Oct. 17, 2010

Evaluation of the Immunogenicity and Safety of Recombinant Human Thrombin After Subsequent Surgical Re-exposure.


Recombinant human thrombin (rThrombin;RECOTHROM®) is an active topical hemostat that is approved by the FDA as an aid to hemostasis. The safety, immunogenicity, and effi cacy of rThrombin have been assessed in clinical studies, including a randomized, double-blind Phase 3 study as well as studies of rThrombin in adult, adolescent, and pediatric burn wound excision.
No safety observations have been deemed clearly causally related to exposure to rThrombin in these studies, and a low rate of non-neutralizing antibody formation to rThrombin product has been consistently observed. Because therapeutic proteins may induce an immune response, it is important to evaluate their potential for immunogenicity upon re-exposure.

Therapeutic proteins typically have a complex production process, potential for immunogenicity,
and limited data on immunogenic potential prior to commercialization.

Some therapeutic proteins have been associated with allergic reactions (e.g., streptokinase, bovine insulin, recombinant Factor VIII, bovine thrombin).

Antibodies to bovine thrombin or bovine Factor V have been associated with immune-mediated coagulopathies in some patients. This has resulted in a “boxed” warning in the labeling of the US bovine thrombin product (Thrombin-JMI®; King Pharmaceuticals®, Inc.) stating that “patients with antibodies to bovine thrombin preparations should not be re-exposed tothese products.”

Immunogenicity of a protein upon secondary exposure represents a key marker of drug tolerability

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