On April 30, 2018, the FDA announced that FDA scientists had compiled the first comprehensive molecular and chemical comparison of all hemoglobin-based oxygen carriers (HBOCs) that have been tested in humans.
HBOCs, a type of artificial blood substitute that scientists have studied extensively as treatments for patients who have suffered serious blood loss, use the natural oxygen-carrying molecule called hemoglobin (Hb) to carry oxygen throughout the body. HBOCs are developed in one of two ways. One way to make HBOCs is to remove molecules of Hb from cells and chemically modify the Hb during processing into a product. HBOCs may also be developed through genetic engineering. HBOC products are usually complex combinations of molecules that have a variety of possible chemical modifications, making it difficult to predict how well they will perform as oxygen carriers.
Another concern is that, because the Hb used for HBOCs is not inside red blood cells, the Hb tends to accumulate to toxic levels in the blood. This cell free Hb can cause high blood pressure. Hb can also escape the blood vessels and damage the kidneys and other organs. Therefore, the FDA has not approved any HBOCs for use in humans and the regulatory agencies of most other countries also have not approved HBOCs. The FDA scientists are working to overcome the problem of Hb toxicity in order to enable industry to manufacture safe and effective HBOCs.
The key to Hb toxicity is that, unlike Hb inside red blood cells, these free molecules undergo a disruptive chemical reaction that cannot be reversed. This reaction, called oxidation, occurs after the HBOCs release their oxygen molecules and leaves the Hb unable to bind to additional oxygen molecules. In addition, the reaction makes the HBOC highly chemically reactive, causing potentially life-threatening high blood pressure, heart attack, and stroke. These complications have prevented full development of HBOC products despite attempts to modify various Hb products to eliminate their toxic effects.
The FDA scientists performed identical biochemical studies of HBOCs, all of which had failed in clinical studies due to their toxicity, in order to create individual profiles of their biochemical actions. Biochemical actions include an HBOC’s ability to bind and release oxygen under various conditions and how an HBOC interacts with cells.
The results of the study are important because they could help to explain the individual safety and efficacy characteristics of each type of HBOC. In turn, this would enable scientists to pick and choose among various biochemical characteristics to support the design of safe and effective products. The FDA’s side-by-side comparison of the various types of HBOCs provides scientists a better understanding of how the structures and chemical activities of these proteins are related to both their ability to carry oxygen in the body and their potential toxicity in humans.
See the FDA Science and Research Announcement
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