Pre-IND FDA Meeting Guidance

Introduction

Pre-IND meetings with the FDA represent a valuable source of insight and feedback for any investigational new drug (IND) applicant. These optional meetings offer many benefits, but it is important to understand the application requirements, timeline, and meeting format in order to obtain the most benefit from these opportunities.

Refresher: What is an IND?

IND stands for investigational new drug, and is an application submitted to the FDA which approves a drug for use in clinical research studies involving human subjects (more information here)

What is the FDA’s Pre-IND Consultation Program?

Developed in 1988 by the FDA’s Office of Infectious Diseases (OID), the Pre-Investigational New Drug (Pre-IND) Consultation Program is an initiative that facilitates clinical research by improving communication between all relevant stakeholders and offering the drug developer or trial sponsor feedback directly from the FDA prior to submitting the IND application and/or conducting preclinical investigations.

The pre-IND meeting serves as the first formal contact between a potential IND applicant and the FDA, and gives applicants a chance to discuss their proposed drug, research methodology, and specific questions with an FDA representative.

While attending a pre-IND meeting is not compulsory, it is a free service offered by the FDA and has several benefits to sponsors, including:

• Building a relationship with the FDA
• Better understanding FDA recommendations and regulations
• Gaining initial agreements on critical aspects of the clinical research
• Gaining insight into building a complete IND application

Sponsors can use the information gained through a pre-IND meeting to improve their IND application, so that it is hopefully subject to fewer change requests from the FDA. This can potentially decrease the clinical development time by several years, further saving the sponsor significant amounts of both time and money.[1]

Pre-IND FDA meeting types

There are three types of pre IND meetings with the FDA:

• Type A Meeting: These meetings are for facilitating a stalled drug development program to address safety concerns or help it move forward.
• Type B Meeting: FDA meetings in this category include pre-IND meetings, IND applications, pre-new drug applications (pre-NDAs), pre-biologics license applications (pre-BLAs), post-action meetings, and end-of-phase (EOP) meetings with the FDA.
• Type C Meeting: FDA meetings other than Type A, Type B, or Type B (EOP). This category includes meetings for preliminary discussions on using certain biomarkers never used before in a proposed research plan.

In which cases is a pre-IND meeting particularly important?

Pre-IND meetings are particularly important for an IND submission for a drug/research that has certain characteristics such as:

• The novel drug is experimental and unapproved by the FDA
• The novel drug has a new molecular formulation
• The novel drug is a proposed treatment for a life-threatening or serious condition
• The novel drug has toxicological, pharmacological, or other safety concerns
• An FDA-approved drug is being used for an unapproved indication
• There are no current guidelines or documentation for the proposed research methodology
• The clinical research is targeted at pediatric patients

Pre-IND meeting timeline

A Pre-IND meeting falls under the jurisdiction of two main divisions of the FDA, depending on the drug:

• The CBER for biological drugs. Meetings are held 1 year before the IND submission, and should be held before toxicology studies.
• The CDER for small molecule drugs. Meetings are taken 6 months before the IND submission and can be held after one or more toxicology studies.

The general timeline for a Pre-IND meeting is given below, although this varies depending on the type of meeting (type A, B, or C)[2]:

FDA’s Response to Pre-IND meeting request: 21 days after receiving a request. This response will either grant or deny a meeting. If denied, the FDA will provide a reason.

Scheduling of the meeting: The date and time will be given within 60 days of receiving the request.

Submission of Pre-IND package: Must be sent 30 days before the scheduled meeting date.

FDA’s preliminary answers to questions in the package: Within 2 days of the scheduled meeting. Applies to teleconference or videoconference meetings.

Applicant’s response to FDA’s answers to questions: Within 24 hours of the scheduled meeting. Applies to teleconference or videoconference meetings.

Pre-IND meeting time: 60 minutes

FDA provides minutes of the meeting: Within 30 days after the meeting is held.

It is important to note that if the FDA’s preliminary answers to the questions in the Pre-IND packet are sufficient and no additional information is needed, the scheduled meeting can be canceled. This initial response would thus become the final feedback of the meeting.

Requesting a Pre-IND meeting

If you are requesting a Pre-IND meeting for the first time, you need to get a PIND number 30 days before sending the meeting request by contacting the relevant FDA division. Contact options include:

• Emailing the CBER
• Emailing the CDER
• Via the CDER NextGen Portal

A Pre-IND application has two parts: the written Pre-IND request and a follow up with the Pre-IND package when a Pre-IND meeting is granted.

1. Request the meeting: Pre-IND submission checklist

A Pre-IND meeting request is emailed to CBER or CDER with the relevant subdivision in cc. In this request, you must include the following information:

• The PIND number
• The known and chemical name of the drug with its structure
• The reason for the drug development
• The specific type of FDA meeting request [For a Pre-IND, it is Type B]
• The Pre-IND meeting format [WRO, in-person, videoconference, teleconference]
• A list of potential dates and times you are available for a meeting
• The objective and agenda of the meeting
• A list of questions, grouped by disciplines, so relevant FDA personnel can be present for the meeting
• A list of the people who will attend the meeting from the sponsor’s side, along with their titles, organizations, and affiliations. This includes interpreters and consultants.
• The date the pre-IND briefing packet will be delivered

2. Pre-IND Briefing Package

If the meeting is granted, a Pre-IND briefing package must be sent no later than 30 days before the meeting date. This comprehensive packet includes the same information as the request letter (as given above), in addition to the following additional elements:

• Chemical properties and details of the drug
• Documentation of the drug’s (and placebo, if applicable) manufacturing and controls, characteristics, release assays, and analytical methods
• Development plan for the clinical trial
• In vitro and In vivo pharmacology studies
• Toxicology studies (if available)
• Nonclinical studies
• Prior clinical research for the proposed indication (if available)
• Information about the medical condition or disease being prevented or treated
• Standard care options
• The medical rationale for the novel drug or new indication

Note that the Pre-IND package is not limited to the items listed above, and supplementary information can be added if it is particularly relevant to your Pre-IND meeting.

Pre-IND FDA meeting guidance

With only one hour available for the meeting, it is vital that you and your attendees are well-prepared and focused. Some FDA meeting guidance to keep in mind:

1. Know the science and position of your research, as your impression on the FDA will be defined by this first meeting

2. Create an agenda and formally rehearse questions before the meeting

3. Assign roles to the attendees, for example:

• A primary voice to lead the meeting
• A secondary voice to ask scientific questions
• Someone to take meeting notes

4. Answer questions from the FDA succinctly and transparently

5. Stay on topic and only ask the questions you have submitted with your Pre-IND meeting request. It is important to know that pre IND meetings are not open-dialogue sessions.

6. There may be more people than you expect on the FDA’s side of the meeting, but that is not a matter of concern. Pre IND meetings are discussions, not a review or investigation.

Conclusion

Submitting an IND in clinical trials is a daunting task, especially for sponsors or investigators who do not have prior experience, which is why it may be worth the time to request a Pre-IND meeting. Using the FDA’s early feedback, you can optimize your drug development and preclinical research plan to set yourself up for IND approval, potentially reducing time to eventual FDA approval of your new drug by years.