[Federal Register Volume 72, Number 82 (Monday, April 30, 2007)]
[Notices]
[Pages 21266-21270]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-8141]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2006N-0215]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Applications for Food 
and Drug Administration Approval to Market a New Drug: Patent 
Submission and Listing Requirements and Application of 30-Month Stays 
on Approval of Abbreviated New Drug Applications Certifying That a 
Patent Claiming a Drug Is Valid or Will Not Be Infringed

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995 (the PRA).

[[Page 21267]]


DATES: Fax written electronic comments on the collection of information 
by May 30, 2007.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-6974. All comments should be identified with the OMB 
control number 0910-0513. Also include the FDA docket number found in 
brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of the 
Chief Information Officer (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1482.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Applications for FDA Approval to Market a New Drug: Patent Submission 
and Listing Requirements and Application of 30-Month Stays on Approval 
of Abbreviated NDAs Certifying That a Patent Claiming a Drug Is Invalid 
or Will Not Be Infringed (OMB Control Number 0910-0513)--Extension

    FDA is requesting that OMB revise and extend approval under the PRA 
for the information collection contained in the final rule entitled 
``Applications for FDA Approval to Market a New Drug: Patent Submission 
and Listing Requirements and Application of 30-Month Stays on Approval 
of Abbreviated New Drug Applications Certifying That a Patent Claiming 
a Drug Is Invalid or Will Not Be Infringed'' (68 FR 36676, June 18, 
2003) (the June 2003 final rule).
    Section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act (the 
act) (21 U.S.C. 355(b)(1)) requires all NDA applicants to file, as part 
of the NDA, ``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 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.'' Section 505(c)(2) of the act imposes a similar patent 
submission obligation on holders of approved NDAs when the NDA holder 
could not have submitted the patent information with its application. 
Under section 505(b)(1) of the act, we publish patent information after 
approval of an NDA application in the list entitled ``Approved Drug 
Products with Therapeutic Equivalence Evaluations'' (the Orange Book). 
If patent information is submitted after NDA approval, section 
505(c)(2) of the act directs us to publish the information upon its 
submission.
    The June 2003 final rule clarified the types of patent information 
that must and must not be submitted to FDA as part of an NDA, an 
amendment, or a supplement. The June 2003 final rule also required 
persons submitting an NDA, an amendment, or a supplement, or submitting 
information on a patent after NDA approval, to make a detailed patent 
declaration using required forms (Form FDA 3542a and Form FDA 3542).
    Certain sections of the June 2003 final rule regarding the 
application of 30-month stays on approval of certain abbreviated new 
drug applications (ANDAs) and certain other NDAs, known as 505(b)(2) 
applications, submitted under the act, were superseded by the Medicare 
Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) 
(Public Law 108-173), signed December 8, 2003. The affected sections of 
the regulations issued in the June 2003 final rule--under part 314 (21 
CFR part 314), Sec. Sec.  314.52(a)(3) and 314.95(a)(3)--were revoked 
by the technical amendment to the June 2003 final rule, published in 
the Federal Register of March 10, 2004 (69 FR 11309). Accordingly, 
FDA's request to extend approval under the PRA for the collection of 
information contained in the June 2003 final rule is revised to exclude 
the revoked sections of the regulations, Sec. Sec.  314.52(a)(3) and 
314.95(a)(3), and certain sections of the regulations, Sec. Sec.  
314.50(i)(1)(i) and 314.94(a)(12), which were included in the estimated 
annual reporting burden to describe an information collection burden 
associated with the revoked sections of the regulations.
    The reporting burden for submitting an NDA, an amendment, or 
supplement in accordance with Sec.  314.50(a) through (f), and (k) has 
been estimated by FDA and the collection of information has been 
approved by OMB under OMB control number 0910-0001, most recently until 
May 31, 2008, (70 FR 35099, June 16, 2005). In addition, the reporting 
burden associated with the previously-referenced Sec. Sec.  
314.50(i)(1)(i) and 314.94(a)(12), regarding patent certification 
requirements for 505(b)(2) applications and ANDAs also has been 
estimated and included within the collection of information approved by 
OMB under OMB control number 0910-0001. We are not re-estimating these 
approved burdens in this document. Only the reporting burdens 
associated with patent submission and listing in the final rule are 
estimated in this document.
    The information collection reporting requirements are as follows:
    Section 314.50(h) requires that an NDA, an amendment, or a 
supplement contain patent information described under Sec.  314.53.
    Section 314.53 requires that an applicant submitting an NDA, an 
amendment, or a supplement, except as provided in Sec.  314.53(d)(2), 
submit on FDA Forms 3542 and 3542a, the required patent information 
described in the section.
    Compliance with the information collection burdens under Sec. Sec.  
314.50(h) and 314.53 consists of submitting with an NDA, an amendment, 
or a supplement (collectively referred to as ``application'') the 
required patent declaration(s) on Form FDA 3542a for 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'' (Sec.  314.53(b)). 
Such patents claim the drug substance (active ingredient), drug product 
(formulation and composition), or method of use. If a patent is issued 
after the application is filed with FDA but before the application is 
approved, the applicant must submit the required patent information on 
Form FDA 3542a as an amendment to the application, within 30 days of 
the date of issuance of the patent.
    Within 30 days after the date of approval of an application, the 
applicant must submit Form FDA 3542 for each patent that claims the 
drug substance (active ingredient), drug product (formulation and 
composition), or approved method of use for listing in the Orange Book. 
In addition, for patents issued after the date of approval of an 
application, Form FDA 3542 must be submitted within 30 days of the date 
of issuance of the patent.
    In the Federal Register of June 2, 2006 (71 FR 32099), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one comment from the 
Pharmaceutical Research and Manufacturers of America (PhRMA). The 
comment stated, generally, that FDA underestimated the resources 
required to satisfy the collection of information. Further, the comment

