Workshop Report: A Study Roadmap to Evaluate the Safety of Recombinant Human Lactoferrin Expressed in Komagataella phaffii Intended as an Ingredient in Conventional Foods

Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komagataella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) structurally similar to hmLF, intended as a food ingredient. Because earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered questions about immunogenicity/immunotoxicity risks of orally ingested rhLF, Helaina convened a panel of leading scientists to build and vet a safety study roadmap containing the studies and endpoints needed to address these questions. The one-day virtual workshop (June 2023) and ensuing discussions covered the physicochemical properties of LF, the regulatory history of bovine LF and rhLF as food ingredients, and synopses of publicly available studies on immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and ADME of rhLF. Panelists concluded that the roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults, with broad applicability to other recombinant milk proteins with immunomodulatory functions.