec. 314.94(a)(12)(iii) would affect eligibility for the 180-
day exclusivity period. The comment explained that the statute requires 
ANDA applicants to make patent certifications under section 
505(j)(2)(A)(vii) of the act and statements for method of use patents 
under section 505(j)(2)(A)(viii) of the act. However, the comment 
stated, for method of use patents, the proposed rule could be 
interpreted as giving ANDA applicants the option of making a patent 
certification of noninfringement under proposed 
Sec. 314.94(a)(12)(i)(A)(4) or a statement that the applicants' drug 
products do not involve a patented claim under proposed 
Sec. 314.94(a)(12)(iii).
    FDA does not intend Sec. 314.94(a)(12)(i)(A)(4) to authorize 
certifications with respect to patents that claim a use for the listed 
drug for which the applicant is not seeking approval. The statute 
requires patent certifications only if the patent ``claims a use for 
[the] listed drug for which the applicant is seeking approval * * *'' 
(section 505(j)(2)(A)(vii) of the act). The statute requires an 
applicant to make a patent statement when a method of use patent ``does 
not claim a use for which the applicant is seeking approval * * *'' 
(section 505(j)(2)(A)(viii) of the act).) The proposed rule recognized 
this distinction. FDA stated that if a patent claims a method of using 
the listed drug, and labeling for the ANDA applicant's proposed drug 
product does not contain any indications covered by the method of use 
patent, the ANDA applicant ``should not submit a certification under 
Sec. 314.94(a)(12)(i)(A) for such a patent'' (54 FR 28872 at 28886). 
The preamble also indicated that if the labeling for the ANDA 
applicant's product did contain an indication that was claimed by a 
patent, the applicant should make a certification under 
Sec. 314.94(a)(12)(i)(A). (Id.) Thus, the two provisions cited by the 
comment are not overlapping, and an applicant does not have the option 
of making a certification under Sec. 314.94(a)(12)(i)(A)(4) in lieu of, 
or in addition to, a statement under Sec. 314.94(a)(12)(iii).
    If, however, there are listed patents that present both a product 
and method of use claim, the applicant may file a paragraph IV 
certification with respect to the product patent or patent claim and a 
statement that the product that is the subject of the application does 
not involve a patented method of use with respect to the method of use 
patent or patent claim.
    47. One comment recommended revising proposed Sec. 314.94(a)(12)(v) 
to provide NDA holders the opportunity to consent to licensing 
agreements between ANDA applicants and patent owners. As written, 
proposed Sec. 314.94(a)(12)(v) did not address this issue.
    Neither the statute nor the legislative history suggests that NDA 
holders should be given such a right, and the agency is not prepared to 
infer such a right to interfere in the patent holder's enjoyment of its 
right to license. However, as stated earlier, FDA has elected to remove 
the language in Sec. 314.94(a)(12)(v) regarding consent by the patent 
owner.
    48. One comment objected, in part, to proposed 
Sec. 314.94(a)(12)(vi), which would require an ANDA applicant to 
provide a patent certification in response to an untimely submission of 
patent information if the ANDA was submitted after the untimely 
submission of patent information or did not contain an appropriate 
patent certification at the time the patent information was submitted. 
The comment correctly noted that FDA may refuse to approve or may even 
withdraw approval of an application for failure to submit patent 
information (see section 505 (d)(6) and (e)(4) of the act). The comment 
said these sanctions emphasize the importance of filing patent 
information, and FDA ``should not provide any benefit to the NDA 
applicant who ignores the statutory requirement for timely submission 
of such information.''
    Section 314.94(a)(12)(vi) is intended to effectuate Congress' 
intent to enforce timely submission of patent information. As discussed 
more fully in the response to comment 7 above, FDA believes a less 
severe sanction than the withdrawal of NDA approval for late submission 
of patent information would ordinarily effectuate congressional intent. 
For the reasons discussed in response to comment 7 FDA has concluded 
that if an NDA applicant submits required patent information on an 
approved drug product more than 30 days after issuance of the patent, 
the agency will publish the untimely information but will not require 
ANDA applicants with pending applications who have previously submitted 
a certification that was correct at the time it was submitted, i.e., 
those applicants who would be prejudiced by the late submission, to 
recertify as to the new patent. Applicants who initially submit ANDA's 
after the submission of the patent information or whose pending 
applications do not contain a valid certification at the time of the 
submission would be required to submit a certification as to that 
patent. The agency, therefore, declines to revise this provision.
    FDA also notes that, if an ANDA applicant with a pending 
application voluntarily makes a patent certification for an untimely 
filed patent, the ANDA applicant may withdraw the patent certification 
for the untimely filed patent. The agency, on its own initiative, has 
amended Sec. 314.94(a)(12)(viii) to make this clear. Additionally, if 
the patent certification for the untimely filed patent was a paragraph 
IV certification (claiming that the patent is invalid or would not be 
infringed), the agency would not consider the withdrawn paragraph IV 
certification to preclude FDA from granting 180-day exclusivity to 
another ANDA applicant.
    49. Proposed Sec. 314.94(a)(12)(vii) would permit an ANDA applicant 
to seek confirmation of the correctness of patent information, but 
would also require an ANDA applicant to submit the appropriate patent 
certification if the disputed patent information was not amended or 
withdrawn. One comment suggested amending proposed 
Sec. 314.94(a)(12)(vii) to declare the end of the error correction 
process for patent information to be final agency action. The comment 
explained that this section permits challenges to listed patents but, 
in conjunction with proposed Sec. 314.53(f), neglects to contain a 
process to require patent owners to withdraw or modify patent listings. 
The comment said that declaring the end of the error correction process 
to be final agency action would enable ANDA applicants to seek judicial 
review rather than wait for the patent owner to voluntarily correct the 
patent information.
    FDA disagrees with the comment. Disputes between ANDA applicants 
and patent holders regarding the validity or correctness of the listed 
patent information must be resolved among the ANDA applicants and the 
patent holders rather than by agency action. FDA stated this position 
in the preamble to the proposed rule (see 54 FR 28872 at 28910).
    50. One comment addressed proposed Sec. 314.94(a)(12)(viii) and 
asked FDA to permit applicants to amend their patent certifications if 
a patent is declared invalid. The comment proposed that any amendment, 
with the exception of a paragraph IV certification being changed to a 
paragraph III certification, be considered nunc pro tunc (now for 
then). If a patent were declared invalid, the comment suggested that an 
amendment from paragraph IV to paragraph III be considered ``as if a 
III were originally filed, subject to a prior IV certificant's 
exclusivity rights during the remaining lifetime of the patent.'' 
Finally, the comment said that applicants should be permitted to make a 
paragraph I certification if the patent were removed from the list.
    FDA agrees in part with the comment. An applicant may change its 
certification at any time. Although there is no need for the agency to 
pronounce such changes in certification nunc pro tunc, the agency 
agrees that the protection offered by 180-day exclusivity should not be 
undermined by changes from paragraph IV certification or by the filing 
of original certifications other than paragraph IV certifications. If a 
patent were removed from the list immediately upon a court decision 
that the patent is invalid or unenforceable, an applicant with a 
subsequently filed application might seek to certify that there is no 
relevant patent and seek an immediately effective approval. To ensure 
that this does not occur, the agency has required that a patent remain 
on the list after being declared invalid or unenforceable until the end 
of any applicable 180-day exclusivity period. This means that a patent 
is deemed to be relevant under Sec. 314.94(a)(12)(ii) until the end of 
the term of the patent or applicable 180-day exclusivity period, 
whichever occurs first. Thus, where there is a patent that has been 
challenged by a paragraph IV applicant, a subsequent applicant will not 
be able to file a certification that there is no relevant patent or 
seek an immediately effective approval until either the patent or the 
180-day exclusivity period expires. The agency has amended 
Sec. 314.94(a)(12)(viii)(B) and made a similar change to 
Sec. 314.50(i)(6)(ii) to reflect this position.
    The agency also notes that an applicant may withdraw its patent 
certification at any time. However, as stated earlier, if an ANDA 
applicant made a paragraph IV certification and later withdraws that 
certification, the agency will not regard the withdrawn paragraph IV 
certification as precluding the agency from granting 180-day 
exclusivity to a subsequent ANDA applicant.
    51. One comment suggested that ANDA applicants amend their patent 
certifications to a paragraph I certification if FDA or the NDA holder 
``delists'' a patent.
    As stated in the preamble to the proposed rule, the agency believes 
that a certification under Sec. 314.94(a)(12)(ii), stating that no 
relevant patents claim the listed drug, would be more appropriate if a 
patent is ``delisted'' (see 54 FR 28872 at 28886).
    52. One comment asked FDA to clarify proposed 
Sec. 314.94(a)(12)(viii)(A) so that an amended patent certification 
would be required if a patent were held valid and infringed but not 
required if a patent were held infringed, but not valid.
    If a claim is found to be invalid or unenforceable, the patent will 
ordinarily be removed from the list, and applicants with pending 
applications containing certifications with respect to that patent must 
amend their certifications accordingly to certify that no relevant 
patents claim the drug or, if another relevant patent claims the drug, 
to make an appropriate certification regarding that patent. In the 
amendment, the applicant must state the reason for the change in 
certification (that the patent has been removed from the list). A 
patent that is the subject of a lawsuit under Sec. 314.107(c) will not 
be removed from the list until FDA determines either that no delay in 
effective dates of approval is required as a result of the lawsuit or 
that any such period of delay in effective dates of approval is ended. 
The agency has amended Sec. 314.94(a)(12)(viii)(B) to clarify its 
position regarding certifications and patents removed from the list.
    The agency also advises applicants to submit any patent 
certification changes by letter if the applicant has not received a 
``not approvable'' letter from the agency. If the applicant has 
received a ``not approvable'' letter, it may include the amended 
certification along with the complete response to the deficiencies in 
the ``not approvable'' letter. This will enable FDA to process 
amendments more efficiently.
    53. Six comments addressed amended certifications under proposed 
Sec. 314.94(a)(12)(viii)(C)(2) which would not require applicants to 
amend their patent certifications when patent information is submitted 
after the abbreviated application's approval ``whether or not the 
approval of the abbreviated application is effective.'' One comment 
would require amended patent certifications only if a new patent issued 
after the ANDA had been submitted and make supplements optional after 
ANDA approval. Five comments would require ANDA applicants to amend 
patent certifications until the effective date of their ANDA approvals 
because the existence of a patent would affect the ANDA's effective 
date of approval.
    In the Federal Register of April 28, 1992 (57 FR 17950 at 17953), 
FDA stated that it had clarified its policies with respect to drug 
products with delayed effective dates of approval. The agency stated 
that an approval with a delayed effective date is tentative and does 
not become final until the effective date. Therefore, FDA has amended 
Sec. 314.94(a)(12)(viii)(C)(2) by deleting the phrase ``whether or not 
the approval of the abbreviated application is effective,'' and, 
consistent with this change, and in response to the comments, by 
requiring an ANDA applicant to amend its patent certifications until 
the effective date of ANDA approval.

G. Section 314.95--Notice of Certification of Invalidity or 
Noninfringement of a Patent

    Proposed Sec. 314.95 described an ANDA applicant's obligations with 
respect to a notice of certification of invalidity or noninfringement 
of a patent. Proposed Sec. 314.95(a), for example, would require an 
ANDA applicant to provide notice to the patent owner and the NDA 
holder. Proposed Sec. 314.95(b) would require an ANDA applicant to send 
the notice when it receives an acknowledgment letter from FDA stating 
that the ANDA is sufficiently complete for review to begin. Proposed 
Sec. 314.95(c) prescribed the contents of a notice of certification of 
invalidity or noninfringement of a patent, including ``a detailed 
statement of the factual and legal basis of the applicant's opinion 
that the patent is not valid or will not be infringed.''
    54. One comment recommended that FDA revise the regulation by 
adding a mechanism whereby FDA or the United States Patent and 
Trademark Office would review notices of certification of invalidity or 
noninfringement. The comment would have FDA suspend the 45-day period 
provided by section 505(j)(4)(B)(iii) of the act until FDA or the 
United States Patent and Trademark Office determined that the notice 
was sufficient.
    FDA declines to adopt the comment. As stated elsewhere in this 
preamble, FDA lacks expertise in patent law. Moreover, neither FDA nor 
the United States Patent and Trademark Office currently has access to 
the additional resources that would be necessary to review these 
notices, and a patent certification review system would subject the 
agency's decisions to questioning that would require further resource 
expenditures and create delays in the statutory patent certification 
and challenge process.
    The agency does note, however, that in cases where the notice was 
deemed inadequate by the patent owner or exclusive patent licensee and 
where the ANDA applicant subsequently amends the notice, the agency 
may, if the applicant amends its ANDA with a written statement that the 
date of receipt of the amended notification should be considered the 
date of receipt of notice, use the date of the amended notification to 
begin the 45-day statutory period for institution of an action for 
patent infringement (see 54 FR 28872 at 28888; see also 
Sec. 314.95(f)).
    55. Two comments addressed return receipts under proposed 
Sec. 314.95(a). One comment would amend the rule to provide for signed 
receipts while the second would revise the rule to permit reliance on 
``any appropriate federal rule for transmitting notice to another party 
or for receipt of such notice.''
    Under Sec. 314.95(e), applicants are required to document receipt 
of a notice of invalidity or noninfringement by submitting ``a copy of 
the return receipt or other similar evidence of the date the 
notification was received.'' The rule states that FDA will accept 
return receipts, letters acknowledging receipt by the person provided 
the notice, or ``another form of documentation only if FDA has agreed 
to such documentation in advance.'' Thus, the rule provides several 
methods for documenting receipt of a notice, so the comment's 
recommendations are unnecessary.
    56. One comment asked FDA to clarify when multiple notices might be 
required.
    Section 314.95(a) requires applicants to send notices to each 
patent owner and each holder (or its attorney, agent, or other 
authorized official) of the approved application under section 505(b) 
of the act for the listed drug that is claimed by the patent and for 
which the applicant is seeking approval (Sec. 314.95 (a)(1) and 
(a)(2)). Consequently, applicants could be obliged to send multiple 
notices under several situations. For example, a patent owner is 
usually an individual whereas the holder of an approved application is 
often a corporation. The applicant, therefore, would send one notice to 
the patent owner and another to the firm holding the approved 
application. If several patents cover the listed drug, there may be 
several different patent owners, so the applicant would be required to 
provide separate notices to each patent owner.
    57. Two comments suggested revising proposed Sec. 314.95(a)(1) to 
include the patent owner's name and address in the Orange Book.
    The patent owner's name and address are printed on each patent. As 
a result, whenever a prospective applicant examines a patent to 
determine whether its proposed product would infringe any of the patent 
claims, the applicant would have access to the patent owner's name and 
address. The comment's suggestion, therefore, is unnecessary.
    58. Several comments asked when and how applicants should send 
notices under proposed Sec. 314.95(b). Two comments would have an 
applicant provide a statement to FDA declaring that the applicant 
``will give,'' rather than ``has provided,'' notice of certification of 
invalidity or noninfringement of a patent. These comments explained 
that the statute does not specify a time for the notice, so the rule 
should permit applicants to decide when to send such notices. One 
comment would revise the rule to give FDA 30 days to determine whether 
the ANDA was complete before the applicant would be required to send a 
notice of certification of invalidity or noninfringement of a patent.
    The legislative history discussing a notice of certification of 
invalidity or noninfringement of a patent clearly states that ANDA 
applicants should provide notice ``simultaneously with the submission 
of an ANDA'' and that Congress did ``not intend that applicants be 
permitted to circumvent this notice requirement by filing sham ANDA's 
or ANDA's which are substantially incomplete'' (see H. Rept. 857, 98th 
Cong., 2d sess. 24 (1984)). Thus, to permit applicants to state that 
they ``will provide'' notice to the patent owner and holder of the 
approved application would be contrary to congressional intent. 
Moreover, such a statement would be redundant relative to that required 
under Sec. 314.94(a)(12)(i) and would not inform FDA whether notice 
has, in fact, been provided. With regard to the suggestion of a 30-day 
deadline for FDA to respond before an applicant sends notice, FDA 
believes such a requirement would be impractical. The time required to 
review an application may vary depending upon the application's 
complexity, the review division's workload, the timing and scope of an 
applicant's response to FDA's questions or requests, etc. Although FDA 
intends to review applications expeditiously, current resources and 
priorities may not, in all instances, enable the agency to determine 
whether an application is sufficiently complete for review to begin 
within 30 days after receiving the application. Consequently, FDA 
declines to adopt the comments.
    59. One comment argued that proposed Sec. 314.95(b) creates a delay 
that is detrimental to ANDA applicants and is contrary to the 1984 
amendments and the legislative history. The comment said that proposed 
Sec. 314.95(b) would deprive ANDA applicants of ``statutory rights'' 
associated with the 45-day period and the 30-month period for the 
effective date of an ANDA approval and could present problems among 
competing ANDA applicants. The comment said FDA should permit ANDA 
applicants to provide notice upon submission of an application or have 
ANDA applicants await an initial FDA determination (presumably as to 
whether the application is received) before providing notice.
    FDA disagrees with the comment. As stated above, the legislative 
history expressly states that notice of certification of invalidity or 
noninfringement of a patent must be given simultaneously with the 
submission of an ANDA and that the ANDA cannot be a ``sham'' ANDA or 
one that is substantially incomplete (see H. Rept. 857, 98th Cong., 2d 
sess. 24 (1984)). As written, Sec. 314.95(b) is consistent with the 
legislative history because it requires the ANDA applicant to provide 
notice once FDA has determined that the ANDA is substantially complete 
to permit a substantive review. To permit an ANDA applicant to provide 
notice before FDA has determined whether the ANDA is sufficiently 
complete would be contrary to the legislative history because it would 
only encourage ANDA applicants to file incomplete or ``sham'' ANDA's 
and to supplement them later to secure a place in the review queue in 
an attempt to secure the first ANDA approval.
    60. FDA received five comments regarding the exact contents of a 
notice of certification of invalidity or noninfringement of a patent. 
Two comments would revise the rule to require applicants to disclose 
all components, including active and inactive ingredients, in the 
applicant's prospective formulation, the proportions of those 
components, and all grounds supporting the applicant's assertion that 
the patent is invalid or will not be infringed. Three comments opposed 
disclosure of the applicant's formulation or composition information or 
a detailed statement of the applicant's legal reasoning. These comments 
explained that such information and statements might compromise the 
applicant's trade secrets and adversely affect the applicant's ability 
to engage in litigation.
    As noted above in comment 18, the agency did not anticipate that 
the list in proposed Sec. 314.95(c) would generate the debate reflected 
in the comments and, again, reiterates that the agency does not have 
the expertise or the desire to become involved in issues concerning 
patent law and sufficiency of notice. Therefore, FDA has revised 
Sec. 314.95 to require that the detailed statement of the factual and 
legal basis behind the applicant's opinion that the patent is invalid, 
unenforceable, or will not be infringed include the following: (1) For 
each claim of a patent alleged not to be infringed, a full and detailed 
explanation why the claim is not infringed; and (2) for each claim of a 
patent alleged to be invalid or unenforceable, a full and detailed 
explanation of the grounds supporting the allegation (see 
Secs. 314.52(c)(6)(i) and (c)(6)(ii) and 314.95(c)(6)(i) and 
(c)(6)(ii)). Disputes involving the sufficiency of the notice must be 
resolved by the applicant, patent owner, and holder of the approved 
application rather than by action on the part of FDA.
    61. FDA also received five comments opposing the use of a referee 
or designated intermediary under proposed Sec. 314.95(c)(6)(iii). The 
proposal would have required an ANDA applicant to describe a mechanism 
for disclosing the formulation or composition of the proposed drug 
product to the patent owner or to a ``designated intermediary who will 
act as a referee'' on the subject of patent invalidity or 
noninfringement. The comments said that the concept was legally 
unauthorized and interfered with the traditional judicial process for 
resolving patent disputes.
    FDA agrees that traditional processes for resolving patent 
disputes, which do not involve the agency's regulations, are 
appropriate under these circumstances. Therefore, the agency has 
deleted the provision in its entirety.
    62. Proposed Sec. 314.95(f) would presume a notice of certification 
of invalidity or noninfringement to be complete and sufficient if the 
ANDA applicant complied with the regulatory requirements under 
Sec. 314.95(a) through (e) and would start the 45-day clock for filing 
a patent infringement suit on the date following receipt of the notice. 
One comment challenged the presumption that a notice is complete and 
sufficient to permit the statutory 45-day period to begin. The comment 
would revise the rule to require applicants to file a complete copy of 
the certification and notice of service with FDA and delay the start of 
the 45-day period if any dispute over the certification's sufficiency 
arose. A second comment argued that an approved application holder who 
is also an exclusive patent licensee might have different interests 
than the patent owner. The comment would revise the rule to require 
notice to both the patent owner and to the licensee or approved 
application holder.
    With respect to FDA's presumption that a notice is complete and 
sufficient to begin the 45-day period, Sec. 314.95(c), as amended, 
paraphrases the statutory language concerning notices and does not 
attempt to establish more detailed requirements for ``sufficiency'' of 
a notice. FDA has revised Sec. 314.95(f) to state that it will begin 
the 45-day period on the first day after the documented date of receipt 
by the person(s) receiving the notice. FDA will be able to determine 
this date because Sec. 314.95(e) requires applicants to submit 
documentation of receipt of notice. FDA may, if the applicant amends 
its ANDA with a written statement that a later date should be used, 
count from the later date.
    FDA also agrees that an exclusive patent licensee's interests may 
differ from those of the patent owner. Therefore, FDA has revised 
Secs. 314.52(f) and 314.95(f) to start the 45-day period on the day 
following the date of receipt of the notice by the patent owner or its 
representative and by the approved application holder.

