Concentrate safety and efficacy

Abstract

Safety from transmission of infections through plasma-derived clotting factor concentrates is assured by improved donor screening, serological testing of individual donations and direct viral testing of small plasma pools. Modern viral-inactivation techniques are highly effective. Recombinant concentrates stabilized in human albumin are being superaeded by those with other stabilizers. Recently reported discrepancies between estimates of concentrate potency from in vitro assays versus in vivo recovery, depending upon type of assay and reference standard used, are not fully resolved.

Effect of Ca2+ and Mg2+ concentration in culture medium on the activation of recombinant factor IX produced in Chinese hamster ovary cells

“…Its deficiency due to expression of defective protein or lack of FIX expression causes a severe bleeding disorder, hemophilia B (Sharathkumar et al, 2009). To avoid the limitations and dangers associated with plasma-derived products, recombinant human FIX (rhFIX), which has been expressed to high levels in Chinese hamster ovary (CHO) cells (Kaufman et al, 1986;Dadehbeigi et al, 2008), is desired for the treatment of hemophilia B (Kasper, 2002;UKHCDO, 2003).…”

The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B

“…[7][8][9] In addition, the introduction of improved viral attenuation methods during manufacture has reduced the risk of viral transmission with pdFIX products. 10 Nevertheless, current viral attenuation methods may not eliminate nonenveloped viruses, including hepatitis A (HAV) and parvovirus, or bloodborne prions associated with transmissible spongiform encephalopathies, such as variant Creutzfeldt-Jacob disease. 10,11 Concern also remains regarding the transmission of blood-borne pathogens with pdFIX products, despite manufacturing improvements such as the introduction of nanofiltration steps.…”

“…10 Nevertheless, current viral attenuation methods may not eliminate nonenveloped viruses, including hepatitis A (HAV) and parvovirus, or bloodborne prions associated with transmissible spongiform encephalopathies, such as variant Creutzfeldt-Jacob disease. 10,11 Concern also remains regarding the transmission of blood-borne pathogens with pdFIX products, despite manufacturing improvements such as the introduction of nanofiltration steps. 11 The cloning of human FIX 12 led to the expression of human recombinant FIX (rFIX) in Chinese hamster ovary (CHO) cells.…”

Therapeutic plasma proteins – application of proteomics in process optimization, validation, and analysis of the final product

“…The basic requirements that have to be fulfilled for these very sensitive therapeutic protein products are virus safety, effectiveness, and the absence of side effects [16][17][18][19]79]. The most serious complication in the treatment of hemophilia A is the development of activity-inhibiting antibodies, so-called inhibitors [86,87]. The inhibitors almost always develop in previously untreated patients at an early stage of therapy [88].…”