Potential Clinical Consequences of Antibodies to Animal-Derived Products in Surgery

Many therapeutically effective animal-derived biopharmaceuticals and biomaterials, e.g., bovine thrombin, heparin and collagen, have been used successfully for decades during surgery, despite the potential formation of antibodies. Whether biological products are derived from human or animal sources or are recombinant proteins, an antigenic response can be provoked by many different factors inherent to biopharmaceuticals or biomaterials, including differences in amino acid sequences and glycosylation, impurities/contaminants in the biological preparations and patient-specific factors. Administration of products containing biological proteins can result in a range of reactions and the development of antibodies that can be serious but does not always have significant clinical consequences. Overall, only small proportions of treated patients develop severe reactions to these products. For example, out of the millions of patients treated with erythropoietin, 175 patients developed pure red cell aplasia, and of 4109 patients with injectable collagen implants, treatment-related adverse reactions (mostly localized swelling and erythema) occurred in 1.3% of patients. Despite their potential immunogenicity, physicians still use animal-derived products because of the beneficial effects on patient outcomes during surgery. Since retrospective clinical and immunogenicity assessments of these commonly used products is unlikely, the key for new animal-derived biopharmaceuticals is to carry out comprehensive immunogenicity assessments during clinical development before they reach the marketplace.