[Federal Register Volume 82, Number 185 (Tuesday, September 26, 2017)]
[Notices]
[Pages 44803-44807]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-20521]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-5319]


Devices Proposed for a New Use With an Approved, Marketed Drug; 
Public Hearing; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing a public hearing on a potential approach for device sponsors 
who seek to obtain marketing authorization for their products that are 
labeled for a new use with an approved, marketed drug when the sponsor 
for the approved drug does not wish to pursue or collaborate on the new 
use.

DATES: The public hearing will be held on November 16, 2017, from 9 
a.m. to 5 p.m. The public hearing may be extended or may end early 
depending on the level of public participation. Persons seeking to 
attend or to present at the public hearing must register by October 26, 
2017. Sections II and III provides attendance and registration 
information. Electronic or written comments will be accepted after the 
public hearing until January 15, 2018. Late, untimely filed comments 
will not be considered.

ADDRESSES: The public hearing will be held at the FDA White Oak Campus, 
10903 New Hampshire Ave., Building 31 Conference Center, the Great Room 
(Rm. 1503, Section A), Silver Spring, MD 20993-0002. Entrance for the 
public hearing participants (non-FDA employees) is through Building 1, 
where routine security check procedures will be performed. For parking 
and security information, please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.

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 44804]]

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-2017-N-5319 for ``Devices Referencing Drugs; Public Hearing; 
Request for Comments.'' 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.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: John Barlow Weiner, Associate Director 
for Policy, Office of Combination Products, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5129, Silver 
Spring, MD 20933, 301-796-8930, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Medical products are often intended and labeled for use in 
conjunction with other medical products marketed by different sponsors 
(as used in this document, ``sponsor'' includes an applicant or 
manufacturer). In some cases, the medical products are of different 
types (such as drug and device, biological product and device, or drug 
and biological product). Typically, the different sponsors collaborate 
when the two products are to be used together for a new intended use. 
In some cases, products intended for use with one another comprise a 
``combination product'' as the term is defined in 21 CFR 3.2(e). 
Regardless of whether the products meet the definition of a combination 
product, collaboration between the sponsors can facilitate product 
development and obtaining marketing authorization for the products for 
the combined use, and can, thereby, enable access to innovative 
treatment options for patients. Inclusion of the combined use in the 
labeling of both products helps ensure user understanding, and the 
collaboration can also be important to ensuring the ongoing safety and 
effectiveness of the products for the combined use.
    Sometimes, however, sponsors seek marketing authorization from FDA 
for a medical product for a new use with the approved, marketed medical 
product of another sponsor (i.e., not included in the labeling for the 
approved, marketed product), and the sponsor of the approved, marketed 
product does not wish to pursue the new use or work with the other 
product sponsor. Generally, such proposed products have been devices 
proposing new uses with approved, marketed drugs (referred to in this 
notice as devices referencing drugs or DRDs), though other scenarios 
have been proposed as well, such as drugs proposed for new uses with 
cleared or approved, marketed devices. This notice focuses on DRDs.
    In FDA's experience, DRDs may be proposed: (1) To enhance the 
safety or effectiveness of the marketed drug for its already approved 
indication; (2) for use with the approved drug for an indication for 
which the drug is not approved; or (3) to provide some other benefit, 
such as increasing user comfort or convenience. Such new uses have 
generally also involved a change in how the drug is used or 
administered, such as a change in dose, route, or rate of 
administration.
    FDA seeks to ensure that safe and effective medical products can be 
brought onto the market in a timely manner. The Agency encourages 
development of products that advance public health, particularly those 
that significantly improve the safety or effectiveness of an existing 
treatment or that address an unmet medical need. DRDs have the 
potential to advance the public health by offering new uses with 
approved, marketed drugs that might not otherwise be developed, because 
the drug sponsor does not wish to pursue the new use. At the same time, 
DRDs raise unique public health, scientific, regulatory, and legal 
issues.
    FDA, in cooperation with the Drug Information Association, held a 
public meeting in 2005 on combined uses of separately distributed 
products.\1\ That meeting focused on the public health, legal, 
regulatory, and scientific issues \2\ that arise when sponsors seek to 
develop or market a product of one type (device, drug, or biological 
product) that would be labeled for use with an approved product of a 
different type, where the proposed use is not included in the labeling 
for the approved product.
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    \1\ Links to the Federal Register notice for the workshop, 
presentations given, and a full transcript of the proceedings are 
available at: https://www.fda.gov/combinationproducts/meetingsconferencesworkshops/ucm116623.htm.
    \2\ Although the issues discussed at the meeting were described 
as public health or legal issues, they also included scientific and 
regulatory issues.
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    As reflected in the notice for that meeting and the presentations 
and discussions at the meeting, devices intended for a new combined use 
with a drug raise unique public health, scientific, regulatory and 
legal issues when the sponsors for the two products do not work 
together on the new combined use of the two products. Since that time, 
FDA has gained greater experience with these issues and believes that 
many of these issues for DRDs could be addressed under the approach 
described below.
    FDA wishes to obtain further public input through a more focused 
hearing

[[Page 44805]]

on the Agency's potential approach for premarket review of proposed 
DRDs. The Agency is seeking this type of public engagement because of 
the potential importance of the issue for the public health and the 
need for input across the medical product industry and among public 
health stakeholders regarding how FDA should proceed.