[[Page 21268]]

suggested that the information collection burden could be reduced by 
clarifying several questions in FDA Forms 3542a and 3542, and deleting 
or revising questions in these forms that appear, to the comment, to 
serve no statutory purpose. In the following section of this document, 
FDA describes the comments submitted by PhRMA, and our responses (the 
word ``Response'' appears in parentheses before our response).
    First, the comment stated that the information collection burden 
associated with FDA Forms 3542a and 3542 was underestimated ``in part 
because completion of each form may involve personnel from legal, 
patent, regulatory, medical, and scientific divisions within a 
company.''
    (Response) FDA published for public comment its initial estimate of 
this collection of information in the proposed rule published in the 
Federal Register of October 24, 2002 (67 FR 65448 at 65458 and 65459). 
This estimate of the information collection burden was revised through 
the rulemaking process and further described in the preamble to the 
June 2003 final rule (68 FR 36676 at 36698 and 36699). In connection 
with the request that OMB extend approval for the collection of certain 
information described in the June 2003 final rule, FDA updated, 
unbundled, and revised its estimate of the burden associated with the 
collection of information on FDA Forms 3542a and 3542 to 20 hours and 5 
hours, respectively. This proposed revision was based on FDA's 
experience and other information. The comment provides no data to 
support its statement that the burden was underestimated, and does not 
propose any alternative estimate. Accordingly, FDA declines to revise 
its estimate. We note, however, that clarifications and revisions to 
FDA Forms 3542a and 3542 described in this document would be expected 
to reduce the overall burden associated with this collection of 
information.
    Second, the comment stated that question 4 on FDA Forms 3542a and 
3542 ``requires completion of the form on a claim-by-claim basis.'' The 
comment further contended that ``[t]his is not authorized under the 
statute, it serves no statutory purpose, and it significantly increases 
the burden on applicants.'' In the alternative, the comment requested 
that FDA amend question 4.2 to ``specifically allow an applicant to 
list together multiple claims for the same or related labeled 
indications.''
    (Response) FDA addressed comments related to listing individual 
patent claims for method-of-use patents in the response to comments 7 
and 11 in the preamble to the June 2003 final rule. In the June 2003 
final rule, we explained that the ``specific method-of-use claims are 
essential to our review because sections 505(j)(2)(A)(viii) and 
505(b)(2)(B) of the act allow ANDA and 505(b)(2) applicants to file 
statements which assert that the method-of-use patent does not claim a 
use for which the applicant is seeking approval [a ``section viii 
statement'']. The ANDA or 505(b)(2) applicant does not have to seek 
approval for all uses approved for the reference listed drug'' (68 FR 
36676 at 36685). A method of use may be omitted for ANDA labeling if it 
is protected by exclusivity or a listed patent (Sec.  
314.94(a)(8)(iv)). We further stated: ``Thus, the claim-by-claim 
listing of method-of-use patents will permit ANDA and 505(b)(2) 
applicants to assess whether they are seeking approval for a use 
claimed in the listed patent, and thus determine whether to submit a 
patent certification or a section viii statement. Additionally, we can 
verify that the certification or statement is correct, and that only 
the appropriate methods of use are included in the proposed labeling 
for the ANDA or 505(b)(2) drug product'' (68 FR 36676 at 36685).
    In the alternative, PhRMA requested that FDA amend question 4.2 to 
``specifically allow an applicant to list together multiple claims for 
the same or related labeled indications.'' FDA agrees, consistent with 
our regulations at Sec.  314.53(b)(1), that an applicant may list 
together multiple patent claims for each pending or approved method of 
use. However, each pending or approved method of use must be separately 
identified and therefore will require separate listing(s) of method of 
use information in section 4 of FDA Forms 3542a and 3542. Therefore, if 
a patent claims one or more methods of use that apply to a pending 
application or approved product, each pending or approved method of use 
would need to be listed separately along with the patent claim 
number(s) for the patent claim(s) for the pending or approved method of 
use. A single Form FDA 3542a or Form FDA 3542, as appropriate, may be 
used to list a patent claiming more than one method of use, provided 
that each method of use is listed separately along with the patent 
claim number(s) for the patent claim(s) for the pending or approved 
method of use. This regulatory approach accomplishes the statutory 
objective of providing adequate information to permit ANDA and 
505(b)(2) applicants to file statements which assert that the method-
of-use patent does not claim a use for which the applicant is seeking 
approval.
    FDA that the instructions and text of section 4 on FDA Forms 3542a 
and 3542 may warrant clarification in light of the text of the 
regulations at Sec.  314.53(b)(1). FDA's regulations on submission of 
patent information state, in pertinent part: ``The applicant shall 
separately identify each pending or approved method of use and related 
patent claim'' (Sec.  314.53(b)(1) (emphasis added)). Section 4 of FDA 
Forms 3542a and 3542 states: ``Sponsors must submit the information in 
section 4 separately for each patent claim claiming an approved method 
of using the approved drug product. For each method of use claim 
referenced, provide the following information* * *'' (emphasis added). 
Currently, some applicants list multiple patent claims together for 
each separately identified pending or approved method of use. FDA is 
revising FDA Forms 3542a and 3542 to clarify that this is an acceptable 
practice and conform the text of these Forms to our existing 
regulations. The text of Section 4 of these Forms is being revised to 
delete the word ``separately'' from the first sentence of text and add 
other clarifying text. FDA also is adding clarifying text to the 
information and instructions for these Forms.
    Third, the comment questioned the specific statutory purpose for 
requiring a sponsor to ``link'' the method of use claimed by the patent 
to language identifying the use in the approved (or, with respect to 
Form FDA 3542a, the proposed) labeling for the drug product.
    (Response) FDA previously has explained the basis for requiring a 
description of each individual method of use for which a patent is 
submitted for listing, and identification of the corresponding language 
found in the labeling of the approved NDA that corresponds to that 
method of use. As discussed in more detail in the June 2003 final rule, 
this approach provides for effective implementation of the patent 
certification and ``section viii statement'' provisions of the act by 
enabling ANDA and 505(b)(2) applicants, and FDA, ``to assess whether 
the ANDA or 505(b)(2) applicant is seeking approval for a use the 
sponsor states is claimed in the listed patent, and thus determine 
whether the applicant must submit a patent certification or may submit 
a section viii statement under section 505(b)(2)(B) or 
505(j)(2)(A)(viii) of the act'' (68 FR 36676 at 36682). A ``section 
viii statement'' refers to a statement under section 505(b)(2)(B) or 
505(j)(2)(A)(viii)

