Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products; Public Hearing; Request for Comments, 60299-60304 [2016-21062]
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FOR FURTHER INFORMATION CONTACT:
Todd Stevenson, Office of the Secretary,
U.S. Consumer Product Safety
Commission, Room 820, 4330 East West
Highway, Bethesda, MD 20814;
telephone (301) 504–6833.
SUPPLEMENTARY INFORMATION: The
Commission received a petition from
the Halogenated Solvents Industry
Alliance, Inc. (Petitioner) requesting
that the Commission amend the
agency’s Statement of Interpretation and
Enforcement Policy regarding labeling
of household products containing
methylene chloride (Policy Statement).
The Policy Statement provides the
Commission’s guidance for labeling of
household products containing
methylene chloride, focusing
particularly on paint strippers. 52 FR
34698 (Sep. 14, 1987). The Policy
Statement sets forth general principles
and examples for labeling to warn
consumers of potential cancer hazards;
it does not address acute hazards.
The Petitioner asks the Commission to
expand the Policy Statement to address
acute hazards from inhalation of
methylene chloride vapors. Petitioner
notes that the Occupational Safety and
Health Administration (OSHA) and the
National Institute for Occupational
Safety and Health (NIOSH) issued a
Hazard Alert identifying at least 14
deaths associated with use of methylene
chloride-containing paint strippers by
professional bathtub refinishing
operations (https://www.osha.gov/dts/
hazardalerts/methylene_chloride_
hazard_alert.html). Although the
Petitioner refers to incidents involving
workers, as the Commission’s Policy
Statement indicates, methylene chloride
paint strippers are household products
available for consumers to purchase and
use. Petitioner asserts that revising the
Policy Statement to give specific
guidance on labeling for the acute
hazard posed by inhalation of
methylene chloride vapors, particularly
when used in an enclosed space, such
as when refinishing bathtubs, would
help to prevent future fatalities.
By this notice, the Commission seeks
comments concerning this petition.
Interested parties may obtain a copy of
the petition from the Commission’s Web
site: https://www.cpsc.gov/RegulationsLaws--Standards/Rulemaking/Petitions/
or by writing or calling the Office of the
Secretary, U.S. Consumer Product
Safety Commission, Room 820, 4330
East West Highway, Bethesda, MD
20814; telephone (301) 504–7923. A
copy of the petition is also available for
viewing under ‘‘Supporting and Related
Materials’’ in: www.regulations.gov,
under Docket No. CPSC–2016–0019 .
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Dated: August 2, 2016.
Todd A. Stevenson,
Secretary, U.S. Consumer Product Safety
Commission.
[FR Doc. 2016–20928 Filed 8–31–16; 8:45 am]
BILLING CODE 6355–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 15
[Docket No. FDA–2016–N–1149]
Manufacturer Communications
Regarding Unapproved Uses of
Approved or Cleared Medical
Products; Public Hearing; Request for
Comments
AGENCY:
Food and Drug Administration,
HHS.
Notification of public hearing;
request for comments.
ACTION:
The Food and Drug
Administration (FDA or Agency) is
announcing a 2-day public hearing to
obtain input on issues related to
communications by manufacturers,
packers, and distributors, including
their representatives (collectively
‘‘firms’’), regarding FDA-regulated drugs
and medical devices for humans,
including those that are licensed as
biological products, and animal drugs
(collectively, ‘‘medical products’’). FDA
is engaged in a comprehensive review of
its regulations and policies governing
firms’ communications about
unapproved uses of approved/cleared
medical products, and the input from
this meeting will inform FDA’s policy
development in this area. FDA is
seeking input on a number of specific
questions, but is interested in any other
pertinent information participants
would like to share.
DATES: The public hearing will be held
on November 9 and 10, 2016, from 9
a.m. to 5 p.m. The meeting may be
extended or end early depending on the
level of public participation. Persons
seeking to attend or present at the
public hearing must register by October
19, 2016. Electronic or written
comments will be accepted after the
public hearing until January 9, 2017.
ADDRESSES: The public hearing will be
held at the FDA White Oak Campus,
10903 New Hampshire Ave., Bldg. 31
Conference Center, the Great Room (Rm.
1503), Silver Spring, MD 20993–0002.
Entrance for the public meeting
participants (non-FDA employees) is
through Building 1 where routine
SUMMARY:
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security check procedures will be
performed. For parking and security
information, please refer to https://
www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/
WhiteOakCampusInformation/
ucm241740.htm.
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): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Division of Dockets
Management, 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–
2016–N–1149 for ‘‘Manufacturer
Communications Regarding
Unapproved Uses of Approved or
Cleared Medical Products; Public
Hearing; Request for Comments.’’
Received comments will be placed in
the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
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https://www.regulations.gov or at the
Division of Dockets Management
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 Division of Dockets
Management. 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.fda.gov/
regulatoryinformation/dockets/
default.htm.
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 Division of Dockets
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
A link to the live Webcast of this
public hearing will be available at
https://www.fda.gov/
CommunicationsPublicMeeting on the
day of the public hearing. A video
record of the public hearing will be
available at https://www.fda.gov/
CommunicationsPublicMeeting
following the meeting. A video record of
the public hearing will be available at
the same Web site address for 1 year.
FOR FURTHER INFORMATION CONTACT:
Kristin Davis, Office of Policy, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 32, Rm. 4252,
Silver Spring, MD 20993, 301–796–
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0418, email: CommunicationsPublic
Meeting@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is responsible for regulating
medical products (i.e., drugs and
medical devices for humans, including
those that are licensed as biological
products, and animal drugs) under the
Federal Food, Drug, and Cosmetic Act
(the FD&C Act) and the Public Health
Service Act (PHS Act) as well as all
relevant implementing regulations
(collectively, ‘‘FDA Authorities’’) to
promote and protect the public health
by helping to ensure that these products
are safe and effective for their intended
uses. As we announced in 2014, FDA is
currently engaged in a comprehensive
review of the regulatory framework
related to firms’ communications about
unapproved uses of approved/cleared
medical products 1—medical products
that may be legally introduced into
interstate commerce for at least one
other intended use.2 The purpose of this
review is to help ensure that our
implementation of the FDA Authorities
(including promulgating and amending
regulations, issuing guidance,
developing policies, and taking
enforcement action) best protects and
promotes the public health in view of
ongoing developments in science and
technology, medicine, health care
delivery, and constitutional law.
Under the FDA Authorities, in
general, firms are required to submit
data and other information to FDA for
premarket review demonstrating a
medical product is safe and effective for
each of its intended uses before they
introduce the product into interstate
commerce for those intended uses.
During FDA premarket review of
medical products, the Agency also
generally reviews proposed labeling for
the intended use(s) of the product to
ensure that the labeling provides
adequate information for the safe and
effective use of the product. The FDA
Authorities also prohibit firms from
marketing medical products with false
or misleading labeling and similarly
restrict certain medical product
advertising.
The premarket review and labeling
and advertising provisions of the FDA
Authorities address critical public
health objectives. The current regulatory
1 In this document, the term ‘‘unapproved use’’
encompasses additional intended uses of approved
drugs and approved/cleared devices, including
devices that are currently marketed pursuant to a
510(k) clearance or exemption.
