[Federal Register Volume 85, Number 105 (Monday, June 1, 2020)]
[Notices]
[Pages 33169-33173]
[FR Doc No: 2020-11684]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1127]

Listing of Patent Information in the Orange Book; Establishment
of a Public Docket; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of a public docket; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the establishment of a docket to solicit comments on the listing of
patent information in the FDA publication, ``Approved Drug Products
With Therapeutic Equivalence Evaluations'' (commonly known as the
``Orange Book''). We are soliciting comments on the types of patents
currently listed in the Orange Book and the impact that any change to
current patent listing practices may have on drug product development.
This notice is not intended to communicate our regulatory expectations
on these issues but is instead intended to seek early input from the
public to inform further regulatory action if determined to be
appropriate.

DATES: Submit either electronic or written comments by August 31, 2020.

ADDRESSES: FDA is establishing a docket for public comments on this
document. The docket number is Docket No. FDA-2020-N-1127. The docket
will close on August 31, 2020. Submit either electronic or written
comments by that date. Please note that late, untimely filed comments
will not be considered. Electronic comments must be submitted on or
before August 31, 2020. The https://www.regulations.gov electronic
filing system will accept comments until 11:59 p.m. Eastern Time at the
end of August 31, 2020. 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.
    You may submit comments as follows:

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 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-2020-N-1127 for ``Listing of Patent Information in the Orange
Book.'' Received comments 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 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.govinfo.gov/content/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: Elizabeth Giaquinto Friedman, Center
for Drug Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 75, Rm. 1670, Silver Spring, MD 20993, 240-
402-7930<EMAIL_ADDRESS>

SUPPLEMENTARY INFORMATION:

I. Background

A. The Orange Book

    On May 31, 1978, the FDA Commissioner sent a letter to officials of
each state, in response to requests from State health agencies for FDA
assistance in administering their laws relating to substitution of drug
products, announcing FDA's intent to provide a list of all prescription
drug products that had been approved by FDA for safety and
effectiveness, along with therapeutic equivalence determinations for
multisource prescription products. This list was distributed as a
proposal in January 1979 (see 44 FR 2932, January 12, 1979). The
proposed list, which later became known as the Orange Book, included
only prescription drug products that had been approved by FDA and were
marketed at the time of publication. On October 31, 1980, FDA published
a final version of the list, which was the first Orange Book (45 FR
72582).
    On September 24, 1984, the President signed into law the Drug Price
Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417)
(Hatch-Waxman Amendments). The Hatch-Waxman Amendments require that
FDA, among other things, make publicly available a list of approved
drug products with monthly supplements. The Orange Book and its monthly
Cumulative Supplements satisfy this requirement.
    The Orange Book identifies drug products approved on the basis of
safety and effectiveness by FDA under the Federal Food, Drug, and
Cosmetic Act (FD&C Act). The main criterion for the inclusion of a
product is that it has a new drug application (NDA) or abbreviated new
drug application (ANDA) that has been approved and that has not been
withdrawn for safety or efficacy reasons.

