One of the greatest mistakes that the Sponsor of a 505(b)(2) can make is to have an unsuccessful Pre-IND meeting. Common errors occur at the Pre-IND meeting because Sponsors and CROs that are more familiar with traditional 505(b)(1) drug development programs fail to appreciate the different goals and the impact of a Pre-IND meeting on a 505(b)(2) program.
The goal of a 505(b)(1) Pre-IND meeting is to introduce the FDA to the novel drug, discuss standard toxicology study results, and propose a first-in-human study. In contrast, a properly prepared and conducted 505(b)(2) Pre-IND meeting presents the proposed strategy and the entire development program, including the justification for leveraging existing data in place of required studies. Therefore, the approval strategy presented in the 505(b)(2) Pre-IND meeting is paramount, requiring productive discussion and alignment with the FDA.
We cannot overemphasize that getting FDA feedback on the entire development program at the Pre-IND meeting is the critical path to success in 505(b)(2) drug development. The Pre-IND meeting must be successful.
What Is Pre-IND Meeting Success?
How does Camargo define “successful Pre-IND meeting?” All too often we are approached by companies after their Do-It-Yourself Pre-IND meeting asking us ‘what studies do we need to do?’ They tell me that they had a great Pre-IND meeting, found out their product was ‘likely’ a 505(b)(2) and didn’t get any negative ‘vibes.’ Ouch.
Camargo expects after a Pre-IND meeting that a client will know:
- What studies are needed –the endpoints, measurements, etc. information sufficient for a protocol design (not: a pharmacokinetics study, but what pharmacokinetics study)
- What the studies should cost, how long they should take, what the order should be, what the risks are
In other words, you should come out of a Pre-IND meeting with a solid plan. That is success. Anything less is a failure.
Preparing for a Pre-IND Meeting
A Pre-IND is a Type B meeting, also known as a milestone meeting. The FDA typically only grants one meeting for each milestone such as Pre-IND, End-of-Phase, and Pre-NDA meetings. This makes the conduct and preparation for these meetings critical. The Sponsor determines the questions that it would like the FDA to answer.
An initial version of these questions is sent to the FDA with a meeting request letter that describes the proposed product, including its chemical identity, intended indication, and route of administration. The FDA uses the information in the meeting request to determine whether a meeting will be granted, and if so, which staff will be present. The FDA has the option of granting or denying a meeting, depending on the appropriateness of the questions and the product, or providing written responses in lieu of a meeting.
At Camargo, we believe good preparation for the meeting request is important, as improving the chance of a face-to-face meeting with the FDA is almost always in a Sponsor’s best interest. Having said that, some Divisions provide written responses only for almost all Pre-IND meeting requests.
As outlined in the Draft Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, a response to the meeting request is usually provided within 21 days, and the FDA aims to schedule the meeting within 60 days of receipt of the meeting request letter. However, with increasing workloads, many Divisions are increasingly unable to meet this goal, and the recent hiring freeze at the FDA is unlikely to help the situation.
The Sponsor must submit a meeting package that contains the final version of the questions and background information at least 1 month before the meeting date. Some Divisions request the package even earlier. For a product seeking approval via the 505(b)(2) pathway, the package will need to include the data from sources other than Sponsor studies, with a justification for how and why it can be leveraged to reduce the size of a full development program. The data must be of a standard suitable for the FDA to assess, and the plan to establish a scientific bridge between the drug used in the data and the Sponsor’s product must be clearly demonstrated.
What Happens in a Pre-IND Meeting?
A Pre-IND Meeting usually starts with introductions from the FDA review team, including the Division Director or a designee, and the Sponsors representatives. The project manager at the FDA or the Sponsor may then choose to give an introduction or to proceed straight to the questions.
Typically, the FDA will provide written preliminary responses to the Sponsor’s questions, within a few days or hours of the formal meeting. The Sponsor generally advises the project manager from the FDA prior to the meeting which questions the Sponsor would like to discuss, and in which order. The selected questions and the FDA responses are discussed and clarifications are provided. The goal is to gain FDA agreement firstly upon the most critical aspects of the development plan, and continue through to the most straightforward aspects, within the allocated time (usually 1 hour but as little as 30 minutes for some Divisions).
Dos and Don’ts for a Pre-IND Meeting
From Camargo’s experience of leading 1100+ FDA meetings, here are some important points for getting the most out of your Pre-IND meeting:
- Do leave behind the slide presentation. In most cases, a slide presentation from the CEO takes up valuable time without changing the outcome of a Pre-IND meeting. Sponsor presentations are more typical for a Pre-Submission meeting with the Center for Devices and Radiological Health (CDRH), but not a requirement. Within the Center for Drug Evaluation and Research (CDER), most Divisions do not welcome slide presentations. Go straight to the prepared questions and the discussion of data. You will get more out of your meeting and the FDA will appreciate the concise nature of the agenda.
- Do prioritize carefully. Questions upon which the FDA agrees with your proposed development plan require less discussion, if at all, than questions upon which the FDA does not agree. The Sponsor can determine which questions are addressed and in which order, so it is important to prioritize the questions in order of importance for discussion in the allotted time period.
- Do listen to what the FDA is saying. In many cases, the FDA has a unified opinion on how a study should be conducted or how an issue should be addressed. Think about ways to accommodate what the FDA is trying to communicate. Countless Sponsors pursue their own agenda, despite the FDA advising otherwise, only to end up repeating a study or worse, stalling the entire program indefinitely.
- Do make your point if you have something new to add. In some cases it is okay to push back if you have a logical justification, and the point has not been adequately made in the meeting package, or if additional information has become available. An example of this is when a new issue arises in the meeting, and one of the experts on your team has experience in addressing the issue. But be careful not to continue to push if you have already made your point and the FDA does not agree. The goal is to gain insight into the FDA’s requirements for the program, rather than to reach agreement on every aspect during the meeting.
- Don’t forget to watch the time. You only get an hour (or 30 minutes in some cases), so be mindful of how much time any particular issue is worth in relation to the rest of the agenda. The representative that the Sponsor chooses to lead the meeting should be adept in calling on the subject matter experts to speak when needed, and on ending the discussion when enough has been said. Rather than debating a minor technical detail, know when to move on.
It helps to have a good understanding of what the FDA is expecting, and on which points some negotiation is possible. At Camargo, we lead 3 to 6 Pre-IND meetings per month, with all Divisions at CDER and Pre-Submission meetings at the Center for Devices and Radiological Health (CDRH). Also check out our Camargo Counsel column written by K. Gary Barnette, Ph.D., our Senior Vice President of Scientific and Regulatory Affairs on the importance of getting the Pre-IND meeting right the first time.
To learn more about how to optimize the Pre-IND or Pre-Submission meeting outcome for your product, or to get advice on your drug/device development program, contact us.
Angela Drew, PhD, Product Ideation Consultant, Camargo Pharmaceutical Services
Kristi Norris, PhD, Senior Scientific and Regulatory Manager, Camargo Pharmaceutical Services
Ken Phelps, CEO, Camargo Pharmaceutical Services