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###### Department of Health and Human Services

###### Food and Drug Administration

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

# 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 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 This guidance finalizes the draft guidance entitled “Rare Diseases: Common Issues in Drug Development” issued on February 1, 2019.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                            ( print page 88925)                          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)  (§ 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);                           ( print page 88926)      
    - Submitting under § 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 § 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 §§ 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)  (§ 312.23(a)(6)(i)) a protocol for the duration of a trial and the criteria to enter a trial and under § 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 § 312.23(a)(3)(i) a brief introductory statement and general investigational plan, including the route of administration of a drug;
    - Submitting under § 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 § 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 § 312.32(c)(1) IND safety reports;
    - Submissions under §§ 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