B. Submission and Listing of Patent Information

    The FD&C Act establishes requirements for FDA, NDA applicants, and
NDA holders related to submission of patent information and the listing
of patent information in the Orange Book. The FD&C Act requires NDA
applicants to file with their application the patent number and
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 (see section
505(b)(1) of the FD&C Act; see also 21 CFR 314.53). An NDA applicant is
required to amend its application to include this information if a
patent that claims such drug or a method of using such drug is issued
after the filing date but before approval of the application. After
approval of an NDA (including certain types of supplements to an NDA)
but within certain time frames prescribed in the FD&C Act and FDA's
implementing regulations, NDA holders must submit the required
information on any patent that claims the approved drug or an approved
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,
including information on patents that are issued after the application
is approved (see section 505(c)(2) of the FD&C Act (21 U.S.C.
355(c)(2)) and 21 CFR 314.53). The FD&C Act requires FDA to regularly
revise the Orange Book to include, among other things, patent
information submitted under section 505(b)(1) or 505(c)(2) of the FD&C
Act (see section 505(j)(7)(A)(iii) of the FD&C Act). We note that FDA
has a ministerial role with regard to the listing of patent information
(see, e.g., ``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,'' final
rule, 68 FR 36676 at 36683 (June 18, 2003)) (Indeed, the requirement of
prompt publication (``upon submission''), combined with the 30-day
timeframe for updating the Orange Book, are strong evidence that
Congress did not intend us to undertake anything other than a
ministerial action.)). Since enactment of the Hatch-Waxman Amendments,
FDA has provided recommendations and issued regulations pertaining to
patent listing requirements of the FD&C Act to facilitate
implementation. Below is a brief summary of those efforts.
    Following the enactment of the Hatch-Waxman Amendments, FDA
provided NDA applicants and application holders with advice on how to
comply with these new amendments, including the new requirements for
submission of patent information, via letters to industry (see, e.g.,
Letter from Harry M. Meyer, Jr., M.D. to the Pharmaceutical
Manufacturers Association (March 26, 1985), available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072884.pdf). These letters demonstrated how FDA's thinking
on the appropriateness of the listing of certain patents evolved, even
after a short period following the implementation of the Hatch-Waxman
Amendment's patent information submission requirements. For example,
shortly after enactment the Agency indicated that formulation patents
were not covered by the FD&C Act and therefore should not be submitted
for listing in the Orange Book. However, in 1985, the Director of the
Center for Drugs and Biologics issued a letter to industry stating, in
part, that FDA reconsidered its original position and that FDA now
intends to publish composition patents, including formulation patents,
claiming the drug for which the NDA was submitted and for which a claim
of patent infringement could reasonably be asserted in the event of
unlicensed manufacture, use, or sale of the drug.
    In 1989, FDA issued a proposed rule to implement the Hatch-Waxman
Amendments, including proposed regulations detailing the types of
patents that FDA regarded as covered by the requirements in section
505(b)(1) and 505(c)(2) of the FD&C Act. In particular, FDA proposed
that to comply with section 505(b)(1) and 505(c)(2) of the FD&C Act,
NDA applicants would be required to submit information on drug
(ingredient) patents, drug product (formulation and composition)
patents, and method-of-use patents (see ``Abbreviated New Drug
Application Regulations,'' proposed rule, 54 FR 28872 at 28918 (July
10, 1989)). The proposed rule, though, specifically excluded process
patents. When FDA issued a final rule in 1992, FDA declined to finalize
those requirements, and stated that because the Agency would be issuing
final regulations governing patent certification and marketing
exclusivity requirements at a future date, FDA was revising or deleting
cross-references to those provisions and, where possible, replacing
them with statutory citations (see ``Abbreviated New Drug Application
Regulations,'' final rule, 57 FR 17950 at 17951 (April 28, 1992)). In
1994, FDA finalized the regulations governing certain patent and
exclusivity provisions of the Hatch-Waxman Amendments (see
``Abbreviated New Drug Application Regulations; Patent and Exclusivity
Provisions,'' final rule, 59 FR 50338 (October 3, 1994)). In response
to a comment suggesting proposed revisions to the regulations to

