It has been an eventful week for mRNA vaccine manufacturer Moderna and the US Food and Drug Administration (FDA). On 10 February, the FDA notified Moderna that it would not approve the company’s submission for a new influenza vaccine – a verdict that supposedly saw senior officials overruling recommendations from FDA personnel, a claim that the agency refuted. A week later, the FDA has changed its stance and is now accepting the medication for evaluation.
As Chemistry World columnist Derek Lowe remarked on his blog, such a refusal-to-file process is quite uncommon, but it conveys a message to organizations innovating new therapies – especially vaccines – that the agency is no longer adhering to its established protocols. Moderna had seemingly sought guidance from the FDA on clinical trial designs for its vaccine, following standard practices, and while the agency suggested that the company should also assess performance against a high-dose flu vaccine control for older demographics, it ultimately approved the trial designs – only to later declare them insufficient.
Experts like Gary Nabel, former director of the US National Institutes of Health’s Vaccine Research Center and current chief scientist at Sanofi, who now runs a vaccine and cancer startup, stated to Stat that it establishes a ‘harmful precedent that will jeopardize the future of vaccine development and the leadership of American research’. Similar sentiments resonated throughout industry and academic research.
Thus, while the turnaround is undoubtedly positive news for Moderna, the specter of uncertainty and apprehension will remain. Drug regulation is a multifaceted endeavor, and typically not one that companies (in general) take lightly, given the potential repercussions of even minor errors. In exchange, they anticipate regulators to function along consistent and transparent lines. When senior officials can intervene and – almost single-handedly – override protocols or dismiss evidence-based decision-making, then trust in the regulatory system is compromised.
This principle holds true whether such decisions hinder or facilitate a drug’s advancement through the system, and there have been instances of both in recent years. Approvals of gene therapies for Duchenne muscular dystrophy, as well as the anti-amyloid antibodies for Alzheimer’s disease could be seen as optimistic, and certainly involved significant influence from FDA leaders at the time, for example.
The current administration’s unpredictability, coupled with a clear aversion to vaccines, has the capacity to cause profound damage to future vaccine development. This impact extends beyond the US, as numerous countries with less sophisticated regulatory frameworks heavily depend on FDA rulings to guide their own approvals.