2 See FDA response letter, Docket Nos. FDA–
2011–P–0512 and FDA–2013–P–1079 (June 6,
2014), available at https://www.regulations.gov.
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framework was developed in response
to public health tragedies, particularly
those that occurred when firms could
distribute drugs and devices without
independent, premarket review of
scientific evidence of the products’
safety and efficacy.3 Medical product
firms are required to develop highquality data to demonstrate that medical
products are safe and effective for their
intended uses before marketing of the
products for those uses. This
requirement helps ensure that the use of
medical products is based on sound
science, not mere anecdotal experience
or misleading promotional tactics, and
helps prevent direct and indirect patient
harm from products and uses that are
unsafe and/or ineffective. When using a
medical product for its FDA approved/
cleared intended use, health care
professionals and patients and their
caregivers can be assured that the
decision to use the product is supported
by robust premarket review of scientific
data and other appropriate scientific
evidence by an independent scientific
agency and that the benefits and risks of
the use are described in the product’s
FDA-approved or required labeling.
These important assurances are absent
for unapproved uses. The premarket
review requirements also reflect
Congress’s determination that exclusive
reliance on postmarket remedies, such
as enforcement actions for false or
misleading labeling, is unacceptable as
a public health strategy because it does
not prevent harm and injury to patients.
3 The Federal Food, Drug, and Cosmetic Act of
1938, which introduced the requirement that firms
demonstrate a drug product to be safe before being
marketed, followed the deaths of approximately 100
people, mostly children, from ingesting ‘‘Elixir
Sulfanilamide,’’ in which the lethal substance
diethylene glycol was used as a solvent. Prior to
1938, there were no premarket requirements that
mandated that the firm test its product’s safety. The
passage of the 1962 drug amendments was
precipitated in part by the distribution of
thalidomide, a sedative that caused birth defects
when taken by pregnant women. See Wallace F.
Janssen, Outline of the History of U.S. Drug
Regulation and Labeling, 36 Food Drug-Cosm. L.J.
420 (1981). Significant problems with medical
devices likewise preceded the Medical Device
Amendments of 1976, including significant defects
in cardiac pacemakers that led to 34 voluntary
recalls involving 23,000 units, and serious side
effects following implantation of intraocular lenses,
including serious impairment of vision and the
need to remove the eyes of some patients (H.R. Rep.
No. 94–853, at 8 (1976)). See also Henry A.
Waxman, A History of Adverse Drug Experiences:
Congress Had Ample Evidence to Support
Restrictions on the Promotion of Prescription Drugs,
58 Food & Drug L.J. 299 (2003); see also Kate
Greenwood, The Ban on ‘‘Off-Label’’
Pharmaceutical Promotion: Constitutionally
Permissible Prophylaxis Against False and
Misleading Commercial Speech?, 37 Am. J. L. and
Med. 278, 291–92 (2011) (describing the history of
misleading firm claims in promoting unapproved
uses).
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Congress also determined that safety
and effectiveness must be evaluated for
each intended use of a medical product
to prevent the harm that occurs when
patients are prescribed or use ineffective
treatments and to ensure that the
benefits of an intended use outweigh its
risks. Under the FDA Authorities, FDA
evaluates whether a medical product is
safe for a particular use by comparing
the expected therapeutic benefits
against the risk associated with that use.
The weighing of benefit and risk for
each intended use is necessary as a
matter of science to protect the public
health: A product considered ‘‘safe and
effective’’ for one disease or condition
or patient population cannot
automatically be considered ‘‘safe and
effective’’ for another disease or
condition or patient population. For
example, a drug with severe adverse
effects may be considered safe and
effective for treating metastatic lung
cancer, but be unlikely to have a
positive benefit-risk balance for treating
high blood pressure. Similarly, a nonabsorbable suture cleared or approved
for wound closure on the skin’s surface
might raise significant new safety and
effectiveness concerns if used
internally.
Notwithstanding the importance of
the FDA Authorities in protecting
public health, health care professionals
are generally permitted to prescribe or
use approved/cleared medical products
for unapproved uses when they judge
that the unapproved use is medically
appropriate for their individual
patients,4 and relevant, truthful, and
non-misleading scientific or medical
information regarding unapproved uses
of approved medical products may help
health care professionals make better
individual patient decisions. For
example, health care professionals may
consider prescribing or using approved/
cleared medical products for
unapproved uses in circumstances
where a patient has a disease for which
there is no approved treatment or has
exhausted all approved treatments. In
such a situation, relevant, truthful, and
non-misleading scientific or medical
information about an unapproved use
may help a health care professional to
4 FDA generally does not seek to interfere with
the exercise of the professional judgment of health
care providers in prescribing, for unapproved uses
for individual patients, most legally marketed
medical products. This longstanding position has
been codified with respect to devices. See 21 U.S.C.
396. While FDA generally recognizes the
professional judgment of veterinarians, certain
unapproved uses of drugs in animals are not
permitted and result in the drug being deemed
unsafe under section 512 of the FD&C Act. See
section 512(a)(4) and (5) of the FD&C Act (21 U.S.C.
360b(a)(4) and (5)) and 21 CFR part 530.
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make treatment decisions in the absence
of scientific data or information that is
capable of satisfying FDA’s premarket
review requirements.
Health care professionals already can
access considerable scientific
information about unapproved uses, for
example, through public sources such as
scientific journals, clinical practice
guidelines, and compendia or by
requesting that information from firms.5
FDA is interested in comment on the
extent to which additional
communications from firms about
unapproved uses can provide access to
information that is relevant,
scientifically sound, responsibly
presented, and provides as full an
understanding as possible about the
limitations of the available evidence, as
well as comment on the extent to which
health care professionals currently face
impediments to accessing such
information, whether from firms or from
other sources. FDA is interested in
comment and information addressing
whether and in what ways firms’
communications of unapproved use
information are distinct and perhaps
provide unique benefits compared to
other sources.
Not all communications of
information about unapproved uses
help support public health. For
example, communications that
emphasize a medical product’s claimed
benefits, while minimizing the
limitations of the supporting evidence,
or minimizing the product’s known or
potential adverse effects, may
inappropriately influence prescribing or
use decisions in a manner that is not in
a patient’s best interest. FDA is
interested in comment on both the pros
and cons for public health associated
with firms’ communications of
unapproved use information and the
kinds of limitations or requirements that
would be appropriate to protect patients
from harm. We are also interested in any
supporting data related to these issues.
In addition, allowing additional
communications about unapproved uses
could have other indirect consequences
on public health, which are important to
understand and anticipate. For example,
FDA is interested in information to
better understand how increased
communications about unapproved uses
would impact incentives to conduct
biomedical research submitted for FDA
review and subjects’ willingness to
participate in such research.