clarify that submission of patent information on patented manufacturing
processes is not appropriate, the preamble to the final rule reiterated
that the regulation at Sec.  314.53(b) clearly states that information
on process patents should not be submitted to FDA (59 FR 50338 at
50345).
    In 2002, FDA issued a proposed rule in response to: (1) Disputes
over whether certain listed patents met the regulatory requirements for
listing in the Orange Book and (2) a request from the Federal Trade
Commission to issue a regulation or guidance clarifying whether an NDA
holder can list various types of patents in the Orange Book (see
``Applications for FDA Approval to Market a New Drug: Patent 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,'' proposed rule, 67 FR 65448
at 65449 (October 24, 2002)). The proposed rule addressed: (1) The
types of patents that must and must not be listed, including, among
others, certain patents that claim methods of use; (2) the patent
certification statement that NDA applicants must submit as part of an
NDA or a supplement to an NDA; and (3) the 30-month stay of approval
for a 505(b)(2) application or an ANDA set out in the Hatch-Waxman
Amendments (see also section 505(c)(3)(C) and 505(j)(5)(B)(iii) of the
FD&C Act). In addition to proposing to clarify that NDA holders and NDA
applicants must not submit information on patents that claim methods of
use that are not approved for the listed drug or are not the subject of
the pending application, respectively, the proposed regulation at Sec.
314.53(a) proposed to prohibit the listing of information on patents
claiming packaging, patents claiming metabolites, and patents claiming
intermediates (67 FR 65448 at 65451). The proposed rule, however,
proposed to require NDA applicants and NDA holders to submit
information on product-by-process patents (i.e., patents that claim a
product by using or listing process steps to wholly or partially define
the claimed product) and patents that claim a drug substance even when
the patented drug substance was a different form than the drug
substance that is the subject of the pending or approved NDA as long as
the drug substances are the same (67 FR 65448 at 65452).
    FDA issued the final rule on patent listing requirements, with
certain revisions, on June 18, 2003. The final rule revised FDA's
regulations to: (1) Incorporate the proposals described above with
certain revisions; (2) prohibit the submission of patents claiming
packaging, intermediates, or metabolites; (3) require the submission of
certain patents claiming a different polymorphic form of the active
ingredient described in the NDA; and (4) add a requirement that for
submission of polymorph patents, the NDA holder must have test data
demonstrating that a drug product containing the polymorph will perform
the same as the drug product described in the NDA (see 68 FR 36676 at
36677). We also note that certain sections of the June 2003 final rule
were superseded by the Medicare Prescription Drug, Improvement, and
Modernization Act of 2003 (MMA) and subsequently revoked (see
``Application of 30-Month Stays on Approval of ANDAs and Certain NDAs
Containing a Certification That a Patent Claiming the Drug Is Invalid
or Will Not Be Infringed; Technical Amendment'' (69 FR 11309 (March 10,
2004)). The preamble to the final rule addressed comments on the types
of patents that must and must not be submitted, including comments
stating that patents claiming devices or containers that are `integral'
to the drug product or require prior FDA approval should be submitted
and listed (68 FR 36676 at 36680). The comments described a distinction
between packaging and devices such as metered dose inhalers and
transdermal patches, which are drug delivery systems used and approved
in combination with a drug. In response to the comment, FDA agreed that
patents claiming a package or container must not be submitted, and
clarified that such packaging and containers are distinct from the drug
product and thus fall outside of the requirements for patent submission
(68 FR 36676 at 36680). FDA did not expressly address device-related
patents, but clarified the rule to require submission of patents that
claim the drug product as defined in FDA's regulation at Sec.
314.3(b), which defines drug product as a finished dosage form, e.g.,
tablet, capsule, or solution, that contains a drug substance,
generally, but not necessarily, in association with one or more other
ingredients. FDA explained that the ``key factor'' in determining
whether the patent must or must not be submitted for listing is whether
the patent claims the finished dosage form of the approved drug
product. Patents must not be submitted for bottles or containers and
other packaging, as these are not `dosage forms' (68 FR 36676 at
36680).
    In 2015, FDA proposed regulations to implement portions of Title XI
of the MMA, which amended provisions of the FD&C Act that govern the
approval of 505(b)(2) applications and ANDAs, and FDA also proposed to
amend certain regulations, including regulations regarding the
submission of patent information, to facilitate compliance with and
efficient enforcement of the FD&C Act (``Abbreviated New Drug
Applications and 505(b)(2) Applications,'' proposed rule, 80 FR 6802
(February 6, 2015)). Among other things, the final rule, issued in
2016, revised and streamlined the requirements for submission of patent
information on: (1) Patents that claim the drug substance and/or drug
product and meet the requirements for patent listing on that basis; (2)
drug substance patents that claim only a polymorph of the active
ingredient; and (3) certain NDA supplements (``Abbreviated New Drug
Applications and 505(b)(2) Applications; Final Rule,'' 81 FR 69580
(October 6, 2016)) (MMA Final Rule). For example, FDA clarified that an
applicant need only satisfy the requirements for patent listing set
forth in section 505(b)(1) and (c)(2) of the FD&C Act and, subject to
the requirements for submission of method-of-use patent information,
need not identify each basis on which the patent claims the drug (see
81 FR 69580 at 69596). Accordingly, if a patent is eligible for listing
as claiming both the drug substance and the drug product, an applicant
would only be required to identify one of these two bases for listing
(see Sec.  314.53(c)(2)(i)(S) and (c)(2)(ii)(T)). The MMA final rule
also codified FDA's longstanding position that the NDA holder's
description of the patented method of use required for publication must
contain adequate information 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 (see
Sec.  314.53(c)(2)(ii)(P)(3)). For example, the rule requires that if
the method(s) of use claimed by the patent does not cover an indication
or other approved condition of use in its entirety, then the applicant
must describe only the specific approved method of use claimed by the
patent for 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 (see Sec.
314.53(c)(2)(ii)(P)(3)).

