[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