Does EMEA Have a Clinical Bias?
The EU guidelines on LMWH “seem very clinically biased,” opines Shea, “rather than allowing for the fact that you might have the ability to do more work on the chemistry side.” In this sense, the guidelines mirror those published by the EMEA for other categories of biologics including biosimilar erythropoietin, growth hormone, insulin and granulocyte colony stimulating factor (G-CSF). The guidance states that “because the heterogeneity of LMWH is very high, the mode of action not completely understood, and it is uncertain whether PD [pharmacodynamic] markers are representative for clinical outcome, the major burden of demonstrating that two LMWHs are similar biological products is on a clinical trial.” Besides PK/PD trials in healthy volunteers, the guidance calls for biosimilar drugs to prove therapeutic equivalence to the branded product in “at least one adequately-powered, randomized, double-blind parallel group trial,” ideally in the setting of prevention of venous thromboembolism
