Only subsequently did the in vitro (laboratory-based) heating exp

Only subsequently did the in vitro (laboratory-based) heating experiments suggest that heat-treated products might reduce (if not eliminate) the risk for transmitting HIV, but no actual clinical (in vivo) data existed on the efficacy of heat-treated factor in reducing HIV infection. Normally, clinical PD0332991 efficacy, determined by prospective clinical trials, would be required before licensing. However, a significant and growing portion of the haemophilia population was being infected in 1984 and the haemophilia community was desperate for any possible preventive measure.

Most readily accepted the use of heat-treated concentrates based only on the in vitro data with evaluation of the level of viral safety by subsequent surveillance [1]. Although DHF established surveillance mechanisms to identify possible HIV seroconversions in patients taking heat-treated clotting factors, several problems made the task difficult. Logistically, the surveillance was voluntary and passive, rendering it less sensitive. Second, the majority of infected haemophilia patients were still unidentified, either by clinical symptoms or testing. These patients had to be distinguished from persons seroconverting from the new heat-treated products. Patients

often used more than one brand of clotting factor concentrate; when these persons were included, identifying an unsafe product depended Trametinib clinical trial on statistical analysis of a number of suspected seroconversions. Finally, although most patients in the United States were using heat-treated clotting factors in early 1985, some physicians

and organizations still objected to its use. Unfortunately, this resistance caused delay in utilizing the new products in some countries. Large, expensive inventories of non-heat-treated clotting factors still existed in manufacturers’, distributors’, hospitals’ and clinics’ storage. Although in retrospect, these should have immediately been destroyed, the FDA did not order a formal recall of non-heat-treated products, but allowed manufacturers to ‘phase in’ distribution of the heat-treated factors; therefore non-heat-treated products continued to be available in many countries for another year [6]. Reportedly, Dolutegravir in vitro this policy was justified by the lack of clinical effectiveness data for heat-treated products and concern in the haemophilia community that the withdrawal of untreated clotting factor would create shortages. For example, following MASAC’s recommendation, the Canadian Bureau of Biologics, in November 1984, issued directives to the Canadian Red Cross and manufacturers to switch to heat-treated products ‘as soon as possible’ [7]. However, the sole Canadian manufacturer of clotting factor, Connaught Laboratories, did not have the equipment or technology to produce heat-treated products [7].

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