Description:
Summary
Red blood cell (RBC) products for transfusion undergo metabolic and physical changes in both the cellular and plasma fractions during storage (RBCs can be stored up to 42 days currently) which may be associated with non-infectious risks and reduced tissue oxygenation capacity. The changes that occur during storage have been referred to in the literature as the RBCs “storage lesion”. Many of these changes have been characterized and include increasing levels of microparticles and potassium; free hemoglobin release; decrease in pH, adenosine triphosphate, and 2,3-diphosphoglycerate; loss of RBC membrane flexibility; and changes in enzymatic functionality resulting in a loss of nitric oxide (NO) signaling. Current research suggests that the storage lesion may result in extravascular hemolysis and inflammation, vasoconstriction, and potentially suboptimal tissue oxygenation. Many retrospective and prospective studies, including a recent meta-analysis of 21 studies, have demonstrated that the transfusion of RBC units which have been stored for longer periods (up to 42 days) appears to be associated with increased recipient morbidity and mortality; but these associations may be confounded by severity of illness. Two large blinded, multi-center randomized trials are currently underway in the United States and in Canada to determine if “younger” vs. “older” or “standard age” blood is equally safe and effective in complex cardiovascular surgery and ICU patients, respectively, but the results of these studies will not be known for several years.
While it is unclear at this stage whether the RBC storage lesion results in serious adverse clinical outcomes in transfusion recipients, it would seem biologically plausible that a reduction in the number of potentially toxic elements in RBC supernatants, as well as an increase in the concentration of well-preserved RBCs, would be beneficial in many ways. These potential benefits could include 1) improved effectiveness of RBC products; 2) markedly reduced adverse events; and 3) optimal tissue oxygenation by fully functioning RBCs. Developing improved blood bank storage and transfusion processes and practices to mitigate the RBCs “storage lesion”, improve the effectiveness of transfusion, and safely maintain the shelf-life of RBC components at or near the current FDA mandated maximal storage limit of 42 days, will be important to assuring blood availability for future public health needs.
There is scientific evidence that some of the RBC storage lesion changes might be reduced, restored or mitigated by changes in blood storage conditions and/or through manipulation prior to transfusion with processes such as washing, filtration and/or renitrosylation. Multiple strategies may be needed because targeting any single parameter may be insufficient to markedly improve RBC product quality.
The National Blood Collection and Utilization Survey Report estimates that a total of 17.3 million blood units were collected and 14.6 million RBCs units were transfused in the United States in 2008. Except for pediatric transfusions, blood banks always deliver the oldest available RBC units when a RBC transfusion is requested to optimize their inventory management. It is anticipated that a product and/or process developed for this contract Depending on the product, the market may be any or all of the following: blood centers, blood banks, and hospitals as these are the facilities that collect, produce and/or transfuse RBC component units.
Applicants are encouraged to explore utilization of the NHLBI SMARTT program (https://www.nhlbismartt.org/ ) to assist with the preclinical and early clinical study planning and regulatory support for IND/IDE applications associated with this contract topic.
Project Goals
The purpose of this SBIR contract solicitation is to develop new additive solutions, storage bags and/or new processes to enhance RBCs function and survival after storage and transfusion and/or reduce non-infectious complications associated with allogeneic RBC component transfusions.
Accepted products, devices or technologies for the contract topic include, but are not limited to:
• New additive solutions for RBC component storage,
• Novel RBC component storage bags or modification of current storage bags,
• Small footprint cell washer and associated disposables for use in hospital blood banks and transfusion services,
• Pre- or post-storage processes and systems that will deliver a more therapeutic, less toxic transfused RBC component,
• Development of kits, including combinatorial approaches such as devices and technologies, to achieve the project goals.
Development of products and/or procedures for the sole purpose of leukoreduction will not be considered responsive to this solicitation.
Phase I Activities and Expected Deliverables
In Phase I, the investigator(s) are expected to complete proof-of-concept, become knowledgeable of regulatory requirements for required IND/IDE approval, and present the Phase I results and the development plan to NHLBI staff. The Phase I research plan must contain specific, quantifiable, and testable feasibility milestones along with alternate approaches if unexpected data are generated. The new technology needs to result in a demonstrable reduction in the development of the RBC storage lesion such as a decrease in the number of red blood cell microparticles and/or better preserved RBC rheology.
Phase II Activities and Expected Deliverables
Phase II should follow the development plan laid out in the Phase I if the FDA has approved the approach and feasibility has been demonstrated. Phase II studies should focus on developing the required technologies and working towards the initiation of clinical testing.
Deliverables include the provision of evidence of having initiated the process leading to IND/IDE submission (and hopefully approval), and the documentation that the plan is feasible and that there are alternate approaches if any contradictory data are generated. When appropriate, it must be documented that production of sufficient amount of clinical grade material suitable for an early clinical trial can occur. The Phase II research plan must contain specific, quantifiable, and testable feasibility milestones.