The Agency is aware of technological
and business changes that are
increasingly affecting medical decision
making and prescribing. There are a
growing number of entities in the health
care system with a stake in evaluating
evidence to assess the rational and
systematic use of medical products. As
medical providers have increasingly
been consolidated into integrated
systems, the use of system
measurements of quality and
measurements of the appropriate use of
medical products has increased, and
insurance carriers, health care systems,
and similar entities may restrict
coverage for medical products based on
assessments of value and employ
performance measures to monitor
appropriate use and outcomes. FDA is
interested in understanding whether
and how these changes may be able to
provide an impetus for the development
of additional high-quality data to
address the balance of benefits and risks
of each use of a medical product and,
if so, in what way they would affect
incentives for submission of this data to
the Agency for marketing authorization.
5 See ‘‘Guidance for Industry: Responding to
Unsolicited Requests for Off-Label Information
About Prescription Drugs and Medical Devices—
Draft Guidance’’ (December 2011), available at
https://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/
Guidances/UCM285145.pdf. FDA has also issued
guidance documents to describe some of the
circumstances when it would not consider a
manufacturer’s distribution of reprints, clinical
practice guidelines, or reference texts regarding
unapproved uses of approved drugs to be evidence
of intended use and/or false or misleading. See
‘‘Revised Draft Guidance for Industry: Distributing
Scientific and Medical Publications on Unapproved
New Uses—Recommended Practices’’ (February
2014), available at https://www.fda.gov/downloads/
Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM387652.pdf (‘‘Revised Good Reprint
Practices Draft Guidance’’); and ‘‘Guidance for
Industry: Good Reprint Practices for Distribution of
Medical Journal Articles and Medical or Scientific
Reference Publications on Unapproved New Uses of
Approved Drugs and Approved or Cleared Medical
Devices’’ (January 2009), available at https://
www.fda.gov/oc/op/goodreprint.html (‘‘Good
Reprint Practices Guidance’’).
II. Purpose and Scope of the Public
Hearing
The purpose of this public hearing is
to obtain comments on FDA’s regulation
of firms’ communications about medical
products, with a particular focus on
firms’ communications about
unapproved uses of their approved/
cleared medical products. FDA is
seeking feedback from a broad group of
stakeholders, including, but not limited
to, health care professionals and
professional societies, patients and their
caregivers, patient advocates,
representatives from regulated industry,
health care organizations, payors and
insurers, academic institutions, public
interest groups, and the general public.
To facilitate stakeholder feedback,
FDA sets forth some questions in this
section. These questions are not meant
to be exhaustive. We encourage
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interested stakeholders to address these
and/or other issues related to firms’
communications about their medical
products. In all cases, FDA encourages
stakeholders to provide the rationale
and basis for their comments, including
any available data and information, and
to explicitly articulate any underlying
assumptions. FDA also encourages
commenters to explain the basis for any
distinctions they would draw as to
audience, vehicle of communication,
type of medical product, type and
source of information, or any other
aspect of communication.
1. FDA is interested in input from
stakeholders on how increased
communications from firms about
unapproved uses could impact the
public health, and on whether the
impact would differ across different
categories of medical products. For
example,
a. What are the benefits for clinical
decision making, research, coverage,
reimbursement, or other purposes
(please specify) if firms communicate to
health care professionals, payors,
researchers, and/or patients more
information, including preliminary or
inconclusive information, about
unapproved uses of approved/cleared
medical products? What are the
drawbacks and risks? Are there
safeguards or requirements that would
effectively mitigate any drawbacks or
risks?
b. What information or systems exist
to help FDA determine how firms’
increased communication of
information about unapproved uses of
approved/cleared medical products
could affect prescribing as well as
medical product development and
research into new uses of approved/
cleared products?
c. How could firms’ increased
communication of information about
unapproved uses of approved/cleared
medical products affect patient
incentives to enroll in clinical trials?
Related to this, FDA is interested in
information on how firms’ increased
communication of this information
could impact their incentives to
generate robust data to fully assess the
risks and benefits of new uses and to
apply for FDA marketing authorization
for new uses of approved/cleared
products.
d. Do the answers to the previous
questions vary for different categories of
medical products (e.g., human drugs
and biologics, medical devices, animal
drugs) or for different disease areas or
patient populations?
2. FDA is aware of changes happening
in the health care system that are
outside of FDA’s role, which may
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provide an impetus for the development
of high-quality data to fully assess the
risks and benefits of new uses of
medical products.
a. To what extent do changes
occurring in the health care system that
give payors and formulary committees
more influence on prescribing decisions
(including by denying, limiting, or
endorsing coverage of unapproved uses
of approved medical products) provide
incentives for firms to generate the highquality data needed to demonstrate
safety and effectiveness for new uses?
b. To what extent do these changes
affect (to preserve, enhance, or
suppress) incentives for firms to seek
FDA approval/clearance of new uses?
3. FDA recognizes that information
about medical products, including
information about unapproved uses of
approved/cleared medical products, is
now broadly available from a wide
variety of sources (e.g., academic and
governmental organizations, scientific
journals, professional societies,
compendia) in both traditional and new
communication vehicles and platforms,
particularly electronic communication
platforms (e.g., the Internet). What is the
impact of the increasing availability of
this information on firms’ incentives to
communicate information about
unapproved uses of approved/cleared
products? FDA is also interested in
input on other factors that firms may
consider when making decisions about
providing information about
unapproved uses of their approved/
cleared medical product, including
financial considerations.
4. Given the importance of the
scientific integrity of the information
that may be relied on in making
decisions about the use of medical
treatments, FDA is interested in input
from stakeholders on the standards that
should apply to unapproved use
communications to minimize the
potential of these communications to be
misleading or otherwise cause harm. For
example:
a. Given the wide range of quality of
information potentially available to
firms on unapproved uses of their
approved/cleared medical products,
what processes do firms use to evaluate
whether such information is
scientifically appropriate to
communicate to health care
professionals and other entities?
b. What criteria should the Agency
consider in determining whether a
study or analysis that is the basis of a
firm’s communication is scientifically
appropriate to support the presentations
or conclusions in the communication?
c. What do health care professionals
generally understand about the quality
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and utility of different kinds or levels of
scientific evidence related to
unapproved uses? Can the same
information be misleading to some
audiences of health professionals and
not others?
d. What information is most
important to health care professionals
and other entities in allowing them to
judge the validity and utility of firms’
communications about unapproved
uses, including the level of uncertainty
of the evidence, and why? Does the
answer to this question differ depending
on the recipient’s purpose—e.g., making
treatment decisions for an individual
patient, informing the direction of
further research, making formulary or
institutional supply chain contracting
decisions, or making coverage
determinations?
5. FDA is interested in input from
stakeholders on factors that the Agency
should consider in evaluating whether
firms’ communications about
unapproved uses of approved/cleared
medical products are truthful and nonmisleading, including what information
firms should disclose in these
communications to help ensure
audiences are not misled, and on
general considerations related to the
audience for these communications and
on communication vehicles and
techniques. For example:
a. What information should firms
communicate to make audiences aware
that the medical product is unapproved
for the use discussed and to otherwise
distinguish between the approved/
cleared use(s) of the medical product
and the unapproved use? How could the
means of communication affect a
recipient’s ability to distinguish
between unapproved and approved/
cleared uses or otherwise impede the
disclosure of necessary contextual
information?
b. What factors are most relevant to
determining whether a firms’
communication about a medical product
concerns an unapproved use? How do
firms evaluate whether or not their
communications concern unapproved
uses and whether the messages
communicated are accurate and nonmisleading?
c. What other information should
firms’ disclose in these communications
to help ensure audiences are not misled
(e.g., about the risks of the product, the
nature and weight of the evidence
supporting the unapproved use, the
regulatory history relating to the
unapproved use, the financial
involvement of firms in the research
described, etc.)?
d. How can disclosures in firms’
unapproved use communications be
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made most effective in conveying
material information while minimizing
chances of confusion or inattention?
