
[Federal Register Volume 78, Number 180 (Tuesday, September 17, 2013)]
[Notices]
[Pages 57164-57166]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-22540]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0662]


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

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.

DATES: Fax written comments on the collection of information by October 
17, 2013.

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: 202-395-7285, or emailed to oira_submission@omb.eop.gov. 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: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, PRAStaff@fda.hhs.gov.

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 New Drug Applications Certifying That a Patent Claiming 
a Drug Is Invalid or Will Not Be Infringed--(OMB Control Number 0910-
0513)--Extension

    Section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 355(b)(1)) requires all new drug application (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 FD&C Act (21 U.S.C. 355(c)(2)) 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 FD&C Act, we publish patent 
information after approval of an NDA 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 FD&C Act directs us to publish the information upon 
its submission.
    FDA regulations at Sec. Sec.  314.50(h) (21 CFR 314.50(h)) and 
314.53 (21 CFR 314.53) clarify the types of patent information that 
must and must not be submitted to FDA as part of an NDA, an amendment, 
or a supplement, and require 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 Forms FDA 3542 
and 3542a.
    The reporting burden for submitting an NDA, an amendment, or a 
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. We are not 
reestimating these approved burdens in this document. Only the 
reporting burdens associated with patent submission and listing, as 
explained in the following paragraphs, 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

[[Page 57165]]

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 Forms FDA 3542 and 3542a, the required patent information 
described in this 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 17, 2013 (78 FR 36193), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one comment from a private 
citizen. The comment stated, generally, that ``it would be appropriate 
to require, along with the submission of any patents on the original 
drug and its formulation, any associated patents or claimed patent 
submission on metabolites or secondary products of the original 
drugs.''
    (FDA Response) FDA disagrees with the comment. FDA's regulations at 
Sec.  314.53(b) prohibit submission of drug substance (active 
ingredient) patents claiming metabolites when the metabolite is not the 
active ingredient described in the NDA. Section 314.53(b) states, in 
relevant part: ``For patents that claim the drug substance, the 
applicant shall submit information only on those patents that claim the 
drug substance that is the subject of the pending or approved 
application or that claim a drug substance that is the same as the 
active ingredient that is the subject of the approved or pending 
application. . . . Process patents, patents claiming packaging, patents 
claiming metabolites, and patents claiming intermediates are not 
covered by this section, and information on these patents must not be 
submitted to FDA.'' FDA clarified the criteria for listing patent 
information in the Orange Book in response to a request by the Federal 
Trade Commission (FTC) in its July 2002 report on ``Generic Drug Entry 
Prior to Patent Expiration: An FTC Study'' (see 68 FR 36676; June 18, 
2003, and http://www.ftc.gov/os/2002/07/genericdrugstudy.pdf). FDA 
determined that a patent claiming a metabolite does not claim an 
approved drug and thus does not meet the statutory requirements for 
listing in the Orange Book (see 67 FR 65448 at 65451; October 24, 
2002). However, if a patent claims an approved method of using an 
approved drug to administer a metabolite, the submission of the patent 
would be permissible as long as all of the conditions for submitting 
``method-of-use'' patents are met (see 68 FR 36676 at 36680; June 18, 
2003). Section 314.53(c)(2)(i)(M)(4) and 314.53(c)(2)(ii)(N)(4) require 
that an applicant submit on Forms FDA 3542a or 3542, as appropriate, 
information on whether a drug substance patent claims only a metabolite 
of the active ingredient that is described in the application or 
supplement, so that FDA can determine whether the patent is eligible 
for listing in the Orange Book (see section 2.5 of Forms FDA 3542a and 
3542).
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of                        Average
   21 CFR 314.50  (citing Sec.       Number of     responses per   Total  annual    burden per      Total hours
             314.53)                respondents     respondent       responses       response
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Form FDA 3542...................             183             2.8             512               5           2,560
Form FDA 3542a..................             201             2.8             563              20          11,260
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    Total.......................  ..............  ..............  ..............  ..............          13,820
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    The numbers of patents submitted to FDA for listing in the Orange 
Book in 2010, 2011, and 2012 were 351, 329, and 458, respectively, for 
an annual average of 379 (351 patents + 329 patents + 458 patents)/3 
years = 379 patents/year). Because many of these individual patents are 
included in multiple NDA submissions, there could be multiple 
declarations for a single patent. From our previous review of 
submissions, we believe that approximately 14 percent of the patents 
submitted are included in multiple NDA submissions, and thus require 
multiple patent declarations. Therefore, we estimate that 53 (379 
patents x 14 percent) patents will be multiple listings, and there will 
be a total of 432 patents (379 patents + 53 patents = 432 patents) 
declared on Form FDA 3542. We approved 84, 93, and 86 NDAs in 2010, 
2011, and 2012, respectively, of which approximately 71 percent 
submitted patent information for listing in the Orange Book. The 
remaining NDAs submitted Form FDA 3542 as required and declared that 
there were no relevant patents. We also approved approximately 101, 83, 
and 101 NDA supplements in 2010, 2011, and 2012, respectively, for 
which submission of a patent declaration would be required. We estimate 
there will be 183 instances (based on an average of 88 NDA approvals 
and 95 supplement approvals per year) where an NDA holder would be 
affected by the patent declaration requirements, and that each of these 
NDA holders would, on average, submit 2.8 declarations (432 patent 
declarations + 76 no relevant patent declarations)/183 instances = 2.8 
declarations per instance) on Form FDA 3542. We filed 96, 91, and 112 
NDAs in 2010, 2011,

[[Page 57166]]

and 2012, respectively, and 100, 91, and 112 NDA supplements in 2010, 
2011, and 2012, respectively, for which submission of a patent 
declaration would be required. We estimate there will be 201 instances 
(based on an average of 100 NDAs filed and 101 NDA supplements filed 
per year) where an NDA holder would be affected by the patent 
declaration requirements. We estimate, based on a proportional increase 
from the number of declarations for approved NDAs, that there will be 
an annual total of 563 declarations (201 instances x 2.8 declarations 
per instance = 563 declarations) on Form FDA 3542a submitted with these 
applications. Based upon information provided by regulated entities and 
other information, we previously estimated that the information 
collection burden associated with Sec.  314.50(h) (citing Sec.  314.53) 
and FDA Forms 3542 and 3542a will be approximately 5 hours and 20 hours 
per response, respectively.

    Dated: September 11, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-22540 Filed 9-16-13; 8:45 am]
BILLING CODE 4160-01-P


