[Federal Register Volume 84, Number 131 (Tuesday, July 9, 2019)]
[Notices]
[Pages 32749-32751]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-14528]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2019-N-2281]
Incorporating Alternative Approaches in Clinical Investigations
for New Animal Drugs; Public Meeting; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting; request for comment.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing a public meeting entitled ``Incorporating Alternative
Approaches in Clinical Investigations for New Animal Drugs.'' This
public meeting and request for comments is intended to support FDA
guidance development as required by the Animal Drug and Animal Generic
Drug User Fee Amendments of 2018. The topics to be discussed will
inform the development of guidance to assist sponsors in incorporating
complex adaptive and other novel investigation designs, data from
foreign countries, real world evidence (including ongoing surveillance
activities, observational studies, and registry data), biomarkers, and
surrogate endpoints into proposed clinical investigation protocols and
applications for new animal drugs under the Federal Food, Drug, and
Cosmetic Act (FD&C Act). FDA is seeking comments from stakeholders,
including representatives of regulated industry, consumer groups,
academia, veterinarians, and food producers.
DATES: The public meeting will be held on July 16, 2019, from 8:30 a.m.
to 5 p.m. Submit either electronic or written comments on this public
meeting by August 17, 2019.
ADDRESSES: The public meeting will be held at Johns Hopkins
University--Montgomery County, Gilchrist Hall, 9601 Medical Center Dr.,
Rockville, MD 20850. Free parking is available on site.
You may submit comments as follows. Please note that late, untimely
filed comments will not be considered. Electronic comments must be
submitted on or before August 17, 2019. The https://www.regulations.gov
electronic filing system will accept comments until 11:59 p.m. Eastern
Time at the end of August 17, 2019. Comments received by mail/hand
delivery/courier (for written/paper submissions) will be considered
timely if they are postmarked or the delivery service acceptance
receipt is on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2019-N-2281 for ``Incorporating Alternative Approaches in Clinical
Investigations for New Animal Drugs.'' Received comments, those filed
in a timely manner (see ADDRESSES), 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
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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: Susan Storey, Center for Veterinary
Medicine, Food and Drug Administration, 7500 Standish Pl., HFV-131,
Rockville, MD 20855, 240-402-0578, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing a public meeting entitled ``Incorporating
Alternative Approaches in Clinical Investigations for New Animal
Drugs.'' This public meeting and request for comment is intended to
support FDA guidance development as required under section 305 of the
Animal Drug and Animal Generic Drug User Fee Amendments of 2018 (Pub.
L. 115-234). Section 305 directs FDA to develop guidance to address
several alternative approaches in clinical investigations for new
animal drugs, including incorporating complex adaptive and other novel
investigation designs, data from foreign countries, real world evidence
(including ongoing surveillance activities, observational studies, and
registry data), biomarkers, and surrogate endpoints into proposed
clinical investigation protocols and applications for new animal drugs
under sections 512 and 571 of the FD&C Act (21 U.S.C. 360b, 360ccc).
Section 305 also directs FDA to conduct a public meeting to allow the
Agency to gather input from stakeholders, including representatives of
regulated industry, consumer groups, academia, veterinarians, and food
producers before developing the guidance.
II. Topics for Discussion at the Public Meeting
The purpose of this public meeting is to facilitate discussion and
obtain input from stakeholders about the use of complex adaptive and
other novel investigation designs, data from foreign countries, real
world evidence, and biomarkers and surrogate endpoints in drug
development and regulatory decision making.
The meeting is expected to include four sessions that focus on the
following topics: (1) Complex adaptive and other novel investigation
designs; (2) data from foreign countries; (3) real world evidence; and,
(4) biomarkers and surrogate endpoints. Within each session and
following all sessions there will be an opportunity for public comment.
To facilitate the development of guidance on these topics, please
consider the following questions. When responding please identify the
topic and question in your response.
Topic 1: Complex Adaptive and Other Novel Investigation Designs
1. In September 2018, FDA published draft Guidance for Industry:
Adaptive Designs for Clinical Trials of Drugs and Biologics, which
applies to human drugs and biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics). How should these apply to study designs
for animal drugs? What are the potential study adaptation features that
could be applied to animal drug investigations? What are the challenges
and possible solutions to apply these adaptations to studies for animal
drugs? To what type of studies for animal drugs would these study
designs be most applicable?
2. How does complex adaptive design differ from adaptive design?
What constitutes other novel investigation designs? What examples are
directly applicable to animal drug development?
3. Are there partnerships that can be formed between FDA and the
regulated industry, academia, or other groups to facilitate the
development or use of these novel investigational designs for animal
drug development? What strategic work is needed to enable the regulated
industry to make full use of these novel investigational designs for
animal drug development? What methods are needed, such as the use of
simulations or modeling, to facilitate the use of these novel
investigational designs for animal drug development?
Topic 2: Data From Foreign Countries
For the purposes of this meeting, FDA considers data from foreign
countries to be data from investigations or studies conducted outside
the United States (U.S.). FDA can accept data from studies conducted
outside the United States to support a new animal drug application,
provided the applicant demonstrates that the data are adequate under
applicable standards to support approval (section 569B of the FD&C Act;
21 U.S.C. 360bbb-8b). FDA also accepts data from studies conducted
outside the United States to support a food additive petition for a
food additive intended for use in animal food, when provided by the
petitioner (section 409(k)(1) of the FD&C Act; 21 U.S.C. 348(k)(1)).
While the regulatory standards for approval differ between animal drugs
and animal food additives, data from foreign countries can be used to
support either approval if the data meet the appropriate regulatory
standards.
1. What challenges and potential solutions do you have in meeting
the requirements of substantial evidence of effectiveness, as defined
in 21 CFR 514.4, when using data from foreign countries for an animal
drug?
