Drug developers see Food and Drug Administration approval as a difficult uphill climb, requiring large investments of resources and time. But when it comes to new drug applications and biologics license applications, it’s usually not the FDA that slows down the process.
The main reason for delays and extensions is that sponsors submit their applications too soon.
That’s our assessment as individuals who have guided drug development and modeling clinical trials and as a former reviewer (J.B.) with the FDA.
The culprit is pressure. We’ve seen drug developers move quickly but without all of the data needed to take them through to approval. If they rush forward, urged on by their various stakeholders, they can experience delays when the FDA requests additional data to fill gaps. This pressure to submit affects the drug approval journey in ways that can be anticipated — and avoided.
The drug development process should benefit patients with safe, effective therapies that are arrived at as quickly as possible. But the FDA is not a consulting company and can grow weary of the unprepared. When a drug developer moves hastily, lacks depth of data, and negotiates over completing studies it should have done, it sends a message to regulators that this is a company developing for profits, not patients.
To move along the approval process with speed — and without haste — we urge developers to take these three key steps:
Don’t cut corners on data collection. When drug companies and biotech startups begin the research journey, they need to gather substantive data with the level of rigor necessary for successful approval. Some, though, wait until proof of concept has been shown and then back-fill gaps that should have been addressed when the drug was first evaluated in humans. Detailed data collection early in development — not only on efficacy and safety but also on labeling, clinical pharmacology, and commercialization — speeds processes later. It’s the equivalent of the carpenter’s “measure twice, cut once” maxim.
Share information as early as possible. When regulators review clinical trial data and other information, they are drinking from the proverbial firehose. Drug developers can make FDA reviewers’ jobs easier by sharing with them early in the process any proprietary technologies or new therapies they are advancing. We counsel shelving hypothetical questions based on assumptions about how data will turn out until data are available to support the questions. This allows the FDA to understand your outcomes and provide informed advice and critical feedback, further speeding the process.
Communicate with regulators. Although FDA regulators provide several avenues for drug developers to obtain advice, not all developers take advantage of them. As the FDA has gotten busier, meetings scheduled before permission to start clinical trials has been granted have become increasingly written-response-only, which are considered final. Furthermore, dealing with the strictures imposed by Covid-19 means that these and other milestone meetings at the end of Phase 1 and 2 trials are now done by teleconference.
Companies should make the most of all of these opportunities and take the time to organize their data and questions carefully and succinctly. Because regulators are managing heavy workloads, a well-organized briefing package that asks the right questions and includes the data necessary for the FDA to provide advice is a vital asset for any development program.
The process can also be improved from the regulators’ side. For example, it’s positive for the process when regulators admit they don’t know what the best endpoint would be since data are limited. Owning uncertainty is constructive; it allows the agency and drug developers to learn together, considering novel endpoints and study designs. The FDA has worked to be more visible and approachable through meetings and workshops, and these public initiatives have helped the agency and drug developers gain mutual understanding of what’s needed for approval.
With deep experience and full access to data and programs, FDA regulators know why drugs succeed and, other than drug developers, they are the only ones who truly understand why clinical trials fail. Based on their knowledge, regulators can make suggestions to a drug developer, but they can’t share specifics.
We believe that being able to better tap into what the FDA has learned about what works and what doesn’t from previous trials would greatly improve and accelerate drug development and approval processes by preventing developers from repeating others’ mistakes. Clearing the FDA to share lessons from previous trials in a confidential, non-specific way would provide a great resource, saving money and lives. If regulators transparently published their rationale for rejecting a new drug application, or published a bi-yearly document explaining why applications were rejected, that would be more beneficial. Sponsors should also be encouraged to publish what they learn from failed trials or programs so others can learn from their experience — for the ultimate benefit of patients — though we understand that many companies may be reluctant to share information, based on competitiveness or proprietary information and other legal concerns.
Until then — though it may seem counterintuitive — drug developers should take time to be thorough early in the process; otherwise, they will pay for it later when they can least afford it. And prioritizing only safety and efficacy data over data on chemistry, manufacturing, and controls; dosing and specific populations; and food effect may ultimately undercut these important program components, which are also essential for approval.
Though seemingly time-consuming, obtaining timely, robust data and communicating early and often with regulators will diminish delays later in development and approval. Clinical trials take place, patients participate, and programs move forward — but if data are not collected and information isn’t shared because companies believe it will slow down approval timelines, they are making the wrong call.
William F. Feehery is CEO of Certara and the former president of DuPont Industrial Biosciences. Julie Bullock is vice president and global head of clinical pharmacology and translational medicine at Certara and former team leader and senior clinical pharmacology reviewer at the FDA.