[Federal Register Volume 84, Number 22 (Friday, February 1, 2019)]
[Notices]
[Pages 1156-1157]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-00677]



[[Page 1156]]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-2818]


Rare Diseases: Common Issues in Drug Development; Draft Guidance 
for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Rare 
Diseases: Common Issues in Drug Development.'' This draft guidance 
assists sponsors of drug and biological products intended to treat or 
prevent rare diseases in conducting more efficient and successful 
development programs through discussions of selected issues commonly 
encountered in rare disease drug development. This draft guidance 
addresses the following important aspects of drug development: Adequate 
description and understanding of the disease's natural history, 
adequate understanding of the pathophysiology of the disease and the 
drug's proposed mechanism of action, nonclinical pharmacotoxicology 
considerations to support the proposed clinical investigation or 
investigations, reliable endpoints and outcome assessment, standard of 
evidence to establish safety and effectiveness, drug manufacturing 
considerations during drug development, participation of patients, 
caretakers, and advocates in development programs, and interactions 
with the Agency. This guidance revises and replaces the draft guidance 
of the same name issued on August 17, 2015.

DATES: Submit either electronic or written comments on the draft 
guidance by April 2, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-2818 for ``Rare Diseases: Common Issues in Drug Development; 
Draft 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 the draft 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 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 draft guidance document.

FOR FURTHER INFORMATION CONTACT: Lucas Kempf, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6460, Silver Spring, MD 20993-0002, 301-
796-1140, 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.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Rare Diseases: Common Issues in Drug Development.'' This 
draft guidance assists sponsors of drug and biological products 
intended to treat or prevent rare diseases in conducting more efficient 
and successful development

[[Page 1157]]

programs through a discussion of selected issues commonly encountered 
in rare disease drug development. This draft guidance addresses the 
following important aspects of drug development:

 Adequate description and understanding of the disease's 
natural history
 Adequate understanding of the pathophysiology of the disease 
and the drug's proposed mechanism of action
 Nonclinical pharmacotoxicology considerations to support the 
proposed clinical investigation or investigations
 Reliable endpoints and outcome assessment
 Standard of evidence to establish safety and effectiveness
 Drug manufacturing considerations during drug development

This guidance revises and replaces the draft guidance for industry of 
the same name issued on August 17, 2015 (80 FR 49246). This revision 
includes the following:

 Updates to the natural history section
 Inclusion of issues for evaluation of biomarkers for 
consideration as surrogate endpoints
 Description of nonclinical flexibility
 Additional information on historical (external) controls and 
early randomization
 Addition of safety section
 Retitled Chemistry, Manufacturing, and Controls section to 
Pharmaceutical Quality Considerations
 Additional information on changes to drug substance or 
manufacturing process with clarification on areas of flexibility
 Addition of a considerations section addressing several topics 
including participation of patients, caretakers, and advocates; 
consideration of pediatric issues; and interactions with FDA
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Rare 
Diseases: Common Issues in Drug Development.'' 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 draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
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 following collections of information in the draft guidance have 
been approved under OMB control number 0910-0001:
     Submitting under 21 CFR 314.50(c)(1)(iv) and (d)(3) (Sec.  
314.50(c)(1)(iv) and (d)(3)) a summary of the nonclinical pharmacology 
and toxicology section and the human pharmacokinetics and 
bioavailability section of new drug application (NDAs);
     Submitting under Sec.  314.50(d)(1)(i) chemistry, 
manufacturing, and controls information, including the drug substance, 
for the content and format of a NDA for rare diseases; and
     Submitting under Sec.  314.50(d)(5) and (d)(5)(iv) 
clinical data of a drug, including a description of any other data 
information relevant to an evaluation of the safety and effectiveness 
of a drug.
    The following collections of information in the draft guidance have 
been approved under OMB control number 0910-0014:
     Submitting under 21 CFR 312.23(a)(6)(i) (Sec.  
312.23(a)(6)(i)) a protocol for the duration of a trial and the 
criteria to enter a trial and under Sec.  312.23(a)(6)(i), 
(a)(6)(iii)(d) and (g) a description of an estimate of patients that 
will be involved in a trial, including a description of the safety 
exclusions and a description of clinical procedures, laboratory, or 
other methods;
     Submitting under Sec.  312.23(a)(3)(i) a brief 
introductory statement and general investigational plan, including the 
route of administration of a drug;
     Submitting under Sec.  312.23(a)(7) and (a)(7)(iv)(a) 
chemistry, manufacturing, and controls information for the content and 
format of an investigational new drug application (IND) and the safety 
and effectiveness of such information;
     Submitting under Sec.  312.23(a)(8) and (a)(8)(i) 
pharmacology, toxicology, and drug disposition information for rare 
diseases;
     Submitting under 312.23(a)(10)(iii) plans for assessing 
pediatric safety and effectiveness;
     Submitting under Sec.  312.32(c)(1) IND safety reports;
     Submissions under Sec. Sec.  312.305(b) and 312.310(b) for 
expanded access uses and treatment of an individual patient.
    The collections of information in 21 CFR part 316 for submitting 
the content and format of NDAs for orphan drugs have been approved 
under OMB control number 0910-0167.
    The collections of information under Sec.  314.80 for submitting 
postmarketing reporting of adverse drug experiences have been approved 
under OMB control number 0910-0230.
    The collections of information under Sec. Sec.  312.47 and 312.82 
for requesting meetings with FDA about drug development programs have 
been approved under OMB control number 0910-0429.
    The following collections of information have been approved under 
OMB control number 0910-0765: (1) Requests under 21 CFR part 314, 
subpart H to grant accelerated approval for INDs to treat rare diseases 
that are serious or life threatening and (2) as a basis for accelerated 
approval requests, submissions of evidence to support that an endpoint 
reasonably likely to predict clinical benefit.

III. Electronic Access

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

    Dated: January 16, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-00677 Filed 1-31-19; 8:45 am]
 BILLING CODE 4164-01-P