[[Page 21269]]

of the act asserting that a listed method of use patent does not claim 
a use for which the applicant is seeking approval. In addition, 
information regarding the approved labeling corresponding to a listed 
method of use patent assists FDA in determining which labeling should 
be omitted when a 505(b)(2) application or ANDA includes a ``section 
viii statement'' indicating that it is not seeking approval for the use 
claimed in the patent.
    Fourth, with reference to section 4.2b of Form FDA 3542, the 
comment questioned the need for a sponsor to provide a proposed ``Use 
Code'' describing the approved indication or method of use for 
inclusion in the Orange Book. The comment stated that inclusion of 
``Use Codes'' is not required by the act, and noted that ``although FDA 
has suggested that requiring NDA applicants to supply use codes is 
necessary to assist generic applicants, the agency also stated that a 
generic applicant should not rely on the information concerning method 
of use patents provided by the NDA applicant, but should conduct an 
independent review and evaluation of the relevant patent(s) and 
approved labeling'' (citing the June 2003 final rule, 68 FR 36676 at 
36683 and 36685). Further, the comment stated that FDA has ``provided 
no guidance to innovators on appropriate content of `use codes''' and 
such information may be duplicative of other information provided in 
the form.
    (Response) As discussed in the previous response, section 
505(b)(2)(B) and 505(j)(2)(A)(viii) of the act permit a 505(b)(2) and 
ANDA applicant, respectively, to assert that a listed method of use 
patent does not claim a use for which the applicant is seeking 
approval. FDA has consistently required that a 505(b)(2) or ANDA 
applicant filing a section viii statement must ``carve out'' from the 
proposed labeling, the labeling protected by the listed patent (see 68 
FR 36676 at 36682). The regulatory requirement that an applicant 
provide a ``use code'' for method of use patents listed in the Orange 
Book facilitates the implementation of the certification and section 
viii statement provisions of the act (see section 701 of the act (21 
U.S.C. 371)). Accordingly, the use code should contain adequate 
information, within the 240-character limitation of FDA's database 
system, to assist 505(b)(2) and ANDA applicants in determining whether 
a listed method of use patent claims a use for which the 505(b)(2) or 
ANDA applicant is not seeking approval and thus has been carved out of 
the proposed labeling.
    Fifth, the comment states that ``Question 2 requires unnecessary 
information relating to patents that claim polymorphs.'' The comment 
contends that ``[t]he fact that a properly listed patent may also claim 
other forms is irrelevant * * * it is only if the patent claims only a 
different form that the agency needs to ask applicants to certify that 
the substance is, nevertheless, the `same.''' The comment suggests that 
subquestion 2.2 should be revised accordingly to state: ``Does the 
patent claim only a drug substance that is a polymorph of the active 
ingredient in the pending NDA, amendment, or supplement?''
    (Response) FDA's regulations at Sec. Sec.  314.53(c)(2)(i)(M)(2) 
and 314.53(c)(2)(ii)(N)(2) require information on whether the patent 
claims a polymorph that is the same active ingredient that is described 
in the pending application or supplement. This requirement is described 
at section 2.2 of Forms 3542a and 3542. The revision that you have 
proposed would require revision of FDA's regulations. In continuing to 
implement Title XI of the MMA, FDA plans to initiate a rulemaking to 
amend certain regulations regarding 505(b)(2) applications and ANDAs to 
facilitate compliance with and efficient enforcement of the act. FDA 