How effective are disclosures in
ensuring that limitations concerning
data about unapproved uses are
adequately communicated and
comprehended? For example, how
could the content and format of
disclosures be developed to optimize
the usefulness of this information for
audiences? FDA is interested in
empirical evidence to assess whether
health care professionals or other
entities follow or disregard different
types or formats of disclosures or
disclaimers.
e. To what extent is it appropriate for
firms to communicate information about
unapproved uses of their approved/
cleared medical products to patient and
consumer audiences? What disclosures
and additional information would be
needed to help ensure that a
communication to lay audiences is
truthful and non-misleading, given
consumers’ lack of medical training and
expertise in critically evaluating this
type of information?
6. Another important consideration in
the changing health care environment is
transparency, including the growing
expectation that data from human
studies will be made available for public
review. If a firm bases a communication
on data that is not publicly available,
should information be provided
publicly to ensure that the quality and
integrity of the supportive scientific
information can be adequately evaluated
before any prescribing or use decision?
If so, how should transparency of this
information be monitored?
7. FDA is interested in public input
on how the Agency should monitor
firms’ communications about
unapproved uses of their medical
products, and what actions FDA should
take with respect to firms’
communications that are determined to
be false or misleading or that otherwise
raise public health issues. For example,
what kinds of surveillance and
monitoring could be undertaken to
measure and assess the public health
impacts of unapproved use
communications and by whom?
8. As discussed previously, the
Agency is evaluating its regulations and
policies governing firms’
communications about unapproved uses
of approved/cleared medical products
and considering whether revisions are
appropriate in order to provide greater
legal certainty and clarity to regulated
entities. As an initial step, in the
Federal Register of September 25, 2015
(80 FR 57756), FDA issued a notice of
proposed rulemaking that proposed
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changes to existing regulations at 21
CFR 201.128 and 801.4 to provide
clarity for drug and device firms
regarding FDA’s interpretation and
application of its existing intended use
regulations.
a. What additional changes, if any,
should FDA consider in its regulations
related to firms’ communications about
medical products, such as the
regulations related to what is false or
misleading, adequate directions for use,
the definition of labeling, or other
relevant provisions?
b. With respect to proposed
alternatives to the current regulations,
as well as other proposed alternatives
suggested in litigation briefs and journal
articles, what are the advantages and
disadvantages of these approaches as
they relate to the public health
objectives that the FDA Authorities are
designed to advance?
III. Attendance and Registration
The FDA Conference Center at the
White Oak location is a Federal facility
with security procedures and limited
seating. Attendance is free and early
registration is recommended.
Individuals who wish to attend must
register on or before October 19, 2016,
at https://www.fda.gov/
CommunicationsPublicMeeting and
provide complete contact information,
including name, title, affiliation, email,
and phone number. Those without
Internet access may register by
contacting Kristin Davis at 301–796–
0418. FDA may allow onsite registration
if space is available. If registration
reaches maximum capacity, FDA will
post a notice closing registration at
https://www.fda.gov/
CommunicationsPublicMeeting.
Individuals who wish to present at
the public hearing must register as
noted at https://www.fda.gov/
CommunicationsPublicMeeting and
identify the questions (see section II)
they wish to address in their
presentation to 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 do its best
to accommodate requests to speak and
will determine the amount of time
allotted for each oral presentation and
the approximate time that each oral
presentation is scheduled to begin. FDA
will notify registered presenters of their
scheduled times and make available an
agenda at https://www.fda.gov/
CommunicationsPublicMeeting on or
before November 2, 2016. Once FDA
notifies registered presenters of their
scheduled times, presenters must
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submit an electronic copy of their
presentation to
CommunicationsPublicMeeting@
fda.hhs.gov by October 26, 2016.
If you need special accommodations
because of a disability, please send an
email to
CommunicationsPublicMeeting@
fda.hhs.gov at least 7 days before the
meeting.
A link to the live Webcast of this
public hearing will be available at
https://www.fda.gov/
CommunicationsPublicMeeting on the
day of the public hearing. A video
record of the public hearing will be
available at https://www.fda.gov/
CommunicationsPublicMeeting
following the meeting. A video record of
the public hearing will be available at
the same Web site address for 1 year.
IV. Notice of Public Hearing Under 21
CFR Part 15
The Commissioner of Food and Drugs
is announcing that the public hearing
will be held in accordance with part 15
(21 CFR part 15). The hearing will be
conducted by a presiding officer,
accompanied by FDA senior
management from the Office of the
Commissioner and the relevant centers/
offices.
Under § 15.30(f) (21 CFR 15.30(f)), the
hearing is informal and the rules of
evidence do not apply. Only the
presiding officer and panel members
may question any person during or at
the conclusion of each presentation
(§ 15.30(e)). 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)
(§ 10.203(a)). Under § 10.205,
representatives of the electronic 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 § 15.30(b) (see section V). To the
extent that the conditions for the
hearing as described in this document
conflict with any provisions set out in
part 15, this notice acts as a waiver of
those provisions as specified in
§ 15.30(h).
V. 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 Division of Dockets Management
(see ADDRESSES). A transcript will also
be available in either hardcopy or on
CD–ROM, after submission of a
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Freedom of Information request. The
Freedom of Information office address is
available on the Agency’s Web site at
https://www.fda.gov.
Dated: August 29, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016–21062 Filed 8–31–16; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HOUSING AND
URBAN DEVELOPMENT
24 CFR Part 35
[Docket No. FR–5816–P–01]
RIN 2501–AD77
Requirements for Notification,
Evaluation and Reduction of LeadBased Paint Hazards in Federally
Owned Residential Property and
Housing Receiving Federal
Assistance; Response to Elevated
Blood Lead Levels
Office of Lead Hazard Control
and Healthy Homes, HUD.
ACTION: Proposed rule.
AGENCY:
This proposed rule would
amend HUD’s lead-based paint
regulations on reducing blood lead
levels in children under age 6 who
reside in federally-owned or -assisted
pre-1978 housing and formally adopt
the revised definition of ‘‘elevated blood
lead levels’’ in children under the age of
6 in accordance with guidance of the
Centers for Disease Control and
Prevention (CDC), and establish more
comprehensive testing and evaluation
procedures for the housing where such
children reside. In 2012, the CDC issued
guidance revising its definition of
elevated blood lead level in children
under age 6 to be a blood lead level
based on the distribution of blood lead
levels in the national population. Since
CDC’s revision of its definition, HUD
has applied the revised definition to
funds awarded under its Lead-Based
Paint Hazard Control grant program and
its Lead Hazard Reduction
Demonstration grant program, and has
updated its Guidelines for the
Evaluation and Control of Lead-Based
Paint Hazards in Housing to reflect this
definition. CDC is continuing to
consider, with respect to evolution of
scientific and medical understanding,
how best to identify childhood blood
lead levels for which environmental
interventions are recommended.