C. Patent Certifications and Exclusivities--Timing of Approval of
505(b)(2) Applications and ANDAs

    The timing of approval for a 505(b)(2) application and an ANDA
(including a

petitioned ANDA) is subject to certain patent and marketing exclusivity
protections.
    A 505(b)(2) application and ANDA must include an appropriate patent
certification or statement for each patent that claims the listed
drug(s) relied upon or the reference listed drug (RLD), respectively,
or a method of using such drug and for which information is required to
be filed under section 505(b) or 505(c) of the FD&C Act. The 505(b)(2)
or ANDA applicant must submit one or more of the following
certifications or statements:
     That such patent information has not been filed (a
paragraph I certification);
     that such patent has expired (a paragraph II
certification);
     the date on which such patent will expire (a paragraph III
certification);
     that such patent is invalid, unenforceable, or will not be
infringed by the manufacture, use, or sale of the drug product for
which the 505(b)(2) application or ANDA is submitted (a paragraph IV
certification);
     that there are no patents that claim the listed drug(s) or
that claim a use of such drug (a ``no relevant patents'' statement,
which is submitted instead of a patent certification); or
     that a method-of-use patent does not claim a use for which
the 505(b)(2) or ANDA applicant is seeking approval (a 505(b)(2)(B) or
(j)(2)(A)(viii) statement).

An applicant that submits a paragraph IV certification is required to
give notice of the paragraph IV certification to the NDA holder for the
listed drug(s) relied upon or RLD and each owner of the patent that is
the subject of the certification. Notice of a paragraph IV
certification subjects the 505(b)(2) or ANDA applicant to the risk that
it will be sued for patent infringement. If the NDA holder or patent
owner initiates a patent infringement action within 45 days after
receiving notice of the paragraph IV certification, there generally
will be a statutory 30-month stay of approval of the 505(b)(2)
application or ANDA while the patent infringement litigation is pending
(see section 505(c)(3)(C) and (j)(5)(B)(iii) of the FD&C Act).
    If a patent is timely listed in the Orange Book after a 505(b)(2)
application or ANDA is submitted but before it is approved, the
applicant generally must amend its application and provide an
appropriate patent certification or statement to the newly listed
patent, but a 30-month stay of approval will not be available (see
section 505(c)(3)(C) and 505(j)(5)(B)(iii) of the FD&C Act).

