The US Food and Drug Administration is kicking off a top-to-bottom review of how it approaches rare disease drug development and approvals.

The Rare Disease Framework Initiative, being announced Wednesday, aims to develop a system that gives patients more input and companies more clarity in the regulatory process.

This comes after a tumultuous year in which several rare disease drugs were unexpectedly rejected or delayed under former FDA commissioner Marty Makary, who left the agency in May. That led to congressional inquiries, appeals by companies to the White House and pushback by patient groups.

In an interview, senior officials at the agency denied that the initiative had anything to do with the earlier controversies. They said it was a continuing effort to improve the rare disease drug development process at a time when such medicines make up an ever-increasing percentage of drug approvals.

“This is a true approach to transform the way we review rare diseases,” said Karim Mikhail, head of the agency’s Center for Biologics Evaluation and Research, which regulates cell and gene therapies.

The new framework is intended to enable patient input at earlier stages and at milestones throughout the development and review process. It also aims to provide greater clarity and consistency to drug developers on regulatory decision making. The agency said in a statement that it should take into account what evidence is reasonably attainable, given the nature of rare diseases.

Currently, patients typically weigh in at advisory panels when a medicine is up for approval — after clinical trials have concluded and the FDA reviewers have largely completed their work. Companies can also spend significant resources on testing, only to bump heads with the FDA on what data are needed for approval.

Amy Comstock Rick, the agency’s associate director for rare disease strategy, said FDA officials should be “clear along the way” with drug developers. “There shouldn’t be surprises,” she added.

Roughly 30 million Americans live with a rare disease. As of 2025, only around 5% of the 7,000 to 10,000 recognized rare diseases have an FDA approved treatment, according to the agency. The new initiative kicks off with a meeting on Oct. 28 that will take input from patient groups, disease advocates, industry and others.

The effort is much broader than an earlier initiative started under Makary, called a “plausible mechanism” pathway. That initiative focused on the rarest diseases, ones afflicting only handfuls of people.

Instead of taking a top-down approach, the new framework aims to incorporate input from rank-and-file agency staff, Center for Drug Evaluation and Research Director Michael Davis said. “We’re really trying to do this initiative the right way,” Davis said.

The initiative could result in official guidance or regulations. Internally, the goal is to have initial recommendations by February though that timeline could change based on the feedback they receive, FDA officials said in the interview.

The FDA has been without a permanent leader since Makary’s departure. White House policy aide Heidi Overton’s nomination to lead the agency is pending in the Senate. Mikhail and Davis were announced as the permanent leaders of their centers last month.