Mark Lane is vice president of Development Consulting and Scientific Affairs at PharmaLex.

Mark Lane

Think of regulators as allies. They share the goal of bringing life changing medications to the patients that need them and are partners in development. Meetings with regulators should, therefore, not be seen as discussions to avoid or as hurdles to overcome but as opportunities for sharing critical information and gaining alignment.

Aside from gaining the regulatory agency’s feedback on your development programme, such meetings enable drug developers to build strong relationships that facilitate moving a drug to market. Through such meetings, it is possible to gain a better understanding of what regulators need and when they need it, which increases the ability to reach an aligned position.

In this article, the top 10 considerations for meetings with regulators are detailed.

1. What are the various types of meetings that sponsors can expect to have with regulators?

The United States Food and Drug Administration (FDA) has four basic types of regulatory meetings for new chemical entities: Type A is generally when a programme is stalled; Type B is typically an end-of-phase or key milestone meeting; Type C is designed to capture everything else needed for a development not included in the other meeting types and includes meetings to facilitate early consultations on the use of a biomarker as a new surrogate endpoint that has never been previously used as the primary basis for product approval in the proposed context of use. Type D is a newer meeting designed to address a narrow spectrum of issues in a shorter time frame. FDA expects the sponsor to present a position on their development strategy, to which FDA can provide input.

When establishing a clinical trial in a targeted country in Europe, meetings with regulators might be held at the national level, whereas scientific advice meetings would be held with the European Medicines Agency (EMA). Innovator companies seeking to navigate within EMA can take advantage of Innovation Task Force (ITF) briefing meetings.

2. What are some of the key differences between FDA meetings and those with EMA or national authorities?

In Europe, requests for meetings with EMA are submitted via a defined calendar, whereas meetings can be requested at any time with FDA. In the United States, the type of meeting a company/drug developer is interested in is pre-defined based on the meeting types described earlier and all requests for meetings, briefing documents, and other collateral are submitted based on specific schedules outlined in the FDA guidance. The meeting request and associated briefing book describe the drug under development, the status of the programme, the questions addressed to FDA and an associated company position and rationale for the position.

In contrast, the EMA scientific advice process takes the form of questions posed by the product developer, along with the way the company plans to develop the product and its potential solutions. EMA offers its recommendations on the proposals and, depending on the complexity of the questions, may request a meeting with the developer. Another difference is that there is no charge for meetings with FDA whereas in Europe, depending on the status of the developer, there may be a fee.

3. Are there timelines that regulators must meet when responding to a company request?

There is significant variation within FDA, depending on the type of meeting requested. This includes when the agency must respond to the request, when the meeting has to be scheduled, the timing of the meeting, and the delivery of the briefing package to the agency. It’s not just one process.

In Europe, timings also vary according to the nature of the meeting requested and the complexity of the questions. For both agencies, relevant laws and regulations allow for flexibility around scheduling meetings, so it’s important to properly position the request so that the agency understands the urgency of the matter.

4. What are common mistakes that companies might make regarding agency meetings?

Underpreparing. A strategy must be well thought out and finalized, and the briefing book must be in a mature stage before submitting a meeting request. This means having a clear understanding of the objective of the meeting requested and preparing accordingly. Invariably the content of the specific questions will change somewhat based on the details of the company position and rationale. EMA, for example, will respond to specific questions on the development plan about a specific medicine, so a target product profile is important when preparing a briefing package. It is also critical to have a fallback position that will advance the programme in the event FDA does not align with the company position. This makes proper preparation key, so rehearsals and clearly defined roles and responsibilities for each team member are recommended.

5. What are the key points to remember?

The regulatory agency should be viewed as a partner, and it is recommended for the company/drug developer to become familiar with how the agency might view the development programme before a meeting is requested. The agency is focused on safety and efficacy, so may have a different perspective to company clinicians or key opinion leaders—try to get on the same page before the meeting. Furthermore, assume that the agency has a broader view on the matter and may have information that is not openly accessible, such as other sponsors’ programmes. It is essential to have the right subject matter experts in these meetings. For example, experts in preclinical models for early-stage meetings versus clinical experts at later phases of development.

6. Are there tips on how to develop a plan and timeline for meeting with regulators in different regions?

FDA and EMA do have an option for obtaining joint advice. Of course, the advantage is obtaining the view of both agencies at or nearly at the same time. However, this does not afford the possibility of adapting the questions or, perhaps most importantly, the company position and rationale for meeting with additional agencies based on the feedback from the first agency. Treatment guidelines, regulatory guidance, and precedence often differ, for example, between FDA and EMA. Meeting with one first before meeting with the other likely strengthens the company position and increases the likelihood of gaining alignment.

7. Are there particular schemes or designations in the US to consider?

FDA has numerous special designation programmes that are designed to assist sponsors who are developing products that are innovative and/or hold promise in certain disease areas. These programmes vary in their requirements and benefit to the sponsor, so careful consideration of the suitability of each designation is critical.

8. Are there also particular schemes in Europe that should be considered?

In addition to the orphan drug designation, EMA’s Priority Medicines scheme (PRIME) is designed to enhance the support of drugs that target an unmet need. The scheme enables companies to build a close relationship with EMA, with continuous support dialogue. However, the eligibility criteria for this scheme are strict, with only about a quarter of applicants being successful.

9. What should be done to keep to timelines set for meetings with regulators?

It is critical that the sponsor or their service provider designate a project manager (PM) who ensures that the team adheres to timelines built in for all stages. The PM also serves as point of contact for their counterpart at the agency. Have a clear understanding of questions and goals before requests for meetings with agencies are submitted. Agencies expect information to be delivered when they ask for it, so, prior to requesting a meeting, the project should be at the refining stage, not starting the package from scratch.

10. What is different about FDA’s Type D meetings?

This is a new meeting type that gives companies the opportunity to address more focused issues in a shorter timeline than Types A, B, and C. For example, if there is a follow-up question from a previous meeting with the regulator, or if there is a narrow issue that requires agency input, and there are only a limited number of questions, a Type D meeting can be requested. The benefit of these meetings is the timelines generally result in answers quicker than Type B or C meetings.

When referring to this article, please cite it as Lane, M. Top 10 Considerations when Meeting with Regulators. 

Articles

Preparation is essential for regulatory meetings—it not only crystallizes what is needed from the regulators, it helps them better understand the development programme and potential challenges.  