Prion transmission in blood and urine: what are the implications for recombinant and urinary-derived gonadotrophins?

Evidence is emerging that suggests that the protease-resistant isoform (PrP(sc)) of the normal cellular prion protein (PrP(c)) can be detected in the blood and urine of animals and humans with transmissible spongiform encephalopathies (TSEs). The production of the human menopausal and recombinant gonadotrophin preparations for use in ovarian stimulation protocols in fertility treatment is one area where the pharmaceutical industry needs to be vigilant and take appropriate steps to ensure that the safety of such drugs remains as high as ever. The recombinant preparations utilize fetal calf serum or other animal sera or proteins as part of a culture medium during production. Human urinary-derived menotrophin preparations are exposed to the theoretical risk of infection from menopausal donors of urine. Nevertheless, the failure to demonstrate irrefutably infectivity following intracerebral inoculation with urine from TSE-infected hosts suggests that the risk associated with products derived from urine is merely theoretical. Despite the paucity of evidence to date and its relevance to the infectious spread of TSEs, it is important that robust measures are implemented to either remove or inactivate PrP(sc) in order to minimize contamination. Validation of each production process is required to assess the likelihood of contamination.