[Federal Register Volume 84, Number 185 (Tuesday, September 24, 2019)]
[Notices]
[Pages 50045-50047]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-20629]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0035]


Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment; 
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 
``Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment.'' The 
guidance provides FDA's current thinking on the clinical development 
program and clinical trial designs for drugs to support an indication 
for the treatment of amyotrophic lateral

[[Page 50046]]

sclerosis (ALS). The guidance addresses the clinical development of 
drugs intended to treat the main motor aspects of ALS, i.e., muscle 
weakness and its direct consequences, including shortened life 
expectancy. It does not address in detail the development of drugs to 
treat other symptoms that may arise in ALS, such as muscle cramps, 
spasticity, sialorrhea, pseudobulbar affect, and others. This guidance 
finalizes the draft guidance of the same name issued on February 16, 
2018.

DATES: The announcement of the guidance is published in the Federal 
Register on September 24, 2019.

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-2013-N-0035 for ``Amyotrophic Lateral Sclerosis: Developing Drugs 
for Treatment.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at https://www.regulations.gov or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    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; or the 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. 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: Billy Dunn, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 4332, Silver Spring, MD 20993-0002, 301-796-2250; or 
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Amyotrophic Lateral Sclerosis: Developing Drugs for 
Treatment.'' ALS is a progressive neurodegenerative disease that 
primarily affects motor neurons in the cerebral motor cortex, 
brainstem, and spinal cord, leading to loss of voluntary movement and 
the development of difficulty in swallowing, speaking, and breathing. 
The purpose of this guidance is to assist sponsors in the clinical 
development of drugs for the treatment of ALS.
    The guidance addresses the clinical development of drugs intended 
to treat the main motor aspects of ALS (i.e., muscle weakness and its 
direct consequences, including shortened survival). It does not address 
in detail the development of drugs to treat other symptoms that may 
arise in ALS, such as muscle cramps, spasticity, sialorrhea, and 
pseudobulbar affect.
    The guidance covers considerations for early phase clinical 
development, drug development population, clinical efficacy study 
design and endpoints, and risk-benefit, as well as other factors, such 
as relevant nonclinical safety and pharmacokinetic/pharmacodynamic 
considerations. This guidance finalizes the draft guidance of the same 
name issued on February 16, 2018 (83 FR 7047). Changes made to the 
guidance took into consideration written and verbal comments received. 
Information was added about strategies to expedite clinical trials in 
ALS and minimize exposure to placebo, about the importance of broad 
inclusion criteria in ALS clinical trials, encouraging the use

[[Page 50047]]

of patient input and experience in the development of new outcome 
measures that are capable of measuring clinically meaningful effects in 
patients, and encouraging the incorporation of exploratory biomarkers 
in ALS development programs. Language was also added to provide greater 
context on the use of historical control data in ALS clinical trials, 
to suggest approaches to minimize patient burden during clinical 
trials, and to clarify safety data expectations for new ALS treatments. 
Finally, additions emphasize FDA's willingness to exercise flexibility 
in applying the statutory standards for approval of drugs for the 
treatment of serious diseases with unmet medical needs, while 
preserving appropriate assurances for safety and effectiveness.
    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 ``Amyotrophic Lateral Sclerosis: Developing 
Drugs for Treatment.'' 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. This guidance is not subject to Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR part 312 have been 
approved under OMB control number 0910-0014, the collections of 
information in 21 CFR part 314 have been approved under OMB control 
number 0910-0001, and the collections of information referred to in the 
guidance for industry entitled ``Establishment and Operation of 
Clinical Trial Data Monitoring Committees'' (available at https://www.fda.gov/media/75398/download) have been approved under OMB control 
number 0910-0581.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, or https://www.regulations.gov.

    Dated: September 18, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-20629 Filed 9-23-19; 8:45 am]
BILLING CODE 4164-01-P


