Document ID: FDA-2013-D-1170-0016
Agency: fda
Document Type: Notice
Title: Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral
Drugs for Treatment; Guidance for Industry; Availability
Posted Date: 2017-11-07T05:00Z

[Federal Register Volume 82, Number 214 (Tuesday, November 7, 2017)]
[Notices]
[Pages 51636-51637]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-24195]

[[Page 51636]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-D-1170]

Chronic Hepatitis C Virus Infection: Developing Direct-Acting 
Antiviral 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 guidance for industry entitled ``Chronic 
Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs 
for Treatment.'' The purpose of this guidance is to assist sponsors in 
all phases of development of direct-acting antiviral (DAA) drugs for 
the treatment of chronic hepatitis C. This guidance finalizes the draft 
guidance of the same name issued on May 4, 2016.

DATES: The announcement of the guidance is published in the Federal 
Register on November 7, 2017.

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-D-1170 for ``Chronic Hepatitis C Virus Infection: Developing 
Direct-Acting Antiviral Drugs for Treatment; Guidance for Industry; 
Availability.'' 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. 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: Jeffrey Murray, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6360, Silver Spring, MD 20993-0002, 301-
796-1500.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-
Acting Antiviral Drugs for Treatment.'' This guidance addresses 
nonclinical development, early phases of clinical development, and 
phase 3 protocol designs. Important issues addressed in this guidance 
include: trial design options, choice of noninferiority margins for 
active-controlled phase 3 trials in the evaluation of interferon (IFN)-
free regimens, and trial design options and safety evaluations for 
specific populations including patients with decompensated cirrhosis, 
patients either pre- or post-liver transplant, and patients with 
chronic kidney disease and clinical virology considerations. This 
guidance finalizes the draft guidance of the same name issued on May 4, 
2016 (81 FR 26805). Changes made to the guidance took into 
consideration comments received. In addition to editorial changes 
primarily for clarification, the major changes are as follows:
     Modification of several sections to focus on IFN-free DAA 
regimens.
     Additional clarification on trial designs for combinations 
of investigational DAAs with or without ribavirin.
     Additional clarification on the recommended trial 
population to

[[Page 51637]]

include patients with clinical or laboratory evidence of chronic 
hepatitis C disease, such as the presence of fibrosis by biopsy or 
noninvasive tests.
     Additional details on DAA drug development in patients 
with decompensated cirrhosis, including recommendations for a review by 
an independent adjudication committee for all serious hepatic events, 
deaths, liver transplantations, and changes in prespecified alanine 
transaminase, aspartate transaminase, and bilirubin parameters and a 
recommendation for long-term followup to characterize clinical outcomes 
such as progression or regression of liver disease, liver-related 
mortality, occurrence of hepatocellular carcinoma, or liver failure 
requiring liver transplantation.
     Additional clarification on efficacy endpoints, 
specifically additional post-treatment followup (e.g., 1 year or 
longer) may be needed if one or more drugs in the regimen has a long 
plasma or intracellular half-life or prolonged antiviral activity.
    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 ``Chronic Hepatitis C Virus Infection: 
Developing Direct-Acting Antiviral 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. The 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 parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: November 2, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-24195 Filed 11-6-17; 8:45 am]
 BILLING CODE 4164-01-P