testiculus
Active Member
HCG derived from purified urine has the potential to contain infectious agents from the urine donors. I've found the following papers that address these risks. Overall it seems that the risk of viral or prion infection from urinary HCG is low, but not zero.
Expert Workshop on CJD Risk and Urine-derived Medicinal Products
The main conclusions of the meeting were:
1. At the time of the meeting, TSE infectivity in urine had been reported in a hamster model. Infectivity was detected at a low titre (similar to that in plasma) during the clinical phase of the disease. There was no experimental evidence to support a direct relationship between the infectivity in urine and infectivity in other tissues (e.g. blood, kidney, urinary bladder). The origin of the infectivity in urine remains unclear. The data presented were considered rather convincing but should be confirmed in other animal models.
4. There is still no confirmed immunochemical or any other chemical detection of PrPSc in urine.
5. There is no epidemiological evidence of CJD or vCJD transmission by urine-derived medicinal products. The available epidemiological data are reassuring, although epidemiological data alone do not seem a sufficient basis to confirm the safety of such products. For vCJD, the epidemiological experience is too limited, given the long incubation periods, to reach conclusions on whether or not vCJD could be transmitted by urine-derived medicinal products.
7. Risk assessments of urine-derived medicinal products consider the theoretical prion load, the prion clearance capacity of the manufacturing process and the product yield. They are strongly influenced by estimates of the reduction factor of each manufacturing step, which can be of great variability. In addition, the relevance of data on urine infectivity from animal experiments to the human situation is unknown.
8. From the results obtained on the evaluation of the risk reduction from the manufacturing processes, manufacturers consider that the potential exposure of patients undergoing fertility treatments with urine-derived medicinal products is low and unlikely to result in any iatrogenic transmission of CJD. These risk assessments were based on the estimations of the prevalence of sCJD and vCJD in countries where the urine is collected, data available on urine infectivity (taken from the hamster model), the results of the investigational studies from the different manufacturing processes and the maximal quantity of urine used in the manufacture of the products per treatment. Prion clearance resulting from the investigation of different manufacturing steps with potential TSE reduction capacity, such as filtration, adsorption, chromatographic steps, or nanofiltration, ranged from 1 to 6 logs.
Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach
Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).
Efficient Prion Removal from Gonadotropin Solutions by Nanofiltration Membranes
The authors explore whether a nanofiltration process can be effectively leveraged for removal of prions under conditions used for the manufacture of urine-derived gonadotropins.
The physiological PrP[SUP]C[/SUP] is present in significant amounts in various regions of the body as a monomer with a molecular weight and molecular features similar to those of gonadotropins. Therefore, low traces of this protein can be found in the final preparation in some purification processes (9). Even a nanofiltration step, if present into the purification process, cannot efficiently separate gonadotropins from PrP[SUP]C[/SUP]. But because infectivity of PrP[SUP]Sc[/SUP] is strictly connected to the formation of high molecular weight aggregates of the same protein the differences in the molecular dimensions between PrP[SUP]Sc[/SUP] and gonadotropins are sufficient to predict a high level of performance of the nanofiltration step using Viresolve NFP filters (6, 28). Indeed, in spite of the fact that no evidence exists about the real prion removal mechanism by nanofilters, the aggregation status and the differences in the molecular weight between gonadotropins and PrP[SUP]Sc[/SUP] could in principle explain the high value of log reduction of infectivity observed in this experimental study and the efficiency of this nanofiltration step. Together, these observations demonstrate that the nanofiltration technology can significantly increase the level of prion safety of human-derived biological products.
Expert Workshop on CJD Risk and Urine-derived Medicinal Products
The main conclusions of the meeting were:
1. At the time of the meeting, TSE infectivity in urine had been reported in a hamster model. Infectivity was detected at a low titre (similar to that in plasma) during the clinical phase of the disease. There was no experimental evidence to support a direct relationship between the infectivity in urine and infectivity in other tissues (e.g. blood, kidney, urinary bladder). The origin of the infectivity in urine remains unclear. The data presented were considered rather convincing but should be confirmed in other animal models.
4. There is still no confirmed immunochemical or any other chemical detection of PrPSc in urine.
5. There is no epidemiological evidence of CJD or vCJD transmission by urine-derived medicinal products. The available epidemiological data are reassuring, although epidemiological data alone do not seem a sufficient basis to confirm the safety of such products. For vCJD, the epidemiological experience is too limited, given the long incubation periods, to reach conclusions on whether or not vCJD could be transmitted by urine-derived medicinal products.
7. Risk assessments of urine-derived medicinal products consider the theoretical prion load, the prion clearance capacity of the manufacturing process and the product yield. They are strongly influenced by estimates of the reduction factor of each manufacturing step, which can be of great variability. In addition, the relevance of data on urine infectivity from animal experiments to the human situation is unknown.
8. From the results obtained on the evaluation of the risk reduction from the manufacturing processes, manufacturers consider that the potential exposure of patients undergoing fertility treatments with urine-derived medicinal products is low and unlikely to result in any iatrogenic transmission of CJD. These risk assessments were based on the estimations of the prevalence of sCJD and vCJD in countries where the urine is collected, data available on urine infectivity (taken from the hamster model), the results of the investigational studies from the different manufacturing processes and the maximal quantity of urine used in the manufacture of the products per treatment. Prion clearance resulting from the investigation of different manufacturing steps with potential TSE reduction capacity, such as filtration, adsorption, chromatographic steps, or nanofiltration, ranged from 1 to 6 logs.
Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach
Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).
Efficient Prion Removal from Gonadotropin Solutions by Nanofiltration Membranes
The authors explore whether a nanofiltration process can be effectively leveraged for removal of prions under conditions used for the manufacture of urine-derived gonadotropins.
The physiological PrP[SUP]C[/SUP] is present in significant amounts in various regions of the body as a monomer with a molecular weight and molecular features similar to those of gonadotropins. Therefore, low traces of this protein can be found in the final preparation in some purification processes (9). Even a nanofiltration step, if present into the purification process, cannot efficiently separate gonadotropins from PrP[SUP]C[/SUP]. But because infectivity of PrP[SUP]Sc[/SUP] is strictly connected to the formation of high molecular weight aggregates of the same protein the differences in the molecular dimensions between PrP[SUP]Sc[/SUP] and gonadotropins are sufficient to predict a high level of performance of the nanofiltration step using Viresolve NFP filters (6, 28). Indeed, in spite of the fact that no evidence exists about the real prion removal mechanism by nanofilters, the aggregation status and the differences in the molecular weight between gonadotropins and PrP[SUP]Sc[/SUP] could in principle explain the high value of log reduction of infectivity observed in this experimental study and the efficiency of this nanofiltration step. Together, these observations demonstrate that the nanofiltration technology can significantly increase the level of prion safety of human-derived biological products.
