The U.S. Food and Drug Administration (FDA) is experiencing significant unrest following the sudden departure of its top drug regulator, revealing internal tensions and challenges in leadership. Two weeks after George Tidmarsh resigned as director of the Center for Drug Evaluation and Research (CDER), officials have struggled to fill the role, highlighting cracks in the agency long known for stability and consistency. The Department of Health and Human Services (HHS) recently announced that Richard Pazdur, a respected oncology expert and longtime FDA employee, was approached for the position. However, Pazdur reportedly declined, forcing leaders to search for other candidates. Peter Lurie, a former FDA associate commissioner and president of the Center for Science in the Public Interest, described the situation as “reversals upon reversals,” adding that the upheaval raises concerns about the agency’s decision-making and internal cohesion. Tidmarsh, who was appointed CDER director in late July, stepped down in early November amid allegations of retaliation against a former business partner and reports of internal conflict. The accusations were outlined in a high-profile lawsuit claiming that Tidmarsh misused his position to harm his former partner. Before his departure, Tidmarsh opposed a new rapid drug approval program called the “Commissioner’s National Priority Voucher,” questioning its legal validity. He also reportedly clashed with Vinay Prasad, the FDA’s chief medical and scientific officer and director of the Center for Biologics Evaluation and Research (CBER), who allegedly bypassed Tidmarsh to assign tasks directly to CDER staff. The HHS declined to comment on the power struggle between Tidmarsh and Prasad but confirmed that Tidmarsh no longer works at the agency. Prasad’s own history at the agency reflects similar instability. He resigned in July but returned less than a week later, reportedly with the support of FDA chief Marty Makary. Lurie noted that Prasad’s aggressive approach has further strained relationships among center directors, which are vital for the FDA’s smooth functioning. Inside the agency, the turmoil has made the CDER director role less appealing. One FDA employee, speaking anonymously, called the position a “career killer” due to high turnover and constant internal conflict. Concerns about Prasad’s oversight were also cited as a deterrent. Following Tidmarsh’s exit, long-serving FDA employees showed limited interest in the role. Sara Brenner, the agency’s principal deputy commissioner, even sent an email inviting applications from CDER staff, a move Lurie described as a sign of desperation. Choosing an experienced FDA insider like Pazdur is seen as a step toward stabilizing the agency and restoring morale. Lurie emphasized that both the pharmaceutical industry and the public value predictability and stability from the FDA. Disruption in regulatory processes could undermine trust in the agency’s drug reviews and expert advice. Decades of careful procedures for evaluating drugs, biologics, and medical devices have been challenged by the current leadership upheaval. The new rapid approval programs could allow for extremely fast drug reviews, which some critics argue threaten established regulatory standards. “The industry and public rely on consistent FDA oversight,” Lurie said. “Sudden changes and internal disputes risk eroding confidence in the agency.” The recent turbulence at the FDA highlights the delicate balance between innovation in drug approvals and the need for institutional stability. Experts warn that continued internal conflict may damage both the agency’s credibility and the public’s trust in scientific expertise. With leadership decisions still unfolding, the FDA faces the challenge of maintaining its reputation for reliability while navigating internal discord and political pressures.