II. Purpose and Scope of the Public Hearing

    The purpose of the public hearing is to obtain comment from 
stakeholders on the potential approach described below, for premarket 
review of DRDs. As described above, DRDs, for purposes of this document 
and hearing, are devices that are intended for a use with an approved, 
marketed drug that is not in the labeling for the approved drug, where 
the drug application is held by a different sponsor that does not wish 
to pursue or collaborate on the new use with the device sponsor. The 
approach described below might be appropriate, for example, for drug 
delivery systems seeking to be labeled for use with an approved drug, 
for an indication for which that drug has not been approved (e.g., to 
administer the drug to treat a different disease or condition or a new 
patient population). We also welcome comment on any public health, 
scientific, regulatory, or legal considerations relating to DRDs and 
other medical products seeking to be labeled for new uses with 
approved, marketed medical products of a different type where the 
sponsor for the approved, marketed product does not wish to pursue or 
collaborate on the new use. The comments that FDA receives from this 
public hearing may help inform the further development of this 
approach.

A. A Potential Approach for Premarket Review of DRDs

    FDA strongly recommends collaboration between sponsors on new 
combined uses of their medical products. The Agency is prepared to work 
with sponsors to facilitate such collaboration. When sponsors work 
together, they usually have an ongoing relationship that enables them 
to resolve many of the public health, scientific, regulatory, and legal 
issues that may arise as a result of two products being the 
responsibility of two independent sponsors. Such collaboration also can 
provide important information to support a regulatory decision (see 
below). Where collaboration between sponsors is not feasible, for 
example, because one sponsor does not wish to collaborate, FDA believes 
that the following factors could help address many of the public 
health, scientific, regulatory, and legal issues associated with DRDs. 
In doing so, these factors could allow for a DRD to be reviewed and 
approved via a device premarket authorization pathway \3\ without 
approval of conforming labeling changes for the approved, marketed drug 
through a new drug application (NDA) or supplement to an NDA (see 
Section II.B Submission Considerations for further discussion).
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    \3\ FDA has not determined at this time whether DRDs may be 
reviewed through other device premarket authorization pathways 
besides premarket approval applications (PMAs), but FDA intends to 
consider this issue and welcomes comment on it.
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B. Factors

    DRD sponsors should be able to address the following issues as 
discussed below:
    1. Safety and Effectiveness of the New Use of the Drug. The DRD 
sponsor is able to demonstrate the safety and effectiveness of the new 
use of the drug that is included in the DRD labeling, by providing 
substantial evidence that the drug will have the effect it purports or 
is represented to have under the conditions of use described in the 
proposed DRD labeling and showing that the drug is safe for use under 
the conditions prescribed, recommended, or suggested in the proposed 
DRD labeling, as this is the standard that applies to new uses of drugs 
(see 21 U.S.C. 355(c) and (d)). If there are multiple approved versions 
of the approved drug product(s) referenced in the DRD labeling 
(including generic versions), the DRD sponsor is able to demonstrate 
the generalizability of the new use with all such versions of the drug 
product.
    2. User Confusion and Medication Error/Use Error. Given the 
potential for user confusion or medication error/use error, for 
example, due to certain differences in the labeling for the DRD and the 
approved drug that it is referencing, the DRD sponsor is able to 
demonstrate that the potential for user confusion or error has been 
adequately addressed. The DRD labeling must provide adequate directions 
for the new use with the approved, marketed drug.
    3. Postmarket Change Management. The DRD sponsor is able to 
demonstrate that it is able to address safety or effectiveness issues 
associated with changes to the approved, marketed drug, for example, by 
demonstrating: That the likelihood of changes to the approved, marketed 
drug is low; changes to the drug are unlikely to raise safety or 
effectiveness issues with respect to the conditions of use with the 
drug as described in the DRD labeling; and periodic testing will be 
conducted and be adequate to assure ongoing safety and effectiveness of 
the combined use. It is important that these issues be addressed 
because the DRD sponsor does not have a relationship with the sponsor 
for the approved, marketed drug, and, therefore, any changes to the two 
products will not be coordinated or communicated in advance.
    4. Postmarket Safety. The DRD sponsor is able to demonstrate that 
it has a postmarket safety plan to adequately address adverse events, 
including medication errors, related to the drug when used with the 
DRD. It is important that its postmarket safety plan allows the DRD 
sponsor to adequately capture, report, and respond appropriately to 
adverse events associated with the new drug use described in the DRD 
labeling, because the DRD sponsor does not have a relationship with the 
sponsor(s) of the approved, marketed drug and because the DRD sponsor 
will often be uniquely positioned to understand and address adverse 
events resulting from the new use of the drug described in the DRD 
labeling.
    5. Data Reliance. The DRD sponsor is able to provide all 
information needed to evaluate the safety and effectiveness of the new 
use with the approved drug referenced in the DRD labeling, without 
relying on any proprietary information for the approved drug (e.g., by 
instead relying on non-product-specific published literature, 
generalizable knowledge). The DRD sponsor may also be able to include 
in its application safety and effectiveness data and information from 
the marketing application for the drug that are publicly available, for 
example, if the approved reference listed drug has been withdrawn from 
sale, provided that FDA has determined that the approved reference 
listed drug was not withdrawn from sale for reasons of safety or 
effectiveness (see 21 U.S.C. 355(l) and 21 CFR 314.161 and 314.430). 
Generally, a DRD sponsor would not have a right of reference to 
proprietary information on the approved drug with which the DRD is 
proposed to be used because the DRD sponsor has no relationship with 
the sponsor of the approved drug.