H. Section 314.101--Filing an Application and an Abbreviated Antibiotic 
Application and Receiving an Abbreviated New Drug Application (21 CFR 
314.101)

    63. The agency, on its own initiative, is revising Sec. 314.101(e) 
to add a new paragraph stating that the agency will refuse to file a 
505(b)(2) application or receive an ANDA if the drug product that is 
the subject of the 505(b)(2) application or ANDA is protected by a 5-
year exclusivity period under section 505(c)(3)(D)(ii) and 
(j)(4)(D)(ii) of the act. This amendment is consistent with the 
statutory language and Sec. 314.108(b)(2).

I. Section 314.107--Effective Date of Approval of a 505(b)(2) 
Application or Abbreviated New Drug Application Under Section 505(j) of 
the Act)

    Proposed Sec. 314.107 was intended to codify the requirements under 
section 505(c)(3) and (j)(4) of the act regarding the effective dates 
of approval for a 505(b)(2) application or an ANDA. For example, if the 
505(b)(2) applicant or ANDA applicant certified that there are no 
relevant patents, that patent information has not been submitted, that 
the patent has expired, or that the patent is invalid, unenforceable, 
or not infringed, and the patent owner has not brought suit for patent 
infringement, proposed Sec. 314.107(b)(1) would treat the date FDA 
issues an approval letter as the effective date of approval. If the 
505(b)(2) applicant or ANDA applicant certified that the patent would 
expire on a specific date, proposed Sec. 314.107(b)(2) would treat that 
specific date as the effective date of approval. Proposed 
Sec. 314.107(b)(3) described several situations in which the effective 
date of approval could vary, depending upon the disposition of patent 
litigation.
    Proposed Sec. 314.107 also implemented the ``180-day exclusivity 
period'' described in section 505(j)(4)(B)(iv) of the act. In brief, 
section 505(j)(4)(B)(iv) of the act states that if an ANDA contains a 
paragraph IV patent certification (declaring the patent to be invalid 
or not infringed) and the ANDA is for a drug for which a previous ANDA 
containing a paragraph IV patent certification has been submitted, 
approval of the subsequently submitted ANDA will be made effective 180 
days after the date FDA receives from the previous ANDA applicant 
notice of the first commercial marketing of the drug or the date a 
court holds the patent that is the subject of the patent certification 
to be invalid or not infringed, whichever date is earlier (see section 
505(j)(4)(B)(iv) of the act). Proposed Sec. 314.107(c) provided that an 
applicant must be the first ANDA applicant to submit a substantially 
complete application with a paragraph IV certification and must have 
been sued for patent infringement in order to qualify for 180-day 
exclusivity.
    64. One comment asked FDA to permit any person to contact FDA 
informally to determine whether the listed patent information was 
correct and later petition the agency to correct any errors. As 
proposed, Sec. 314.107 did not provide for inquiries concerning patent 
information.
    Sections 314.53(f) and 314.94(a)(12)(vii) describe the procedures 
that an applicant can use to question the validity of patent 
information. In brief, if an applicant disputes the accuracy or 
relevance of patent information, it should first notify FDA in writing 
and state the reasons for the disagreement. FDA will then request that 
the relevant NDA holder confirm the validity of the patent information, 
but will not change the patent information itself unless the NDA holder 
withdraws or amends the patent information. The agency believes that 
these procedures for determining the validity of patent information are 
sufficient, and, therefore, declines to adopt the change suggested by 
the comment.
    65. FDA, on its own initiative, has amended Sec. 314.107(b)(1) to 
state that an approval will become effective on the date FDA issues an 
approval letter except as provided under paragraphs (b)(3), pertaining 
to approvals resulting from the disposition of patent litigation; 
(b)(4), pertaining to approvals where an applicant has submitted 
multiple certifications; and (c), regarding subsequent ANDA 
submissions. These changes are to clarify that there are other 
situations that may make an approval effective.
    66. Two comments would revise proposed Sec. 314.107(b)(1)(iv) 
regarding a certification that a patent is ``invalid or will not be 
infringed.'' The comments would have this certification state that the 
patent is ``invalid and will not be infringed.''
    FDA declines to adopt the suggested language. The provision simply 
paraphrases the statutory language for a paragraph IV certification 
(see section 505(j)(2)(A)(vii)(IV) of the act). The agency has, 
however, amended the provision to account for a certification that a 
patent is unenforceable and, as stated earlier, removed the language 
regarding consent from the patent holder.
    67. One comment asked FDA to amend proposed 
Sec. 314.107(b)(1)(iv)(B)(2) to require NDA holders to have a role in 
or consent to licensing agreements between patent owners and ANDA 
applicants. The proposed rule would consider the effective date of 
approval for a 505(b)(2) application or an ANDA to be the date FDA 
issues an approval letter if, among other things, the drug product is 
covered by a patent licensing agreement and the 505(b)(2) application 
or ANDA contains a statement that the applicant has been granted a 
patent license and a statement from the patent owner that it has a 
licensing agreement with the applicant for the proposed drug product 
and that the patent owner consents to an immediate effective date.
    As stated elsewhere in this final rule, FDA believes that the 
negotiations surrounding licensing agreements and the parties entering 
into such agreements are outside the scope of this rule. Additionally, 
as stated in the response to comment 43 above, the agency has deleted 
the provisions in Sec. 314.107(b)(1)(iv) relating to consent by a 
patent owner to an immediate effective date of approval for a licensee.
    68. The agency, on its own initiative, has made minor grammatical 
changes and other revisions to Sec. 314.107 (b)(2) and (b)(3). These 
revisions replace ``Upon patent expiration'' with ``Patent Expiration'' 
and ``Upon disposition of patent litigation'' with ``Disposition of 
patent litigation.'' Additionally, the changes specify that the patent 
owner must receive the notice of certification and clarify, in 
Sec. 314.107(b)(3)(i)(B), the effective date of approval.
    69. Proposed Sec. 314.107(b)(3) described the effective date of 
approval of a 505(b)(2) application or ANDA upon disposition of patent 
litigation. Under proposed Sec. 314.107(b)(3)(i)(A), if an applicant 
certified that the relevant patent was invalid or would not be 
infringed, and the patent owner or its representative brought suit for 
patent infringement, the effective date of approval for the 505(b)(2) 
application or ANDA would be 30 months after the date of receipt of the 
notice of certification of patent invalidity or noninfringement by the 
patent owner or its representative unless a court extended or reduced 
the 30-month period. Proposed Sec. 314.107(b)(3)(i)(B) described the 
effective date of approval of a 505(b)(2) application or an ANDA upon 
disposition of patent litigation when the patented drug product also 
qualified for 5 years of market exclusivity. Proposed 
Sec. 314.107(b)(3)(ii) through (b)(3)(iv) represented additional 
modifications to the effective date of approval due to court decisions 
or orders.
    One comment concerned the proposed language in 
Sec. 314.107(b)(3)(i) regarding the 30-month period. The comment would 
amend this provision to shorten or lengthen the 30-month period 
pursuant to a court order.
    The suggested change is unnecessary because Sec. 314.107(b)(3)(i) 
through (b)(3)(iv) explains how the 30-month period may be changed due 
to court decisions or orders.
    The agency also emphasizes that disposition of patent litigation 
will not result in automatic approval of a pending application. FDA 
notes that section 505(c)(3)(C) and (j)(4)(B)(iii) of the act describe 
when approval of a 505(b)(2) application or an ANDA shall be made 
effective if an applicant submitting a 505(b)(2) application or ANDA 
has made a paragraph IV certification and has or has not been sued for 
patent infringement. For example, if the applicant made a paragraph IV 
certification, was sued for patent infringement, and the court hearing 
the patent infringement suit decided that the patent was either invalid 
or not infringed, section 505(c)(3)(C)(i) and (j)(4)(B)(iii)(I) of the 
act state, respectively, that approval of the 505(b)(2) application or 
ANDA may ``be made effective on the date of the court decision.'' 
However, the agency interprets these provisions of the act as 
requiring, as a preliminary matter, final agency approval of the 
application in order for any approval to be made effective. Thus, an 
applicant with a tentative approval may not begin marketing its drug 
product until it has received an approval letter from the agency 
because a tentative approval letter does not constitute a final 
``approval'' of the application. In such cases, the agency will examine 
the application to determine whether there have been any changes in the 
conditions under which the application was tentatively approved. The 
tentative approval would become final and, therefore, effective only 
when the agency sends an approval letter to the applicant.
    Similarly, an applicant that has not yet received a tentative 
approval letter may not begin marketing its drug product in the event 
that a court reaches a decision in any related patent infringement 
litigation because there is no final ``approval'' by FDA that could be 
made ``effective'' within section 505(c)(3)(C)(i) or (j)(4)(B)(iii) of 
the act.
    Other provisions of the act support this interpretation of section 
505(c)(3)(C)(i) and 505(j)(4)(B)(iii) of the act as they relate to the 
expiration of the 30-month period or the date of the court decision. 
For example, section 505(j)(3) of the act states that the agency shall 
approve an ANDA unless certain circumstances are found to exist. 
Section 505(j)(3)((A) of the act prevents the agency from approving an 
ANDA if the agency finds that ``the methods used in, or the facilities 
and controls used for, the manufacture, processing, and packing of the 
drug are inadequate to assure and preserve its identity, strength, 
quality, and purity.'' Consequently, until FDA assesses the available 
information, often from an additional current good manufacturing 
practices inspection, it cannot determine whether the applicant's 
methods and controls used for the manufacture, processing, and packing 
of the drug are adequate to assure and preserve the drug's identity, 
strength, quality, and purity and therefore, under section 505(j)(3) of 
the act, whether the ANDA should be approved. Thus, unless FDA has 
formally approved an ANDA under section 505(j)(3) of the act, there is 
no ``approval'' that could be made effective under section 505(j)(4)(B) 
of the act upon resolution of the patent litigation. (Section 505(d) of 
the act establishes an analogous approval requirement for 505(b)(2) 
applications.)
    The legislative history provides additional support for FDA's 
interpretation. In describing the provisions regarding effective dates 
of approval and court decisions, the House Report states:

    The Committee wishes to emphasize that the court may not order 
an ANDA approved under this provision. These are times when approval 
of an ANDA may be made effective if the FDA has approved the ANDA.

    See H. Rept. 857, 98th Cong., 2d sess., Part 1, 27-28 (1984) 
(emphasis added). The same concept is applicable to 505(b)(2) 
applications (see id. at 34).
    This interpretation of section 505(j)(4)(B) of the act reflects 
current FDA practice and revises the agency's previous policy that was 
stated in the preamble to the proposed rule (see 54 FR 28872 at 28894). 
It also clarifies the agency's position on delayed effective dates of 
approvals as expressed in the preamble to the final rule on ANDA 
content and format that was published in the Federal Register on April 
28, 1992 (57 FR 17950 at 17956). Consequently, FDA, on its own 
initiative, has amended Sec. 314.107(b)(3) to clarify when approval of 
an application may become effective and by adding a new paragraph 
(b)(3)(v) to state that, in order for an approval to become effective 
under paragraph (b)(3), the applicant must first receive a final 
approval letter from the agency.
    70. One comment would restrict proposed Sec. 314.107(b)(3)(ii) to 
district court orders. The comment would revise the rule to state: ``If 
before the expiration of the 30-month period, or 7\1/2\ years where 
applicable, the district court decides such patent is invalid or not 
infringed, the approval will be made effective on the date of the 
district court order or judgment.'' The comment would also replace the 
words ``a final order'' in proposed Sec. 314.107(b)(3)(iii) and 
(b)(3)(iv) with ``an order or judgment.''
    FDA declines to limit the rule to district court orders. As stated 
in the preamble to the proposed rule, FDA interprets the requirement of 
a ``court decision'' to mean ``a final decision of a court from which 
no appeal can or has been taken'' (see 54 FR 28872 at 28895). Beginning 
the 180-day exclusivity period before the resolution of the appeals 
process would render the exclusivity valueless to a prudent applicant 
who delayed marketing until the issues were resolved on appeal.
    FDA has, however, revised Sec. 314.107(b)(3)(iii) and (b)(3)(iv) to 
refer to an ``order or judgment'' because both terms are sometimes used 
to refer to actions that terminate an action or decide a matter in 
litigation.
    71. Proposed Sec. 314.107(b)(4) concerned applicants who made 
multiple patent certifications. In essence, the proposed provision 
would consider the approval of a 505(b)(2) application or an ANDA to be 
effective on the last applicable date. One comment would amend proposed 
Sec. 314.107(b)(4) by adding a new sentence stating:

    If the applicant has submitted certifications under 
Sec. 314.50(i) or Sec. 314.94(a)(12) and has submitted notice to the 
owner of the patent pursuant to Sec. 314.95, and FDA subsequently 
receives a stipulation or order by the district court notifying it 
that the applicant has amended its answer to add new arguments, not 
included in that notice, in any ensuing suit for patent 
infringement, the date of approval will be calculated based on a 30-
month period starting at the date of receipt by FDA of each such 
stipulation or order, and the approval will become effective on the 
last applicable date.