Through this rule, HUD formally adopts
through regulation the CDC’s approach
to the definition of ‘‘elevated blood lead
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levels’’ in children under the age of 6
and addresses the additional elements
of the CDC guidance pertaining to
assisted housing.
DATES: Comment Due Date: October 31,
2016.
ADDRESSES: Interested persons are
invited to submit comments regarding
this proposed rule to the Regulations
Division, Office of General Counsel,
Department of Housing and Urban
Development, 451 7th Street SW., Room
10276, Washington, DC 20410–0500.
Communications must refer to the above
docket number and title. There are two
methods for submitting public
comments. All submissions must refer
to the above docket number and title.
1. Submission of Comments by Mail.
Comments may be submitted by mail to
the Regulations Division, Office of
General Counsel, Department of
Housing and Urban Development, 451
7th Street SW., Room 10276,
Washington, DC 20410–0500.
2. Electronic Submission of
Comments. Interested persons may
submit comments electronically through
the Federal eRulemaking Portal at
https://www.regulations.gov. HUD
strongly encourages commenters to
submit comments electronically.
Electronic submission of comments
allows the commenter maximum time to
prepare and submit a comment, ensures
timely receipt by HUD, and enables
HUD to make comments immediately
available to the public. Comments
submitted electronically through the
https://www.regulations.gov Web site can
be viewed by other commenters and
interested members of the public.
Commenters should follow the
instructions provided on that site to
submit comments electronically.
Note: To receive consideration as public
comments, comments must be submitted
through one of the two methods specified
above. It is not acceptable to submit
comments by facsimile (fax). Again, all
submissions must refer to the docket number
and title of the rule.
Public Inspection of Public
Comments. All properly submitted
comments and communications
submitted to HUD will be available for
public inspection and downloading at
https://www.regulations.gov.
FOR FURTHER INFORMATION CONTACT:
Warren Friedman, Office of Lead Hazard
Control and Healthy Homes,
Department of Housing and Urban
Development, 451 7th Street SW., Room
8236, Washington, DC 20410–3000,
telephone number (202) 402–7698 or
email your inquiry to lead.regulations@
hud.gov. For legal questions, contact
John B. Shumway, Office of General
PO 00000
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Counsel, Department of Housing and
Urban Development, 451 7th Street,
Room 9262, Washington, DC 20410–
0500; telephone number (202) 402–
5190. The above telephone numbers are
not toll-free numbers. Hearing and
speech-impaired persons may access the
above telephone numbers via TTY by
calling the toll-free Federal Relay
Service at 1–800–877–8339.
SUPPLEMENTARY INFORMATION:
I. Background
A. HUD’s Long-Term and Ongoing
Efforts To Reduce Lead Poisoning in
Children
Childhood lead poisoning has long
been recognized as causing reduced
intelligence, low attention span, reading
and learning disabilities, and has been
linked to juvenile delinquency,
behavioral problems, and many other
adverse health effects. Current reviews
by the U.S. Department of Health and
Human Services (HHS), including by its
Agency for Toxic Substances and
Disease Registry (ATSDR) and National
Institute of Environmental Health
Sciences (NIEHS) and by the U.S.
Environmental Protection Agency (EPA)
Office of Research and Development
have described these effects in detail.1
The removal of lead-based gasoline and
paint from commerce has drastically
reduced the number of children exposed
to levels of lead associated with the
most significant among these problems.
Data from CDC’s National Center for
Health Statistics show that mean blood
lead levels among children ages 1 to 5
dropped from 16.0 mg/dL in 1976–1980
to 2.6 mg/dL in 1991–1994, to 0.97 mg/
dL in 2011–2012.2 However, national
statistics mask the fact that blood lead
monitoring continues to find some
children exposed to elevated blood lead
levels due to their specific housing
environment. As sources of lead paint
1 See the following: Agency for Toxic Substances
and Disease Registry. Toxicological profile for lead.
Atlanta: U.S. Department of Health and Human
Services (HHS), August 2007. www.atsdr.cdc.gov/
toxprofiles/tp13.pdf. HHS, National Institute of
Environmental Health Sciences, National
Toxicology Program. NTP Monograph on Health
Effects of Low-Level Lead. NIH Publication No. 12–
5996. June 13, 2012. https://ntp.niehs.nih.gov/
pubhealth/hat/noms/lead/. Office of
Research and Development. Integrated Science
Assessment for Lead. Research Triangle Park, NC.
U.S. Environmental Protection Agency (EPA), June
2013. https://cfpub.epa.gov/ncea/risk/
recordisplay.cfm?deid=255721. (See esp. pp.
lxxxvii–lxxxxviii, and 1–20—1–24. See also Memo
Regarding a Study Assessed in the 2013 ISA for
Lead—Dated May 9, 2014. https://ofmpub.epa.gov/
eims/eimscomm.getfile?p_download_id=518543.)
2 Porter, K. National Health and Nutrition
Examination Survey. 2015 National Conference on
Health Statistics, August 24, 2015, www.cdc.gov/
nchs/ppt/nchs2015/Porter_Monday_SalonE_A6.pdf.
p. 48.
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Agencies
[Federal Register Volume 81, Number 170 (Thursday, September 1, 2016)]
[Proposed Rules]
[Pages 60299-60304]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-21062]
=======================================================================
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 15
[Docket No. FDA-2016-N-1149]
Manufacturer Communications Regarding Unapproved Uses of Approved
or Cleared Medical Products; Public Hearing; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notification of public hearing; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
a 2-day public hearing to obtain input on issues related to
communications by manufacturers, packers, and distributors, including
their representatives (collectively ``firms''), regarding FDA-regulated
drugs and medical devices for humans, including those that are licensed
as biological products, and animal drugs (collectively, ``medical
products''). FDA is engaged in a comprehensive review of its
regulations and policies governing firms' communications about
unapproved uses of approved/cleared medical products, and the input
from this meeting will inform FDA's policy development in this area.
FDA is seeking input on a number of specific questions, but is
interested in any other pertinent information participants would like
to share.
DATES: The public hearing will be held on November 9 and 10, 2016, from
9 a.m. to 5 p.m. The meeting may be extended or end early depending on
the level of public participation. Persons seeking to attend or present
at the public hearing must register by October 19, 2016. Electronic or
written comments will be accepted after the public hearing until
January 9, 2017.
ADDRESSES: The public hearing will be held at the FDA White Oak Campus,
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room
(Rm. 1503), Silver Spring, MD 20993-0002. Entrance for the public
meeting 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.
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): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, 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-2016-N-1149 for ``Manufacturer Communications Regarding Unapproved
Uses of Approved or Cleared Medical Products; Public Hearing; Request
for Comments.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at
[[Page 60300]]
https://www.regulations.gov or at the Division of Dockets Management
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 Division of Dockets Management. 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.fda.gov/regulatoryinformation/dockets/default.htm.
