Frequently Asked Questions (FAQs)
What is the right time for a drug developer/sponsor to apply for MIDD?
MIDD approaches can add value throughout drug development; therefore, sponsors/developers can submit a request at any time during development. A drug developer/sponsor can apply for the MIDD Pilot program when they have an active development program (active PIND or IND), meet the eligibility criteria of the program, and have clearly defined drug development issues and the relevant information to support the discussion of MIDD approaches with the Agency. Early engagement is encouraged, and the submission should be timed so that the discussions between sponsors/developers and FDA can be considered and incorporated into development.
Are discussions between a sponsor and the FDA confidential under the MIDD meetings pilot program?
Yes, these discussions are subject to the same FDA regulations governing confidentiality and disclosure that apply to ordinary regulatory submissions outside the MIDD pilot program (e.g., type C meetings). Other FDA pilot programs may have different criteria relating to confidentiality and disclosure as a condition for participation. We plan to disseminate high-level metadata on metrics of the program and lessons learned in the administration of the pilot, but there will be no disclosure of program-specific issues unless deemed appropriate by the sponsor/applicant.
How does the MIDD Meeting Pilot Program differ from FDA’s End of Phase 2a meeting program?
The MIDD pilot program is not limited to the EOP2A milestone. FDA is encouraging early meeting discussions to provide advice on how specific, proposed MIDD approaches can be used in a specific drug development program. Additionally, past practice at the inception of the EOP2A program involved extensive modeling and simulation by FDA staff. FDA staff will not routinely perform extensive modeling and simulation under the MIDD meeting pilot program. This will allow for more focus on the conceptual issues in a drug development program.
Can the drug developer of a new biological entity apply for MIDD with only preclinical data (in vivo and toxicology)?
Yes. For example, first-in-human study design and other relevant drug development questions heavily informed by non-clinical data are within scope of the MIDD meeting pilot program.
Will the meetings be used to approve the specific methods that will be used?
Typically, discussion around specific methods/models will focus on the applicability of the proposed approach to address the specific drug development questions. As with other FDA/applicant meetings, the outcome will be to summarize important discussion points, areas of alignment, clarifications, and action items. In terms of model acceptance, meetings may result in a specific agreement on a model-based approach, but will not likely focus on qualification of a model for broad contexts of use.
Who is among the internal review group that will review and select proposals? How will they choose among them?
The selection committee is comprised of senior staff from both CDER (e.g., the Office of Clinical Pharmacology, Office of Biostatistics, Office of New Drugs, and Office of Regulatory Policy) and CBER. The selection committee will assess the extent to which the submitted proposals 1) meet the eligibility criteria for consideration; and 2) outline a pertinent drug development issue (or issues) for which regulatory input on a model-informed strategy would be important for the development program.
Is the pilot program open to other MIDD applications outside of the stated priorities?
Our initial priorities strategies for dose selection or estimation (e.g., for dose/dosing regimen selection or refinement); clinical trial simulation (e.g., based on drug-trial-disease models to inform the duration of a trial, select appropriate response measures, predict outcomes); and predictive or mechanistic safety evaluation (e.g., use of systems pharmacology/mechanistic models for predicting safety or identifying critical biomarkers of interest). However, as stated in the Federal Register Notice announcing the program (insert link), we welcome submissions related to any relevant MIDD topics (especially those with special emphasis on pharmacological models).
How does the follow-up meeting differ from the initial meeting – i.e., what might FDA and/or the sponsor do in the interim to advance upon the topics discussed at the first meeting?
FDA expects that each meeting will be unique relative to the specific drug development questions and therefore cannot speculate as to what might be needed for each program. As an example, the first meeting may be used to introduce a modeling approach, followed by a period of more in-depth review and/or analysis on the part of FDA or the sponsor, and then a second meeting to provide more specific feedback. FDA and the sponsor may agree to not hold the second meeting. The goal is to foster useful interactions between FDA and sponsors to facilitate the development and application of modeling approaches.
Are there examples of how model risk assessment can be performed?
For an example of model risk assessment in MIDD, see: Kuemmel et al. 2020 [PMID: 31652029].