Abstract：
Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA\'s generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions.
摘要：
人乳乳铁蛋白（hmLF）是一种糖蛋白，对免疫功能具有众所周知的作用。Helaina,公司使用了一种糖工程酵母，Komatagaellaphafii,生产重组人乳铁蛋白(HelainarhLF，Effera™）在结构上类似于hmLF，用作食品成分。然而,早期FDA对rhLF的审查由于安全性数据不足和FDA提出的关于口服rhLF的免疫原性/免疫毒性风险的安全性问题而被撤回.Helaina组织了一个由领先科学家组成的小组，以建立和审查安全研究路线图，其中包含解决这些问题所需的研究和安全终点。小组成员在2023年6月参加了为期一天的虚拟研讨会，随后讨论到2023年7月。相关研讨会主题包括LF的物理化学性质，在FDA公认的安全（GRAS）计划中，牛LF和rhLF作为食品成分的监管历史，以及关于免疫原性/同种免疫的公开研究的概要，免疫毒理学,铁稳态，和吸收，分布，新陈代谢，和rhLF的排泄。小组成员得出结论，安全性研究路线图解决了未解决的安全性问题以及rhLF作为食品成分的预期安全使用，并同意该路线图的广泛应用，以评估具有免疫调节功能的其他重组乳蛋白的安全性和支持GRAS。