Alternatively, the comment suggested that an ANDA applicant who amended 
its answer to a patent infringement suit to include arguments that were 
not in the notice to the patent owner under Sec. 314.95 would be 
considered to have been uncooperative in expediting the lawsuit. The 
comment explained that these revisions would prevent generic drug 
companies from amending their answers during patent infringement 
litigation to delay completion of a trial and also delay the start of 
the 30-month period.
    FDA declines to adopt the comment's suggestion. As stated above, 
FDA has revised the notice requirements in Secs. 314.52(c) and 
314.95(c) to parallel the statutory language rather than specify notice 
requirements. The agency has neither the resources nor the expertise to 
engage in patent disputes or questions regarding sufficiency of notice. 
The statute leaves the issue of extending the 30-month period (based on 
a lack of cooperation between the parties in patent litigation) to the 
discretion of the trial court. The agency believes that the trial court 
should make determinations of cooperation on a case-by-case basis. 
Accordingly, the agency declines to amend the rule to consider an 
applicant to be uncooperative and to extend the 30-month period if the 
applicant amends an answer to a complaint in patent litigation to 
include an argument not reflected in the notice to the patent holder.
    72. FDA received several comments on proposed Sec. 314.107(c) and 
the 180-day exclusivity period against subsequent ANDA's. As proposed, 
Sec. 314.107(c) would provide 180-day exclusivity to the first ANDA 
applicant that made a paragraph IV patent certification (that the 
patent was invalid or not infringed) and was sued for patent 
infringement. Seven comments said the language requiring an ANDA 
applicant to have been sued in order for the 180-day exclusivity period 
to become effective was contrary to the statute and to a judicial 
ruling in the U.S. District Court for the District of Columbia.
    Section 505(j)(4)(B)(iv) of the act can be applied 
straightforwardly only when an applicant who seeks the 180-day period 
of exclusive marketing has been involved in a patent infringement 
lawsuit. To apply the section where there has been no lawsuit would 
require that the agency ignore the textual relationship between section 
505(j)(4)(B)(iii) and (j)(4)(B)(iv) of the act and assume that Congress 
intended, contrary to the goals it stated in the legislative history, 
to create an incentive for delay in generic competition, without any 
countervailing benefit to society. Moreover, it would provide a 
windfall to an applicant who has not devoted the considerable time and 
money necessary for patent litigation. Thus, consistent with the 
agency's longstanding interpretation of the act, Sec. 314.107(c) 
applies only when the first applicant has been sued. Although, as the 
comments state, one Federal district court reached a contrary 
conclusion, the agency appealed that decision and, on appeal, the 
decision was vacated as moot (Inwood Laboratories, Inc. v. Young, 723 
F.Supp. 1523 (D.D.C. 1989), vacated as moot, no. 89-5209 (D.C. Cir., 
November 13, 1989). The agency has not altered its interpretation of 
the act.
    FDA has, however, revised Sec. 314.107(c) to clarify other issues, 
such as the start and end of the 180-day exclusivity period, and to 
make minor editorial changes.
    73. One comment suggested revising proposed Sec. 314.107(c) to 
state that the 180-day exclusivity period does not apply to delay the 
effective date of approval of licensees to the NDA holder.
    As stated above, FDA does not believe that an ANDA applicant who 
has made a paragraph IV certification and obtained a patent license 
should be able to circumvent a 180-day exclusivity period. 
Consequently, the agency declines to amend the provision as requested 
by the comment.
    74. Two comments would revise proposed Sec. 314.107(c) to extend 
the 45-day period in which patent owners have to file suit against an 
ANDA applicant. The proposal referred to the statutory 45-day period in 
which a patent owner would have to file suit against an ANDA applicant. 
The comments would extend the 45-day period upon request or when the 
ANDA applicant and the patent owner agree to an extension.
    FDA declines to accept the comments' suggestion. The 45-day period 
for filing a lawsuit against an ANDA applicant is fully consistent with 
section 505(j)(4)(B)(iii) of the act, and the agency finds that there 
are sound policy reasons that outweigh extensions of the 45-day period. 
For example, if an ANDA applicant has provided notice to a patent owner 
stating that the ANDA applicant believes that the patent is invalid or 
would not be infringed (a paragraph IV certification), the patent owner 
may elect to bring suit against the ANDA applicant for patent 
infringement. If the suit is brought within 45 days from the date the 
ANDA applicant provided the notice, section 505(j)(4)(B)(iii) of the 
act precludes the agency from granting a final approval of the ANDA. If 
suit is not brought within 45 days, FDA could grant a final approval of 
the ANDA upon expiration of this time period, assuming that the ANDA 
met all applicable requirements for approval. Thus, amending the rule 
to provide the patent owner an extension to file suit beyond the 45-day 
period would not prevent the agency from approving ANDA's during the 
extension (because the statutory restriction against making an approval 
effective would no longer apply), even if the patent owner later 
decided to bring suit against the ANDA applicant and prevailed in that 
lawsuit. Such a result would waste agency and industry resources.
    FDA also notes that, in situations where an ANDA applicant has 
amended its notification to the patent owner and approved NDA holder to 
make it more complete, the agency may, under Sec. 314.95(f), consider 
the 45-day period to begin on the day after the date of receipt of the 
amended notification.
    75. One comment would revise proposed Sec. 314.107(c) to begin the 
180-day exclusivity period ``on the first day that a court would allow 
non-infringing marketing (unless that decision were stayed)'' or ``30 
months from receipt of notice.''
    The agency declines to revise the rule as suggested. The rule, 
which paraphrases the statutory language at section 505(j)(4)(B)(iv) of 
the act, better reflects the plain meaning of the act. Revising the 
rule as requested by the comment would begin the 180-day exclusivity 
period at the end of the 30-month period without regard to whether the 
applicant had commenced marketing on that date.
    76. Proposed Sec. 314.107(c)(1)(i) would provide 180-day 
exclusivity to the first ANDA applicant to submit a complete ANDA with 
a paragraph IV patent certification and ``to be sued within 45 days of 
the patent owner's receipt of notice.'' One comment said the rule, as 
drafted, created an incentive for frivolous claims of patent invalidity 
or noninfringement because it would give ANDA applicants exclusivity 
even if the applicant was unsuccessful in defending against the patent 
owner's lawsuit. The comment would replace the phrase ``to be sued 
within 45 days'' with ``and to successfully defend a suit brought 
within 45 days.''
    FDA agrees and has amended Sec. 314.107(c) accordingly.
    77. FDA received several comments regarding proposed 
Sec. 314.107(c)(1)(i) and (c)(1)(ii). These provisions concerned the 
start of the 180-day exclusivity period. Proposed Sec. 314.107(c)(1)(i) 
would begin the 180-day exclusivity period on the date of the first 
commercial marketing of the drug product by the first ANDA applicant 
who submitted a substantially complete ANDA containing a certification 
that the patent was invalid or not infringed and who was sued for 
patent infringement within 45 days after providing notice to the patent 
owner. Alternatively, proposed Sec. 314.107(c)(1)(ii) would begin the 
180-day exclusivity period on the ``date a decision of the court 
holding the relevant patent invalid or not infringed'' if that date was 
earlier than the date of the first commercial marketing. One comment 
would revise proposed Sec. 314.107(c)(1)(ii) to include a cross-
reference to the language in Sec. 314.107(b)(3) on patent litigation.
    FDA declines to adopt the suggested revision. The agency believes 
that the meaning of Sec. 314.107(c)(1)(ii) is sufficiently clear so 
that the court referred to in Sec. 314.107(c)(1)(ii) is the court 
deciding the patent infringement suit. However, for reasons stated 
elsewhere in this document, the agency has amended this provision to 
include a reference to unenforceable patents.
    78. One comment would amend Sec. 314.107(c), (c)(1)(i), and 
(c)(1)(ii) to permit an ANDA applicant to decide whether to start the 
180-day exclusivity period on the date it notifies the agency that the 
applicant has begun commercial marketing of the drug product or to wait 
to see whether the court decision is appealed. If an appeal did result, 
the comment would permit the ANDA applicant to have the 180-day period 
begin when a court issues a decision on the appeal.
    FDA declines to amend the provision as suggested by the comment. 
The provision is consistent with section 505(j)(4)(B)(iv) of the act by 
beginning the 180-day period on the date the first ANDA applicant has 
notified the agency that it has begun commercial marketing of the drug 
product or the date of a court decision holding the patent to be 
invalid or not infringed, ``whichever is earlier'' (see section 
505(j)(4)(B)(iv) of the act).) Allowing an applicant to begin marketing 
before the commencement of the 180-day exclusivity period would, in 
effect, extend the exclusivity period in a manner that is inconsistent 
with the plain meaning of the act. FDA also notes that the court 
decision must be a final decision from which no appeal can be or has 
been taken (see 54 FR 28872 at 28895).
    79. FDA received four comments regarding ``substantially complete'' 
applications under proposed Sec. 314.107(c)(2). Proposed 
Sec. 314.107(c)(2) would consider an ANDA to have been ``previously 
submitted'' with respect to another application for the same listed 
drug ``if the date on which the first application was both 
substantially complete and contained a certification that the patent 
was invalid or not infringed is earlier than the date on which the 
second application was both substantially complete and contained the 
same certification.'' The proposal also stated that a ``substantially 
complete'' application ``must contain the results of any required 
bioequivalence studies, or, if applicable, a request for a waiver of 
such studies.''
    One comment asked FDA to provide information as to which ANDA was 
the first ``substantially complete'' ANDA. The comment suggested that 
disclosing such information did not present any confidentiality 
problems because the ANDA applicant would have revealed the existence 
of the ANDA when it provided notice of certification of invalidity or 
noninfringement of the patent to the patent owner and NDA holder.
    FDA agrees, in part, with the comment. Disclosing whether an ANDA 
had been received for a specific listed drug would enable manufacturers 
to decide whether to develop a generic version of that drug and perhaps 
conserve the manufacturer's resources. Such knowledge could, in turn, 
effectively reduce the number of applications for the same product and 
thus also conserve agency resources. The agency, therefore, will 
disclose whether an ANDA has been received for a particular drug, but, 
in order to preserve the confidentiality of the applicant, will not 
disclose when the application had been received or the applicant's 
identity. Potential applicants who wish to inquire whether an ANDA for 
a specific drug has been received can contact the Regulatory Support 
Branch (HFD-615), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 301-594-0315.
    80. Two comments disagreed with the language regarding 
``substantially complete'' applications. One comment said FDA should 
only determine whether an ANDA contains a bioequivalence test or waiver 
request and not focus on the results of any required bioequivalence 
studies. The second comment suggested that a ``substantially complete'' 
ANDA be one that contained a paragraph IV patent certification and a 
bioequivalence study that is ultimately approved. The comment said this 
change would deter ANDA applicants from submitting ``superficial'' 
bioequivalence tests. The comment also suggested that the agency 
establish criteria as to whether changes to an ANDA were so substantial 
that the ANDA could no longer be considered as the first to be filed.
    Since publication of the proposed rule, FDA has clarified its 
policies regarding the submission of incomplete ANDA's. Under the 
earlier policy, ANDA applicants could submit ANDA's with bioequivalence 
study protocols and could provide bioequivalence study data at a later 
date. This policy resulted in a significant and unwarranted expenditure 
of resources in reviewing applications that had little potential for 
approval. Thus, in the Federal Register of April 28, 1992, FDA 
announced that it would no longer accept an ANDA that does not contain 
complete bioequivalence study data if such data are required for 
approval (see 57 FR 17950 at 17959). A ``substantially complete'' 
application, therefore, should have a complete bioequivalence study, or 
other information to show bioequivalence that could support approval of 
the application. FDA will examine the bioequivalence information upon 
submission and, if the agency determines that the bioequivalence 
information is facially insufficient to support a finding of 
bioequivalence, the agency will not review the application under 
Sec. 314.101(d). A decision by the agency after receipt of an 
application that the bioequivalence information is inadequate for 
approval does not necessarily mean that the application was not 
substantially complete at the time of submission.
    FDA also declines to establish criteria to establish whether 
changes to an ANDA were so substantial that it could not be considered 
to have been filed. While certain changes in an ANDA (e.g., a change in 
the listed drug) would amount to a new filing for purposes of 
Sec. 314.107(c)(2), other changes (e.g., minor labeling changes) would 
not. The agency believes a case-by-case approach is preferable because 
many products and manufacturers may be unique.
    81. The agency, on its own initiative, has revised the provisions 
in Sec. 314.107 (c)(2) and (c)(3) to clarify their intent. These 
provisions address the issues of the ``applicant submitting the first 
application'' for exclusivity purposes, what constitutes a 
``substantially complete'' application, and the effective dates of 
approval for subsequently submitted applications if the first applicant 
is not ``actively pursuing'' approval. FDA has made similar editorial 
changes at Sec. 314.107(c)(4).
    82. Four comments addressed proposed Sec. 314.107(c)(3). The 
proposed provision would make an ANDA that had been received after FDA 
had already received an ANDA for the same drug immediately effective if 
the agency concluded that the first ANDA applicant ``is not actively 
pursuing approval of its abbreviated application.'' Three comments 
asked FDA to define the phrase ``actively pursuing approval.''
    For purposes of this rule, the phrase ``actively pursuing 
approval'' is intended to encompass a drug sponsor's good faith effort 
to pursue marketing approval in a timely manner. In determining whether 
a sponsor is actively pursuing marketing approval, FDA will consider 
all relevant factors, such as the sponsor's compliance with regulations 
and the timeliness of its responses to FDA's questions or application 
deficiencies during the review period.
    83. One comment would revise proposed Sec. 314.107(c)(3) to make a 
subsequently received ANDA immediately effective upon a finding that 
the first applicant is not actively pursuing approval ``if [the 
subsequent application is] otherwise eligible for an immediately 
effective approval.''
    The agency agrees and has amended the provision accordingly. This 
change will remind applicants that FDA will make approval of a 
subsequent abbreviated application immediately effective if it 
satisfies all applicable requirements and FDA has concluded that the 
first applicant is not actively pursuing approval of its abbreviated 
application.
    84. FDA received five comments regarding the interpretation of 
``the court'' and court judgments in proposed Sec. 314.107(e)(1). 
Proposed Sec. 314.107(e)(1) stated that ``the court'' in 
Sec. 314.107(b) and (c) referred to ``the court that enters final 
judgment from which no appeal can be or has been taken.'' Three 
comments supported the proposal, but two comments argued that FDA had 
misconstrued the 1984 amendments. One comment argued that the court 
finding a patent to be invalid or not infringed should be ``the court 
of first instance'' or district court because a decision that a patent 
was invalid or not infringed or a decision to issue an injunction would 
be done by a district court. Another comment argued that interpreting 
``the court'' to mean the court that enters final judgment 
``effectively gives a patent owner an additional extension of the 
patent * * * for the duration of the appeal'' and delay generic 
competition. The comment would revise the rule to permit an ANDA 
applicant to market its drug product after it had prevailed at the 
trial court level.
    FDA declines to amend Sec. 314.107(e)(1) as suggested by the 
comments. To construe ``the court'' as a district court, regardless of 
any appeal of the district court decision, would deny the benefits of 
exclusivity to a prudent applicant that delayed marketing its product 
until resolution of an appeal by the patent holder (see 54 FR 28872 at 
28894). Moreover, if the patent holder appealed the district court 
decision and were able to obtain a stay or an injunction against the 
marketing of the applicant's product, the applicant could lose the 
entire 180-day exclusivity period before the stay or injunction were 
lifted.
    Given these considerations, FDA believes that any reference to 
``the court'' must be the court that enters final judgment from which 
no appeal can be or has been taken. (The reference to ``appeals'' does 
not include the certiorari process. The likelihood of an appellate 
court decision being heard and overruled by the Supreme Court is too 
remote to warrant delaying marketing and exclusivity pending resolution 
of a petition for writ of certiorari.) This interpretation avoids 
potentially premature decisions on the effective date of ANDA approval 
and the loss of 180-day exclusivity. FDA has, however, also revised 
Sec. 314.107(e)(2) to clarify which court decisions will represent the 
``final'' judgment.
    85. One comment would revise proposed Sec. 314.107(e)(2) to refer 
to a court order or judgment rather than simply a court judgment.
    As amended, Sec. 314.107(e)(2) refers to a court ``decision,'' 
which could be in the form of either an order or a judgment. The agency 
has also made minor changes to Sec. 314.107(e)(2) to clarify that the 
court decisions involve patent issues and that a higher court can hold 
or affirm a lower court decision that a patent is invalid, 
unenforceable, or not infringed.
    86. A second comment would revise proposed Sec. 314.107(e)(2) to 
require applicants to submit copies of a court order or judgment to the 
Division of Generic Drugs or ``New Drug Evaluation Division (where 
applicable).''
    FDA agrees with the comment, and has added Sec. 314.107(e)(2)(iv) 
to require applicants to send a copy of a final decision to the Office 
of Generic Drugs, or to the appropriate division in the Office of Drug 
Evaluation I or the Office of Drug Evaluation II, whichever is 
applicable.
    87. Proposed Sec. 314.107(f) described how the 45-day period for 
filing a patent infringement suit would be determined. In brief, under 
proposed Sec. 314.107(f)(1), the 45-day period would begin on the day 
after the date the patent owner or approved application holder, if an 
exclusive patent licensee, received a notice of certification of 
invalidity or noninfringement of the patent. Proposed 
Sec. 314.107(f)(2) would require the 505(b)(2) applicant or ANDA 
applicant to notify FDA whether an action for patent infringement had 
been filed. Several comments objected to language in proposed 
Sec. 314.107(f) that would consider notice to or actions by exclusive 
licensees to be equivalent to notice to or actions by a patent owner. 
The comments said that exclusive licensees do not always share the 
patent owner's interests.
    FDA agrees and has revised the rule to remove language that would 
consider exclusive licensees to be equivalent to patent owners.
    88. One comment objected to proposed Sec. 314.107(f)(1) because it 
would start the 45-day period on the day after the date the patent 
owner or the approved application holder, if an exclusive patent 
licensee, received notice of invalidity or noninfringement of a patent. 
The comment argued that the 45-day period should begin on the day after 
the date that the patent owner and the approved application holder 
received notice and, if these dates differed, the latest date should 
mark the start of the 45-day period.
    The agency agrees with the comment and has revised 
Sec. 314.107(f)(1) to begin the 45-day period on the day after the date 
the patent owner and the approved application holder have received the 
applicant's notice of certification of invalidity or noninfringement of 
a patent.
    89. FDA received several comments on proposed Sec. 314.107(f)(2). 
Absent a notice of an action for patent infringement, the proposal 
would make the approval of an ANDA or 505(b)(2) application effective 
immediately upon the expiration of the 45-day period for filing a 
patent infringement suit or upon FDA's completion of the review and 
approval process, whichever is later. The comments noted that the 
regulation would have ANDA or 505(b)(2) applicants notify FDA whether a 
patent infringement suit had been filed and asked FDA to permit, by 
regulation, patent owners to notify FDA whether it had brought suit. 
Alternatively, some comments would require the ANDA or 505(b)(2) 
applicant certify that it had not been sued. The comments explained 
that these changes were necessary because ANDA and 505(b)(2) applicants 
would have no interest in notifying FDA whether suit had been filed 
because, without such notice, they could immediately secure effective 
approval of an application.
    The agency has amended Sec. 314.107(f)(2) to permit patent owners 
or their representatives to notify FDA whether a patent infringement 
suit has been filed. The statute does not require applicants to certify 
that they have not been sued, and the agency does not believe such a 
burden to be necessary.
    The agency has also made minor revisions to Sec. 314.107(f)(2) to 
place more emphasis on an applicant's obligation to notify FDA 
immediately of the filing of any legal action within 45 days of receipt 
of a notice of certification.
    Additionally, the agency has made a grammatical change in 
Sec. 314.107(f)(2) to clarify that applicants must send the 
notification to the Office of Generic Drugs or to the appropriate 
division in the Center for Drug Evaluation and Research reviewing the 
application.
    90. One comment addressed the requirement in proposed 
Sec. 314.107(f)(2) that a 505(b)(2) applicant or ANDA applicant notify 
FDA whether an action for patent infringement had been filed ``before 
the expiration of the 45-day time period or the completion of the 
agency's review of the application, whichever occurs later.'' The 
comment argued that a patent owner had 45 days to file a lawsuit after 
receiving a notice of certification of invalidity or noninfringement of 
a patent and, therefore, a party should have an additional time period 
beyond the 45-day period for filing an action for patent infringement 
for notifying the agency whether an action had been filed. The comment 
would revise the rule to give a party an additional 15 days beyond the 
45-day period to notify FDA whether an action for patent infringement 
had been filed.
    The agency declines to revise the rule as suggested. FDA believes 
it is important to learn immediately if an action for patent 
infringement is filed before the completion of the 45-day period to 
avoid an erroneous approval with an immediate effective date.
    FDA has, therefore, amended Sec. 314.107(f)(2) to require 
applicants to notify FDA immediately whether any legal action has been 
filed. The agency has also amended this subsection to clarify the 
identity of the ``applicant.''
    91. FDA has, on its own initiative, clarified its notification 
requirements in Sec. 314.107(f)(2)(iii). As proposed, 
Sec. 314.107(f)(2)(iii) would have required parties to identify a drug 
by its established name, but would not have expressly required any 
identification of the drug if no established name existed. The agency 
has amended this provision to require identification of the drug 
product by its established name or, if no established name exists, its 
active ingredient(s).
    92. One comment asked FDA to publish information regarding the 
status and progress of patent infringement suits so other ANDA 
applicants could decide whether to intervene in the suit ``and ask that 
the 30-month period be shortened or lengthened in the event that it 
feels that one or both of the litigants are not reasonably cooperating 
in expediting the action.'' Alternatively, the comment asked FDA to 
permit any interested party to petition the agency ``to remove an ANDA 
from exclusivity considerations if it has not proceeded with due 
diligence--either in prosecution of its ANDA or defense of an 
infringement suit.''
    FDA believes that ANDA applicants are capable of monitoring the 
progress of patent litigation without imposing the additional burden of 
acquiring and publishing information on patent litigation on FDA. The 
agency, therefore, declines to adopt the comment.
    FDA also declines to amend the rule to permit third parties to 
petition the agency to deny exclusivity to an ANDA due to the ANDA 
applicant's actions during litigation. Under the statute, the reduction 
or enlargement of the 30-month period is left to the trial court's 
discretion. Intervention by the agency is unwarranted.
    93. One comment suggested replacing the words, ``action to 
defend,'' in proposed Sec. 314.107(f)(2)(iv) with the words, ``action 
for patent infringement.'' The comment said that ``action to defend'' 
was not a term of art.
    FDA agrees and has adopted the comment.
    94. FDA, on its own initiative, has modified the language regarding 
waivers in Sec. 314.107(f)(3). The change is intended to clarify that 
the patent owner does not object to FDA's approval of an ANDA or 
505(b)(2) application with an immediate effective date and to account 
for those situations where the ANDA applicant or 505(b)(2) applicant 
and the patent owner have agreed to extend the 45-day period.

