Karim Mikhail takes over CBER amid a push to rebuild trust and staffing
The FDA’s Center for Biologics Evaluation and Research is entering a new phase under Karim Mikhail, who has moved from acting director to the post on a permanent basis after one of the center’s most unsettled stretches in recent memory. CBER regulates vaccines, gene therapies and other biologic products, so instability at the top has consequences far beyond internal agency politics. Every leadership shift can alter how companies plan development programs, how reviewers approach risk, and how quickly patients reach therapies that depend on a clear regulatory pathway.
Mikhail stepped into a center that had already absorbed successive leadership changes, staff departures and broader morale problems across the agency. He described the first task in blunt operational terms: hire people, restore confidence and get the organization functioning with a steadier rhythm. Those priorities matter because biologics review is not a volume business in the way routine drug regulation can be; the work depends on specialized scientific judgment, continuity of institutional memory and a bench of reviewers who understand complex manufacturing, immunology and clinical evidence.
He said people around him are beginning to feel that the agency is moving back toward normality. The message is less about optics than it is about bandwidth. A biologics center that is short-staffed or distracted cannot easily absorb controversial submissions, rare disease programs or novel platforms such as gene therapy without slowing the pace of review or narrowing the depth of scientific debate.
One sentence captures the near-term challenge: staffing is a regulatory issue, not just a human-resources issue.
Rare disease review demands a different regulatory architecture
Mikhail has placed rare disease reform near the top of his agenda, arguing that the existing framework was not built for very small populations or for diseases marked by substantial heterogeneity. That critique goes to the center of modern rare disease drug development. When a condition affects only a limited number of patients, conventional trial structures can become difficult to execute, and the signal needed to support approval may be buried beneath variability in phenotype, natural history and measurement tools.
His comments align with the FDA’s new Rare Disease Framework Initiative, which aims to speed development of safe and effective therapies through clearer guidance, greater patient engagement, expert collaboration and new scientific approaches. The initiative brings together the FDA’s Rare Disease Innovation Hub, the Office of the Commissioner, CBER and the Center for Drug Evaluation and Research. In practical terms, that means the agency is trying to make the path more predictable for sponsors while still preserving the core requirement that therapies demonstrate meaningful benefit and acceptable safety.
Mikhail framed the goal as a stepwise model in which sponsors understand the milestones needed at each stage of development. That is especially relevant in rare diseases, where a single trial may not answer every question and where development programs often rely on a mixture of natural history data, surrogate endpoints, biomarker work and carefully selected clinical outcomes. A predictable framework can reduce wasted effort without lowering scientific standards.
His position also reflects a broader truth about biologics regulation: the evidence package often has to be assembled from fragments. Small patient counts, variable disease courses and ethical constraints on placebo use can make traditional models less useful. Regulators then have to weigh whether the available data, taken together, are strong enough to support approval and whether postmarketing commitments can responsibly fill remaining gaps.
Public trust now sits beside scientific judgment
Mikhail has made transparency part of the center’s recovery plan. He said he would like the public to hear more of the safety discussions that happen internally at FDA, and he argued that anything the agency can make public should be made public. In an era when vaccine policy, gene therapy and rare disease decisions can quickly become political flashpoints, transparency is not a public-relations flourish. It is part of the evidentiary contract between the agency and the public.
He also expressed optimism about restoring confidence in rare disease decision-making, while acknowledging that the field rarely follows rigid doctrine. Rare diseases often force individualized judgment because the patient populations are so different from one another. Some conditions have rapidly progressive courses, others have uneven natural histories, and many involve endpoints that are clinically meaningful but hard to measure over short time horizons. In that setting, judgment is unavoidable. The challenge is to make the judgment visible, explainable and scientifically grounded.
Public trust depends partly on how the agency handles uncertainty. If regulators explain why a surrogate endpoint is acceptable in one setting, or why a specific safety signal changes the calculus in another, the decision becomes easier to understand even when the answer is difficult. Mikhail’s comments suggest an appetite for a more open style of review, one that does not hide disagreement or uncertainty behind closed doors.
A transparent safety review can be as important as the final approval itself.
Leadership expectations are shifting along with the science
Mikhail also wants the FDA leadership profile to evolve. He described the ideal leader as someone with technical skill and the ability to think ahead about what the field should look like in 2030 and beyond. That is a notable standard for a regulator, because it implies the agency cannot simply react to submitted data. It has to anticipate the next wave of science, whether that means more individualized therapies, more complex biologics or newer ways of generating evidence in small populations.
The timing adds another layer of uncertainty. The agency is still waiting for confirmation of Commissioner nominee Heidi Overton, and Mikhail said he believes she has scientific integrity. Even so, he emphasized that no one at FDA is waiting passively for the political process to resolve itself. The center has to keep working through the pipeline, keep evaluating applications and keep responding to public questions regardless of who occupies the commissioner’s chair.
His comments on vaccine skepticism and public debate were equally direct. He said there is alignment around what the public believes the FDA should do, and he framed the agency’s duty as verification. In other words, questions raised by the public cannot simply be handed off or ignored. For CBER, which sits at the intersection of vaccine regulation, gene therapy oversight and highly contested science, that posture is likely to shape how the center communicates decisions and handles disputes.
What the next phase of CBER will be judged on
Mikhail’s tenure will likely be measured on whether the center can stabilize its workforce, implement the rare disease framework in a way that is scientifically rigorous and restore confidence in the consistency of FDA decision-making. Those are distinct tasks, but they are tightly linked. A stronger staff can support better review. Better review can make rare disease policy more predictable. Better transparency can make controversial decisions more durable.
He described the job as intense rather than stressful, a distinction that fits the scale of the role. Decisions made at CBER can shape development programs for years and affect access for millions of patients who depend on biologics, vaccines and advanced therapies. For now, the center’s direction appears to be away from volatility and toward a more deliberate model of regulation. The remaining question is how quickly that model can be translated into consistent review decisions, especially as rare disease sponsors continue to ask for a framework built for the realities of small, heterogeneous patient populations.