Contribution of Nucleic Acid Testing of Plasma Source Material to the Viral Safety of Plasma Derived Coagulation Factors: The French Experience.

Viral testing of donations and plasma pools is one of the important elements that guarantee the safety of plasma-derived coagulation factors towards the risk of transmitting pathogenic agents. In the last decade, virus testing has benefited from developments in Nucleic Acid Testing (NAT), which has permitted its implementation initially for the testing of plasma pools and more recently at the donation level. Validated NAT techniques significantly increase the safety margin of plasma-derived products by reducing the initial viral load, which could challenge the efficacy of viral inactivation or elimination during the manufacturing processes. NAT for major blood borne viruses such as HIV and HCV allows the detection of the virus during the window period where the donor may escape from serological detection and the viral load can be very high. Implementation of HCV-NAT on plasma pools in France, has allowed detection of 7 HCV RNA positive/anti-HCV negative donations amongst 8.6 million donations tested (period 1997 – 2001) corresponding to an incidence rate of 1/1 230 000 donations, correlating with the extremely low residual HCV transfusion risk in France. NAT has also been voluntarily applied to increase the safety of coagulation factors with regards to non-enveloped viruses, mostly Parvovirus B19 (B19V) and hepatitis A virus (HAV). These viruses have been transmitted through inactivated coagulation factors because they are more resistant to viral inactivation treatments (e.g. Solvent/Detergent treatment) than enveloped viruses. Very high viremia are observed in B19V infection and testing B19 DNA in manufacturing plasma pools with a threshold concentration of 10⁴ IU/ml allowed a dramatic reduction in the initial viral load (reduction factor ~ 6 – 7 log₁₀). After nearly 10-years experience in France, which is the longest experience reported, the mean incidence rate is 1 in 7 710 donations, with epidemics detected in 1997 and 2005. Annual incidence profiles confirm a seasonal evolution of this virus with an increased incidence in the spring period. The contribution of B19 NAT to the increased safety of coagulation factors is supported by pharmacovigilance data in France, with no reports of B19V transmission associated with a coagulation factor since NATs implementation. NAT represents a significant breakthrough in the viral testing of plasma for fractionation. Automated systems in place can readily be adapted to emerging pathogens as shown, in Northern American countries, with the rapid implementation of West Nile Virus PCR testing in the transfusion setting. NAT represents a state of the art development in the manufacture of increasingly safe plasma-derived products.