will further consider your request for clarification and revision to 
the regulations in the context of that rulemaking.
    Sixth, the comment questioned the need for indicating in subsection 
2.7 and 3.3 of FDA Forms 3542a and 3542 whether the product claimed in 
a product-by-process patent is novel. The comment stated that this 
information is not required by the act and the ``same listing criteria 
used for other product patents should apply to patents that include 
product-by-process claims.'' The comment further noted that ``including 
the term `novel' in the form plunges FDA into complicated issues of 
patent law, which it has said repeatedly are beyond its expertise.''
    (Response) In subsection 2.7 and 3.3 of FDA Forms 3542a and 3542, 
we require applicants to indicate whether the product claimed in the 
product-by-process patent is novel to help ensure that process patents 
are not submitted for listing (see June 2003 final rule, 68 FR 36676 at 
36686). FDA's regulations at Sec. Sec.  314.53(c)(2)(i)(L) and 
314.53(c)(2)(ii)(M) codify this requirement. The June 2003 final rule 
and questions on FDA Forms 3542a and 3542 were intended to clarify 
which patents must and must not be submitted for listing, and avoid 
situations in which applicants may inadvertently submit patents that do 
not meet the statutory and regulatory requirements. We disagree with 
the comment's suggestion that inclusion of the term `novel' in FDA 
Forms 3542a and 3542 ``plunges FDA into complicated issues of patent 
law.'' FDA's patent listing role remains ministerial. As discussed in 
the preamble to the June 2003 final rule, FDA ``will not evaluate a 
patent to assess whether the declaration is accurate or whether the 
patent has been appropriately submitted for listing. * * * We will, 
however, review the declaration for completeness and to determine that 
the information given by the NDA applicant or holder or patent owner 
indicates that the patent is eligible for listing'' (68 FR 36676 at 
36687).
    Seventh, the comment requested clarification of subsection 1f of 
FDA Forms 3542a and 3542, which states ``Is the patent referenced above 
a patent that has been submitted previously for the approved NDA or 
supplement referenced above.''
    (Response) In the preamble to the June 2003 final rule, FDA 
discussed, in response to comment 12, its requirement for information 
on whether the patent being submitted has been submitted previously for 
the NDA or supplement referenced in the declaration. FDA stated: ``We 
require information on whether the patent being submitted has been 
submitted previously for the NDA or supplement referenced in the 
declaration. For example, an earlier listed patent may have included 
several method-of-use claims but only one method of use previously 
approved and submitted. A second method of use may be approved in a 
supplement and must be submitted for listing. Such information will 
assist the Orange Book staff with its administrative listing 
responsibilities'' (68 FR 36676 at 36686). FDA will further consider 
your request for clarification in the context of the rulemaking 
referenced previously.
    Eighth, the comment suggested that FDA clarify that the ``purpose 
of questions 2.1, 3.1, and 4.1 [on Forms 3542a and 3542] is simply to 
differentiate the types of claims that appear in the patents in 
questions (i.e., drug substance, drug product, or method of use). In 
other words, question 2.1 should be answered `yes' only if the patent 
contains `drug substance' claims. Question 3.1 should be answered `yes' 
only if the patent contains drug product claims. Question 4.1 should be 
answered `yes' only if the patent contains method of use claims.''
    (Response) FDA's regulations at Sec.  314.53(c)(2) set forth 
reporting requirements for submission of patent information. These 
regulations require