J. Section 314.108--New Drug Product Exclusivity

    Proposed Sec. 314.108 was intended to implement the new drug 
exclusivity provisions under section 505(c)(3)(D) and (j)(4)(D) of the 
act. This section of the act provides specific time periods, known as 
new drug product exclusivity or market exclusivity, during which the 
effective date of approval for a 505(b)(2) application or an ANDA must 
be delayed or, in some cases, a 505(b)(2) application or an ANDA cannot 
be submitted. For example, section 505(c)(3)(D)(i) and (j)(4)(D)(i) of 
the act grant a 10-year period of exclusivity to new chemical entities 
that were approved during January 1, 1982, to September 24, 1984. 
Section 505(c)(3)(D)(ii) and (j)(4)(D)(ii) of the act grant a 5-year 
period of exclusivity to new chemical entities approved after September 
24, 1984. These sections of the act expressly state that no 505(b)(2) 
application or ANDA may be submitted during the exclusivity period 
except that such applications may be submitted after 4 years if they 
contain a certification of patent invalidity or noninfringement. 
Section 505(c)(3)(D)(iii), (c)(3)(D)(iv), (j)(4)(D)(iii), and 
(j)(4)(D)(iv) of the act grant a 3-year period of exclusivity to an 
application or supplemental application that is approved after 
September 24, 1984, and contains ``reports of new clinical 
investigations (other than bioavailability studies) essential to the 
approval'' of the application or supplemental application and 
``conducted or sponsored by'' the person submitting the application or 
supplemental application.
    Section 505(c)(3)(D)(v) and (j)(4)(D)(v) of the act granted a 2-
year period of exclusivity to drugs that are not chemical entities or 
for certain changes to already approved products that were approved 
during January 1, 1982, to September 24, 1984. FDA did not propose any 
regulations for this 2-year period because it expired on September 24, 
1986.
    The exclusivity provisions of the act do not provide any protection 
from the marketing of a generic version of the same drug product if the 
generic version is the subject of a full NDA submitted under section 
505(b)(1) of the act.
    95. Proposed Sec. 314.108(b)(4) would provide 3 years of 
exclusivity to an application that was submitted under section 505(b) 
of the act, was approved after September 24, 1984, was for a drug 
product containing an active moiety that had been previously approved 
in another application under section 505(b) of the act, and contained 
reports of new clinical investigations (other than bioavailability 
studies) conducted or sponsored by the applicant that were essential to 
approval of the application. Proposed Sec. 314.108(b)(5) would provide 
3 years of exclusivity to a supplemental application that was approved 
after September 24, 1984, and contained reports of new clinical 
investigations (other than bioavailability studies) conducted or 
sponsored by the applicant that were essential to approval of the 
application.
    Several comments addressed the scope of new drug exclusivity. Two 
comments said FDA should grant exclusivity for any change to an 
approved drug product or, alternatively, should grant exclusivity based 
on specific types of studies, such as studies intended to reduce drug 
dosing or drug efficacy study implementation (DESI) upgrade studies. 
One comment disagreed with the preamble to the proposed rule, which 
stated, ``FDA expects that only those changes in an approved drug 
product that affect its active ingredient(s), strength, dosage form, 
route of administration or conditions of use would be granted 
exclusivity'' (54 FR 28872 at 28899). Two comments asked FDA to clarify 
whether a clinical investigation establishing new risks could be 
eligible for exclusivity. The preamble to the proposed rule had 
indicated that such studies would not qualify for exclusivity because 
``protection of the public health demands that all products' labeling 
contain all relevant warnings'' (see 54 FR 28872 at 28899). One comment 
said FDA should accept an applicant's claim of exclusivity alone.
    Two other comments sought to limit exclusivity or clarify its 
scope. One comment argued that the rule was too broad, would confer 
``an unearned windfall,'' and stifle generic competition. The comment 
explained that some variations, such as reductions in dosage, require 
little effort but would nevertheless qualify for exclusivity. The 
comment suggested that the rule define what types of changes would 
qualify for exclusivity. The second comment agreed with the preamble 
that DESI upgrades should not qualify for exclusivity but asked FDA to 
create a procedure whereby parties could contact FDA to determine 
whether exclusivity information was accurate. The comment said this 
would enable third parties to decide whether to challenge decisions to 
grant or deny exclusivity.
    FDA disagrees with those comments that would grant exclusivity for 
any change to an approved drug product or accept, without question, an 
applicant's claim that it is entitled to exclusivity. Under the statute 
and this final rule, certain drugs or changes to drugs can receive 3 
years of exclusivity if the application or supplement to an application 
``contains reports of new clinical investigations (other than 
bioavailability studies) essential to the approval * * *'' (see section 
505(j)(4)(D)(iii) and (j)(4)(D)(iv) of the act). The phrase ``essential 
to the approval'' suggests that the clinical investigations that 
warrant exclusivity must be vital to the application or supplement. As 
stated in the preamble to the proposed rule, ``to qualify for 
exclusivity, there must not be published reports of studies other than 
those conducted or sponsored by the applicant, or other information 
available to the agency sufficient for FDA to conclude that a proposed 
drug product or change to an already approved drug product is safe and 
effective'' (see 54 FR 28872 at 28900). For example, the agency would 
not consider studies to support a switch from prescription to over-the-
counter (OTC) status to be ``essential to approval'' if the agency 
already had sufficient information to conclude that the OTC product 
would be safe and effective. (In OTC switch situations, FDA encourages 
applicants to consult FDA to determine whether clinical investigations 
or any other actions are necessary to permit FDA to approve a switch in 
a product's status.)
    FDA declines to define in the regulation the kinds of supplemental 
applications that, if supported by clinical investigations, would 
warrant 3-year exclusivity. Although the preamble to the proposed rule 
identified certain types of changes in a product that would normally 
warrant exclusivity (changes in active ingredient, strength, dosage 
form, route of administration, or conditions of use), the agency did 
not intend to suggest that other types of changes would not qualify. 
For example, changes in dosing regimen have resulted in grants of 3-
year exclusivity. Changes that would not warrant exclusivity are, as 
discussed in the preamble to the proposed rule, changes in labeling 
that involve warnings or other similar risk information that must be 
included in the labeling of generic competitors. Applicants obtaining 
approval for such changes in labeling would, in any event, have no 
valid interest in precluding such information from the labeling of 
other products. Furthermore, FDA does not consider a study to be 
``essential to approval'' simply because the applicant conducted it and 
submitted the study for agency review (Ref. 1).
    FDA's interpretation is supported by statements that were made 
during the congressional debates surrounding the 3-year exclusivity 
provisions. Senator Orrin Hatch described the 3-year exclusivity 
provisions upon approval of certain supplemental applications as 
protecting ``some changes in strength, indications, and so forth, which 
require considerable time and expense in FDA required clinical 
testing'' (130 Congressional Record S10505, August 10, 1984) (statement 
of Senator Hatch)). Representative Henry Waxman said 3-year exclusivity 
was intended to ``encourage drugmakers to obtain FDA approval for 
significant therapeutic uses of previously approved drugs'' (130 
Congressional Record H9114, (September 6, 1984)). Thus, an applicant is 
not entitled to 3-year exclusivity merely because it supplements an 
approved application based in part on a clinical investigation or 
because it certifies to FDA that the clinical investigation is 
essential to approval of the application or supplement.
    FDA also declines to create a new procedure whereby a party could 
contact FDA to determine whether exclusivity information is accurate. 
Interested parties can obtain information on exclusivity decisions 
through the Freedom of Information Act process (21 CFR part 20). 
Parties who wish to challenge an exclusivity decision can utilize the 
citizen petition procedures (21 CFR 10.30).
    96. One comment suggested that products whose labeling may not 
include certain therapeutic indications (due to exclusivity or patent 
protection) be listed in the Orange Book as not being therapeutically 
equivalent to the innovator product.
    FDA addressed this comment in its response to a citizen petition 
submitted by the Pharmaceutical Manufacturers Association (PMA). The 
response stated, in pertinent part:

    In drafting the 1984 Amendments, the only mechanism that 
Congress provided for enforcing the exclusivity accorded a new 
indication is the requirement that ANDA's and 505(b)(2) applications 
be given delayed effective approval for the exclusive indication. 
During the period that ANDA's and 505(b)(2) applications may not be 
made effective, pioneers thus have the exclusive right to promote 
and label their products for the exclusive indication. Nothing in 
the language of the amended statute or its legislative history, 
however, suggests that Congress intended the granting of exclusivity 
for a new indication to alter therapeutic equivalence ratings. 
Moreover, it would be inconsistent with the established standards 
for making therapeutic equivalence determinations to rate two 
products as not therapeutically equivalent simply because one is 
labeled with fewer than all the approved indications.
    FDA's standards for therapeutic equivalence determinations * * * 
have always been based upon scientific considerations relevant to 
predicting the comparative pharmacological behavior of two products 
in or on the human body. There is no scientific basis for concluding 
that differences in recommended indications are relevant to this 
prediction. For example, the fact that a particular brand of drug is 
recommended in a medical journal article for an unlabeled use, does 
not, from a scientific standpoint, render other brands of the same 
drug therapeutically or biologically inequivalent. Similarly, the 
fact that a pioneer drug is labeled with a protected indication does 
not mean that generic copies of the same drug are not 
therapeutically equivalent to the pioneer.
    In absence of any suggestion in the statute or legislative 
history that Congress intended FDA to alter the scientific basis of 
therapeutic equivalence ratings to enforce exclusivity, FDA declines 
to consider non-scientific criteria, i.e., the existence of 
exclusive indications, in making therapeutic equivalence decisions.

