FDA Released Draft Guidance on Common Issues in Rare Disease Drug Development


After the FDA passed the Orphan Drug Act in 1983, the number of orphan drugs (drugs indicated for the treatment of rare diseases that affect 200,000 people or less in the United States) submitted to (and approved by) the Agency has skyrocketed. Why the sudden increase? The Orphan Drug Act was passed with hopes of motivating companies to develop orphan drugs by offering incentives such as extended marketing exclusivity, user fee waivers, and tax credits.

On Monday, August 17, FDA announced the availability of a draft guidance surrounding some of the common issues and challenges faced by pharmaceutical companies during orphan drug development. This guidance was intended to help sponsors be more efficient and effective in their drug development efforts, and addresses the importance of the following aspects:

  • 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 investigation or investigations;
  • Reliable endpoints and outcome assessment;
  • Standard of evidence to establish safety and effectiveness; and
  • Drug manufacturing considerations during drug development.

The guidance states that if sponsors address the above mentioned issues “efficiently and adequately” they are more likely to have a productive meeting with FDA. It also points out, that while the Orphan Drug Act may provide incentives for companies to develop orphan drugs, the standards for approving orphan drugs is no different than the standard for common conditions.

What does all of this mean? All drugs, for both orphan and common conditions, are required to demonstrate “substantial evidence of effectiveness in treating or preventing the condition and evidence of safety for that use.” However, while orphan drugs must be safe and effective (and your application must convey as much), the FDA does acknowledge the fact that certain aspects of drug development are not possible for rare diseases, which is why the Agency’s “regulations provide flexibility in applying regulatory standards because of the many types and intended uses of drugs.” In addition, the guidance states that “FDA ‘exercise[s] its scientific judgement’ in determining the kind and quantity of data a sponsor is required to provide for individual drug development programs.” So, in translation, what that means is that, although you are still required to show evidence that proves the drug is safe and effective for use for the indicated condition(s), FDA is more flexible with the type and the amount of data that is provided within the applications for drugs with an orphan designation.

Do you have a drug that is indicated for treatment of a rare disease? We can help you obtain orphan designation and achieve a successful interaction with the FDA! We know how difficult it can be to make sure you are adhering to all applicable FDA regulations, but that is why we’re here to help… Combining scientific expertise with extensive regulatory knowledge, we have helped numerous clients with orphan applications as well as all other FDA submissions! Learn more about our services and how we can help you get through FDA successfully by emailing us here!