D. ANDAs Subject to Risk Evaluation and Mitigation Strategies

    The Food and Drug Administration Amendments Act of 2007 (FDAAA)
(Pub. L. 110-85) created section 505-1 of the FD&C Act (21 U.S.C. 355-
1), which authorizes FDA to require a risk evaluation and mitigation
strategy (REMS) if FDA determines that a REMS is necessary to ensure
that the benefits of the drug outweigh its risks. A REMS is a required
risk management strategy that employs tools beyond prescribing
information to ensure that the benefits of a drug outweigh its risks. A
REMS may require a Medication Guide to provide risk information to
patients (see section 505-1(e)(2) of the FD&C Act) and/or a
communication plan to disseminate risk information to health care
providers (see section 505-1(e)(3) of the FD&C Act). FDA may also
require certain elements to assure safe use (ETASU) when such elements
are necessary to mitigate specific serious risks associated with a drug
(see section 505-1(f) of the FD&C Act). ETASU may include, for example,
requirements that health care providers who prescribe the drug have
particular training or experience, that patients using the drug be
monitored, or that the drug be dispensed to patients with evidence or
other documentation of safe-use conditions. An ANDA referencing a drug
with a REMS with ETASU is subject to the same ETASU as its RLD. When a
REMS with ETASU is required for the RLD, section 505-1(i)(1)(C) of the
FD&C Act, as amended by the Further Consolidated Appropriations Act,
2020 (Pub. L. 116-94), requires that the holder of an ANDA approved
under section 505(j) of the FD&C Act use a ``single, shared system''
with the RLD holder for the ETASU, or a ``different, comparable
aspect'' of the ETASU. FDA is aware that some NDA holders have obtained
patents claiming the way one or more of their REMS requirements have
been implemented and that this can impact the ability of a prospective
generic applicant to form a single, shared system with the NDA holder.
The prospect of NDA holders obtaining patents for REMS was also
contemplated by Congress in FDAAA, which, prior to the amendments made
to section 505-1 of the FD&C Act by the Further Consolidated
Appropriations Act, 2020, required the RLD and ANDA holders to use a
single, shared system for the ETASU unless FDA waived the requirement,
and provided that one of the grounds for which FDA could waive the
single, shared system requirement is if an aspect of the ETASU were
claimed by a patent and the ANDA applicant certified that it sought a
license to that aspect and was unable to obtain one (see 21 U.S.C. 355-
1(i)(1)(B)(ii), 2012 ed.). We note that section 505-1(f)(8) of the FD&C
Act provides that no holder of an approved covered application shall
use any ETASU to block or delay approval of an application under
section 505(b)(2) or (j) of the FD&C Act or to prevent application of
such element to a drug that is the subject of an ANDA.

II. Issues for Consideration and Request for Comments

    Stakeholders have requested clarification on whether certain types
of patents fall within the scope of required patent information that
must be submitted for listing in the Orange Book (see, e.g., Docket
Nos. FDA-2005-A-0476, FDA-2006-A-0063, FDA-2007-A-0099, FDA-2011-A-
0363, FDA-2012-A-1169), and FDA is aware that some NDA holders have
submitted patents for listing in the Orange Book, including certain
types of device-related patents and REMS-related patents, for which
there may be uncertainty regarding whether these are in fact the type
of patents that must be submitted. Stakeholders also have informed FDA
that there are both benefits and challenges to the listing of certain
types of patent information in the Orange Book as well as to the
omission of potentially relevant patent information from the Orange
Book. For example, the listing of a patent provides NDA holders with
the opportunity to identify which patents in the categories described
in the FD&C Act apply to its approved drug products. Patent listing can
help 505(b)(2) and ANDA applicants assess the intellectual property
assertions related to an NDA holder's product that could potentially
block entry of their proposed follow-on drug product or generic drug
product and determine their approach to these patents. Patent listing
also provides 505(b)(2) and ANDA applicants the opportunity to
challenge a patent while their applications are still under review by
the Agency, so that such claims can be litigated prior to commercial
marketing of the follow-on or generic drug product. However, this also
creates the possibility of a stay of approval of the 505(b)(2)
application or ANDA and implicates other statutory procedures and
requirements under the Hatch-Waxman framework.
    In light of these and other considerations, as part of an Agency-
wide effort to modernize the Orange Book, we are examining whether FDA
should further evaluate or provide additional clarity regarding the
types of patent information listed in the Orange