(Ref. 2)

FDA has not changed this position and, therefore, declines to adopt the 
comment.
    97. Many comments objected to the definition of ``active moiety'' 
and the references to active moieties and new chemical entities 
throughout proposed Sec. 314.108. The comments said the definitions 
lacked statutory support and were contrary to two court decisions, 
Abbott Laboratories v. Young, 691 F.Supp. 462 (D. D.C. 1988), remanded, 
920 F.2d 984 (D.C. Cir. 1990), and Glaxo Operations UK Ltd. v. Quigg, 
706 F.Supp. 1224 (E.D. Va. 1989), aff'd, 894 F.2d 392 (Fed. Cir. 1990). 
Two comments added that the definition of ``active moiety'' was also 
too restrictive because it excluded chelates, clathrates, and other 
noncovalent derivatives. The comments, in general, would delete all 
references to ``active moiety'' and ``new chemical entity'' and refer 
only to ``active ingredients.'' Some comments would also define 
``active ingredient'' as the active ingredient found in the finished 
dosage form before the drug is administered to the patient.
    Subsequent to the close of the comment period, the interpretation 
of the act urged by the comments and adopted by the district court in 
Abbott Laboratories v. Young (providing 10 years of exclusivity under 
section 505(j)(4)(D)(i) of the act for products offering the same 
therapeutic moiety in different active ingredient forms if the salt or 
ester form was approved subsequent to the pure therapeutic moiety form) 
was rejected by the United States Court of Appeals for the District of 
Columbia. Noting that such an interpretation would award exclusivity to 
both an active moiety and a salt if the application containing the 
active moiety were submitted first, but would award exclusivity only to 
the salt if the salt were submitted first, the court of appeals 
rejected the interpretation as ``farfetched because it is not 
consistent with any legislative goal'' (see Abbott Laboratories v. 
Young, 920 F.2d 984, 989).
    Although the court of appeals appeared to agree with the agency's 
conclusion that exclusivity should be limited to the first approved 
product containing the active moiety, the court found the agency's 
parsing of the operative statutory phrase ``active ingredient 
(including any salt or ester of the active ingredient)'' to be 
linguistically impermissible as set forth in the agency's 
administrative decision denying 10-year exclusivity to Abbott. Rather 
than interpret the term ``active ingredient'' broadly to include the 
concept of active moiety, the agency interpreted the term narrowly to 
refer to the form of the moiety in the product, but interpreted the 
parenthetical phrase ``(including any salt or ester of the active 
ingredient)'' broadly to include all active ingredients that are 
different but contain the same active moiety. Although the court noted 
that the agency had, subsequent to the administrative decision, voiced 
the more linguistically permissible construction (interpreting the term 
``active ingredient'' to refer to active moiety), the court found that 
it could not consider this construction because it was not relied upon 
in the administrative decision. The court thus remanded the case to the 
district court with instructions to remand the issue to the agency for 
further consideration.
    The agency has concluded that the term ``active ingredient,'' as 
used in the phrase ``active ingredient (including any salt or ester of 
the active ingredient),'' means active moiety. Thus, the agency 
declines to adopt the comments suggesting removal of the definition of, 
and references to, ``active moiety'' from Sec. 314.108.
    FDA disagrees with the assertion that the definition of ``active 
moiety'' should not exclude chelates, clathrates, and other noncovalent 
derivatives. As stated in the preamble to the proposed rule, 
exclusivity is intended to provide incentives for innovation (see 54 FR 
28872 at 28898 and 28899). The addition of a chelate, clathrate, or 
other noncovalent derivative generally does not affect the active 
moiety of a drug product. The agency, therefore, does not believe that 
providing exclusivity for chelates, clathrates, and other noncovalent 
derivatives of a previously approved active moiety would be consistent 
with the statutory intent.
    98. FDA received a number of comments regarding the term 
``substantial support'' in the definition of ``conducted or sponsored 
by the applicant'' in proposed Sec. 314.108(a). The proposed rule 
stated, ``Ordinarily, substantial support will mean providing 50 
percent or more of the cost of conducting the study'' (see 54 FR 28872 
at 28930). The comments said the 50 percent figure was unrealistic, 
unnecessary, or unauthorized by law and argued that cost should not be 
a controlling factor in determining new drug exclusivity. Other 
comments said the rule should permit firms to buy studies because there 
is no basis to grant exclusivity to a firm that purchases an NDA and to 
deny exclusivity to a firm that purchases a study. One comment asked 
how FDA would treat a publicly funded study.
    The 50-percent contribution requirement reflects a reasonable 
interpretation of section 505 (j)(4)(D)(iii) and (j)(4)(D)(iv) of the 
act. A study can be conducted by or for only one applicant. Exclusivity 
based on less than 50-percent funding would allow multiple parties to 
claim exclusivity against ANDA applicants as well as each other. 
Moreover, the legislative history indicates that Congress created 3-
year exclusivity to protect products whose development required a 
significant time commitment and ``an investment of some magnitude'' 
(see 130 Congressional Record S10504 (August 10, 1984) (statement of 
Senator Hatch); 130 Congressional Record H9124-H9125 (September 6, 
1984) (statement of Representative Waxman)). Obviously, if a sponsor 
provided 50 percent or more funding to a study, its investment 
represents a substantial portion of the study's funding.
    FDA acknowledges that there may be some rare circumstance in which 
less than 50-percent funding could constitute ``substantial support'' 
and merit exclusivity. FDA has, therefore, revised the rule to require: 
(1) A certified statement from a Certified Public Accountant that the 
applicant provided 50 percent or more of the cost of conducting the 
study; or (2) an explanation from the applicant why FDA should consider 
the applicant to have conducted or sponsored the study if the 
applicant's financial contribution to the study is less than 50 percent 
if the applicant did not sponsor the investigational new drug 
application. The agency has made a corresponding change to 
Sec. 314.50(j)(4)(iii).
    With regard to studies that the applicant has purchased and 
publicly funded studies, FDA agrees that an applicant who has purchased 
exclusive rights to a study should be able to obtain new drug 
exclusivity. FDA, therefore, has revised the definition of ``conducted 
or sponsored by the applicant'' to state that the purchase of 
nonexclusive rights to an investigation does not satisfy the 
definition. FDA emphasizes that the applicant must have exclusive 
rights to the purchased study in order to be deemed to have sponsored a 
study. The purchase of nonexclusive rights by different parties could 
result in multiple claims of exclusivity for the same study. For these 
reasons, FDA also believes that most, if not all, publicly funded 
studies will not qualify for exclusivity. These studies are usually 
publicly available, so FDA will not give one applicant exclusive rights 
based on a study that, by virtue of its funding, belongs to the general 
public and is publicly available.
    99. The agency, on its own initiative, has amended the definition 
of ``date of approval'' to note that the date of approval ``refers only 
to a final approval and not to a tentative approval that may become 
effective at a later date.'' This change reflects FDA's position that 
drug products with delayed effective dates of approval are not listed 
drugs and that an ``approval with a delayed effective date is tentative 
and does not become final until the effective date'' (see 57 FR 17950 
at 17953).
    100. One comment said proposed Sec. 314.108(a) failed to correspond 
to proposed Sec. 314.50(j)(4)(i), which states that Sec. 314.108(a) 
defines ``new'' and ``clinical investigations.'' Proposed 
Sec. 314.50(j)(4)(i) contained an error. The proposed rule does not 
contain separate definitions for ``new'' and ``clinical 
investigations''; it does, however, define ``new clinical 
investigations'' at Sec. 314.108(a). FDA has corrected 
Sec. 314.50(j)(4)(i) accordingly.
    101. One comment objected to the last sentence in the definition of 
``new clinical investigation.'' The comment claimed that the definition 
would ``unnecessarily, and contrary to the Statute, ``expand and award 
an exclusivity for a previously submitted study; and it unjustifiably 
distinguishes between safety and effectiveness.''
    Under the statute, 3-year exclusivity is awarded if the application 
or supplemental application contained reports of new clinical 
investigations that were conducted or sponsored by the applicant and 
were essential to the approval of the application or supplemental 
application (see section 505(j)(4)(D)(iii) and (j)(4)(D)(iv) of the 
act). The legislative history indicates that 3-year exclusivity is for 
investigations requiring a considerable investment of time and money 
and that are necessary for approval of important innovations (see 54 FR 
28872 at 28899). Thus, FDA interprets ``new clinical investigation'' as 
a clinical investigation whose data have not been relied upon by FDA to 
demonstrate substantial evidence of effectiveness of a previously 
approved drug for any indication or safety in a new patient population 
and do not duplicate the results of another investigation relied upon 
by FDA to demonstrate a previously approved drug's effectiveness or 
safety in a new patient population. An applicant is not limited to 
recently conducted clinical investigations; a clinical investigation 
that provides a ``new'' basis for drug approval can qualify for 
exclusivity.
    102. Two comments recommended revising the rule to address 
transfers of new drug exclusivity between an applicant and all 
predecessors in interest, including licensors, assignors, joint venture 
partners, or other parties.
    New drug exclusivity is not a property right, but is rather a 
statutory obligation on the agency. This statutory obligation is based 
on data and information in an approved application. Although an 
applicant may purchase an application or rights to data and information 
in an application (i.e., exclusive rights to a new clinical 
investigation), from which exclusivity would flow, there is no property 
right to exclusivity itself that can be transferred separately and 
apart from the application or data upon which exclusivity is based. The 
agency does, however, permit the submission or approval of an ANDA when 
the holder of the exclusivity permits FDA to receive or approve the 
ANDA.
    FDA notes that joint venture partners differ from licensees, 
assignors, etc., because joint venture partners share in developing a 
drug product. Consequently, FDA suggests that joint venture partners 
carefully consider how they will seek approval of an application and 
define their rights and interests in the application to avoid questions 
regarding applicability of the exclusivity provisions of the act.
    As stated above, FDA has revised the definition of the phrase, 
``conducted or sponsored by the applicant,'' to construe a party who 
has purchased exclusive rights to a study to have ``conducted or 
sponsored'' the study. This change will enable a party who has acquired 
exclusive rights to a study to seek exclusivity.
    103. Four comments asked FDA to create a mechanism that would 
determine whether a study was ``essential for approval'' either before 
an application would be submitted or before the study began. Proposed 
Sec. 314.108(a) stated that ``essential to approval'' with regard to an 
investigation ``means that the application could not be approved by FDA 
without that investigation, even with a delayed effective date.'' The 
proposal, however, did not discuss the procedure by which FDA would 
determine a study to be ``essential to approval.''
    FDA declines to accept the comments. FDA cannot determine whether a 
study is essential for approval until the application is approved. 
Research goals and objectives often change during clinical 
investigations. For example, the results from a study designed to 
support a new indication could generate interest in a completely 
different indication. The product ultimately approved may be a 
different product from that characterized in the original application. 
It is also possible that newly available data in the public domain will 
obviate the need for the study prior to approval. Thus, FDA will decide 
whether a study is essential for approval at the time of approval.
    The agency has, however, amended the definition of ``essential to 
approval'' to delete the reference to a delayed effective date. This 
change is necessary because the agency no longer regards an application 
with a delayed effective date as being approved. Instead, FDA considers 
such applications as being tentatively approved (see 57 FR 17950 at 
17953).
    104. Proposed Sec. 314.108(b)(2) would provide 5 years of 
exclusivity for a new chemical entity if a drug product containing the 
new chemical entity was approved after September 24, 1984, in an 
application submitted under section 505(b) of the act. One comment said 
FDA should deny 5-year exclusivity to any section ``505(b)(2) 
application for a new chemical entity that relies upon one or more 
investigations that are essential for approval of the application but 
which were not conducted or sponsored by the applicant * * *.'' The 
comment explained that a 505(b)(2) applicant could assemble literature 
demonstrating the safety and effectiveness of a drug product marketed 
before 1962 (when the Federal Food, Drug, and Cosmetic Act was amended 
to require new drugs to be safe and effective for their intended uses) 
or 1938 (when the Food and Drugs Act was amended to require new drugs 
to be safe for the conditions of their intended use) and, under the 
rule, seek 5 years of new drug exclusivity. The comment said granting 
exclusivity to such drugs would be inconsistent with statutory intent 
and the legislative history.
    Under the statute, a drug product may qualify for 5 years of 
exclusivity if its active moiety has not been previously approved in 
any other application (see section 505(c)(3)(D)(ii) and (j)(4)(D)(ii) 
of the act). For some drug products marketed before 1938 or 1962, the 
active moiety will have been the subject of an approved application 
(under prior versions of the act or as part of a combination product 
approved under the act), so the active moiety will be ineligible for 5-
year exclusivity.
    FDA also notes that the statute provides 5-year exclusivity for 
applications approved under section 505(b) of the act and that such 
applications are submitted by persons who wish to introduce or deliver 
for introduction into interstate commerce ``any new drug.'' (See 
section 505(a) and (c)(3)(D)(ii).) The term ``new drug'' is defined in 
section 201(p) of the act (21 U.S.C. 321(p)). Drug products with active 
ingredients marketed before 1938 or 1962 may be ``new drugs,'' 
especially where there has been a change in the product's labeling, 
composition, or manufacturer.
    Products falling within the definition of a ``new drug'' must be 
approved under section 505(b) of the act and, as a result, may qualify 
for 5-year exclusivity under the language of the act and consistent 
with legislative history.
    105. One comment said that FDA should provide 5 years of 
exclusivity for a single enantiomer of a previously approved racemate. 
The comment asserted that FDA approval of a racemic drug mixture covers 
the mixture rather than the enantiomers that compose the mixture.
    The agency declines to revise the rule as requested by the comment. 
As stated in the preamble to the proposed rule, the agency's position 
is that ``a single enantiomer of a previously approved racemate 
contains a previously approved active moiety and is therefore not 
considered a new chemical entity'' (see 54 FR 28872 at 28898).
    106. One comment asked FDA to interpret the phrase ``conditions of 
approval'' in proposed Sec. 314.108(b)(4)(iv) narrowly to limit 
exclusivity to studies conducted by the original applicant. Proposed 
Sec. 314.108(b)(4) stated that if an application: (i) Was submitted 
under section 505(b) of the act; (ii) was approved after September 24, 
1984; (iii) was for a drug product that contains an active moiety that 
has been previously approved in another application under section 
505(b) of the act; and (iv) contained reports of new clinical 
investigations (other than bioavailability studies) conducted or 
sponsored by the applicant that were essential to approval of the 
application, the agency will not make effective for a period of 3 years 
after the date of approval of the application the approval of a 
505(b)(2) application, or an ANDA for the conditions of approval of the 
original application, or an ANDA submitted pursuant to an approved 
petition under section 505(j)(2)(C) of the act that relies on the 
information supporting the conditions of approval of an original NDA. 
The comment said subsequent applicants who conduct their own studies to 
obtain approval should not be subject to the original applicant's 
exclusivity.
    FDA believes that the comment misinterprets the scope of 
exclusivity. As stated in the preamble to the proposed rule and the 
preamble to this final rule, market exclusivity does not provide any 
protection from the marketing of a generic version of the same drug 
product if the generic version is the subject of a full NDA submitted 
under section 505(b)(1) of the act (see 54 FR 28872 at 28896). As 
discussed earlier, the statute does not require that the original 
applicant ``conduct'' the study to obtain exclusivity. FDA interprets 
the act to allow for exclusivity where the applicant has supported the 
study by providing more than 50 percent of the funding or by purchasing 
exclusive rights to the study.

IV. Analysis of Impacts

    FDA has examined the impacts of this rule under Executive Order 
12866 and the Regulatory Flexibility Act (Pub. L. 96-354). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the final 
rule is not a significant regulatory action as defined by the Executive 
Order and so is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact on small 
entities. Title I of Pub. L. 98-417 eliminated unnecessary regulatory 
barriers for generic drug products and has resulted in generic 
competition on many important post-1962 drugs. Generic drug sales 
account for a significant portion of total prescription drug sales, and 
many of these sales would not have occurred in the absence of Pub. L. 
98-417. This competition has saved consumers hundreds of millions of 
dollars per year, and FDA concludes that this impact is directly 
attributable to the statute. This rule will not affect the pace or 
magnitude of this economic impact. The rule simply clarifies and 
facilitates implementation of the act. Thus, FDA certifies that this 
rule will not have a significant economic impact on a substantial 
number of small entities. Therefore, under the Regulatory Flexibility 
Act, no further analysis is required.

V. Environmental Impact

    The agency has determined under 21 CFR 25.24(a)(8) that this action 
is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

VI. Paperwork Reduction Act of 1980

    This final rule contains information collections which have been 
submitted for approval to the Office of Management and Budget under the 
Paperwork Reduction Act of 1980. The title, description, and respondent 
description of the information collection are shown below with an 
estimate of the annual reporting and recordkeeping burden. Included in 
the estimate is the time for reviewing instructions, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing the collection of information.
    Title: Abbreviated New Drug Application Regulations; Patent and 
Exclusivity Provisions.
    Description: The information requirements collect information from 
persons who must obtain FDA approval before marketing new human drug 
products or generic versions of previously approved drug products. 
These persons must submit information to FDA in the form of 
applications, notices, and certifications. FDA will use this 
information to determine whether patent information for a drug product 
has been submitted and whether an applicant is seeking market 
exclusivity for a particular drug product.
    Description of Respondents: Businesses. 

                               Estimated Annual Reporting and Recordkeeping Burden                              
----------------------------------------------------------------------------------------------------------------
                                                      No. of                                                    
             Section                  No. of       responses per   Total annual      Hours per      Total hours 
                                    respondents     respondent      responses        response                   
----------------------------------------------------------------------------------------------------------------
314.50(i).......................               8               1               8               2              16
314.50(j).......................              50               1              50               2             100
314.52..........................              30               1              30               8             240
314.53..........................             200               1             200               1             200
314.94(a)(12)...................             215               1             215               2             430
314.95..........................              30               1              30              16             480
314.107.........................              10               1              10              10              10
                                                                                                 ---------------
    Total.......................  ..............  ..............  ..............  ..............          1,476 
----------------------------------------------------------------------------------------------------------------

    There were no comments received on the Paperwork Reduction Act 
clearance submission or on the burden estimates. The agency has, 
however, revised the estimate for ANDA's under Sec. 314.94 based on its 
latest figures for the number of ANDA's received.

VII. References

    The following references have been placed on display in the Dockets 
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 
12420 Parklawn Dr., Rockville, MD 20857, and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.

    1. Letter dated September 28, 1992, from Jane E. Henney, Deputy 
Commissioner for Operations, to Alan H. Kaplan and Richard S. Morey, 
Kleinfeld, Kaplan and Becker (FDA Docket No. 90P-0455).
    2. Letter dated December 8, 1987, from John M. Taylor, Associate 
Commissioner for Regulatory Affairs, to Bruce J. Brennan, Senior 
Vice President and General Counsel (FDA Docket No. 86P-0235/CP).

List of Subjects in 21 CFR Part 314

    Administrative practice and procedure, Confidential business 
information, Drugs, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
314 is amended as follows:

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG OR AN 
ANTIBIOTIC DRUG

    1. The authority citation for 21 CFR part 314 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 701, 
704, 721 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 
331, 351, 352, 353, 355, 356, 357, 371, 374, 379e).

