[Federal Register Volume 89, Number 202 (Friday, October 18, 2024)]
[Notices]
[Pages 83892-83894]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-24108]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-D-0112]
Considerations for Long-Term Clinical Neurodevelopmental Safety
Studies in Neonatal Product Development; Guidance for Industry;
Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled
``Considerations for Long-Term Clinical Neurodevelopmental Safety
Studies in Neonatal Product Development; Guidance for Industry.'' This
guidance is intended to provide a framework for considering whether and
what type of long-term neurologic, sensory, and developmental
evaluations could be useful in supporting a determination of safety of
an FDA-regulated ``medical product'' (i.e., drug, biological product,
or medical device) for use in neonates. Although short-term safety
evaluations may be appropriate for adults or other populations, such
evaluations may not identify important adverse events in the neonatal
population, as medical treatment during the neonatal period coincides
with a time of critical growth and physiologic development and latent
effects may not be evident until later in life following early-life
exposures. Consideration of the potential for long-term neurologic,
sensory, and developmental effects in the neonatal population early in
a development program is important for establishing safety of a medical
product intended for use in neonates. This guidance finalizes the draft
guidance of the same title issued on February 13, 2023.
DATES: The announcement of the guidance is published in the Federal
Register on October 18, 2024.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2022-D-0112 for ``Considerations for Long-Term Clinical
Neurodevelopmental Safety Studies in Neonatal Product Development;
Guidance for Industry.'' Received comments will be placed in the docket
and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://www.regulations.gov or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002; Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or
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Office of Policy, Center for Devices and Radiological Health, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431,
Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to
assist that office in processing your requests. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: An Massaro, Office of Pediatric
Therapeutics, Office of Clinical Policy and Programs, Office of the
Commissioner, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 32, 5th Floor, Silver Spring, MD 20993-0002, 301-467-8507; Gerri
Baer, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 5399, Silver
Spring, MD 20993-0002, 240-402-2865; James Myers, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Silver Spring, MD 20993-0002, 240-402-5923;
and Vasum Peiris, Center for Devices and Radiological Health, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Silver Spring,
MD 20993-0002, 301-796-6089.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Considerations for Long-Term Clinical Neurodevelopmental
Safety Studies in Neonatal Product Development; Guidance for
Industry.''
Treatment with medical products during the neonatal period
coincides with a time of critical growth and physiologic development.
Although short-term safety evaluations may be appropriate for adults or
other populations, such short-term evaluations may not identify
important adverse events in the neonatal population, as latent effects
may follow early-life exposures. Historically, most medical products
used to treat neonates and young infants were not approved for use in
these populations, and thus have not undergone comprehensive evaluation
of safety or efficacy for use in neonates.
Neonates should have the same access as other populations to
medical products that have been adequately evaluated for optimal
dosing, efficacy, and safety. There are unique conditions that occur in
term or preterm neonates that do not have analogous clinical conditions
in older populations. As products are developed for unique neonatal
conditions, first-in-human studies may occur in neonates, and these
development programs should demonstrate long-term neurologic, sensory,
and developmental safety. Clinical investigators and sponsors of
neonatal studies should consider both the potential short- and long-
term effects of an investigational therapy, whether the therapy has
been approved for a similar indication in an older population or
whether being developed for a new indication specific to the neonatal
population.
This guidance will discuss general, patient-specific and product-
specific considerations that impact the evaluation of whether and what
type of long-term follow-up assessment should be considered. Types of
follow-up assessments, ranging from neurodevelopmental screening
through a comprehensive neurodevelopmental evaluation, which domains of
assessment may be most pertinent, and the timing and duration of
assessment are discussed.
This guidance finalizes the draft guidance entitled
``Considerations for Long-Term Clinical Neurodevelopmental Safety
Studies in Neonatal Product Development; Guidance for Industry'' issued
on February 13, 2023 (88 FR 9296). FDA considered comments received on
the draft guidance as the guidance was finalized. Changes from the
draft to the final guidance include:
The background section of the guidance addresses the
recommended minimum duration of follow-up and notes that this will
depend on different population- and product-specific factors as
discussed throughout the guidance.
In the section of the guidance that addresses product-
specific considerations when determining whether long-term
neurodevelopmental safety evaluations should be conducted, new text was
added about the impact of the route of product administration.
In the section of the guidance that addresses general
considerations when developing a plan to evaluate long-term
neurodevelopmental safety, new text was added about planning for
clinical referral.
New text was also added to the first paragraph of the
section of the guidance entitled ``What to Measure, When, and for How
Long'' that clarifies that the protocol should specify whether
assessments are conducted as part of standard clinical care or for
research-related purposes only. The new text also clarifies that for
research-related interventions, the benefit-risk determination should
be performed to ensure that the procedure is ethically permissible.
In addition, editorial changes were made to improve clarity noting
that this guidance does not address gene therapy or genomic medical
interventions.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Considerations for Long-Term Clinical
Neurodevelopmental Safety Studies in Neonatal Product Development;
Guidance for Industry.'' It does not establish any rights for any
person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable
statutes and regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information
for submission of investigational new drug applications, 21 CFR part
312, have been approved under 0910-0014. The collections of information
for submission of new drug applications, 21 CFR part 314, have been
approved under 0910-0001. The collections of information for submission
of biologic license applications, 21 CFR part 601, have been approved
under 0910-0338. The collections of information for submission of
premarket notifications, 21 CFR part 807, subpart E; investigational
device exemptions, 21 CFR part 812; premarket approval applications,
part 814 (21 CFR part 814), subparts A through E; humanitarian device
exemptions, part 814, subpart H; De Novo classification requests, 21
CFR part 860, subpart D; and the Q-submission Program, in FDA's
guidance entitled ``Requests for Feedback and Meetings for Medical
Device Submissions: The Q-Submission Program,'' have been approved
under OMB control numbers 0910-0120, 0910-0078, 0910-0231, 0910-0332,
0910-0844, and 0910-0756, respectively.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-
[[Page 83894]]
guidance-documents, or https://www.regulations.gov.
Dated: October 10, 2024.
Eric Flamm,
Acting Associate Commissioner for Policy.
[FR Doc. 2024-24108 Filed 10-17-24; 8:45 am]
BILLING CODE 4164-01-P