Book. In particular, we are seeking comments on the following as they
relate to the submission of patent information under section 505 of the
FD&C Act and the listing of such patent information in the Orange Book:
The listing of patents that claim a device constituent part of a
combination product approved under section 505 of the FD&C Act (e.g., a
drug delivery device); the listing of patents that claim a device whose
use is referenced in approved drug labeling; the listing of patents
associated with an established REMS; and the listing of patents
associated with digital applications (e.g., clinical decision support
software, software as a medical device). We note that the questions
posed below are not meant to be exhaustive and we are interested in any
other pertinent information that stakeholders and any other interested
parties would like to provide on the types of patent information that
should be included in the Orange Book.

A. General Questions

    1. Do 505(b)(2) and ANDA applicants currently encounter any
challenges because certain types or categories of patents are not
listed in FDA's Orange Book?
    2. Given the general increasing complexity of products approved in
an NDA (e.g., drug-device combination products, complex delivery
systems, associated digital applications), are there any aspects of
FDA's interpretation of the statutory requirement for NDA holders to
submit information on a patent that claims the drug or a method of
using such drug that are not sufficiently clear? If there is a lack of
clarity, how could this be resolved?
    3. How would NDA holders and prospective 505(b)(2) and ANDA
applicants weigh any advantages that may result from listing of
additional types or categories of patent in the Orange Book against the
potential need to submit additional patent certifications that could
result in a delay of approval of a 505(b)(2) application or ANDA?
    4. If you think FDA should clarify the type of patents that must be
listed in the Orange Book, what factors should FDA consider in
implementing this clarification? For example, should FDA consider
specific factors in evaluating the timeliness of patent information
submitted after such clarification?
    5. Are there other issues related to the listing of patent
information that we should consider?

B. Drug Product Patents

    1. Are there elements of FDA's regulatory definition of drug
product or dosage form in Sec.  314.3(b) that may be helpful to clarify
to assist NDA holders in determining whether a patent claims the
finished dosage form of an approved drug product?
    2. What factors should FDA consider in providing any clarifications
related to whether device-related patents need to be submitted for
listing as a patent that claims the drug? For example, what are the
advantages and disadvantages of requiring patents that claim a device
constituent part of a combination product approved under section 505 of
the FD&C Act to also claim and/or disclose the active ingredient or
formulation of the approved drug product (or the drug product class) to
fall within the type of patent information that is required to be
submitted to FDA for listing in the Orange Book? Also, how, if at all,
should this analysis be affected by considerations about whether the
device or specific component of device claimed in the patent is
``integral'' (see 68 FR 36676 at 36680) to the administration of the
drug?

C. Method-of-Use Patents

    1. What information should FDA consider regarding when a patent
that claims a method of using a device constituent part, or only a
component of a device constituent part, might or might not meet the
statutory standard for submission by the NDA holder for listing in the
Orange Book as a method-of-use patent? Should FDA consider whether: (1)
The patent claims and/or discloses the active ingredient or formulation
of the approved drug product (or the drug product class)?; (2) the
device constituent part is described in certain sections of the listed
drug labeling?; or (3) use of the device is described in labeling for
the listed drug, but the device is not a constituent part of the drug
product? Should FDA consider whether the drug product labeling states
that the drug is only for use with the specific device? Should FDA also
consider device labeling, for example whether the device labeling
indicates the device is for use with the specific drug?
    2. What information should FDA consider regarding whether there are
circumstances in which a patent claiming the way an approved drug
product is administered would meet the statutory standard for
submission by the NDA holder for listing in the Orange Book as a drug
product patent rather than a method-of-use patent?
    3. What information should FDA consider regarding whether there are
circumstances in which a method-of-use patent claiming the way an
approved drug product is administered that is not described in FDA-
approved product labeling would meet the statutory standard for listing
in the Orange Book?

