[Federal Register Volume 84, Number 192 (Thursday, October 3, 2019)]
[Notices]
[Pages 52886-52887]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-21507]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-1246]


Investigational Enzyme Replacement Therapy Products: Nonclinical 
Assessment; 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) is announcing the 
availability of a final guidance for industry entitled 
``Investigational Enzyme Replacement Therapy Products: Nonclinical 
Assessment.'' The purpose of this guidance is to help sponsors design 
and conduct nonclinical studies needed to support initiation of 
clinical trials, ongoing clinical development, and marketing approval 
of enzyme replacement therapy (ERT) products. This guidance 
incorporates the comments received for and finalizes the draft guidance 
of the same title issued May 13, 2015.

DATES: The announcement of the guidance is published in the Federal 
Register on October 3, 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-2015-D-1246 for ``Investigational Enzyme Replacement Therapy 
Products: Nonclinical Assessment.'' 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.

[[Page 52887]]

     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. 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: Jenny Doan, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 5345, Silver Spring, MD 20903, 301-796-1023; or Sushanta 
Chakder, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 5108, Silver 
Spring, MD 20903, 301-796-0861.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Investigational Enzyme Replacement Therapy Products: 
Nonclinical Assessment.'' The nonclinical study requirements for ERT 
products may be different from products used to treat other diseases 
because of the rare, seriously debilitating, and life-threatening 
nature of the diseases treated by ERT products. Currently, there is no 
other final guidance that provides recommendations about the substance 
and scope of nonclinical information needed to support initiation of 
clinical trials, ongoing clinical development, and marketing approval 
of ERT products. This guidance provides consistent recommendations for 
nonclinical studies to expedite developments of ERT products used to 
treat these rare, life-threatening conditions, especially in pediatric 
patients.
    This guidance finalizes the draft guidance of the same title issued 
May 13, 2015. All public comments received on the draft guidance have 
been considered, and the guidance has been revised as appropriate, 
along with a few editorial changes. Changes from the draft to the final 
include the following: ``Changes in disease-specific biomarkers'' has 
been added as a pharmacodynamic endpoint; a statement on the preference 
for animal disease models in assessing pharmacodynamic activity has 
been added; safety pharmacology parameters to proof-of-concept studies 
were added; a statement was added to clarify the exposure margins; a 
clarification on the rapidly progressing disease phenotype was provided 
by adding ``approximately'' 1 year; a statement on the 3-month 
toxicology study in one species to support marketing approval was 
added; and a statement on recovery animals was added.
    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 ``Investigational Enzyme Replacement Therapy 
Products: Nonclinical Assessment.'' 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, and the information 
collection in the regulations on good laboratory practice for 
nonclinical laboratory studies (21 CFR part 58) is approved under OMB 
control number 0910-0119.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.

    Dated: September 27, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-21507 Filed 10-2-19; 8:45 am]
BILLING CODE 4164-01-P