C. Submission Considerations

    At the investigational stage, depending on the details of the 
investigational plan, a DRD sponsor may seek to submit an 
investigational new drug application (IND) or an investigational device 
exemption application (IDE). Either way, the Center for Drug Evaluation 
and Research

[[Page 44806]]

(CDER) and the Center for Devices and Radiological Health (CDRH) would 
collaborate on the review. DRD sponsors should consult with CDER and 
CDRH as to which application to submit for a particular investigation.
    FDA believes that a PMA would generally be the appropriate device 
marketing application because, e.g., DRDs are expected to represent a 
new intended use or raise different questions of safety or 
effectiveness as compared to a legally marketed predicate device. 
Generally, PMAs for DRDs would be reviewed by CDRH, and CDRH would 
collaborate with CDER on the review of the DRD. CDRH would have the 
lead on device-specific issues, and CDER would have the lead on drug-
specific issues. The Centers would identify any review aspects where 
review considerations overlap, to ensure Agency alignment on how to 
address these considerations and communicate about them to DRD 
sponsors.

D. Questions for Commenters To Address

    FDA welcomes all feedback on the potential approach and on any 
public health, scientific, regulatory, and legal issues raised by it. 
We seek public comment on the factors and submission considerations 
described in this notice, and propose the following questions in an 
effort to prompt substantive input from stakeholders:
    1. Are there public health, scientific, regulatory, or legal issues 
that should be considered with respect to this potential approach for 
DRDs? If so, are there ways to address those issues?
    2. Is each of the factors and submission considerations described 
above appropriate? If not, why not? What modifications would you 
propose and why? Are there additional factors or submission 
considerations that the Agency should take into account? Please provide 
examples to illustrate your view.
    3. Should the approach described in this notice be limited to 
certain situations, such as where the combined use would potentially 
address an unmet medical need for a serious or life-threatening 
condition? If so, please provide a detailed analysis in support of your 
view, including its legal justification.
    4. With respect to the user confusion and medication error/use 
error factor, are there other issues that DRD sponsors should address 
or that FDA should consider, to ensure that the DRD labeling provides 
adequate directions for the new use with the approved, marketed drug, 
without approval of conforming labeling changes for the approved, 
marketed drug? What issues should be considered with respect to 
promotional activities by the DRD sponsor and/or by any sponsors for 
the drug being referenced?
    5. With regard to the postmarket change management factor, what 
would be examples of circumstances in which the DRD sponsor would be 
able to adequately address this factor? What types of postmarket 
changes to the drug should the DRD sponsor be prepared to identify and 
address? What postmarket mechanisms, including specific testing or 
monitoring, would be appropriate to ensure ongoing safety and 
effectiveness of the combined use?
    6. When multiple versions of the drug, including generics, are 
marketed, what challenges exist in identifying which versions of the 
drug can be used with the DRD? How can DRD sponsors make this 
information clear to health care providers, pharmacists, and patients?
    7. What challenges exist at the investigational application stage, 
and how can those challenges be addressed? Are there circumstances 
where an IND would be the more appropriate investigational application 
for a clinical investigation of a DRD? Are there circumstances where an 
IDE would be the more appropriate investigational application?
    8. How may this approach impact future product development?
    9. Would an approach similar to the potential approach presented in 
this notice be appropriate for other types of combined uses (e.g., 
drugs referencing devices where the device sponsor does not wish to 
collaborate on the new use)? If so, how should the factors, submission 
considerations, or both be modified for other types of combined uses? 
Are there additional factors that should be considered for other types 
of combined uses?
    10. Are there other possible approaches that may be used to seek 
marketing authorization for combined uses of drugs and devices where 
product sponsors are unable or unwilling to collaborate? Please provide 
a detailed analysis in support of your proposed approach, including its 
legal justification.
    11. Recognizing that collaboration is preferable, what actions can 
FDA and stakeholders take to encourage and facilitate collaboration 
between device sponsors and sponsors of approved, marketed drugs to 
develop new combined uses of their medical products?
    12. Would an approach similar to the potential approach presented 
in this notice be appropriate in the case where a drug sponsor would 
like to include in the drug labeling the use of one or more approved or 
cleared companion diagnostics for its new drug in the same class as the 
drugs for which the companion diagnostic is approved or cleared but 
none of the companion diagnostic sponsors intend to add the new drug to 
the device labeling? If so, how should the factors, submission 
considerations, or both be modified? Are there additional factors that 
should be considered? Are there other possible approaches that may be 
used for such circumstance? Please provide a detailed analysis in 
support of your proposed approach, including its legal justification.

