Considerations for safety assessment of intractable proteins expressed in genetically modified crops

Current requirements for safety assessment by regulatory agencies necessitate the production of multi-gram quantities of functionally active proteins newly expressed in genetically modified (GM) crops. This presents challenges for so-called intractable proteins (those that are difficult to isolate in an active form). Significant experience and knowledge have been gained by both GM crop developers and global regulatory agencies regarding the safety assessment of the newly expressed proteins (NEPs). By leveraging this knowledge and scientific data that have accumulated over the last several decades, the safety assessments of NEPs can be refined and improved. In this technical review, we examine the options for characterizing intractable NEPs and producing protein test substances from different sources to support the safety assessments of novel GM crops.