Guest Column | April 18, 2023

Congressional Focus Signals Possible Changes For Orphan Drug Approval Process

By Jacqueline R. Berman and Angela Silva, Morgan Lewis

US Capitol Building GettyImages-1176605881

While many provisions of the U.S. Congress’ FY 2023 Consolidated Appropriations Act (omnibus) have received attention, one provision has flown under the radar. In its explanatory statement on the omnibus, Congress indicated that it is keeping an eye on how the FDA approves orphan drug products and, more specifically, on the composition of FDA advisory committees reviewing orphan drugs.

By way of background, FDA advisory committees are panels of independent experts that advise FDA reviewers on issues and questions around a product’s safety, effectiveness, and use and make recommendations to FDA on whether specific products should be approved. While the advice of the advisory committees is not binding on the FDA reviewers, FDA carefully weighs committee feedback.

As It Stands, Advisory Committees May Lack Orphan Drug Experts

The composition of the advisory committees, however, has long plagued FDA and the industry, especially in the rare disease space. Advisory committee members must be “technically qualified experts in their field (e.g., clinical medicine, engineering, biological and physical sciences, biostatistics, and food sciences) and have experience interpreting complex data. Candidates must be able to analyze detailed scientific data and understand its public health significance.”1 Although advisory committee members must be experts in their field, each advisory committee is tasked with a relatively broad charge. For example, there are 18 drug advisory committees within the Center for Drug Evaluation and Research, that are organized around broad disease states (e.g., oncology and cardiovascular/renal conditions). Each committee has a set number of members and, as such, while the individual members may broadly be experts on the overall disease state and be able to broadly provide practice-based guidance and advice to FDA reviewers, they may not have the specialized experience with specific and uncommon subsets of the broader disease category necessary to evaluate certain products intended for rare diseases.

Committee members also may not have specific experience with FDA’s charge with respect to life-threatening or severely debilitating diseases and, namely, the requirement that FDA must “recognize the need for a medical risk-benefit judgment in making the final decision on approvability.”2 In fact, FDA’s regulations state that the agency “will consider whether the benefits of the drug outweigh the known and potential risks of the drug and the need to answer remaining questions about risks and benefits of the drug, taking into consideration the severity of the disease and the absence of satisfactory alternative therapy.”3 This requires a careful balancing of the safety and efficacy data generated in clinical trials against the state of the disease and its treatment, an evaluation that differs from the traditional risk-benefit assessment. 

In the past, different strategies have been suggested to address these critiques. For instance, in 2018 the idea of creating a pool of rare disease experts that could serve on specific advisory committees on an as-needed basis was floated within FDA, but the strategy was ultimately not implemented.

Congress Wants More Experts On Advisory Committees

Despite the idea of a rare disease expert pool failing to move forward, the issue of advisory committee composition has not retreated. Rather, there is renewed congressional attention in the space. In the explanatory statement to the omnibus, Congress “encourage[d] the FDA to work to include no less than two expert members on each advisory committee when that committee is reviewing a drug that has been designated as an orphan drug” and required that FDA “report the percentage of recommendations made by advisory committees with respect to orphan drugs.” Including a provision that encourages FDA to give experts a place on orphan drug advisory committees indicates that Congress shares industry and patient concerns that the FDA advisory committee members and reviewers may not have the necessary experience with certain diseases to make difficult decisions on the risk-benefit analysis for treatments.

Notably, however, the advisory language did not go as far as it could have. For instance, prior versions included recommendations that FDA “work diligently to include no less than two members with an expertise in the indication for which the drug is intended to treat or other relevant rare diseases on each advisory committee” and also required reporting on the percentage of advisory committee decisions relating to rare disease drugs that included at least two rare disease expert members. Moreover, the current congressional language is only advisory and is not binding on FDA. However, if FDA does not adopt Congress’ recommendations, Congress could legislate the requirements, restricting FDA’s autonomy on advisory committee makeup.

More Focus Could Mean More Leverage For Orphan Drug Sponsors

For drug sponsors, congressional focus on the process of approving products for rare diseases will be considered a small step in the right direction and may provide rare disease product sponsors with added leverage to ensure that individuals with the appropriate expertise are reviewing products.

This is not the only action being taken with respect to products for rare diseases. For example, Dr. Peter Marks, director of the Center for Biologics Evaluation and Research, has discussed a planned FDA pilot program that would provide sponsors of certain promising rare disease products with the opportunity to have increased and iterative interactions with FDA, similar to the approach used in Project Warp Speed, to expedite product development.4 FDA plans to issue a federal register notice regarding this pilot later this year.

Dr. Marks has also announced that the agency will be trying to mimic what it did in Project Orbis for cell and gene therapies, products that are frequently intended for rare or ultra-rare diseases.5 Project Orbis provided “a framework for concurrent submission and review of oncology products among international partners” in the United States, Canada, Australia, Brazil, Israel, Singapore, Switzerland, and the United Kingdom.6 The goal of such a review would be to allow sponsors to achieve commercial viability of products faster than they would normally.

In the larger context of FDA approvals for rare disease treatments, the advisory language in the omnibus, as well as other FDA actions in the rare disease space, may be a signal that significant changes in the orphan product review and approval process are on the way. Rare disease product sponsors should keep a close eye on the new regulatory processes being put in place as they may present new opportunities to expedite development programs.


  1. FDA, Advisory Committee Membership Types,
  2. 21 C.F.R. § 312.84.
  3. Id.
  4. You Tube, Session 2: FDA Initiatives to Advance Medical Product Development for Rare Diseases,
  5. Id.
  6. FDA, Project Orbis,

About the Authors:

Jacqueline R. Berman advises companies throughout the U.S. FDA–regulated product supply chain on regulatory and compliance requirements. She helps clients navigate complex issues associated with the development, approval, and commercialization of prescription and nonprescription pharmaceuticals and biologics, including vaccines and cell and gene therapies. She further counsels clients on legal requirements under laws enforced by the U.S. Consumer Product Safety Commission, Federal Trade Commission, U.S. Drug Enforcement Agency, and state licensing agencies for consumer products, controlled substances, pharmaceuticals, and medical devices.

Angela Silva’s practice is primarily focused on matters relating to the FDA, U.S. Drug Enforcement Agency, and the pharmaceutical industry, including the approval, regulation, promotion, and sale of drugs, medical devices, and dietary supplements. She also assists clients with labeling, marketing, advertising, and safety requirements for consumer products under the laws enforced by the U.S. Consumer Product Safety Commission, the Federal Trade Commission, and related enforcement agencies.