FDA Communications Through the Drug Development Lifecycle
As a drug makes its way through the development lifecycle, one of the most important relationships for a sponsor to maintain is with the Food and Drug Administration (FDA).
The FDA is responsible for protecting public safety and public health. Collaborating with sponsors to review and approve new chemical entities, the FDA’s main goals are to ensure the therapy’s safety and efficacy by reviewing the submitted data and providing scientific feedback to help usher the drug forward through approval, including negotiating a final label.
Interacting with the FDA
During the course of drug development, the FDA will grant at least three statutory meetings, including: a pre-investigational new drug (IND) meeting, a meeting at the end of Phase II, and a pre-new drug application (NDA) meeting. While these are three distinct meetings, sponsors may interact with the FDA otherwise on an ad-hoc basis if there is a need.
At each meeting, sponsors have the opportunity to present their program to the FDA, discuss certain issues they may have in mind, and reach an agreement on the proposed clinical plan and regulatory strategy moving forward. The FDA typically allots one hour per meeting, and there are many moving parts. It’s up to the sponsor to pay attention, hear exactly what is said, and to walk away with a sense of clarity. Transparency, scientific integrity, and credibility are of the utmost importance. Both the sponsor and the FDA should understand how the sponsor plans to proceed with the given advice.
Preparing to Meet the FDA
While sponsors will communicate with the FDA throughout a protocol’s lifecycle, being prepared for each meeting will yield great results. Completing a gap analysis beforehand helps sponsors see the bigger picture of the trial at hand – what early protocols will look like in Phase I, as well as the program all the way to approval. For rare disease trials, it’s especially critical to view the trial at large.
Since time with the FDA is finite, nothing is more important than clarity, transparency, and scientific credibility. Especially during the first meeting, sponsors are trying to build credibility with the FDA so the partnership turns into a collaboration. The smoother these meetings go, the better the collaboration between the sponsor and FDA.
When preparing for a pre-IND meeting, sponsors must first submit a letter to the FDA requesting the meeting. The letter should contain itemized questions for the FDA to review and discuss. From there, the FDA will normally set up a meeting 60 days after the initial request. When the meeting is 30 days out, the sponsor needs to submit a briefing document, reiterating the questions and giving scientific detail for each issue discussed. The FDA will meet beforehand to reach an internal agreement before meeting with the sponsor, and to provide the sponsor with the remaining outstanding issues needing further discussion or clarification. This meeting beforehand becomes the basis for an in-person discussion with the sponsor. At the meeting itself, sponsors can focus on the components the FDA might not have addressed completely or at all.
A key aspect of a pre-IND meeting is manufacturing – and if done incorrectly, sponsors risk encountering a refusal to file or delayed approval. An efficient, regulatory strategy needs to include a clinical component and a chemistry, manufacturing, and controls (CMC) component, and both need to be carefully addressed with the FDA for a successful journey to approval.
End of Phase II Meeting
At the end of a Phase II study, sponsors will once again meet formally with the FDA. The purpose of this meeting is to discuss the end of Phase II results, as well as the final design of Phase III. Discussing and agreeing upon the dosage amount is important before initiating a large Phase III program. Sponsors must include what Phase III will look like, and identify any potential adverse events (AE) there may be, efficacy, studies, etc.
During a study, sponsors may generate unexpected data usually stemming from a safety issue. If that is the case, sponsors need to pause the study and communicate with the FDA. It’s not uncommon for the FDA to want to learn more, resulting in possibly putting a study on clinical hold.
The final formal meeting sponsors will have with the FDA is the pre-NDA meeting. Typically scheduled four to six months ahead of a formal submission, this meeting is considered to be an opportunity for the sponsor to talk about the following at a high level:
- Program results
- Location of results within the NDA
- Addressing any issues raised in the development program
- Follow up on any issues raised during the end of Phase II meeting
This meeting allows the FDA to resource plan with regard to review the program and to understand when the application is coming in itself. This is also a time for sponsors to ask questions about data analysis, integrated summaries for efficacy, or anything else relating to the application formatting. Similar to the pre-IND meeting and end of Phase II meeting, sponsors will have to submit material prior to the meeting for the FDA to prepare and review.
Who Goes to FDA Meetings?
Regardless of an organization’s size, key functional development staff for the protocol will attend, including:
- Regulatory strategist
- Clinical expert
- Clinical Pharmacologist
- CMC expert
- Pre-clinical toxicology expert
If a sponsor is presenting on a rare disease trial, the entire team could benefit from an outside expert to attend as well.
Similarly, the FDA will bring key staff to the meeting, including:
- Medical reviewer
- Clinical Pharmacologist
Ultimately, through each of these meetings, the FDA is there to guide sponsors on how to move forward with their program. It’s imperative for sponsors to leave each meeting understanding the FDA’s guidance and how it impacts their program, including any adjustments needed to take place in order to move forward and conduct successful clinical research.
While the FDA provides guidance to sponsors, there are nuances to effective communication derived from experience. This blog series presents an experience-based review of best practices for FDA communication across pivotal milestones in the drug development lifecycle, diving deeper into each formal meeting between the two entities.