One of the most important aspects of any drug development program is the stream of interactions with regulatory authorities like the US Food and Drug Administration (FDA). These interactions can take many forms, from formal submissions to phone calls, face-to-face meetings, or emails. In order to facilitate these interactions and ensure efficient communication between the sponsor (or their representatives) and the FDA, the FDA has published a guidance titled, Best Practices for Communication Between IND Sponsors and FDA During Drug Development.
In this post, we will review some of these best practices, along with valuable lessons taken from our own experience with the FDA.
Roles and Responsibilities for the FDA and Sponsor
Before we discuss communication strategies, it is probably helpful to step back for a moment and think about the FDA’s worldview regarding sponsor vs. FDA responsibilities.
Sponsor Roles: As might be expected, the sponsor’s primary role is to manage the drug development program. This role includes not only overseeing the necessary nonclinical and clinical studies and various quality and manufacturing aspects of the development program but also taking leadership on the regulatory side of things.
For example, the sponsor is responsible for determining the nature and timing of regulatory submissions, whether it is the initial Investigational New Drug (IND) application, IND updates, the marketing application (e.g., NDA, BLA), or some other submission. These submissions should be well-organized and complete, with failure on this point potentially resulting in undesirable consequences that, depending upon the type of submission, may include things like clinical hold, review delays, or rejection of the submission.
In addition to regulatory submissions, the sponsor is responsible for soliciting input from the FDA. This could include anything from quick communications with the FDA regulatory project manager to a request for a special protocol assessment to participation in formal meetings with the FDA.
FDA Roles: While the FDA can and should be seen as a partner in the drug development process, their primary function must always be viewed through the lens of regulatory compliance and patient safety. To this end, the FDA sees two of its primary responsibilities as ensuring the safety and rights of clinical trial participants and determining whether the quality of the scientific evaluations during Phases 2 and 3 is sufficient to permit evaluation of the drug’s safety and effectiveness. As regulators, the FDA is responsible for enforcing statutory requirements, reviewing IND submissions, and taking regulatory action (e.g., clinical hold) when appropriate.
As noted above, the FDA is also a resource for sponsors to get advice on various aspects of their programs (generally provided through formal meetings). This advice may cover a wide range of topics from regulatory issues to clinical trial design, risk evaluation and mitigation, nonclinical studies, product quality issues, and many others.
In addition to these sponsor-facing roles, the FDA is responsible for promoting regulatory science through release of guidance documents, holding workshops, publishing in journals, and so forth. As anyone who has referenced an FDA guidance document or attended one of the FDA’s workshops or webinars can attest, this function is vital for promoting efficiency and regulatory understanding within the drug development industry.
Dos and Don’ts for Effective Communication
The FDA/sponsor relationship is like any other relationship – the key to success lies in effective communication. Here we list some of the key considerations for keeping the communications lines as open and productive as possible.
- Do contact the Regulatory Project Manager (RPM) assigned to your program. The review division RPM will be your primary contact for nearly everything, whether it’s to ask a question, coordinate a meeting, or resolve some other issue. The review division RPM is a co-leader of the FDA review team and will be one of the most well-versed people at the FDA on your particular drug program and its regulatory history.
- Do NOT contact reviewers. Direct communication with reviewers is strongly discouraged. This is important for a number of reasons, not the least of which is that any advice so obtained has not been assessed by the full review team, may not represent FDA’s thinking on the topic, and may not be properly documented.
- Do NOT contact the FDA unless you are authorized to do so. This applies most often to consultants working on behalf of clients. Authorization to act in this capacity must be in writing from the sponsor before any contact is made.
- Do respect the chain of command. If there is a problem with receiving feedback from your assigned RPM, your first level of recourse includes contacting the RPM’s direct supervisor (e.g., the review division’s chief of the project management staff (CPMS) or branch chief). If problems persist, then the issue may be elevated to the review team supervisor or division/office management.
- Do establish a communication strategy. This can be implemented at any time but the most benefit is gleaned when done early in development. These strategies are generally informal agreements but in certain cases it may be appropriate to elevate these to formal communication plans.
- Do set up a secure email. Email will likely be the most commonly used form of communication during the development program. A secure email is necessary for any correspondence containing potentially sensitive or otherwise confidential information. Secure emails can be established by contacting FDA’s Office of Information Management and Technology (OIMT; SecureEmail@fda.hhs.gov). Note that emails are not substitutes for formal submissions, which must be made (with few exceptions) via the FDA’s Electronic Submissions Gateway.
- Do follow-up phone calls with a written communication to the RPM. This is especially critical for anything more than very general or administrative questions or if any follow-up information has been requested by the FDA. Neither phone calls nor follow-up written correspondence is a substitute for a formal submission.
- Do enlist the help of an experienced consultant. Whether you have lots of experience interacting with the FDA or none at all, receiving input from the right consulting group can help increase your chances of success. Nuventra is proud of its track record of successful FDA interactions and the breadth and depth of our consultants’ experience across a wide range of drug programs, at all stages of development.
Timing is Everything
When it comes to timing, keep in mind that FDA resources are limited, which means that while the FDA strives to provide timely responses, you may not get immediate feedback. In general, safety-related inquiries get priority. Complex question(s) or inquiries concerning complex products (e.g., novel or combination products) may also require more time to respond. For this reason, it is recommended to pose complex questions as part of a meeting request or as a formal submission.
While some response times are mandated by statute (e.g., initial IND, complete response to clinical hold), many are not. In cases where there is no mandated response time, the FDA should provide an estimate of timing as part of their correspondence.
As with any relationship, remember that communication is a two-way street. As such, the burden of timely responses does not fall solely on the FDA. This means that sponsors should promptly acknowledge receipt of FDA correspondence and provide the FDA with an estimated response time. If the FDA provides a due date/time for the sponsor to respond to an information request, then the sponsor should make every attempt to submit the requested information by the appointed time. In (the hopefully rare) cases when the FDA’s deadlines cannot be met, the sponsor should alert the FDA as soon as possible with a revised estimate for submission. Sponsors should be aware, however, that delayed responses may result in undesirable and sometimes costly consequences (e.g., clinical hold, delayed review).
The FDA has provided formal guidance on best practices for communication between sponsors and the FDA. This guidance provides a number of helpful strategies for streamlining communication and promoting efficiency.
In addition to what we have covered in this post, there are other nuances to interacting with the FDA that are not addressed in any guidance document, but their importance should not be underestimated. If you have a drug development program that could benefit from the experience that comes from many years of successful interactions with the FDA, please contact one of our senior consultants. We would be happy to show you how to ensure a smooth development process and prevent unnecessary and costly delays.