2. Typically in the United States, when we wish to show a test drug
is no worse than an active control, that active control is an approved
animal drug in the United States. A non-inferiority analysis is used to
statistically demonstrate this relationship. In studies conducted
outside the United States, an active control may be used that is not
approved for that use in the United States. In the absence of a U.S.
approval for the active control, FDA cannot interpret non-inferiority
to the unapproved active control. What challenges exist in utilizing
these studies? What criteria should FDA use to accept a study where the
active control is not approved in the United
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States? What are potential options or solutions to enable FDA to use
these studies?
3. What challenges exist in demonstrating that data from foreign
countries were generated under conditions representative of typical
conditions in the United States for an animal drug or food additive?
What are potential solutions to these challenges?
4. What challenges exist in designing studies for an animal drug or
food additive to meet the approval requirements of different
jurisdictions? What are possible solutions to these challenges?
5. What challenges exist in study conduct and the collection and
interpretability of data from foreign countries (both manual and
electronic) that may influence study quality and data integrity to
support the approval of an animal drug or food additive? What are
possible solutions to these challenges?
6. What other challenges have you encountered and what potential
solutions would you propose with regard to providing data from foreign
countries to FDA?
Topic 3: Real World Evidence
There is significant activity within FDA aimed at clarifying how to
determine if real-world data (RWD) are sufficient to generate real-
world evidence (RWE) that could be used for regulatory decision making
by the Agency. In August 2017, FDA published a guidance document
entitled, ``Guidance for Industry and Food and Drug Administration
Staff: Use of Real-World Evidence to Support Regulatory Decision-Making
for Medical Devices'' (available at https://www.fda.gov/media/99447/download) and, in accordance with the 21st Century Cures Act (Pub. L.
114-255), released a draft framework entitled ``Framework for FDA's
Real-World Evidence Program'' (available at https://www.fda.gov/media/120060/download) in December 2018 for human drug and biological
products.
1. How should FDA define RWE for making regulatory decisions for
animal drugs? What sources of RWD should FDA consider to generate RWE
for animal drugs?
2. What challenges exist for the use of RWE for animal drug
approvals? What are possible solutions to these challenges?
3. In what contexts might RWD/RWE be used to generate clinical
evidence for regulatory decision making for animal drugs?
4. What factors should FDA consider when evaluating RWE for animal
drugs?
Topic 4: Biomarkers and Surrogate Endpoints
Biomarkers have long been a part of veterinary medicine. Examples
include routine tests such as body temperature, heart rate, complete
blood cell count and clinical chemistry, radiographs, and intraocular
pressure. Numerous technological advancements have greatly increased
the number of available biomarkers while reducing their cost.
Unfortunately, many potential biomarkers are not validated for their
use and interpretation in clinical investigations. FDA's Center for
Drug Evaluation and Research (CDER) has a formal Biomarker
Qualification Program, related guidance, and affiliated consortia to
support the development and use of biomarkers in regulatory decision
making for human drugs (https://www.fda.gov/drugs/drug-development-tool-qualification-programs/cder-biomarker-qualification-program). FDA
is seeking stakeholder feedback on how to best support the
identification and development of new biomarkers for new animal drug
applications and on ways to better incorporate biomarkers and surrogate
endpoints into animal drug development.
1. What are the expectations of sponsors, researchers,
veterinarians, and producers for the use of biomarkers in the context
of animal drug regulation and how might biomarkers be used in addition
to surrogate endpoints in the design and conduct of clinical studies?
2. Biomarkers are commonly used for diagnosing disease to enroll
patients, sample size estimations, and pilot/proof-of-concept studies.
What information should be provided to FDA to support their use in
these contexts (e.g., analytical validation, clinical validation,
establishing clinical utility, companion diagnostics etc.)?
3. What are the major challenges in translating potential
biomarkers and/or surrogate endpoints into practical tools in clinical
trials? What are possible solutions to these challenges?
4. How do we determine the evidentiary criteria for evaluating
biomarker use?
5. Should FDA's Center for Veterinary Medicine develop a biomarker
qualification program like CDER's? Would such a program be beneficial,
and is it something that stakeholders (e.g., drug sponsors) would use?
Are there other approaches to the development and acceptance of
biomarkers for animal drugs?
III. Information About the Public Meeting
Additional information about the public meeting is available on our
website at https://www.fda.gov/animal-veterinary/workshops-conferences-meetings/public-meeting-incorporating-alternative-approaches-clinical-investigations-new-animal-drugs. If time and space permit, onsite
registration on the day of the public meeting will be provided
beginning at 8 a.m. We will post a notice on the above website no later
than July 12 as to whether onsite registration is available.
Streaming Webcast of the Public Meeting: This public meeting will
also be webcast. Registration for the webcast is required. Information
to register for the webcast is available at https://www.fda.gov/animal-veterinary/workshops-conferences-meetings/public-meeting-incorporating-alternative-approaches-clinical-investigations-new-animal-drugs. You
can register for the webcast up until the time of the meeting.
If you have never attended a Connect Pro event before, test your
connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. For a quick overview of the Connect Pro program,
visit https://www.adobe.com/go/connectpro_overview. FDA has verified
the website addresses in this document, as of the date this document
publishes in the Federal Register, but websites are subject to change
over time.
Transcripts: Please be advised that as soon as a transcript of the
public meeting is available, it will be accessible at https://www.regulations.gov. It may be viewed at the Dockets Management Staff
(see ADDRESSES). A link to the transcript will also be available at
https://www.fda.gov/animal-veterinary/workshops-conferences-meetings/public-meeting-incorporating-alternative-approaches-clinical-investigations-new-animal-drugs.
Dated: July 2, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-14528 Filed 7-8-19; 8:45 am]
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