    2. Section 314.50 is amended by redesignating existing paragraph 
(h) as paragraph (k) and by adding new paragraphs (h), (i), and (j) to 
read as follows:


Sec. 314.50  Content and format of an application.

* * * * *
    (h) Patent information. The application is required to contain the 
patent information described under Sec. 314.53.
    (i) Patent certification--(1) Contents. A 505(b)(2) application is 
required to contain the following:
    (i) Patents claiming drug, drug product, or method of use. (A) 
Except as provided in paragraph (i)(2) of this section, a certification 
with respect to each patent issued by the United States Patent and 
Trademark Office that, in the opinion of the applicant and to the best 
of its knowledge, claims a drug (the drug product or drug substance 
that is a component of the drug product) on which investigations that 
are relied upon by the applicant for approval of its application were 
conducted or that claims an approved use for such drug and for which 
information is required to be filed under section 505 (b) and (c) of 
the act and Sec. 314.53. For each such patent, the applicant shall 
provide the patent number and certify, in its opinion and to the best 
of its knowledge, one of the following circumstances:
    (1) That the patent information has not been submitted to FDA. The 
applicant shall entitle such a certification ``Paragraph I 
Certification'';
    (2) That the patent has expired. The applicant shall entitle such a 
certification ``Paragraph II Certification'';
    (3) The date on which the patent will expire. The applicant shall 
entitle such a certification ``Paragraph III Certification''; or
    (4) That the patent is invalid, unenforceable, or will not be 
infringed by the manufacture, use, or sale of the drug product for 
which the application is submitted. The applicant shall entitle such a 
certification ``Paragraph IV Certification''. This certification shall 
be submitted in the following form:

I, (name of applicant), certify that Patent No. ____________ (is 
invalid, unenforceable, or will not be infringed by the manufacture, 
use, or sale of) (name of proposed drug product) for which this 
application is submitted.

The certification shall be accompanied by a statement that the 
applicant will comply with the requirements under Sec. 314.52(a) with 
respect to providing a notice to each owner of the patent or their 
representatives and to the holder of the approved application for the 
drug product which is claimed by the patent or a use of which is 
claimed by the patent and with the requirements under Sec. 314.52(c) 
with respect to the content of the notice.
    (B) If the drug on which investigations that are relied upon by the 
applicant were conducted is itself a licensed generic drug of a 
patented drug first approved under section 505(b) of the act, the 
appropriate patent certification under this section with respect to 
each patent that claims the first-approved patented drug or that claims 
an approved use for such a drug.
    (ii) No relevant patents. If, in the opinion of the applicant and 
to the best of its knowledge, there are no patents described in 
paragraph (i)(1)(i) of this section, a certification in the following 
form:

In the opinion and to the best knowledge of (name of applicant), 
there are no patents that claim the drug or drugs on which 
investigations that are relied upon in this application were 
conducted or that claim a use of such drug or drugs.

    (iii) Method of use patent. (A) If information that is submitted 
under section 505 (b) or (c) of the act and Sec. 314.53 is for a method 
of use patent, and the labeling for the drug product for which the 
applicant is seeking approval does not include any indications that are 
covered by the use patent, a statement explaining that the method of 
use patent does not claim any of the proposed indications.
    (B) If the labeling of the drug product for which the applicant is 
seeking approval includes an indication that, according to the patent 
information submitted under section 505 (b) or (c) of the act and 
Sec. 314.53 or in the opinion of the applicant, is claimed by a use 
patent, the applicant shall submit an applicable certification under 
paragraph (i)(1)(i) of this section.
    (2) Method of manufacturing patent. An applicant is not required to 
make a certification with respect to any patent that claims only a 
method of manufacturing the drug product for which the applicant is 
seeking approval.
    (3) Licensing agreements. If a 505(b)(2) application is for a drug 
or method of using a drug claimed by a patent and the applicant has a 
licensing agreement with the patent owner, the applicant shall submit a 
certification under paragraph (i)(1)(i)(A)(4) of this section 
(``Paragraph IV Certification'') as to that patent and a statement that 
it has been granted a patent license. If the patent owner consents to 
an immediate effective date upon approval of the 505(b)(2) application, 
the application shall contain a written statement from the patent owner 
that it has a licensing agreement with the applicant and that it 
consents to an immediate effective date.
    (4) Late submission of patent information. If a patent described in 
paragraph (i)(1)(i)(A) of this section is issued and the holder of the 
approved application for the patented drug does not submit the required 
information on the patent within 30 days of issuance of the patent, an 
applicant who submitted a 505(b)(2) application that, before the 
submission of the patent information, contained an appropriate patent 
certification is not required to submit an amended certification. An 
applicant whose 505(b)(2) application is filed after a late submission 
of patent information or whose 505(b)(2) application was previously 
filed but did not contain an appropriate patent certification at the 
time of the patent submission shall submit a certification under 
paragraph (i)(1)(i) or (i)(1)(ii) of this section or a statement under 
paragraph (i)(1)(iii) of this section as to that patent.
    (5) Disputed patent information. If an applicant disputes the 
accuracy or relevance of patent information submitted to FDA, the 
applicant may seek a confirmation of the correctness of the patent 
information in accordance with the procedures under Sec. 314.53(f). 
Unless the patent information is withdrawn or changed, the applicant 
must submit an appropriate certification for each relevant patent.
    (6) Amended certifications. A certification submitted under 
paragraphs (i)(1)(i) through (i)(1)(iii) of this section may be amended 
at any time before the effective date of the approval of the 
application. An applicant shall submit an amended certification as an 
amendment to a pending application or by letter to an approved 
application. If an applicant with a pending application voluntarily 
makes a patent certification for an untimely filed patent, the 
applicant may withdraw the patent certification for the untimely filed 
patent. Once an amendment or letter for the change in certification has 
been submitted, the application will no longer be considered to be one 
containing the prior certification.
    (i) After finding of infringement. An applicant who has submitted a 
certification under paragraph (i)(1)(i)(A)(4) of this section and is 
sued for patent infringement within 45 days of the receipt of notice 
sent under Sec. 314.52 shall amend the certification if a final 
judgment in the action is entered finding the patent to be infringed 
unless the final judgment also finds the patent to be invalid. In the 
amended certification, the applicant shall certify under paragraph 
(i)(1)(i)(A)(3) of this section that the patent will expire on a 
specific date.
    (ii) After removal of a patent from the list. If a patent is 
removed from the list, any applicant with a pending application 
(including a tentatively approved application with a delayed effective 
date) who has made a certification with respect to such patent shall 
amend its certification. The applicant shall certify under paragraph 
(i)(1)(ii) of this section that no patents described in paragraph 
(i)(1)(i) of this section claim the drug or, if other relevant patents 
claim the drug, shall amend the certification to refer only to those 
relevant patents. In the amendment, the applicant shall state the 
reason for the change in certification (that the patent is or has been 
removed from the list). A patent that is the subject of a lawsuit under 
Sec. 314.107(c) shall not be removed from the list until FDA determines 
either that no delay in effective dates of approval is required under 
that section as a result of the lawsuit, that the patent has expired, 
or that any such period of delay in effective dates of approval is 
ended. An applicant shall submit an amended certification as an 
amendment to a pending application. Once an amendment for the change 
has been submitted, the application will no longer be considered to be 
one containing a certification under paragraph (i)(1)(i)(A)(4) of this 
section.
    (iii) Other amendments. (A) Except as provided in paragraphs (i)(4) 
and (i)(6)(iii)(B) of this section, an applicant shall amend a 
submitted certification if, at any time before the effective date of 
the approval of the application, the applicant learns that the 
submitted certification is no longer accurate.
    (B) An applicant is not required to amend a submitted certification 
when information on an otherwise applicable patent is submitted after 
the effective date of approval for the 505(b)(2) application.
    (j) Claimed exclusivity. A new drug product, upon approval, may be 
entitled to a period of marketing exclusivity under the provisions of 
Sec. 314.108. If an applicant believes its drug product is entitled to 
a period of exclusivity, it shall submit with the new drug application 
prior to approval the following information:
    (1) A statement that the applicant is claiming exclusivity.
    (2) A reference to the appropriate paragraph under Sec. 314.108 
that supports its claim.
    (3) If the applicant claims exclusivity under Sec. 314.108(b)(2), 
information to show that, to the best of its knowledge or belief, a 
drug has not previously been approved under section 505(b) of the act 
containing any active moiety in the drug for which the applicant is 
seeking approval.
    (4) If the applicant claims exclusivity under Sec. 314.108(b)(4) or 
(b)(5), the following information to show that the application contains 
``new clinical investigations'' that are ``essential to approval of the 
application or supplement'' and were ``conducted or sponsored by the 
applicant:''
    (i) ``New clinical investigations.'' A certification that to the 
best of the applicant's knowledge each of the clinical investigations 
included in the application meets the definition of ``new clinical 
investigation'' set forth in Sec. 314.108(a).
    (ii) ``Essential to approval.'' A list of all published studies or 
publicly available reports of clinical investigations known to the 
applicant through a literature search that are relevant to the 
conditions for which the applicant is seeking approval, a certification 
that the applicant has thoroughly searched the scientific literature 
and, to the best of the applicant's knowledge, the list is complete and 
accurate and, in the applicant's opinion, such published studies or 
publicly available reports do not provide a sufficient basis for the 
approval of the conditions for which the applicant is seeking approval 
without reference to the new clinical investigation(s) in the 
application, and an explanation as to why the studies or reports are 
insufficient.
    (iii) ``Conducted or sponsored by.'' If the applicant was the 
sponsor named in the Form FDA-1571 for an investigational new drug 
application (IND) under which the new clinical investigation(s) that is 
essential to the approval of its application was conducted, 
identification of the IND by number. If the applicant was not the 
sponsor of the IND under which the clinical investigation(s) was 
conducted, a certification that the applicant or its predecessor in 
interest provided substantial support for the clinical investigation(s) 
that is essential to the approval of its application, and information 
supporting the certification. To demonstrate ``substantial support,'' 
an applicant must either provide a certified statement from a certified 
public accountant that the applicant provided 50 percent or more of the 
cost of conducting the study or provide an explanation of why FDA 
should consider the applicant to have conducted or sponsored the study 
if the applicant's financial contribution to the study is less than 50 
percent or the applicant did not sponsor the investigational new drug. 
A predecessor in interest is an entity, e.g., a corporation, that the 
applicant has taken over, merged with, or purchased, or from which the 
applicant has purchased all rights to the drug. Purchase of 
nonexclusive rights to a clinical investigation after it is completed 
is not sufficient to satisfy this definition.
* * * * *
    3. New sections 314.52 and 314.53 are added to subpart B to read as 
follows:


Sec. 314.52  Notice of certification of invalidity or noninfringement 
of a patent.

    (a) Notice of certification. For each patent which claims the drug 
or drugs on which investigations that are relied upon by the applicant 
for approval of its application were conducted or which claims a use 
for such drug or drugs and which the applicant certifies under 
Sec. 314.50(i)(1)(i)(A)(4) that a patent is invalid, unenforceable, or 
will not be infringed, the applicant shall send notice of such 
certification by registered or certified mail, return receipt requested 
to each of the following persons:
    (1) Each owner of the patent that is the subject of the 
certification or the representative designated by the owner to receive 
the notice. The name and address of the patent owner or its 
representative may be obtained from the United States Patent and 
Trademark Office; and
    (2) The holder of the approved application under section 505(b) of 
the act for each drug product which is claimed by the patent or a use 
of which is claimed by the patent and for which the applicant is 
seeking approval, or, if the application holder does not reside or 
maintain a place of business within the United States, the application 
holder's attorney, agent, or other authorized official. The name and 
address of the application holder or its attorney, agent, or authorized 
official may be obtained from the Division of Drug Information 
Resources (HFD-80), Center for Drug Evaluation and Research, Food and 
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
    (3) This paragraph does not apply to a use patent that claims no 
uses for which the applicant is seeking approval.
    (b) Sending the notice. The applicant shall send the notice 
required by paragraph (a) of this section when it receives from FDA an 
acknowledgment letter stating that its application has been filed. At 
the same time, the applicant shall amend its application to include a 
statement certifying that the notice has been provided to each person 
identified under paragraph (a) of this section and that the notice met 
the content requirement under paragraph (c) of this section.
    (c) Content of a notice. In the notice, the applicant shall cite 
section 505(b)(3)(B) of the act and shall include, but not be limited 
to, the following information:
    (1) A statement that a 505(b)(2) application submitted by the 
applicant has been filed by FDA.
    (2) The application number.
    (3) The established name, if any, as defined in section 502(e)(3) 
of the act, of the proposed drug product.
    (4) The active ingredient, strength, and dosage form of the 
proposed drug product.
    (5) The patent number and expiration date, as submitted to the 
agency or as known to the applicant, of each patent alleged to be 
invalid, unenforceable, or not infringed.
    (6) A detailed statement of the factual and legal basis of the 
applicant's opinion that the patent is not valid, unenforceable, or 
will not be infringed. The applicant shall include in the detailed 
statement:
    (i) For each claim of a patent alleged not to be infringed, a full 
and detailed explanation of why the claim is not infringed.
    (ii) For each claim of a patent alleged to be invalid or 
unenforceable, a full and detailed explanation of the grounds 
supporting the allegation.
    (7) If the applicant does not reside or have a place of business in 
the United States, the name and address of an agent in the United 
States authorized to accept service of process for the applicant.
    (d) Amendment to an application. If an application is amended to 
include the certification described in Sec. 314.50(i), the applicant 
shall send the notice required by paragraph (a) of this section at the 
same time that the amendment to the application is submitted to FDA.
    (e) Documentation of receipt of notice. The applicant shall amend 
its application to document receipt of the notice required under 
paragraph (a) of this section by each person provided the notice. The 
applicant shall include a copy of the return receipt or other similar 
evidence of the date the notification was received. FDA will accept as 
adequate documentation of the date of receipt a return receipt or a 
letter acknowledging receipt by the person provided the notice. An 
applicant may rely on another form of documentation only if FDA has 
agreed to such documentation in advance. A copy of the notice itself 
need not be submitted to the agency.
    (f) Approval. If the requirements of this section are met, the 
agency will presume the notice to be complete and sufficient, and it 
will count the day following the date of receipt of the notice by the 
patent owner or its representative and by the approved application 
holder as the first day of the 45-day period provided for in section 
505(c)(3)(C) of the act. FDA may, if the applicant amends its 
application with a written statement that a later date should be used, 
count from such later date.


Sec. 314.53  Submission of patent information.

    (a) Who must submit patent information. This section applies to any 
applicant who submits to FDA a new drug application or an amendment to 
it under section 505(b) of the act and Sec. 314.50 or a supplement to 
an approved application under Sec. 314.70, except as provided in 
paragraph (d)(2) of this section.
    (b) Patents for which information must be submitted. An applicant 
described in paragraph (a) of this section shall submit information on 
each patent that claims the drug or a method of using the drug that is 
the subject of the new drug application or amendment or supplement to 
it and with respect to which a claim of patent infringement could 
reasonably be asserted if a person not licensed by the owner of the 
patent engaged in the manufacture, use, or sale of the drug product. 
For purposes of this part, such patents consist of drug substance 
(ingredient) patents, drug product (formulation and composition) 
patents, and method of use patents. Process patents are not covered by 
this section and information on process patents may not be submitted to 
FDA. For patents that claim a drug substance or drug product, the 
applicant shall submit information only on those patents that claim a 
drug product that is the subject of a pending or approved application, 
or that claim a drug substance that is a component of such a product. 
For patents that claim a method of use, the applicant shall submit 
information only on those patents that claim indications or other 
conditions of use of a pending or approved application.
    (c) Reporting requirements--(1) General requirements. An applicant 
described in paragraph (a) of this section shall submit the following 
information for each patent described in paragraph (b) of this section:
    (i) Patent number and the date on which the patent will expire.
    (ii) Type of patent, i.e., drug, drug product, or method of use.
    (iii) Name of the patent owner.
    (iv) If the patent owner or applicant does not reside or have a 
place of business within the United States, the name of an agent 
(representative) of the patent owner or applicant who resides or 
maintains a place of business within the United States authorized to 
receive notice of patent certification under section 505(b)(3) and 
(j)(2)(B) of the act and Secs. 314.52 and 314.95.
    (2) Formulation, composition, or method of use patents--(i) 
Original declaration. For each formulation, composition, or method of 
use patent, in addition to the patent information described in 
paragraph (c)(1) of this section the applicant shall submit the 
following declaration:

    The undersigned declares that Patent No. ________ covers the 
formulation, composition, and/or method of use of (name of drug 
product). This product is (currently approved under section 505 of 
the Federal Food, Drug, and Cosmetic Act) [or] (the subject of this 
application for which approval is being sought):