D. REMS-Related Patents

    1. What information should FDA consider regarding whether patents
that claim how the sponsor has implemented a particular REMS
requirement meet the statutory requirement for the type of patent
information that is required to be submitted to FDA for listing in the
Orange Book? What factors should be considered in making this
determination?
    2. Are there other issues related to patents that claim how the
sponsor has implemented a particular REMS requirement that FDA should
consider with regard to listing patent information in the Orange Book,
including any potential impact listing such patents in the Orange Book
could have on development of REMS for generic versions of products? For
example, does listing patent information in the Orange Book for such
patents pose difficulties for ANDA applicants in developing a single,
shared system REMS for that product?

E. Patents for Digital Applications

    1. If an approved drug product has an associated digital
application (e.g., a mobile application that accepts and records
information from an ingestible sensor in a drug product), what factors
should be considered in determining whether a patent that claims an
aspect of that digital application meets the standards for listing in
the Orange Book?
    2. Are there other issues related to patents for digital
applications associated with approved drugs that should be considered
with regard to listing patent information in the Orange Book?

    Dated: May 26, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-11684 Filed 5-29-20; 8:45 am]
BILLING CODE 4164-01-P


			  UNITED STATES OF AMERICA

		        0DEPARTMENT OF TRANSPORTATION

			  OFFICE OF THE SECRETARY

			          WASHINGTON, D.C.

Issued by the Department of Transportation on February 6, 2004

NOTICE OF ACTION TAKEN -- DOCKET OST-2003-15094

________________________________________________________________________
________________________________________________________

This serves as notice to the public of the action described below, taken
by the Department official indicated (no additional confirming order
will be issued in this matter).

Applicant:   Sun D’or International Airlines				Date Filed:  January
12, 2004

Relief requested: Amend existing exemption authority to the extent
necessary to engage in charter foreign air transportation of persons,
property and mail between any point or points in Israel, on the one
hand, and any point or points in the United States, on the other hand,
either directly or via intermediate points, and beyond for the carriage
of stopover or transiting traffic only.  Sun D’or would conduct these
services only by wet leasing aircraft from a duly authorized and
properly supervised U.S. or foreign air carrier.

Date and citation of last action:  Amends authority granted August 8,
2003, in this docket.

Representative:  John E. Gillick<PHONE_NUMBER>

DOT Analyst:  Gordon H. Bingham<PHONE_NUMBER>

Responsive pleadings:  None filed

DISPOSITION

Action:  Approved									Action date:  February 6, 2004

Effective dates of authority granted:  February 6, 2004-August 8, 2004
(coextensive with the term of authority granted Sun D’or on August 8,
2003, in this docket)

Basis for approval (bilateral agreement/reciprocity):  Bilateral
aviation agreement between the United States and Israel

Except to the extent exempted/waived, this authority is subject to the
terms, conditions, and limitations indicated:

X  Standard exemption conditions (attached)

Special conditions/Partial grant/Denial basis/Remarks:  Sun D’or may
not conduct U.S. operations with its own aircraft and crews without
further order of the Department.

Action taken by:   Paul L. Gretch, Director

		      Office of International Aviation

Under authority assigned by the Department in its regulations, 14 CFR
Part 385, we found that (1) the applicant was qualified to perform the
proposed operations; (2) our action was consistent with Department
policy; (3) grant of the authority was consistent with the public
interest; and (4) grant of the authority would not constitute a major
regulatory action under the Energy Policy and Conservation Act of 1975.
To the extent not granted/deferred/dismissed, we denied all requests in
the referenced Docket.  We may amend, modify, or revoke the authority
granted in this Notice at any time without hearing at our discretion.

