Meeting information package preparation

For the INTERACT meeting, you must include your Meeting Information Package (MIP) together with your request. This package must be no more than 50 pages (average length 20-30 pages) and much less substantial than what is expected for the Pre-IND MIP. Although the content of an INTERACT briefing package is fairly limited, relatively speaking, you must include sufficiently detailed information for the FDA be able to provide substantive feedback on your questions.

Please refer to the guidance below on how to prepare your package using the INTERACT Meeting Request/Meeting Information Package template provided below:

Please refer to CHED-INTERACT-Briefing Package for an example of a briefing package which was developed using the template.

So, what should you include in your MIP?

You should generally include information on Chemistry, Manufacturing, and Controls (CMC), pharmacology/toxicology, clinical information, and any other specific information that will enable the FDA to respond to your questions.

It is important to include detailed questions with the briefing document, which will help the FDA focus on addressing your specific issues. As specified by the Readiness assessment, these questions will be high-level and reflect your early stage of development. According to the FDA guidance, the questions and topics that fall within the scope of the INTERACT meeting include: [2]

• Novel questions for all CBER products in general (i.e., questions where there is no existing guidance or other information in writing you can easily reference from the FDA)

• Choice of appropriate pre-clinical models or necessary toxicology studies

• CMC issues or testing strategies aimed at demonstrating product safety

• Overall advice related to the design of proof-of-concept or other pilot safety/biodistribution studies necessary to support administration of your product in a first-in-human clinical trial

• General recommendations regarding a future first-in-human trial in your target clinical population where the population is novel and there is no prior precedent or guidance

• Recommendations on approach for further development of your product with limited CMC, pharmacology/toxicology, and/or clinical data that were collected outside of a US IND

Some example questions you may consider including in your MIP are:

• Chemistry, Manufacturing and Controls (CMC)

  • Innovative technologies for the qualification of new cell substrates.

  • Product manufacturing (e.g., cell sources, donor eligibility determination for allogenic cellular products and qualification of international donors).

  • Product dependent and manufacturing process dependent reagents, starting materials and critical product components.

  • Qualification of a novel delivery device related to a specific investigational product.

  • Discussion of complex software issues and strategies to support device use in clinical studies.

• Pharmacology/Toxicology

  • Overall advice related to the design of proof-of-concept or other pilot safety/biodistribution studies necessary to support administration of an investigational product in a first-in-human clinical trial.

  • Specific questions on the adequacy of the selected animal models; study design (e.g., endpoints, dose levels, route of administration, dosing regimen); and acceptability of innovative preclinical testing strategies, products and/or delivery modalities.

  • Advice on modification of a preclinical program or study design, as applicable, to ensure judicious use of animals.

You can also provide a high-level overview of the proposed target product profile and an outline of your clinical development plan (e.g., clinical protocol synopsis) so that the FDA can view the CMC and pre-clinical data you provide in the context of the clinical trial and ascertain if the data provided adequately supports the proposed clinical trial plan.

Next, let’s dive into each of the different sections of the INTERACT package and what’s important to note in each of them.

Chemistry, Manufacturing, and Controls (CMC)

In this section you will introduce your product to the FDA by providing a summary of your investigational product and the proposed indication. To simplify the process, consider breaking this out into:

1. A high-level description of your product, manufacturing process, and proposed characterization and lot release tests

2. Your position and justification for your questions

3. References to published information related to your drug, with copies of the publications

You may find that the manufacturing details of your critical material suppliers (e.g., supplier) are proprietary and it may be challenging to provide that information, even at a high level, in the INTERACT package. In this case, we suggest working with those suppliers to understand if a drug master file (DMF) is on file with the FDA (see IND Section: Drug Master File (DMF)) and only providing high-level descriptions, per INTERACT expectations.

Note: Drug master files (DMF) provide the FDA with confidential, detailed information about the facilities, processes, or articles that you may have used in the manufacturing, processing, and storage of your products. For more information on the different types of DMFs and what to include in each, please refer to Drug Master File (DMF) Submission Resources | FDA.

Pharmacology/toxicology

At the INTERACT meeting stage, the main focus of pre-clinical studies is proof-of-concept pharmacology/toxicology conducted in vitro and in vivo with your product. You should provide:

Proof of Concept Studies

A comprehensive summary of all pre-clinical in vitro and in vivo studies conducted thus far using your drug and the results obtained. Don’t forget to include publications relevant to your development program, and copies as well, similar to the CMC section.

Protocol Outlines

In this section, you want to showcase a detailed discussion, with protocol outlines regarding the additional pre-clinical proof-of-concept studies you think you need to conduct to adequately support administration of the intended clinical product in the target patient population. The goal of this meeting is to validate this with the FDA.

At this stage, you do not have to include questions on the acceptability of definitive pre-clinical safety studies – those are more appropriate for the Pre-IND meeting.

Clinical

Since this is early-stage, clinical comments are generally kept at high-level recommendations to guide the overall clinical development program rather than focusing on details of a specific protocol. Please note, it is not uncommon for the FDA to defer to Pre-IND for a discussion on clinical topics.

To prepare you for the Pre-IND and IND submission, you can include:

• Your disease of interest

• The target study population

• Any available natural history information/data on the condition

• Available treatment options for the condition, and

• A brief outline of first-in-human study

Once you’ve submitted the request and package, it’s time to prepare for the actual meeting.