Ultrahigh-concentration biologic therapeutics enabled by spray drying with a glassy surfactant excipient

Biopharmaceuticals such as peptides and antibodies have become critical to health care. Despite their exceptional potency and specificity, biopharmaceuticals are prone to aggregation, which can limit efficacy. These therapies therefore often require low-concentration formulations as well as cold storage to maintain stability; however, high doses are required to treat many diseases. Most approved protein drug products are administered intravenously, imposing excessive burdens on patients. New approaches are needed to formulate proteins at high concentrations to enable less burdensome subcutaneous injection, preferably with an autoinjector that can be used directly by patients. To address this challenge, we report a subcutaneously injectable protein delivery platform composed of spray-dried protein microparticles suspended in a nonsolvent liquid carrier. These microparticles contain only biopharmaceuticals and a high-glass transition temperature polyacrylamide-derived copolymer excipient that affords key benefits over traditional excipients. First, the excipient improved stabilization of biopharmaceuticals through the spray-drying process, and second, it improved morphology and properties of the spray-dried particles, enhancing suspension injectability. We demonstrated with albumin, human immunoglobulin G, and an anti-COVID monoclonal antibody (IDBiologics) that this technology enables ultrahigh-concentration protein formulations (exceeding 500 milligrams per milliliter) that are injectable through standard needles with clinically relevant injection forces. In addition, experiments with two clinically relevant antibody drugs show that these ultrahigh-concentration formulations reduce required injection volumes without altering pharmacokinetics or efficacy in mice. This approach could nearly triple the number of commercial protein drugs amenable to subcutaneous administration, improving access to these critical biopharmaceuticals.