Guidance Documents for Rare Disease Drug Development

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in agency guidances means that something is suggested or recommended, but not required.

Below are selected guidances that are relevant to rare disease drug development, organized by topic. This list does not include all FDA guidances on or relevant to rare disease drug development but represents our most commonly used guidances. This list may be updated periodically.

You can search all FDA Guidances by topic, FDA Center, or issue date hereexternal link, opens in a new tab.

Rare Disease

Rare Diseases: Considerations for the Development of Drugs and Biological Productsexternal link, opens in a new tab
This guidance clarifies FDA’s thinking on important considerations in rare disease drug development to ultimately assist rare disease drug and biologic product developers in conducting successful drug development programs.

Rare Diseases: Natural History Studies for Drug Development: Draft Guidance for Industryexternal link, opens in a new tab
FDA is publishing this draft guidance to help inform the design and implementation of natural history studies that can be used to support the development of safe and effective drugs and biological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.

Rare Pediatric Disease Priority Review Vouchersexternal link, opens in a new tab
This guidance provides information on the implementation of section 908 of the Food and Drug Administration Safety and Innovation Act (FDASIA), which added section 529 to the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Under section 529, FDA will award priority review vouchers to sponsors of certain rare pediatric disease product applications that meet the criteria specified in that section.

Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings : Draft Guidance for Industryexternal link, opens in a new tab
The purpose of this draft guidance is to assist sponsors of drug and biological products for the treatment of rare diseases in planning and conducting more efficient and productive pre-investigational new drug application (pre-IND) meetings. Drug development for rare diseases has many challenges related to the nature of these diseases. This draft guidance is intended to advance and facilitate the development of drugs and biological products for the treatment of rare diseases.

Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies : Guidance for Industryexternal link, opens in a new tab
This document provides guidance to sponsors on the evidence necessary to demonstrate the effectiveness of investigational new drugs or new drug uses intended for slowly progressive, low-prevalence rare diseases that are associated with substrate deposition and are caused by single enzyme defects. This guidance applies only to those low-prevalence rare diseases with well-characterized pathophysiology, and in which changes in substrate deposition can be readily measured in relevant tissue or tissues.

Pediatric Rare Diseases--A Collaborative Approach for Drug Development Using Gaucher Disease as a Model : Draft Guidance for Industryexternal link, opens in a new tab
The purpose of this guidance is to facilitate drug development in pediatric rare diseases. In particular, it discusses a new possible approach to enhance the efficiency of drug development in pediatric rare diseases using Gaucher disease as an example.

Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development: Guidance for Industryexternal link, opens in a new tab
This guidance describes the Food and Drug Administration’s (FDA’s) current recommendations regarding how to optimize and standardize dietary management in clinical trials for the development of drugs that treat inborn errors of metabolism (IEM) for which dietary management is a key component of patients’ metabolic control. Optimizing dietary management in these patients before entry into and during clinical trials is essential to providing an accurate evaluation of the efficacy of new drug products.