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 Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
A link to the live Webcast of this public hearing will be available
at https://www.fda.gov/CommunicationsPublicMeeting on the day of the
public hearing. A video record of the public hearing will be available
at https://www.fda.gov/CommunicationsPublicMeeting following the
meeting. A video record of the public hearing will be available at the
same Web site address for 1 year.
FOR FURTHER INFORMATION CONTACT: Kristin Davis, Office of Policy, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 4252,
Silver Spring, MD 20993, 301-796-0418, email:
CommunicationsPublicMeeting@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is responsible for regulating medical products (i.e., drugs and
medical devices for humans, including those that are licensed as
biological products, and animal drugs) under the Federal Food, Drug,
and Cosmetic Act (the FD&C Act) and the Public Health Service Act (PHS
Act) as well as all relevant implementing regulations (collectively,
``FDA Authorities'') to promote and protect the public health by
helping to ensure that these products are safe and effective for their
intended uses. As we announced in 2014, FDA is currently engaged in a
comprehensive review of the regulatory framework related to firms'
communications about unapproved uses of approved/cleared medical
products \1\--medical products that may be legally introduced into
interstate commerce for at least one other intended use.\2\ The purpose
of this review is to help ensure that our implementation of the FDA
Authorities (including promulgating and amending regulations, issuing
guidance, developing policies, and taking enforcement action) best
protects and promotes the public health in view of ongoing developments
in science and technology, medicine, health care delivery, and
constitutional law.
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\1\ In this document, the term ``unapproved use'' encompasses
additional intended uses of approved drugs and approved/cleared
devices, including devices that are currently marketed pursuant to a
510(k) clearance or exemption.
\2\ See FDA response letter, Docket Nos. FDA-2011-P-0512 and
FDA-2013-P-1079 (June 6, 2014), available at https://www.regulations.gov.
---------------------------------------------------------------------------
Under the FDA Authorities, in general, firms are required to submit
data and other information to FDA for premarket review demonstrating a
medical product is safe and effective for each of its intended uses
before they introduce the product into interstate commerce for those
intended uses. During FDA premarket review of medical products, the
Agency also generally reviews proposed labeling for the intended use(s)
of the product to ensure that the labeling provides adequate
information for the safe and effective use of the product. The FDA
Authorities also prohibit firms from marketing medical products with
false or misleading labeling and similarly restrict certain medical
product advertising.
The premarket review and labeling and advertising provisions of the
FDA Authorities address critical public health objectives. The current
regulatory framework was developed in response to public health
tragedies, particularly those that occurred when firms could distribute
drugs and devices without independent, premarket review of scientific
evidence of the products' safety and efficacy.\3\ Medical product firms
are required to develop high-quality data to demonstrate that medical
products are safe and effective for their intended uses before
marketing of the products for those uses. This requirement helps ensure
that the use of medical products is based on sound science, not mere
anecdotal experience or misleading promotional tactics, and helps
prevent direct and indirect patient harm from products and uses that
are unsafe and/or ineffective. When using a medical product for its FDA
approved/cleared intended use, health care professionals and patients
and their caregivers can be assured that the decision to use the
product is supported by robust premarket review of scientific data and
other appropriate scientific evidence by an independent scientific
agency and that the benefits and risks of the use are described in the
product's FDA-approved or required labeling. These important assurances
are absent for unapproved uses. The premarket review requirements also
reflect Congress's determination that exclusive reliance on postmarket
remedies, such as enforcement actions for false or misleading labeling,
is unacceptable as a public health strategy because it does not prevent
harm and injury to patients.
---------------------------------------------------------------------------
\3\ The Federal Food, Drug, and Cosmetic Act of 1938, which
introduced the requirement that firms demonstrate a drug product to
be safe before being marketed, followed the deaths of approximately
100 people, mostly children, from ingesting ``Elixir
Sulfanilamide,'' in which the lethal substance diethylene glycol was
used as a solvent. Prior to 1938, there were no premarket
requirements that mandated that the firm test its product's safety.
The passage of the 1962 drug amendments was precipitated in part by
the distribution of thalidomide, a sedative that caused birth
defects when taken by pregnant women. See Wallace F. Janssen,
Outline of the History of U.S. Drug Regulation and Labeling, 36 Food
Drug-Cosm. L.J. 420 (1981). Significant problems with medical
devices likewise preceded the Medical Device Amendments of 1976,
including significant defects in cardiac pacemakers that led to 34
voluntary recalls involving 23,000 units, and serious side effects
following implantation of intraocular lenses, including serious
impairment of vision and the need to remove the eyes of some
patients (H.R. Rep. No. 94-853, at 8 (1976)). See also Henry A.
Waxman, A History of Adverse Drug Experiences: Congress Had Ample
Evidence to Support Restrictions on the Promotion of Prescription
Drugs, 58 Food & Drug L.J. 299 (2003); see also Kate Greenwood, The
Ban on ``Off-Label'' Pharmaceutical Promotion: Constitutionally
Permissible Prophylaxis Against False and Misleading Commercial
Speech?, 37 Am. J. L. and Med. 278, 291-92 (2011) (describing the
history of misleading firm claims in promoting unapproved uses).
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[[Page 60301]]
Congress also determined that safety and effectiveness must be
evaluated for each intended use of a medical product to prevent the
harm that occurs when patients are prescribed or use ineffective
treatments and to ensure that the benefits of an intended use outweigh
its risks. Under the FDA Authorities, FDA evaluates whether a medical
product is safe for a particular use by comparing the expected
therapeutic benefits against the risk associated with that use. The
weighing of benefit and risk for each intended use is necessary as a
matter of science to protect the public health: A product considered
``safe and effective'' for one disease or condition or patient
population cannot automatically be considered ``safe and effective''
for another disease or condition or patient population. For example, a
drug with severe adverse effects may be considered safe and effective
for treating metastatic lung cancer, but be unlikely to have a positive
benefit-risk balance for treating high blood pressure. Similarly, a
non-absorbable suture cleared or approved for wound closure on the
skin's surface might raise significant new safety and effectiveness
concerns if used internally.
Notwithstanding the importance of the FDA Authorities in protecting
public health, health care professionals are generally permitted to
prescribe or use approved/cleared medical products for unapproved uses
when they judge that the unapproved use is medically appropriate for
their individual patients,\4\ and relevant, truthful, and non-
misleading scientific or medical information regarding unapproved uses
of approved medical products may help health care professionals make
better individual patient decisions. For example, health care
professionals may consider prescribing or using approved/cleared
medical products for unapproved uses in circumstances where a patient
has a disease for which there is no approved treatment or has exhausted
all approved treatments. In such a situation, relevant, truthful, and
non-misleading scientific or medical information about an unapproved
use may help a health care professional to make treatment decisions in
the absence of scientific data or information that is capable of
satisfying FDA's premarket review requirements.
---------------------------------------------------------------------------
\4\ FDA generally does not seek to interfere with the exercise
of the professional judgment of health care providers in
prescribing, for unapproved uses for individual patients, most
legally marketed medical products. This longstanding position has
been codified with respect to devices. See 21 U.S.C. 396. While FDA
generally recognizes the professional judgment of veterinarians,
certain unapproved uses of drugs in animals are not permitted and
result in the drug being deemed unsafe under section 512 of the FD&C
Act. See section 512(a)(4) and (5) of the FD&C Act (21 U.S.C.
