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At-Home Minimally Invasive Tacrolimus Plasma Level Monitoring Device



OBJECTIVE: To develop an at-home minimally invasive test that would allow transplant patients to monitor plasma levels of the immunosuppressant tacrolimus (and other transplant associated therapeutic drugs) without the burden and cost of frequent visits to a clinical setting. 

DESCRIPTION: Vascularized composite allotransplantation (VCA) is becoming more common for the replacement of severely damaged tissues greatly improving the lives of injured Service Members to support medical/health readiness. Like solid organ (kidney, liver, heart, small bowel, pancreas, lung, trachea, skin, cornea, etc.) or bone marrow transplantation, monitoring the levels of therapeutic drugs is critical for VCA. The safety and efficacy of immunosuppressive drugs is particularly sensitive to proper maintenance of drug plasma levels. The most commonly used immunosuppressant drug for transplantations is tacrolimus (FK506). Tacrolimus and other immunosuppressant drugs have a narrow therapeutic window. Insufficient plasma concentrations of tacrolimus can lead to tissue/organ rejection and high plasma concentrations can lead to toxicity. Additionally, immunosuppressants suffer from high inter-individual pharmacokinetic and pharmacogenetic variability and food and drug interactions. These factors make accurate and frequent monitoring of tacrolimus concentrations critical. Current monitoring requires patients to make frequent visits to clinical settings placing a burden on the patient and the health care system. An at-home minimally invasive test that would allow transplant patients to monitor plasma levels of immunosuppressants may improve clinical outcomes, improve patient compliance and greatly improve the quality of life of transplant patients. 

PHASE I: In the Phase I effort, an innovative device to monitor plasma levels of immunosuppressants will be conceptualized and designed. Phase I efforts can support early concept work (i.e. in vitro studies), or efforts necessary to support a regulatory submission, which do not include animal or human studies. Proposed technologies should be formulated, and the fabrication or production procedures should be developed for a representative device. Specific milestones for the device should include the following: • accurate and reliable measurement of drug concentrations from small volumes • amount of blood needed for each test • how easy it is to use – the device should be useable by a non-expert • pain associated with using the product – the pain of taking the sample should be equivalent to a standard pin-prick glucose test • testing speed – results should be available within minutes • overall size – the device should be easily transportable by hand • ability to store test results in memory • likelihood of interferences 

PHASE II: In the Phase II effort, a prototype technology should be fabricated and demonstrated. The performance of the technology should be fully evaluated in terms of test accuracy and reliability, ease of user control and readability. Phase II results should demonstrate understanding of requirements to successfully enter Phase III, including how Phase II testing and validation will support a regulatory submission. Phase II studies may include animal or human studies, portions of effort associated with the same, or work necessary to support a regulatory submission which does not involve animal or human use, to include, but not limited to: manufacturing development, qualification, packaging, stability, or sterility studies, etc. While syngeneic animals are fine for proof of principal, because of the differences in pharmacokinetic and pharmacogenetics encountered in human populations, definitive efficacy animal studies on outbred animals are preferred in order to capture these differences. Additional parameters to be considered are cost of the meter and any test strips used, technical support provided by the manufacturer and other special features such as automatic timing, error codes, large display screen, or spoken instructions or results. The researcher shall also describe in detail the transition plan for the Phase III effort. As part of the phase II effort, the performer is expected to develop a regulatory strategy to achieve FDA clearance for the new technology. Interactions with the FDA regarding the device classification and an Investigational Device Exemption (IDE), as appropriate, should be initiated. Essential design and development documentation to support FDA clearance, as described in the Quality System Regulation (21 CFR 820.30), should be capture including but not limited to design planning, input, output, review, verification, validation, transfer, changes, and a design history file. The project needs to deliver theoretical/experimental results that provide evidence of efficacy in animal models. The studies should be designed to support an application for FDA clearance. 

PHASE III: During phase III, it is envisioned that requirements to support an application for device clearance from the FDA should be completed. As part of that, scalability, repeatability and reliability of the proposed technology should be demonstrated. Devices should be fabricated using standard fabrication technologies and reliability. The proposal should include a commercialization or technology transition plan for the product that demonstrates how these requirements will be addressed. They include: 1) identifying a relevant patient population for clinical testing to evaluate safety and efficacy and 2) GMP manufacturing sufficient materials for evaluation. The small business should also provide a strategy to secure additional funding from non-SBIR government sources and /or the private sector to support these efforts. This technology monitoring device is envisioned for use with a diverse transplant patient population. As such, the technology should have both military and civilian applications. Procurement of such technology would be at the discretion of the medical treatment facility and prescribed to patients as needed. 


1: Fung AWS, Knauer MJ, Blasutig IM, Colantonio DA, Kulasingam V., 2017, Evaluation of electrochemiluminescence immunoassays for immunosuppressive drugs on the Roche cobas e411 analyzer. Version 2. F1000Res. 2017 Oct 13 [revised 2017 Jan 1]

2: 6:1832.

3:  Kaufman CL, Ouseph R, Marvin MR, Manon-Matos Y, Blair B, Kutz JE., 2013, Monitoring and long-term outcomes in vascularized composite allotransplantation. Curr Opin Organ Transplant. 2013 Dec

4: 18(6):652-8.

KEYWORDS: Immunosuppressant, Vascularized Composite Allotransplantation, Tacrolimus, Readiness 


Tony Gover 

(301) 619-9560 

Lloyd Rose 

(301) 619-8133 

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