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[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 This guidance finalizes the draft 
guidance of the same title issued on February 13, 2023.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

[[Page 83893]]

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
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