Persons entitled to petition the Department for review of the action set
forth in this Notice under the Department’s regulations, 14 CFR §
385.30, may file their petitions within seven (7) days after the date of
issuance of this Notice.  This action was effective when taken, and the
filing of a petition for review will not alter such effectiveness.

An electronic version of this document is available on the World Wide
Web at:

  HYPERLINK "http://dms.dot.gov//reports/reports_aviation.asp"
http://dms.dot.gov//reports/reports_aviation.asp

		Attachment

Foreign Carrier Exemption Conditions

In the conduct of the operations authorized, the foreign carrier
applicant(s) shall:

(1)  Not conduct any operations unless it holds a currently effective
authorization from its homeland for such operations, and it has filed a
copy of such authorization with the Department;

(2)  Comply with all applicable requirements of the Federal Aviation
Administration, including, but not limited to, 14 CFR Parts 129, 91, and
36, and with all applicable U.S. Government requirements concerning
security.  To assure compliance with all applicable U.S. Government
requirements concerning security, the holder shall, before commencing
any new service (including charter flights) from a foreign airport that
would be the holder’s last point of departure for the United States,
contact its Principal Security Inspector (PSI) to advise the PSI of its
plans and to find out whether the Transportation Security Administration
has determined that security is adequate to allow such airport(s) to be
served;

(3)  Comply with the requirements for minimum insurance coverage
contained in 14 CFR Part 205, and, prior to the commencement of any
operations under this authority, file evidence of such coverage, in the
form of a completed OST Form 6411, with the Federal Aviation
Administration’s Program Management Branch (AFS-260), Flight Standards
Service (any changes to, or termination of, insurance also shall be
filed with that office);

(4)  Not operate aircraft under this authority unless it complies with
operational safety requirements at least equivalent to Annex 6 of the
Chicago Convention;

(5)  Conform to the airworthiness and airman competency requirements of
its Government for international air services;

(6)  Except as specifically exempted or otherwise provided for in a
Department Order, comply with the requirements of 14 CFR Part 203,
concerning waiver of Warsaw Convention liability limits and defenses;

(7)  Agree that operations under this authority constitute a waiver of
sovereign immunity, for the purposes of 28 U.S.C. 1605(a), but only with
respect to those actions or proceedings instituted against it in any
court or other tribunal in the United States that are: (a)  based on its
operations in international air transportation that, according to the
contract of carriage, include a point in the United States as a point of
origin, point of destination, or agreed stopping place, or for which the
contract of carriage was purchased in the United States; or (b)  based
on a claim under any international agreement or treaty cognizable in any
court or other tribunal of the United States.  In this condition, the
term "international air transportation" means "international
transportation" as defined by the Warsaw Convention, except that all
States shall be considered to be High Contracting Parties for the
purpose of this definition;

(8)  Except as specifically authorized by the Department, originate or
terminate all flights to/from the United States in its homeland;

(9)  Comply with the requirements of 14 CFR Part 217, concerning the
reporting of scheduled, nonscheduled, and charter data;

(10) If charter operations are authorized, except as otherwise provided
in the applicable aviation agreement, comply with the Department's rules
governing charters (including 14 CFR Parts 212 and 380); and

(11) Comply with such other reasonable terms, conditions, and
limitations required by the public interest as may be prescribed by the
Department, with all applicable orders or regulations of other U.S.
agencies and courts, and with all applicable laws of the United States.

This authority shall not be effective during any period when the holder
is not in compliance with the conditions imposed above.  Moreover, this
authority cannot be sold or otherwise transferred without explicit
Department approval under Title 49 of the U.S. Code.

  The charter authority granted Sun D’or on August 8, 2003, was for
charter operations between Tel Aviv and Orlando and Las Vegas only.

08/2003