[Federal Register Volume 83, Number 21 (Wednesday, January 31, 2018)]
[Notices]
[Pages 4492-4494]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-01890]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-E-2661]


Determination of Regulatory Review Period for Purposes of Patent 
Extension; KEYTRUDA

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) has 
determined the regulatory review period for KEYTRUDA and is publishing 
this notice of that determination as required by law. FDA has made the 
determination because of the submission of an application to the 
Director of the U.S. Patent and Trademark Office (USPTO), Department of 
Commerce, for the extension of a patent which claims that human 
biological product.

DATES: Anyone with knowledge that any of the dates as published (in the 
SUPPLEMENTARY INFORMATION section) are incorrect may submit either 
electronic or written comments and ask for a redetermination by April 
2, 2018. See ``Petitions'' in the SUPPLEMENTARY INFORMATION section for 
more information.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before April 2, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of April 2, 2018. Comments received by 
mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date. Furthermore, any 
interested person may petition FDA for a determination regarding 
whether the applicant for extension acted with due diligence during the 
regulatory review period by July 30, 2018. See ``Petitions'' in the 
SUPPLEMENTARY INFORMATION section for more information.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a

[[Page 4493]]

written/paper submission and in the manner detailed (see ``Written/
Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-E-2661 for ``Determination of Regulatory Review Period for 
Purposes of Patent Extension; KEYTRUDA.'' Received comments, those 
filed in a timely manner (see ADDRESSES), will be placed in the docket 
and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with Sec.  10.20 (21 CFR 10.20) and 
other applicable disclosure law. For more information about FDA's 
posting of comments to public dockets, see 80 FR 56469, September 18, 
2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Beverly Friedman, Office of Regulatory 
Policy, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6250, Silver Spring, MD 20993, 301-796-3600.

SUPPLEMENTARY INFORMATION: 

I. Background

    The Drug Price Competition and Patent Term Restoration Act of 1984 
(Pub. L. 98-417) and the Generic Animal Drug and Patent Term 
Restoration Act (Pub. L. 100-670) generally provide that a patent may 
be extended for a period of up to 5 years so long as the patented item 
(human drug product, animal drug product, medical device, food 
additive, or color additive) was subject to regulatory review by FDA 
before the item was marketed. Under these acts, a product's regulatory 
review period forms the basis for determining the amount of extension 
an applicant may receive.
    A regulatory review period consists of two periods of time: A 
testing phase and an approval phase. For human biological products, the 
testing phase begins when the exemption to permit the clinical 
investigations of the biological product becomes effective and runs 
until the approval phase begins. The approval phase starts with the 
initial submission of an application to market the human biological 
product and continues until FDA grants permission to market the 
biological product. Although only a portion of a regulatory review 
period may count toward the actual amount of extension that the 
Director of USPTO may award (for example, half the testing phase must 
be subtracted as well as any time that may have occurred before the 
patent was issued), FDA's determination of the length of a regulatory 
review period for a human biological product will include all of the 
testing phase and approval phase as specified in 35 U.S.C. 
156(g)(1)(B).
    FDA has approved for marketing the human biologic product KEYTRUDA 
(pembrolizumab). KEYTRUDA is a programmed death receptor-1 (PD-1)-
blocking antibody indicated for the treatment of:
     Patients with unresectable or metastatic melanoma.
     Patients with metastatic non-small cell lung cancer 
(NSCLC) whose tumors have high PD-ligand 1 (PD-L1) expression (Tumor 
Proportion Score (TPS) >= 50%) as determined by an FDA-approved test, 
with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma 
kinase (ALK) genomic tumor aberrations, and no prior systemic 
chemotherapy treatment for metastatic NSCLC.
     Patients with metastatic NSCLC whose tumors express PD-L1 
(TPS >= 1%) as determined by an FDA-approved test, with disease 
progression on or after platinum-containing chemotherapy. Patients with 
EGFR or ALK genomic tumor aberrations should have disease progression 
on FDA-approved therapy for these aberrations prior to receiving 
KEYTRUDA.
     Patients with recurrent or metastatic head and neck 
squamous cell carcinoma with disease progression on or after platinum-
containing chemotherapy. This indication is approved under accelerated 
approval based on tumor response rate and durability of response. 
Continued approval for this indication may be contingent upon 
verification and description of clinical benefit in the confirmatory 
trials.
     Adult and pediatric patients with refractory classical 
Hodgkin lymphoma, or who have relapsed after three or more prior lines 
of therapy. This indication is approved under accelerated approval 
based on tumor response and durability of response. Continued approval 
for this indication may be contingent upon verification and description 
of clinical benefit in the confirmatory trials.
    Subsequent to this approval, the USPTO received a patent term 
restoration application for KEYTRUDA (U.S. Patent No. 8,354,509) from 
Merck Sharp & Dohme B.V., and the USPTO requested FDA's assistance in 
determining this patent's eligibility for patent term restoration. In a 
letter dated October 15, 2015, FDA advised the USPTO that this human 
biological product had undergone a regulatory review period and that 
the approval of KEYTRUDA represented the first permitted commercial 
marketing or use of the product. Thereafter, the USPTO requested that 
FDA determine the product's regulatory review period.

II. Determination of Regulatory Review Period

    FDA has determined that the applicable regulatory review period for

[[Page 4494]]

KEYTRUDA is 1,338 days. Of this time, 1,148 days occurred during the 
testing phase of the regulatory review period, while 190 days occurred 
during the approval phase. These periods of time were derived from the 
following dates:
    1. The date an exemption under section 505(i) of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 355(i)) became effective: January 7, 
2011. The applicant claims January 8, 2011, as the date the 
investigational new drug application (IND) became effective. However, 
FDA records indicate that the IND effective date was January 7, 2011, 
which was the first date after FDA receipt of the IND that the 
investigational studies were allowed to proceed.
    2. The date the application was initially submitted with respect to 
the human biological product under section 351 of the Public Health 
Service Act (42 U.S.C. 262): February 27, 2014. FDA has verified the 
applicant's claim that the biologics license application (BLA) for 
KEYTRUDA (BLA 125514/0) was initially submitted on February 27, 2014.
    3. The date the application was approved: September 4, 2014. FDA 
has verified the applicant's claim that BLA 125514/0 was approved on 
September 4, 2014.
    This determination of the regulatory review period establishes the 
maximum potential length of a patent extension. However, the USPTO 
applies several statutory limitations in its calculations of the actual 
period for patent extension. In its application for patent extension, 
this applicant seeks 83 days of patent term extension.

III. Petitions

    Anyone with knowledge that any of the dates as published are 
incorrect may submit either electronic or written comments and, under 
21 CFR 60.24 ask for a redetermination (see DATES). Furthermore, as 
specified in Sec.  60.30 (21 CFR 60.30), any interested person may 
petition FDA for a determination regarding whether the applicant for 
extension acted with due diligence during the regulatory review period. 
To meet its burden, the petition must comply with all the requirements 
of Sec.  60.30, including but not limited to: Must be timely (see 
DATES), must be filed in accordance with Sec.  10.20, must contain 
sufficient facts to merit an FDA investigation, and must certify that a 
true and complete copy of the petition has been served upon the patent 
applicant. (See H. Rept. 857, part 1, 98th Cong., 2d sess., pp. 41-42, 
1984.) Petitions should be in the format specified in 21 CFR 10.30.
    Submit petitions electronically to https://www.regulations.gov at 
Docket No. FDA-2013-S-0610. Submit written petitions (two copies are 
required) to the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

    Dated: January 24, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-01890 Filed 1-30-18; 8:45 am]
 BILLING CODE 4164-01-P


