Combination ultrafiltration and 6 M urea treatment of human growth hormone effectively minimizes risk from potential Creutzfeldt-Jakob disease virus contamination.

Although genetically engineered human growth hormone (hGH) is now commercially available, native pituitary-derived hGH is still used by physicians in many countries for the treatment of hormone deficiency states. We describe a method using ultrafiltration and 6 M urea that reduced infectivity in human pituitary tissue that had been deliberately contaminated with scrapie virus (an animal analogue of human Creutzfeldt-Jakob disease virus) from an initial level of 10(9.7) infectious units to just 5 infectious units. Based on estimates of the frequency of contamination and infectivity levels in batches of human pituitaries, the use of this protocol to prepare GH from cadaveric human glands yields a calculated probability of exposure to a contaminated vial of not greater than 1 in 3.2 million recipients; therefore, native hormone prepared by this method may be considered to be essentially risk-free. The same methodology may be useful in the preparation of other hormones, such as prolactin, for which no synthetic substitutes are currently available, as well as biological products derived from sheep or cattle, that may be infected with scrapie or bovine spongiform encephalopathy.