360b(a)(4) and (5)) and 21 CFR part 530.
---------------------------------------------------------------------------
Health care professionals already can access considerable
scientific information about unapproved uses, for example, through
public sources such as scientific journals, clinical practice
guidelines, and compendia or by requesting that information from
firms.\5\ FDA is interested in comment on the extent to which
additional communications from firms about unapproved uses can provide
access to information that is relevant, scientifically sound,
responsibly presented, and provides as full an understanding as
possible about the limitations of the available evidence, as well as
comment on the extent to which health care professionals currently face
impediments to accessing such information, whether from firms or from
other sources. FDA is interested in comment and information addressing
whether and in what ways firms' communications of unapproved use
information are distinct and perhaps provide unique benefits compared
to other sources.
---------------------------------------------------------------------------
\5\ See ``Guidance for Industry: Responding to Unsolicited
Requests for Off-Label Information About Prescription Drugs and
Medical Devices--Draft Guidance'' (December 2011), available at
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM285145.pdf. FDA
has also issued guidance documents to describe some of the
circumstances when it would not consider a manufacturer's
distribution of reprints, clinical practice guidelines, or reference
texts regarding unapproved uses of approved drugs to be evidence of
intended use and/or false or misleading. See ``Revised Draft
Guidance for Industry: Distributing Scientific and Medical
Publications on Unapproved New Uses--Recommended Practices''
(February 2014), available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM387652.pdf
(``Revised Good Reprint Practices Draft Guidance''); and ``Guidance
for Industry: Good Reprint Practices for Distribution of Medical
Journal Articles and Medical or Scientific Reference Publications on
Unapproved New Uses of Approved Drugs and Approved or Cleared
Medical Devices'' (January 2009), available at https://www.fda.gov/oc/op/goodreprint.html (``Good Reprint Practices Guidance'').
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Not all communications of information about unapproved uses help
support public health. For example, communications that emphasize a
medical product's claimed benefits, while minimizing the limitations of
the supporting evidence, or minimizing the product's known or potential
adverse effects, may inappropriately influence prescribing or use
decisions in a manner that is not in a patient's best interest. FDA is
interested in comment on both the pros and cons for public health
associated with firms' communications of unapproved use information and
the kinds of limitations or requirements that would be appropriate to
protect patients from harm. We are also interested in any supporting
data related to these issues. In addition, allowing additional
communications about unapproved uses could have other indirect
consequences on public health, which are important to understand and
anticipate. For example, FDA is interested in information to better
understand how increased communications about unapproved uses would
impact incentives to conduct biomedical research submitted for FDA
review and subjects' willingness to participate in such research.
The Agency is aware of technological and business changes that are
increasingly affecting medical decision making and prescribing. There
are a growing number of entities in the health care system with a stake
in evaluating evidence to assess the rational and systematic use of
medical products. As medical providers have increasingly been
consolidated into integrated systems, the use of system measurements of
quality and measurements of the appropriate use of medical products has
increased, and insurance carriers, health care systems, and similar
entities may restrict coverage for medical products based on
assessments of value and employ performance measures to monitor
appropriate use and outcomes. FDA is interested in understanding
whether and how these changes may be able to provide an impetus for the
development of additional high-quality data to address the balance of
benefits and risks of each use of a medical product and, if so, in what
way they would affect incentives for submission of this data to the
Agency for marketing authorization.
II. Purpose and Scope of the Public Hearing
The purpose of this public hearing is to obtain comments on FDA's
regulation of firms' communications about medical products, with a
particular focus on firms' communications about unapproved uses of
their approved/cleared medical products. FDA is seeking feedback from a
broad group of stakeholders, including, but not limited to, health care
professionals and professional societies, patients and their
caregivers, patient advocates, representatives from regulated industry,
health care organizations, payors and insurers, academic institutions,
public interest groups, and the general public.
To facilitate stakeholder feedback, FDA sets forth some questions
in this section. These questions are not meant to be exhaustive. We
encourage
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interested stakeholders to address these and/or other issues related to
firms' communications about their medical products. In all cases, FDA
encourages stakeholders to provide the rationale and basis for their
comments, including any available data and information, and to
explicitly articulate any underlying assumptions. FDA also encourages
commenters to explain the basis for any distinctions they would draw as
to audience, vehicle of communication, type of medical product, type
and source of information, or any other aspect of communication.
1. FDA is interested in input from stakeholders on how increased
communications from firms about unapproved uses could impact the public
health, and on whether the impact would differ across different
categories of medical products. For example,
a. What are the benefits for clinical decision making, research,
coverage, reimbursement, or other purposes (please specify) if firms
communicate to health care professionals, payors, researchers, and/or
patients more information, including preliminary or inconclusive
information, about unapproved uses of approved/cleared medical
products? What are the drawbacks and risks? Are there safeguards or
requirements that would effectively mitigate any drawbacks or risks?
b. What information or systems exist to help FDA determine how
firms' increased communication of information about unapproved uses of
approved/cleared medical products could affect prescribing as well as
medical product development and research into new uses of approved/
cleared products?
c. How could firms' increased communication of information about
unapproved uses of approved/cleared medical products affect patient
incentives to enroll in clinical trials? Related to this, FDA is
interested in information on how firms' increased communication of this
information could impact their incentives to generate robust data to
fully assess the risks and benefits of new uses and to apply for FDA
marketing authorization for new uses of approved/cleared products.
d. Do the answers to the previous questions vary for different
categories of medical products (e.g., human drugs and biologics,
medical devices, animal drugs) or for different disease areas or
patient populations?
2. FDA is aware of changes happening in the health care system that
are outside of FDA's role, which may provide an impetus for the
development of high-quality data to fully assess the risks and benefits
of new uses of medical products.
a. To what extent do changes occurring in the health care system
that give payors and formulary committees more influence on prescribing
decisions (including by denying, limiting, or endorsing coverage of
unapproved uses of approved medical products) provide incentives for
firms to generate the high-quality data needed to demonstrate safety
and effectiveness for new uses?
b. To what extent do these changes affect (to preserve, enhance, or
suppress) incentives for firms to seek FDA approval/clearance of new
uses?
3. FDA recognizes that information about medical products,
including information about unapproved uses of approved/cleared medical
products, is now broadly available from a wide variety of sources
(e.g., academic and governmental organizations, scientific journals,
professional societies, compendia) in both traditional and new
communication vehicles and platforms, particularly electronic
communication platforms (e.g., the Internet). What is the impact of the
increasing availability of this information on firms' incentives to
communicate information about unapproved uses of approved/cleared
products? FDA is also interested in input on other factors that firms
may consider when making decisions about providing information about
unapproved uses of their approved/cleared medical product, including
financial considerations.
