Document ID: FDA-2020-N-1127-0001
Agency: fda
Document Type: Notice
Title: Listing of Patent Information in the Orange Book; Establishment of a Public Docket; Request for Comments
Posted Date: 2020-06-01T04:00Z

[Federal Register Volume 85, Number 105 (Monday, June 1, 2020)]
[Notices]
[Pages 33169-33173]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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, Elizabeth.Giaquinto@fda.hhs.gov.

[[Page 33170]]

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

[[Page 33171]]

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

[[Page 33172]]

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

[[Page 33173]]

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