Therapeutic proteins have an intrinsic potential to induce undesirable immune and allergic responses. The nature of the expression system and the control of the manufacturing process represent extrinsic factors that could modify this potential. Accordingly, regulatory agencies require sponsors to assess the risk of clinical immune and allergic responses that could be associated with the production of therapeutic proteins in transgenic plants. Since factors related to the clinical use of the product--including the immune status and genetic background of subjects--are also relevant, the risk assessment needs to balance the probability of a response induced by a plant-specific factor relative to the likely consequences for the specific product and therapeutic indication.