Description
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Rare Diseases: Natural History Studies for Drug Development.” FDA is publishing this draft guidance to help inform the design and implementation of natural history studies that can be used to support the development of safe and effective drugs and biological products for rare diseases. A natural history study collects information about the natural history of a disease in the absence of an intervention, from the disease's onset until either its resolution or the individual's death. Although knowledge of a disease's natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases.
Scope & Applicability
Product Classes
4Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
development program for drug and biological products
A higher degree of uncertainty is common in drug development programs for rare diseases.
drug development for a rare disease; FDA encourages the sponsor to meet with the relevant drug review division about the use of natural history data to support development of a particular drug for rare disease.
Stakeholders
4Institutional Review Board providing study approvals
Governs top dose in clinical studies
Entity responsible for submitting applications under section 524B
Consulted by lead reviewer for checklist completion
Regulatory Context
Attributes
3potential use of natural history data as an external control in a clinical trial
Methods used for standardizing inter- and intra-rater reliability
Variation in disease presentation across patient populations
Identified Hazards
Hazards
1disproportionately fail to capture patients who enter and rapidly leave the database
Related CFR Sections (3)
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
Related Warning Letters (10)
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Shirish M. Gadgeel, M.D.
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Mark J. Savant, M.D
- 2025-05-20
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United Health Products, Inc.
- 2025-03-25
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Americo F. Padilla, M.D.
- 2024-11-05
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- 2024-10-22
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Namita A. Goyal, M.D.
- 2024-10-08
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Louisiana State University Health Science Center IRB
- 2024-07-16
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Massachusetts Institute of Technology MIT
- 2024-06-18
Clinical Investigator (Sponsor)
Angela D. Ritter, M.D.
- 2024-03-26
Institutional Review Board (IRB)
New York State Psychiatric Institute IRB
See Also (8)
- Draft Guidance for Industry: New Dietary Ingredient Notifications and Related Issues (Status: Draft)
- Sponsor - Investigator - IRB Interrelationship: Guidance for Institutional Review Boards and Clinical Investigators (Status: Final)
- Non-local IRB Review : Guidance for Institutional Review Boards and Clinical Investigators (Status: Final)
- Institutional Review Boards Frequently Asked Questions: Guidance for Institutional Review Boards and Clinical Investigators (Status: Final)
- Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Chapter 48 7348.809A Radioactive Drug Research Committee (Status: Final)
- CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
- Formatting, Assembling and Submitting New Drug and Antibiotic Applications* (Status: Final)