[Federal Register Volume 85, Number 51 (Monday, March 16, 2020)]
[Notices]
[Pages 14949-14951]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-05335]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-2456]


Slowly Progressive, Low-Prevalence Rare Diseases With Substrate 
Deposition That Results From Single Enzyme Defects: Providing Evidence 
of Effectiveness for Replacement or Corrective Therapies; 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 ``Slowly 
Progressive, Low-Prevalence Rare Diseases With Substrate Deposition 
That Results From Single Enzyme Defects: Providing Evidence of 
Effectiveness for Replacement or Corrective Therapies.'' This document 
provides guidance to sponsors on the evidence necessary to demonstrate 
the effectiveness of investigational new drugs or new drug uses 
intended for slowly progressive, low-prevalence rare diseases that are 
associated with substrate deposition and are caused by single enzyme 
defects.
    This guidance applies only to those low-prevalence rare diseases 
with a well-characterized pathophysiology and in which changes in 
substrate deposition can be readily measured in relevant tissue or 
tissues. This guidance incorporates the comments received for and 
finalizes the draft guidance of the same name issued on July 27, 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on March 16, 2020.

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

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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-2018-D-2456 for ``Slowly Progressive, Low-Prevalence Rare Diseases 
With Substrate Deposition That Results From Single Enzyme Defects: 
Providing Evidence of Effectiveness for Replacement or Corrective 
Therapies.'' 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.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.
    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: Hylton Joffe, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6300, Silver Spring, MD 20993-0002, 301-
796-1954; 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 ``Slowly Progressive, Low-Prevalence Rare Diseases With 
Substrate Deposition That Results From Single Enzyme Defects: Providing 
Evidence of Effectiveness for Replacement or Corrective Therapies.'' 
This document provides guidance to sponsors on the evidence necessary 
to demonstrate the effectiveness of investigational new drugs or new 
drug uses intended for slowly progressive, low-prevalence rare diseases 
that are associated with substrate deposition and are caused by single 
enzyme defects. This guidance applies only to those low-prevalence rare 
diseases with a well-characterized pathophysiology and in which changes 
in substrate deposition can be readily measured in relevant tissue or 
tissues.
    This guidance finalizes the draft guidance of the same name issued 
on July 27, 2018 (83 FR 35653). FDA considered comments received on the 
draft guidance in devising this final guidance. Changes from the draft 
to the final guidance include the following: clarification that a ``low 
prevalence'' condition may be defined as one affecting a very small 
population (e.g., approximately a few thousand persons or fewer in the 
United States); clarification that, in the absence of nonhuman data to 
guide a potentially efficacious dose, animal toxicology data can inform 
a safe starting human dose; and removal of language regarding assay 
versus intrasubject variability--approaches to manage intrasubject 
variability within specific drug development programs can be addressed 
via formal sponsor meetings with the relevant division at FDA.
    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 ``Slowly Progressive, Low-Prevalence Rare 
Diseases With Substrate Deposition That Results From Single Enzyme 
Defects: Providing Evidence of Effectiveness for Replacement or 
Corrective Therapies.'' 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

    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-
3521). 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 50 have been approved under OMB control 
number 0910-0755. The collections of information for expedited programs 
in the guidance for industry entitled ``Expedited Programs for Serious

[[Page 14951]]

Conditions--Drugs and Biologics'' (available at https://www.fda.gov/media/86377/download) have been approved under OMB control number 0910-
0765.

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/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, or https://www.regulations.gov.

    Dated: March 10, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-05335 Filed 3-13-20; 8:45 am]
BILLING CODE 4164-01-P