Botulinum Toxin Potency Assay using Tissue Chips (BoT PATCh) (UT1, UT2 Clinical Trail Not Allowed) | RFA TR 22 031

BoT PATCh (RFA-TR-22-031) FAQs

What is the BoT PATCh funding opportunity?

BoT PATCh (Botulinum Toxin Potency Assay using Tissue Chips) is an NIH funding opportunity run in partnership with the FDA. It focuses on developing a neuromuscular junction (NMJ) tissue chip-based assay to measure botulinum toxin potency, with the goal of replacing the long-standing LD50 mouse lethality bioassay (often called the mouse lethality bioassay or MLB).

Which agencies are involved in this program?

The program is an NIH initiative (through NCATS) conducted in partnership with the U.S. Food and Drug Administration (FDA). Awardees should expect close interaction with both NIH and FDA staff.

What problem is this program trying to solve?

The program aims to replace animal lethality testing (the LD50 mouse lethality bioassay) used to measure botulinum toxin potency by funding alternative, non-animal approaches that are suitable for regulated use.

What is the LD50 mouse lethality bioassay (MLB) in this context?

In this opportunity, the LD50 mouse lethality bioassay refers to the traditional potency test for botulinum toxins that relies on mouse lethality outcomes. The FOA positions BoT PATCh as a potential stand-alone alternative to this method.

What approach is the FOA funding to replace the mouse lethality bioassay?

The FOA funds new approach methodologies (NAMs) that use neuromuscular junction (NMJ) tissue chip platforms. The intent is to create an assay that directly models botulinum toxin activity at the neuromuscular junction without relying on animal lethality testing.

What is meant by a "tissue chip" or NMJ tissue chip platform?

Within the scope described, an NMJ tissue chip platform is an organ-on-a-chip style system designed to model the neuromuscular junction, enabling potency assessment based on botulinum toxin action at that junction rather than on animal survival endpoints.

Is the goal limited to early research, or does it extend beyond proof-of-concept?

It extends beyond proof-of-concept. The FOA emphasizes development, regulatory qualification, and commercialization. Applicants are expected to plan for rigor, reproducibility, standardization, and transferability across labs to support regulatory acceptance.

What does it mean that BoT PATCh should become a Drug Development Tool (DDT)?

The FOA highlights establishing BoT PATCh as a Drug Development Tool, meaning the assay is expected to move through evidence-building and documentation steps needed for regulatory qualification, not just demonstrate scientific feasibility.

Does the program expect the new method to be a stand-alone replacement or a supplemental method?

The FOA emphasizes positioning BoT PATCh as a stand-alone replacement for the mouse lethality bioassay, rather than a secondary or supplemental readout. This implies high expectations for robustness and validation.

What kind of federal funding mechanism is used?

This opportunity uses STTR cooperative agreement mechanisms, specifically UT1 and UT2.

Why does the cooperative agreement structure matter?

A cooperative agreement signals substantial, hands-on involvement from government partners. The FOA indicates NIH (through NCATS) and FDA intend to collaborate closely with awardees to coordinate scientific, technical, and regulatory activities so the deliverable is practical for regulated settings.

Are clinical trials allowed under this FOA?

No. The FOA explicitly states that clinical trials are not allowed.

Who is eligible to apply?

Eligibility is limited to U.S.-based applicants. The opportunity is structured as an STTR-focused small business program, meaning eligible applicants are small business concerns that typically partner with a research institution as required under STTR rules.

Are foreign (non-U.S.) organizations eligible to apply?

No. Non-domestic (non-U.S.) entities (foreign institutions) are not eligible to apply.

Can a U.S. organization include non-U.S. components in the project?

No. Non-domestic components of U.S. organizations are also not eligible under the opportunity as described.

What kinds of activities are NIH and FDA expected to collaborate on with awardees?

The FOA indicates NIH and FDA staff will work with awardees to coordinate scientific, technical, and regulatory activities, including developing and implementing a final validation plan for the proposed alternative method.

What does the FOA suggest about validation expectations?

The FOA points toward a structured path to validation, including agreement on performance characteristics, study design, controls, qualification datasets, and clear criteria for success tied to replacing the animal assay.

What characteristics are implied for regulatory acceptance?

The FOA implies expectations around rigor and reproducibility, robustness, standardization, transferability across labs, and a validation strategy that can withstand regulatory scrutiny for the intended context of use.

What is the intended end product of the funded work?

The intended end product is a standardized, commercially viable, regulator-acceptable NMJ tissue chip-based potency assay for botulinum toxins that can realistically be adopted in regulated drug development and quality control settings.

What is the opportunity number and name?

The opportunity is RFA-TR-22-031, titled "The Botulinum Toxin Potency Assay using Tissue Chips (BoT PATCh)."

How is the opportunity categorized?

It is categorized as discretionary funding, uses a cooperative agreement funding instrument, and falls under the health funding activity category.

What CFDA numbers are associated with this opportunity?

The CFDA numbers listed are 93.350 and 93.853.

When was this opportunity posted?

The posting (creation) date listed is 2022-09-19.

What was the original closing date?

The original closing date listed was 2023-08-21.