4. Given the importance of the scientific integrity of the
information that may be relied on in making decisions about the use of
medical treatments, FDA is interested in input from stakeholders on the
standards that should apply to unapproved use communications to
minimize the potential of these communications to be misleading or
otherwise cause harm. For example:
a. Given the wide range of quality of information potentially
available to firms on unapproved uses of their approved/cleared medical
products, what processes do firms use to evaluate whether such
information is scientifically appropriate to communicate to health care
professionals and other entities?
b. What criteria should the Agency consider in determining whether
a study or analysis that is the basis of a firm's communication is
scientifically appropriate to support the presentations or conclusions
in the communication?
c. What do health care professionals generally understand about the
quality and utility of different kinds or levels of scientific evidence
related to unapproved uses? Can the same information be misleading to
some audiences of health professionals and not others?
d. What information is most important to health care professionals
and other entities in allowing them to judge the validity and utility
of firms' communications about unapproved uses, including the level of
uncertainty of the evidence, and why? Does the answer to this question
differ depending on the recipient's purpose--e.g., making treatment
decisions for an individual patient, informing the direction of further
research, making formulary or institutional supply chain contracting
decisions, or making coverage determinations?
5. FDA is interested in input from stakeholders on factors that the
Agency should consider in evaluating whether firms' communications
about unapproved uses of approved/cleared medical products are truthful
and non-misleading, including what information firms should disclose in
these communications to help ensure audiences are not misled, and on
general considerations related to the audience for these communications
and on communication vehicles and techniques. For example:
a. What information should firms communicate to make audiences
aware that the medical product is unapproved for the use discussed and
to otherwise distinguish between the approved/cleared use(s) of the
medical product and the unapproved use? How could the means of
communication affect a recipient's ability to distinguish between
unapproved and approved/cleared uses or otherwise impede the disclosure
of necessary contextual information?
b. What factors are most relevant to determining whether a firms'
communication about a medical product concerns an unapproved use? How
do firms evaluate whether or not their communications concern
unapproved uses and whether the messages communicated are accurate and
non-misleading?
c. What other information should firms' disclose in these
communications to help ensure audiences are not misled (e.g., about the
risks of the product, the nature and weight of the evidence supporting
the unapproved use, the regulatory history relating to the unapproved
use, the financial involvement of firms in the research described,
etc.)?
d. How can disclosures in firms' unapproved use communications be
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made most effective in conveying material information while minimizing
chances of confusion or inattention? How effective are disclosures in
ensuring that limitations concerning data about unapproved uses are
adequately communicated and comprehended? For example, how could the
content and format of disclosures be developed to optimize the
usefulness of this information for audiences? FDA is interested in
empirical evidence to assess whether health care professionals or other
entities follow or disregard different types or formats of disclosures
or disclaimers.
e. To what extent is it appropriate for firms to communicate
information about unapproved uses of their approved/cleared medical
products to patient and consumer audiences? What disclosures and
additional information would be needed to help ensure that a
communication to lay audiences is truthful and non-misleading, given
consumers' lack of medical training and expertise in critically
evaluating this type of information?
6. Another important consideration in the changing health care
environment is transparency, including the growing expectation that
data from human studies will be made available for public review. If a
firm bases a communication on data that is not publicly available,
should information be provided publicly to ensure that the quality and
integrity of the supportive scientific information can be adequately
evaluated before any prescribing or use decision? If so, how should
transparency of this information be monitored?
7. FDA is interested in public input on how the Agency should
monitor firms' communications about unapproved uses of their medical
products, and what actions FDA should take with respect to firms'
communications that are determined to be false or misleading or that
otherwise raise public health issues. For example, what kinds of
surveillance and monitoring could be undertaken to measure and assess
the public health impacts of unapproved use communications and by whom?
8. As discussed previously, the Agency is evaluating its
regulations and policies governing firms' communications about
unapproved uses of approved/cleared medical products and considering
whether revisions are appropriate in order to provide greater legal
certainty and clarity to regulated entities. As an initial step, in the
Federal Register of September 25, 2015 (80 FR 57756), FDA issued a
notice of proposed rulemaking that proposed changes to existing
regulations at 21 CFR 201.128 and 801.4 to provide clarity for drug and
device firms regarding FDA's interpretation and application of its
existing intended use regulations.
a. What additional changes, if any, should FDA consider in its
regulations related to firms' communications about medical products,
such as the regulations related to what is false or misleading,
adequate directions for use, the definition of labeling, or other
relevant provisions?
b. With respect to proposed alternatives to the current
regulations, as well as other proposed alternatives suggested in
litigation briefs and journal articles, what are the advantages and
disadvantages of these approaches as they relate to the public health
objectives that the FDA Authorities are designed to advance?
III. Attendance and Registration
The FDA Conference Center at the White Oak location is a Federal
facility with security procedures and limited seating. Attendance is
free and early registration is recommended. Individuals who wish to
attend must register on or before October 19, 2016, at https://www.fda.gov/CommunicationsPublicMeeting and provide complete contact
information, including name, title, affiliation, email, and phone
number. Those without Internet access may register by contacting
Kristin Davis at 301-796-0418. FDA may allow onsite registration if
space is available. If registration reaches maximum capacity, FDA will
post a notice closing registration at https://www.fda.gov/CommunicationsPublicMeeting.
Individuals who wish to present at the public hearing must register
as noted at https://www.fda.gov/CommunicationsPublicMeeting and identify
the questions (see section II) they wish to address in their
presentation to 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
do its best to accommodate requests to speak and will determine the
amount of time allotted for each oral presentation and the approximate
time that each oral presentation is scheduled to begin. FDA will notify
registered presenters of their scheduled times and make available an
agenda at https://www.fda.gov/CommunicationsPublicMeeting on or before
November 2, 2016. Once FDA notifies registered presenters of their
scheduled times, presenters must submit an electronic copy of their
presentation to CommunicationsPublicMeeting@fda.hhs.gov by October 26,
2016.
If you need special accommodations because of a disability, please
send an email to CommunicationsPublicMeeting@fda.hhs.gov at least 7
days before the meeting.
A link to the live Webcast of this public hearing will be available
at https://www.fda.gov/CommunicationsPublicMeeting on the day of the
public hearing. A video record of the public hearing will be available
at https://www.fda.gov/CommunicationsPublicMeeting following the
meeting. A video record of the public hearing will be available at the
same Web site address for 1 year.
IV. Notice of Public Hearing Under 21 CFR Part 15
The Commissioner of Food and Drugs is announcing that the public
hearing will be held in accordance with part 15 (21 CFR part 15). The
hearing will be conducted by a presiding officer, accompanied by FDA
senior management from the Office of the Commissioner and the relevant
centers/offices.
Under Sec. 15.30(f) (21 CFR 15.30(f)), the hearing is informal and
the rules of evidence do not apply. Only the presiding officer and
panel members may question any person during or at the conclusion of
each presentation (Sec. 15.30(e)). 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)
(Sec. 10.203(a)). Under Sec. 10.205, representatives of the
electronic 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 section V). To the
extent that the conditions for the hearing as described in this
document 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).
V. 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 Division of Dockets Management (see ADDRESSES). A transcript will
also be available in either hardcopy or on CD-ROM, after submission of
a
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Freedom of Information request. The Freedom of Information office
address is available on the Agency's Web site at https://www.fda.gov.
Dated: August 29, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-21062 Filed 8-31-16; 8:45 am]
BILLING CODE 4164-01-P