
[Federal Register Volume 88, Number 246 (Tuesday, December 26, 2023)]
[Notices]
[Pages 88924-88926]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-28310]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Rare Diseases: Considerations for the Development of Drugs and 
Biological Products; 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 ``Rare 
Diseases: Considerations for the Development of Drugs and Biological 
Products.'' This guidance is intended to assist sponsors of drugs and 
biological products for treatment of rare diseases in conducting 
efficient and successful drug development programs through a discussion 
of selected issues commonly encountered in rare disease drug 
development. This guidance finalizes the draft guidance entitled ``Rare 
Diseases: Common Issues in Drug Development'' issued on February 1, 
2019.

DATES: The announcement of the guidance is published in the Federal 
Register on December 26, 2023.

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

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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: Considerations for the Development 
of Drugs and Biological Products.'' 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, 240-402-7500.
     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, 240-402-7500.
    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: Andrea Bell-Vlasov, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6484, Silver Spring, MD 20993-0002, 240-
402-4977; or Anne Taylor, 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 ``Rare Diseases: Considerations for the Development of Drugs 
and Biological Products.'' This guidance is intended to assist sponsors 
of drugs and biological products for treatment of rare diseases in 
conducting efficient and successful product development programs 
through a discussion of selected issues commonly encountered in rare 
disease drug development. This final guidance addresses important 
aspects of drug and biological product development to support the 
proposed clinical investigation(s), including nonclinical pharmacology/
toxicology; trial design and endpoint considerations to ensure quality 
and interpretability of data; standard of evidence to establish safety 
and effectiveness; and drug manufacturing considerations during drug 
development.
    This guidance finalizes the draft guidance entitled ``Rare 
Diseases: Common Issues in Drug Development'' issued February 1, 2019 
(84 FR 1156). Changes made from the draft to the final guidance took 
into consideration comments received. Major changes include the removal 
of the natural history section (because this is addressed in a separate 
guidance), additional considerations regarding nonclinical studies, 
information on the use of external controls and early randomization, a 
section discussing safety considerations, information on changes to 
drug substance or manufacturing process, and sections discussing 
participation of patients/patient groups in drug development programs 
and pediatric considerations in rare disease drug development.
    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 ``Rare Diseases: Considerations for the 
Development of Drugs and Biological Products.'' 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

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521).
    The following collections of information in the final 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);

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     Submitting under Sec.  314.50(d)(1)(i) chemistry, 
manufacturing, and controls information, including the drug substance, 
for the content and format of an 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.
     Submissions under 21 CFR part 314, subpart H, to grant 
accelerated approval of new drugs for serious or life-threatening 
illnesses.
     Submissions under Sec. Sec.  312.47 and 312.82 for 
requesting meetings with FDA about drug development programs.
    The following collections of information in the final 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 
pertaining to postmarketing adverse drug experience reporting have been 
approved under OMB control number 0910-0230. The collections of 
information pertaining to expedited review programs for serious 
conditions, accelerated approval, breakthrough therapy-designation, and 
fast-track designation, have been approved under OMB control number 
0910-0765. The collections of information in 21 CFR part 58 pertaining 
to good laboratory practices have been approved under OMB control 
number 0910-0119. The collection of information pertaining to current 
good manufacturing practices have been approved under OMB control 
number 0910-0139.

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, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: December 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-28310 Filed 12-22-23; 8:45 am]
BILLING CODE 4164-01-P