III. Registration

    Registration and Requests for Oral Presentations: The FDA 
Conference Center at the White Oak location is a Federal facility with 
security procedures and limited seating. Attendance will be free and on 
a first-come, first-served basis. If you wish to attend (either in 
person or by webcast (see Streaming Webcast of the Public Hearing)) 
and/or present at the hearing, please register for the hearing and/or 
make a request for oral presentations or comments at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm572528.htm by 
October 26, 2017 and provide complete contact information for each 
attendee (i.e., name, title, affiliation, address, email address, and 
telephone number). Those without email access can register by 
contacting John Barlow Weiner by October 26, 2017 (see FOR FURTHER 
INFORMATION CONTACT).
    FDA will try to accommodate all persons who wish to make a 
presentation. Individuals wishing to present should identify the number 
of the question, or questions, they wish to address. This will help FDA 
organize the presentations. Individuals and organizations with common 
interests should consolidate or coordinate their presentations and 
request time for a joint presentation. FDA will notify registered 
presenters of their scheduled presentation times. The time allotted for 
each presentation will depend on the number of individuals who wish to 
speak. Once FDA notifies registered presenters of their scheduled 
times, they are encouraged to submit an electronic copy of their 
presentation to [email protected] on or before November 2, 2017. 
Persons registered to make an oral presentation are encouraged to 
arrive at the hearing room early and check in at the onsite 
registration table to confirm their designated presentation time. An

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agenda for the hearing and any other background materials will be made 
available 5 days before the hearing at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm572528.htm.
    If you need special accommodations because of a disability, please 
contact the Office of Combination Products at 301-796-8930 or 
[email protected] at least 7 days before the hearing.
    Streaming Webcast of the Public Hearing: For those unable to attend 
in person, FDA will provide a live webcast of the hearing. To join the 
hearing via the webcast, please go to https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm572528.htm.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at https://www.regulations.gov. It may 
be viewed at the Dockets Management Staff (see ADDRESSES). A transcript 
will also be available in either hard copy or on CD-ROM, after 
submission of a Freedom of Information request. The Freedom of 
Information office address is available on the Agency's Web site at 
https://www.fda.gov.

IV. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with 21 CFR part 15. The hearing 
will be conducted by a presiding officer, who will be accompanied by 
FDA senior management from the Office of the Commissioner, the Center 
for Drug Evaluation and Research, the Center for Devices and 
Radiological Health, and the Center for Biologics Evaluation and 
Research. Under Sec.  15.30(f), the hearing is informal and the rules 
of evidence do not apply. No participant may interrupt the presentation 
of another participant. Only the presiding officer and panel members 
may pose questions; they may question any person during or at the 
conclusion of each presentation. Public hearings under part 15 are 
subject to FDA's policy and procedures for electronic media coverage of 
FDA's public administrative proceedings (21 CFR part 10, subpart C). 
Under Sec.  10.205, representatives of the media may be permitted, 
subject to certain limitations, to videotape, film, or otherwise record 
FDA's public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in Sec.  
15.30(b) (see Transcripts). To the extent that the conditions for the 
hearing, as described in this notice, conflict with any provisions set 
out in part 15, this notice acts as a waiver of those provisions as 
specified in Sec.  15.30(h).

    Dated: September 19, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-20521 Filed 9-25-17; 8:45 am]
 BILLING CODE 4164-01-P