Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel

Food Chem Toxicol. 2024 Aug:190:114817. doi: 10.1016/j.fct.2024.114817. Epub 2024 Jun 14.

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 However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested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.

Keywords: Clinical studies; Immune safety; Immunotoxicology; Ingredient risk assessment; Toxicokinetics.

MeSH terms

  • Animals
  • Cattle
  • Food Ingredients
  • Food Safety
  • Humans
  • Lactoferrin*
  • Recombinant Proteins* / toxicity
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • United States
  • United States Food and Drug Administration

Substances

  • Lactoferrin
  • Recombinant Proteins
  • Food Ingredients