----------------------------------------------------------------------

    (ii) Amendment of patent information upon approval. Within 30 days 
after the date of approval of its application, if the application 
contained a declaration required under paragraph (c)(2)(i) of this 
section, the applicant shall by letter amend the declaration to 
identify each patent that claims the formulation, composition, or the 
specific indications or other conditions of use that have been 
approved.
    (3) No relevant patents. If the applicant believes that there are 
no patents which claim the drug or the drug product or which claim a 
method of using the drug product and with respect to which a claim of 
patent infringement could reasonably be asserted if a person not 
licensed by the owner of the patent engaged in the manufacture, use, or 
sale of the drug product, it shall so declare.
    (4) Authorized signature. The declarations required by this section 
shall be signed by the applicant or patent owner, or the applicant's or 
patent owner's attorney, agent (representative), or other authorized 
official.
    (d) When and where to submit patent information--(1) Original 
application. An applicant shall submit with its original application 
submitted under this part, including an application described in 
section 505(b)(2) of the act, the information described in paragraph 
(c) of this section on each drug (ingredient), drug product 
(formulation and composition), and method of use patent issued before 
the application is filed with FDA and for which patent information is 
required to be submitted under this section. If a patent is issued 
after the application is filed with FDA but before the application is 
approved, the applicant shall, within 30 days of the date of issuance 
of the patent, submit the required patent information in an amendment 
to the application under Sec. 314.60.
    (2) Supplements. (i) An applicant shall submit patent information 
required under paragraph (c) of this section for a patent that claims 
the drug, drug product, or method of use for which approval is sought 
in any of the following supplements:
    (A) To change the formulation;
    (B) To add a new indication or other condition of use, including a 
change in route of administration;
    (C) To change the strength;
    (D) To make any other patented change regarding the drug, drug 
product, or any method of use.
    (ii) If the applicant submits a supplement for one of the changes 
listed under paragraph (d)(2)(i) of this section and existing patents 
for which information has already been submitted to FDA claim the 
changed product, the applicant shall submit a certification with the 
supplement identifying the patents that claim the changed product.
    (iii) If the applicant submits a supplement for one of the changes 
listed under paragraph (d)(2)(i) of this section and no patents, 
including previously submitted patents, claim the changed product, it 
shall so certify.
    (iv) The applicant shall comply with the requirements for amendment 
of formulation or composition and method of use patent information 
under paragraphs (c)(2)(ii) and (d)(3) of this section.
    (3) Patent information deadline. If a patent is issued for a drug, 
drug product, or method of use after an application is approved, the 
applicant shall submit to FDA the required patent information within 30 
days of the date of issuance of the patent.
    (4) Copies. The applicant shall submit two copies of each 
submission of patent information, an archival copy and a copy for the 
chemistry, manufacturing, and controls section of the review copy, to 
the Central Document Room, Center for Drug Evaluation and Research, 
Food and Drug Administration, Park Bldg., rm. 2-14, 12420 Parklawn Dr., 
Rockville, MD 20857. The applicant shall submit the patent information 
by letter separate from, but at the same time as, submission of the 
supplement.
    (5) Submission date. Patent information shall be considered to be 
submitted to FDA as of the date the information is received by the 
Central Document Room.
    (6) Identification. Each submission of patent information, except 
information submitted with an original application, and its mailing 
cover shall bear prominent identification as to its contents, i.e., 
``Patent Information,'' or, if submitted after approval of an 
application, ``Time Sensitive Patent Information.''
    (e) Public disclosure of patent information. FDA will publish in 
the list the patent number and expiration date of each patent that is 
required to be, and is, submitted to FDA by an applicant, and for each 
use patent, the approved indications or other conditions of use covered 
by a patent. FDA will publish such patent information upon approval of 
the application, or, if the patent information is submitted by the 
applicant after approval of an application as provided under paragraph 
(d)(2) of this section, as soon as possible after the submission to the 
agency of the patent information. Patent information submitted by the 
last working day of a month will be published in that month's 
supplement to the list. Patent information received by the agency 
between monthly publication of supplements to the list will be placed 
on public display in FDA's Freedom of Information Staff. A request for 
copies of the file shall be sent in writing to the Freedom of 
Information Staff (HFI-35), Food and Drug Administration, rm. 12A-16, 
5600 Fishers Lane, Rockville, MD 20857.
    (f) Correction of patent information errors. If any person disputes 
the accuracy or relevance of patent information submitted to the agency 
under this section and published by FDA in the list, or believes that 
an applicant has failed to submit required patent information, that 
person must first notify the agency in writing stating the grounds for 
disagreement. Such notification should be directed to the Drug 
Information Services Branch (HFD-84), Center for Drug Evaluation and 
Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, 
MD 20857. The agency will then request of the applicable new drug 
application holder that the correctness of the patent information or 
omission of patent information be confirmed. Unless the application 
holder withdraws or amends its patent information in response to FDA's 
request, the agency will not change the patent information in the list. 
If the new drug application holder does not change the patent 
information submitted to FDA, a 505(b)(2) application or an abbreviated 
new drug application under section 505(j) of the act submitted for a 
drug that is claimed by a patent for which information has been 
submitted must, despite any disagreement as to the correctness of the 
patent information, contain an appropriate certification for each 
listed patent.
    4. Section 314.54 is amended by adding new paragraph (a)(1)(vii) to 
read as follows:


Sec. 314.54  Procedure for submission of an application requiring 
investigations for approval of a new indication for, or other change 
from, a listed drug.

    (a) * * *
    (1) * * *
    (vii) If the applicant believes the change for which it is seeking 
approval is entitled to a period of exclusivity, the information 
required under Sec. 314.50(j).
* * * * *
    5. Section 314.70 is amended by adding new paragraph (f) to read as 
follows:


Sec. 314.70  Supplements and other changes to an approved application.

* * * * *
    (f) Claimed exclusivity. If an applicant claims exclusivity under 
Sec. 314.108 upon approval of a supplemental application for a change 
to its previously approved drug product, the applicant shall include 
with its supplemental application the information required under 
Sec. 314.50(j).
    6. Section 314.94 is amended by adding a new paragraph (a)(12) to 
read as follows:


Sec. 314.94  Content and format of an abbreviated application.

    (a) * * *
    (12) Patent certification--(i) Patents claiming drug, drug product, 
or method of use. (A) Except as provided in paragraph (a)(12)(iv) of 
this section, a certification with respect to each patent issued by the 
United States Patent and Trademark Office that, in the opinion of the 
applicant and to the best of its knowledge, claims the reference listed 
drug or that claims a use of such listed drug for which the applicant 
is seeking approval under section 505(j) of the act and for which 
information is required to be filed under section 505(b) and (c) of the 
act and Sec. 314.53. For each such patent, the applicant shall provide 
the patent number and certify, in its opinion and to the best of its 
knowledge, one of the following circumstances:
    (1) That the patent information has not been submitted to FDA. The 
applicant shall entitle such a certification ``Paragraph I 
Certification'';
    (2) That the patent has expired. The applicant shall entitle such a 
certification ``Paragraph II Certification'';
    (3) The date on which the patent will expire. The applicant shall 
entitle such a certification ``Paragraph III Certification''; or
    (4) That the patent is invalid, unenforceable, or will not be 
infringed by the manufacture, use, or sale of the drug product for 
which the abbreviated application is submitted. The applicant shall 
entitle such a certification ``Paragraph IV Certification''. This 
certification shall be submitted in the following form:

    I, (name of applicant), certify that Patent No. ____________ (is 
invalid, unenforceable, or will not be infringed by the manufacture, 
use, or sale of) (name of proposed drug product) for which this 
application is submitted.

The certification shall be accompanied by a statement that the 
applicant will comply with the requirements under Sec. 314.95(a) with 
respect to providing a notice to each owner of the patent or their 
representatives and to the holder of the approved application for the 
listed drug, and with the requirements under Sec. 314.95(c) with 
respect to the content of the notice.
    (B) If the abbreviated new drug application refers to a listed drug 
that is itself a licensed generic product of a patented drug first 
approved under section 505(b) of the act, the appropriate patent 
certification under paragraph (a)(12)(i) of this section with respect 
to each patent that claims the first-approved patented drug or that 
claims a use for such drug.
    (ii) No relevant patents. If, in the opinion of the applicant and 
to the best of its knowledge, there are no patents described in 
paragraph (a)(12)(i) of this section, a certification in the following 
form:

    In the opinion and to the best knowledge of (name of applicant), 
there are no patents that claim the listed drug referred to in this 
application or that claim a use of the listed drug.

    (iii) Method of use patent. (A) If patent information is submitted 
under section 505(b) or (c) of the act and Sec. 314.53 for a patent 
claiming a method of using the listed drug, and the labeling for the 
drug product for which the applicant is seeking approval does not 
include any indications that are covered by the use patent, a statement 
explaining that the method of use patent does not claim any of the 
proposed indications.
    (B) If the labeling of the drug product for which the applicant is 
seeking approval includes an indication that, according to the patent 
information submitted under section 505(b) or (c) of the act and 
Sec. 314.53 or in the opinion of the applicant, is claimed by a use 
patent, an applicable certification under paragraph (a)(12)(i) of this 
section.
    (iv) Method of manufacturing patent. An applicant is not required 
to make a certification with respect to any patent that claims only a 
method of manufacturing the listed drug.
    (v) Licensing agreements. If the abbreviated new drug application 
is for a drug or method of using a drug claimed by a patent and the 
applicant has a licensing agreement with the patent owner, a 
certification under paragraph (a)(12)(i)(A)(4) of this section 
(``Paragraph IV Certification'') as to that patent and a statement that 
it has been granted a patent license.
    (vi) Late submission of patent information. If a patent on the 
listed drug is issued and the holder of the approved application for 
the listed drug does not submit the required information on the patent 
within 30 days of issuance of the patent, an applicant who submitted an 
abbreviated new drug application for that drug that contained an 
appropriate patent certification before the submission of the patent 
information is not required to submit an amended certification. An 
applicant whose abbreviated new drug application is submitted after a 
late submission of patent information, or whose pending abbreviated 
application was previously submitted but did not contain an appropriate 
patent certification at the time of the patent submission, shall submit 
a certification under paragraph (a)(12)(i) of this section or a 
statement under paragraph (a)(12)(iii) of this section as to that 
patent.
    (vii) Disputed patent information. If an applicant disputes the 
accuracy or relevance of patent information submitted to FDA, the 
applicant may seek a confirmation of the correctness of the patent 
information in accordance with the procedures under Sec. 314.53(f). 
Unless the patent information is withdrawn or changed, the applicant 
shall submit an appropriate certification for each relevant patent.
    (viii) Amended certifications. A certification submitted under 
paragraphs (a)(12)(i) through (a)(12)(iii) of this section may be 
amended at any time before the effective date of the approval of the 
application. However, an applicant who has submitted a paragraph IV 
patent certification may not change it to a paragraph III certification 
if a patent infringement suit has been filed against another paragraph 
IV applicant unless the agency has determined that no applicant is 
entitled to 180-day exclusivity or the patent expires before the 
lawsuit is resolved or expires after the suit is resolved but before 
the end of the 180-day exclusivity period. If an applicant with a 
pending application voluntarily makes a patent certification for an 
untimely filed patent, the applicant may withdraw the patent 
certification for the untimely filed patent. An applicant shall submit 
an amended certification by letter or as an amendment to a pending 
application or by letter to an approved application. Once an amendment 
or letter is submitted, the application will no longer be considered to 
contain the prior certification.
    (A) After finding of infringement. An applicant who has submitted a 
certification under paragraph (a)(12)(i)(A)(4) of this section and is 
sued for patent infringement within 45 days of the receipt of notice 
sent under Sec. 314.95 shall amend the certification if a final 
judgment in the action against the applicant is entered finding the 
patent to be infringed. In the amended certification, the applicant 
shall certify under paragraph (a)(12)(i)(A)(3) of this section that the 
patent will expire on a specific date. Once an amendment or letter for 
the change has been submitted, the application will no longer be 
considered to be one containing a certification under paragraph 
(a)(12)(i)(A)(4) of this section. If a final judgment finds the patent 
to be invalid and infringed, an amended certification is not required.
    (B) After removal of a patent from the list. If a patent is removed 
from the list, any applicant with a pending application (including a 
tentatively approved application with a delayed effective date) who has 
made a certification with respect to such patent shall amend its 
certification. The applicant shall certify under paragraph (a)(12)(ii) 
of this section that no patents described in paragraph (a)(12)(i) of 
this section claim the drug or, if other relevant patents claim the 
drug, shall amend the certification to refer only to those relevant 
patents. In the amendment, the applicant shall state the reason for the 
change in certification (that the patent is or has been removed from 
the list). A patent that is the subject of a lawsuit under 
Sec. 314.107(c) shall not be removed from the list until FDA determines 
either that no delay in effective dates of approval is required under 
that section as a result of the lawsuit, that the patent has expired, 
or that any such period of delay in effective dates of approval is 
ended. An applicant shall submit an amended certification. Once an 
amendment or letter for the change has been submitted, the application 
will no longer be considered to be one containing a certification under 
paragraph (a)(12)(i)(A)(4) of this section.
    (C) Other amendments. (1) Except as provided in paragraphs 
(a)(12)(vi) and (a)(12)(viii)(C)(2) of this section, an applicant shall 
amend a submitted certification if, at any time before the effective 
date of the approval of the application, the applicant learns that the 
submitted certification is no longer accurate.
    (2) An applicant is not required to amend a submitted certification 
when information on a patent on the listed drug is submitted after the 
effective date of approval of the abbreviated application.
* * * * *
    7. New section 314.95 is added to subpart C to read as follows:


Sec. 314.95  Notice of certification of invalidity or noninfringement 
of a patent.

    (a) Notice of certification. For each patent that claims the listed 
drug or that claims a use for such listed drug for which the applicant 
is seeking approval and that the applicant certifies under 
Sec. 314.94(a)(12) is invalid, unenforceable, or will not be infringed, 
the applicant shall send notice of such certification by registered or 
certified mail, return receipt requested to each of the following 
persons:
    (1) Each owner of the patent which is the subject of the 
certification or the representative designated by the owner to receive 
the notice. The name and address of the patent owner or its 
representative may be obtained from the United States Patent and 
Trademark Office; and
    (2) The holder of the approved application under section 505(b) of 
the act for the listed drug that is claimed by the patent and for which 
the applicant is seeking approval, or, if the application holder does 
not reside or maintain a place of business within the United States, 
the application holder's attorney, agent, or other authorized official. 
The name and address of the application holder or its attorney, agent, 
or authorized official may be obtained from the Division of Drug 
Information Resources (HFD-80), Center for Drug Evaluation and 
Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, 
MD 20857.
    (3) This paragraph does not apply to a use patent that claims no 
uses for which the applicant is seeking approval.
    (b) Sending the notice. The applicant shall send the notice 
required by paragraph (a) of this section when it receives from FDA an 
acknowledgment letter stating that its abbreviated new drug application 
is sufficiently complete to permit a substantive review. At the same 
time, the applicant shall amend its abbreviated new drug application to 
include a statement certifying that the notice has been provided to 
each person identified under paragraph (a) of this section and that the 
notice met the content requirements under paragraph (c) of this 
section.
    (c) Contents of a notice. In the notice, the applicant shall cite 
section 505(j)(2)(B)(ii) of the act and shall include, but not be 
limited to, the following information:
    (1) A statement that FDA has received an abbreviated new drug 
application submitted by the applicant containing any required 
bioavailability or bioequivalence data or information.
    (2) The abbreviated application number.
    (3) The established name, if any, as defined in section 502(e)(3) 
of the act, of the proposed drug product.
    (4) The active ingredient, strength, and dosage form of the 
proposed drug product.
    (5) The patent number and expiration date, as submitted to the 
agency or as known to the applicant, of each patent alleged to be 
invalid, unenforceable, or not infringed.
    (6) A detailed statement of the factual and legal basis of the 
applicant's opinion that the patent is not valid, unenforceable, or 
will not be infringed. The applicant shall include in the detailed 
statement:
    (i) For each claim of a patent alleged not to be infringed, a full 
and detailed explanation of why the claim is not infringed.
    (ii) For each claim of a patent alleged to be invalid or 
unenforceable, a full and detailed explanation of the grounds 
supporting the allegation.
    (7) If the applicant does not reside or have a place of business in 
the United States, the name and address of an agent in the United 
States authorized to accept service of process for the applicant.
    (d) Amendment to an abbreviated application. If an abbreviated 
application is amended to include the certification described in 
Sec. 314.94(a)(12)(i)(A)(4), the applicant shall send the notice 
required by paragraph (a) of this section at the same time that the 
amendment to the abbreviated application is submitted to FDA.
    (e) Documentation of receipt of notice. The applicant shall amend 
its abbreviated application to document receipt of the notice required 
under paragraph (a) of this section by each person provided the notice. 
The applicant shall include a copy of the return receipt or other 
similar evidence of the date the notification was received. FDA will 
accept as adequate documentation of the date of receipt a return 
receipt or a letter acknowledging receipt by the person provided the 
notice. An applicant may rely on another form of documentation only if 
FDA has agreed to such documentation in advance. A copy of the notice 
itself need not be submitted to the agency.
    (f) Approval. If the requirements of this section are met, FDA will 
presume the notice to be complete and sufficient, and it will count the 
day following the date of receipt of the notice by the patent owner or 
its representative and by the approved application holder as the first 
day of the 45-day period provided for in section 505(j)(4)(B)(iii) of 
the act. FDA may, if the applicant provides a written statement to FDA 
that a later date should be used, count from such later date.
    8. Section 314.101 is amended by revising paragraph (e) to read as 
follows:


Sec. 314.101  Filing an application and an abbreviated antibiotic 
application and receiving an abbreviated new drug application.