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the submission of information and verification of patent information to 
ensure not only that the patent contains drug substance, drug product, 
or method of use claims, but that the patent claims the drug substance, 
drug product, or method of using the drug product for which approval is 
sought or has been granted. The clarification that you have requested 
would require revision of FDA's regulations. FDA will further consider 
your request for clarification and revision to the regulations in the 
context of the rulemaking referenced previously.
    Finally, the comment stated that the submission of FDA Forms 3542a 
and 3542 with submission and upon approval, respectively, of an NDA 
supplement is redundant where the information has not changed since the 
form last was filed, imposes a burden on sponsors, and serves no 
statutory purpose.
    (Response) FDA's regulation at Sec.  314.53(b)(1) requires any 
applicant who submits to FDA a supplement to an approved application 
that meets the criteria of Sec.  314.53(d)(2) to submit FDA Forms 3542a 
and 3542, as appropriate. The revision that you have proposed would 
require revision of FDA's regulations. FDA will further consider your 
request for clarification and revision to the regulations in the 
context of the rulemaking referenced previously.
    FDA estimates that the collection of information resulting from 
these regulations is as follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                                              No. of         No. of Responses       Total Annual        Hours per
                       FDA Form                            Respondents        per Respondent         Responses           Response         Total Hours
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Form FDA 3542a                                                        114                   3.2                365                 20              7,300
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Form FDA 3542                                                          96                   3.2                308                  5              1,540
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Total                                                                                                                                              8,840
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: April 23, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-8141 Filed 4-27-07; 8:45 am]
BILLING CODE 4160-01-S