* * * * *
    (e) The agency will refuse to file an application or abbreviated 
antibiotic application or will consider an abbreviated new drug 
application not to have been received if any of the following applies:
    (1) The drug product is subject to licensing by FDA under the 
Public Health Service Act (42 U.S.C. 201 et seq.) and subchapter F of 
this chapter.
    (2) In the case of a 505(b)(2) application or an abbreviated new 
drug application, the drug product contains the same active moiety as a 
drug that:
    (i) Was approved after September 24, 1984, in an application under 
section 505(b) of the act, and
    (ii) Is entitled to a 5-year period of exclusivity under section 
505(c)(3)(D)(ii) and (j)(4)(D)(ii) of the act and Sec. 314.108(b)(2), 
unless the 5-year exclusivity period has elapsed or unless 4 years of 
the 5-year period have elapsed and the application or abbreviated 
application contains a certification of patent invalidity or 
noninfringement described in Sec. 314.50(i)(1)(i)(A)(4) or 
Sec. 314.94(a)(12)(i)(A)(4).
* * * * *
    9. New sections 314.107 and 314.108 are added to subpart D to read 
as follows:


Sec. 314.107  Effective date of approval of a 505(b)(2) application or 
abbreviated new drug application under section 505(j) of the act.

    (a) General. A drug product may be introduced or delivered for 
introduction into interstate commerce when approval of the application 
or abbreviated application for the drug product becomes effective. 
Except as provided in this section, approval of an application or 
abbreviated application for a drug product becomes effective on the 
date FDA issues an approval letter under Sec. 314.105 for the 
application or abbreviated application.
    (b) Effect of patent on the listed drug. If approval of an 
abbreviated new drug application submitted under section 505(j) of the 
act or of a 505(b)(2) application is granted, that approval will become 
effective in accordance with the following:
    (1) Date of approval letter. Except as provided in paragraphs 
(b)(3), (b)(4), and (c) of this section, approval will become effective 
on the date FDA issues an approval letter under Sec. 314.105 if the 
applicant certifies under Sec. 314.50(i) or Sec. 314.94(a)(12) that:
    (i) There are no relevant patents; or
    (ii) The applicant is aware of a relevant patent but the patent 
information required under section 505 (b) or (c) of the act has not 
been submitted to FDA; or
    (iii) The relevant patent has expired; or
    (iv) The relevant patent is invalid, unenforceable, or will not be 
infringed.
    (2) Patent expiration. If the applicant certifies under 
Sec. 314.50(i) or Sec. 314.94(a)(12) that the relevant patent will 
expire on a specified date, approval will become effective on the 
specified date.
    (3) Disposition of patent litigation. (i)(A) Except as provided in 
paragraphs (b)(3)(ii), (b)(3)(iii), and (b)(3)(iv) of this section, if 
the applicant certifies under Sec. 314.50(i) or Sec. 314.94(a)(12) that 
the relevant patent is invalid, unenforceable, or will not be 
infringed, and the patent owner or its representative or the exclusive 
patent licensee brings suit for patent infringement within 45 days of 
receipt by the patent owner of the notice of certification from the 
applicant under Sec. 314.52 or Sec. 314.95, approval may be made 
effective 30 months after the date of the receipt of the notice of 
certification by the patent owner or by the exclusive licensee (or 
their representatives) unless the court has extended or reduced the 
period because of a failure of either the plaintiff or defendant to 
cooperate reasonably in expediting the action; or
    (B) If the patented drug product qualifies for 5 years of exclusive 
marketing under Sec. 314.108(b)(2) and the patent owner or its 
representative or the exclusive patent licensee brings suit for patent 
infringement during the 1-year period beginning 4 years after the date 
the patented drug was approved and within 45 days of receipt by the 
patent owner of the notice of certification, the approval may be made 
effective at the expiration of the 7\1/2\ years from the date of 
approval of the application for the patented drug product.
    (ii) If before the expiration of the 30-month period, or 7\1/2\ 
years where applicable, the court issues a final order that the patent 
is invalid, unenforceable, or not infringed, approval may be made 
effective on the date the court enters judgment;
    (iii) If before the expiration of the 30-month period, or 7\1/2\ 
years where applicable, the court issues a final order or judgment that 
the patent has been infringed, approval may be made effective on the 
date the court determines that the patent will expire or otherwise 
orders; or
    (iv) If before the expiration of the 30-month period, or 7\1/2\ 
years where applicable, the court grants a preliminary injunction 
prohibiting the applicant from engaging in the commercial manufacture 
or sale of the drug product until the court decides the issues of 
patent validity and infringement, and if the court later decides that 
the patent is invalid, unenforceable, or not infringed, approval may be 
made effective on the date the court enters a final order or judgment 
that the patent is invalid, unenforceable, or not infringed.
    (v) In order for an approval to be made effective under paragraph 
(b)(3) of this section, the applicant must receive an approval letter 
from the agency indicating that the application has received final 
approval. Tentative approval of an application does not constitute 
``approval'' of an application and cannot, absent a final approval 
letter from the agency, result in an effective approval under paragraph 
(b)(3) of this section.
    (4) Multiple certifications. If the applicant has submitted 
certifications under Sec. 314.50(i) or Sec. 314.94(a)(12) for more than 
one patent, the date of approval will be calculated for each 
certification, and the approval will become effective on the last 
applicable date.
    (c) Subsequent abbreviated new drug application submission.
    (1) If an abbreviated new drug application contains a certification 
that a relevant patent is invalid, unenforceable, or will not be 
infringed and the application is for a generic copy of the same listed 
drug for which one or more substantially complete abbreviated new drug 
applications were previously submitted containing a certification that 
the same patent was invalid, unenforceable, or would not be infringed 
and the applicant submitting the first application has successfully 
defended against a suit for patent infringement brought within 45 days 
of the patent owner's receipt of notice submitted under Sec. 314.95, 
approval of the subsequent abbreviated new drug application will be 
made effective no sooner than 180 days from whichever of the following 
dates is earlier:
    (i) The date the applicant submitting the first application first 
commences commercial marketing of its drug product; or
    (ii) The date of a decision of the court holding the relevant 
patent invalid, unenforceable, or not infringed.
    (2) For purposes of paragraph (c)(1) of this section, the 
``applicant submitting the first application'' is the applicant that 
submits an application that is both substantially complete and contains 
a certification that the patent was invalid, unenforceable, or not 
infringed prior to the submission of any other application for the same 
listed drug that is both substantially complete and contains the same 
certification. A ``substantially complete'' application must contain 
the results of any required bioequivalence studies, or, if applicable, 
a request for a waiver of such studies.
    (3) For purposes of paragraph (c)(1) of this section, if FDA 
concludes that the applicant submitting the first application is not 
actively pursuing approval of its abbreviated application, FDA will 
make the approval of subsequent abbreviated applications immediately 
effective if they are otherwise eligible for an immediately effective 
approval.
    (4) For purposes of paragraph (c)(1)(i) of this section, the 
applicant submitting the first application shall, if sued for patent 
infringement, notify FDA of the date that it commences commercial 
marketing of its drug product. Commercial marketing commences with the 
first date of introduction or delivery for introduction into interstate 
commerce outside the control of the manufacturer of a drug product, 
except for investigational use under part 312 of this chapter, but does 
not include transfer of the drug product for reasons other than sale 
within the control of the manufacturer or application holder. If an 
applicant does not promptly notify FDA of such date, the effective date 
of approval shall be deemed to be the date of the commencement of first 
commercial marketing.
    (d) Delay due to exclusivity. The agency will also delay the 
effective date of the approval of an abbreviated new drug application 
under section 505(j) of the act or a 505(b)(2) application if delay is 
required by the exclusivity provisions in Sec. 314.108. When the 
effective date of an application is delayed under both this section and 
Sec. 314.108, the effective date will be the later of the 2 days 
specified under this section and Sec. 314.108.
    (e) Court actions. (1) References to actions of ``the court'' in 
paragraphs (b) and (c) of this section are to the court that enters 
final judgment from which no appeal can be or has been taken.
    (2) For purposes of establishing the effective date of approval 
based on a court judgment, the following dates shall be deemed to be 
the date of the final decision of the court on the patent issues:
    (i) If the district court enters a decision that the patent is 
invalid, unenforceable, or not infringed, and the decision is not 
appealed, the date on which the right to appeal lapses.
    (ii) If the district court enters a decision that the patent is 
invalid, unenforceable, or not infringed, and the decision is appealed, 
the date of the first decision or order by a higher court holding or 
affirming the decision of the district court that the patent is 
invalid, unenforceable, or not infringed.
    (iii) If the district court enters a decision that the patent is 
infringed, and the decision is appealed, the date on which the district 
court enters a judgment that the patent is invalid, unenforceable, or 
not infringed pursuant to a mandate issued by a court of appeals.
    (iv) The applicant shall submit a copy of the entry of the order or 
judgment to the Office of Generic Drugs (HFD-600), or to the 
appropriate division in the Office of Drug Evaluation I (HFD-100) or 
Office of Drug Evaluation II (HFD-500), whichever is applicable, within 
10 working days of a final judgment.
    (f) Computation of 45-day time clock. (1) The 45-day clock 
described in paragraph (b)(3) of this section begins on the day after 
the date of receipt of the applicant's notice of certification by the 
patent owner or its representative, and by the approved application 
holder. When the 45th day falls on Saturday, Sunday, or a Federal 
holiday, the 45th day will be the next day that is not a Saturday, 
Sunday, or a Federal holiday.
    (2) The abbreviated new drug applicant or the 505(b)(2) applicant 
shall notify FDA immediately of the filing of any legal action filed 
within 45 days of receipt of the notice of certification. If the 
applicant submitting the abbreviated new drug application or the 
505(b)(2) application or patent owner or its representative does not 
notify FDA in writing before the expiration of the 45-day time period 
or the completion of the agency's review of the application, whichever 
occurs later, that a legal action for patent infringement was filed 
within 45 days of receipt of the notice of certification, approval of 
the abbreviated new drug application or the 505(b)(2) application will 
be made effective immediately upon expiration of the 45 days or upon 
completion of the agency's review and approval of the application, 
whichever is later. The notification to FDA of the legal action shall 
include:
    (i) The abbreviated new drug application or 505(b)(2) application 
number.
    (ii) The name of the abbreviated new drug or 505(b)(2) application 
applicant.
    (iii) The established name of the drug product or, if no 
established name exists, the name(s) of the active ingredient(s), the 
drug product's strength, and dosage form.
    (iv) A certification that an action for patent infringement 
identified by number, has been filed in an appropriate court on a 
specified date.
    The applicant of an abbreviated new drug application shall send the 
notification to FDA's Office of Generic Drugs (HFD-600). A 505(b)(2) 
applicant shall send the notification to the appropriate division in 
the Center for Drug Evaluation and Research reviewing the application. 
A patent owner or its representative may also notify FDA of the filing 
of any legal action for patent infringement. The notice should contain 
the information and be sent to the offices or divisions described in 
this paragraph.
    (3) If the patent owner or approved application holder who is an 
exclusive patent licensee waives its opportunity to file a legal action 
for patent infringement within 45 days of a receipt of the notice of 
certification and the patent owner or approved application holder who 
is an exclusive patent licensee submits to FDA a valid waiver before 
the 45 days elapse, approval of the abbreviated new drug application or 
the 505(b)(2) application will be made effective upon completion of the 
agency's review and approval of the application. FDA will only accept a 
waiver in the following form:

    (Name of patent owner or exclusive patent licensee) has received 
notice from (name of applicant) under (section 505(b)(3) or 
505(j)(2)(B) of the act) and does not intend to file an action for 
patent infringement against (name of applicant) concerning the drug 
(name of drug) before (date on which 45 days elapses. (Name of 
patent owner or exclusive patent licensee) waives the opportunity 
provided by (section 505(c)(3)(C) or 505(j)(B)(iii) of the act) and 
does not object to FDA's approval of (name of applicant)'s 
(505(b)(2) or abbreviated new drug application) for (name of drug) 
with an immediate effective date on or after the date of this 
letter.


Sec. 314.108  New drug product exclusivity.

    (a) Definitions. The following definitions of terms apply to this 
section:
    Active moiety means the molecule or ion, excluding those appended 
portions of the molecule that cause the drug to be an ester, salt 
(including a salt with hydrogen or coordination bonds), or other 
noncovalent derivative (such as a complex, chelate, or clathrate) of 
the molecule, responsible for the physiological or pharmacological 
action of the drug substance.
    Approved under section 505(b) means an application submitted under 
section 505(b) and approved on or after October 10, 1962, or an 
application that was ``deemed approved'' under section 107(c)(2) of 
Pub. L. 87-781.
    Clinical investigation means any experiment other than a 
bioavailability study in which a drug is administered or dispensed to, 
or used on, human subjects.
    Conducted or sponsored by the applicant with regard to an 
investigation means that before or during the investigation, the 
applicant was named in Form FDA-1571 filed with FDA as the sponsor of 
the investigational new drug application under which the investigation 
was conducted, or the applicant or the applicant's predecessor in 
interest, provided substantial support for the investigation. To 
demonstrate ``substantial support,'' an applicant must either provide a 
certified statement from a certified public accountant that the 
applicant provided 50 percent or more of the cost of conducting the 
study or provide an explanation why FDA should consider the applicant 
to have conducted or sponsored the study if the applicant's financial 
contribution to the study is less than 50 percent or the applicant did 
not sponsor the investigational new drug. A predecessor in interest is 
an entity, e.g., a corporation, that the applicant has taken over, 
merged with, or purchased, or from which the applicant has purchased 
all rights to the drug. Purchase of nonexclusive rights to a clinical 
investigation after it is completed is not sufficient to satisfy this 
definition.
    Date of approval means the date on the letter from FDA stating that 
the new drug application is approved, whether or not final printed 
labeling or other materials must yet be submitted as long as approval 
of such labeling or materials is not expressly required. ``Date of 
approval'' refers only to a final approval and not to a tentative 
approval that may become effective at a later date.
    Essential to approval means, with regard to an investigation, that 
there are no other data available that could support approval of the 
application.
    FDA means the Food and Drug Administration.
    New chemical entity means a drug that contains no active moiety 
that has been approved by FDA in any other application submitted under 
section 505(b) of the act.
    New clinical investigation  means an investigation in humans the 
results of which have not been relied on by FDA to demonstrate 
substantial evidence of effectiveness of a previously approved drug 
product for any indication or of safety for a new patient population 
and do not duplicate the results of another investigation that was 
relied on by the agency to demonstrate the effectiveness or safety in a 
new patient population of a previously approved drug product. For 
purposes of this section, data from a clinical investigation previously 
submitted for use in the comprehensive evaluation of the safety of a 
drug product but not to support the effectiveness of the drug product 
would be considered new.
    (b) Submission of and effective date of approval of an abbreviated 
new drug application submitted under section 505(j) of the act or a 
505(b)(2) application. (1) [Reserved]
    (2) If a drug product that contains a new chemical entity was 
approved after September 24, 1984, in an application submitted under 
section 505(b) of the act, no person may submit a 505(b)(2) application 
or abbreviated new drug application under section 505(j) of the act for 
a drug product that contains the same active moiety as in the new 
chemical entity for a period of 5 years from the date of approval of 
the first approved new drug application, except that the 505(b)(2) 
application or abbreviated application may be submitted after 4 years 
if it contains a certification of patent invalidity or noninfringement 
described in Sec. 314.50(i)(1)(i)(A)(4) or Sec. 314.94(a)(12)(i)(A)(4).
    (3) The approval of a 505(b)(2) application or abbreviated 
application described in paragraph (b)(2) of this section will become 
effective as provided in Sec. 314.107(b)(1) or (b)(2), unless the owner 
of a patent that claims the drug, the patent owner's representative, or 
exclusive licensee brings suit for patent infringement against the 
applicant during the 1-year period beginning 48 months after the date 
of approval of the new drug application for the new chemical entity and 
within 45 days after receipt of the notice described at Sec. 314.52 or 
Sec. 314.95, in which case, approval of the 505(b)(2) application or 
abbreviated application will be made effective as provided in 
Sec. 314.107(b)(3).
    (4) If an application:
    (i) Was submitted under section 505(b) of the act;
    (ii) Was approved after September 24, 1984;
    (iii) Was for a drug product that contains an active moiety that 
has been previously approved in another application under section 
505(b) of the act; and
    (iv) Contained reports of new clinical investigations (other than 
bioavailability studies) conducted or sponsored by the applicant that 
were essential to approval of the application, the agency will not make 
effective for a period of 3 years after the date of approval of the 
application the approval of a 505(b)(2) application or an abbreviated 
new drug application for the conditions of approval of the original 
application, or an abbreviated new drug application submitted pursuant 
to an approved petition under section 505(j)(2)(C) of the act that 
relies on the information supporting the conditions of approval of an 
original new drug application.
    (5) If a supplemental application:
    (i) Was approved after September 24, 1984; and
    (ii) Contained reports of new clinical investigations (other than 
bioavailability studies) that were conducted or sponsored by the 
applicant that were essential to approval of the supplemental 
application, the agency will not make effective for a period of 3 years 
after the date of approval of the supplemental application the approval 
of a 505(b)(2) application or an abbreviated new drug application for a 
change, or an abbreviated new drug application submitted pursuant to an 
approved petition under section 505(j)(2)(C) of the act that relies on 
the information supporting a change approved in the supplemental new 
drug application.

    Dated: September 23, 1994.
William K. Hubbard,
Interim Deputy Commissioner for Policy.
[FR Doc. 94-24052 Filed 9-30-94; 8:45 am]
BILLING CODE 4160-01-P