Congress report: Online workshop on assessment of technical files for blood screening in vitro diagnostics for sub-Sahara African countries.

OBJECTIVES: The online workshop on IVD regulation was performed to broaden the understanding of the technical documentation needed for IVD licensing and the strategies to asses it. BACKGROUND: Testing of blood donors and donations significantly reduces the risk of transmitting transfusion-transmissible infections. Many test systems are commercially available, but not all meet the recommended sensitivity and specificity standards. Many African countries either lack functional structures for the regulation of IVDs this poses a threat to the quality of the blood supply. MATERIALSAND METHODS: The Paul-Ehrlich-Institut BloodTrain organised an online workshop in September 2021 to introduce staff from several National Regulatory Authorities (NRAs) in Africa to the regulation of IVD and the technical information that need to be provided by the manufacturers of blood screening IVD. Their evaluation was trained in practical exercises. RESULTS: This online workshop brought together over hundred participants from NRAs of 12 African countries. Speakers from PEI, Blood Train, WHO and academia, with experience in IVD regulation trained participants in the various topics addressed during this workshop. CONCLUSIONS: This workshop presented a great starting point for most participating NRAs to set up and/or strengthen their regulatory structures for IVDs.

Impact of vCJD on blood supply.

Variant Creutzfeldt-Jakob disease (vCJD) is an at present inevitably lethal neurodegenerative disease which can only be diagnosed definitely post mortem. The majority of the approximately 200 victims to date have resided in the UK where most contaminated beef materials entered the food chain. Three cases in the UK demonstrated that vCJD can be transmitted by blood transfusion. Since BSE and vCJD have spread to several countries outside the UK, it appears advisable that specific risk assessments be carried out in different countries and geographic areas. This review explains the approach adopted by Germany in assessing the risk and considering precautionary measures. A fundamental premise is that the feeding chain of cattle and the food chain have been successfully and permanently cleared from contaminated material. This raises the question of whether transmissions via blood transfusions could have the potential to perpetuate vCJD in mankind. A model calculation based on actual population data showed, however, that this would not be the case. Moreover, an exclusion of transfusion recipients from blood donation would add very little to the safety of blood transfusions, but would have a considerable impact on blood supply. Therefore, an exclusion of transfusion recipients was not recommended in Germany.

Sensitivity of HCV RNA and HIV RNA blood screening assays.

BACKGROUND: The FDA requirement for sensitivity of viral NAT methods used in blood screening is a 95-percent detection limit of 100 copies per mL, whereas the NAT screening system should have a sensitivity of at least 5000 copies per mL per individual donation. According to the Common Technical Specifications of the European Directive 98/79/EC for in vitro diagnostics, viral standard dilutions (calibrated against the WHO standard) should be tested at least 24 times for a statistically valid assessment of the 95-percent detection limit. STUDY DESIGN AND METHODS: Viral standard dilution panels (PeliCheck, VQC-CLB) were prepared for HCV RNA genotypes 1 and 3 and for HIV RNA genotypes B and E. In a multicenter study, 23 laboratories tested the panels all together in 8 to 91 test runs per NAT method. RESULTS: The following 95-percent detection limits (and 95% CIs) were found on the HCV RNA genotype 1 reference panels (shown as geq/mL): Gen-Probe TMA, 85 (64-118); AmpliScreen, 126 (83-225); AmpliScreen with NucliSens Extractor, 21 (13-44); Amplicor with NucliSens Extractor, 69 (50-102), and Amplicor with Qiagen extraction technology, 144 (74-102). On HIV RNA genotype B dilution panels, the following 95-percent detection limits were found (shown as geq/mL): Gen-Probe TMA, 31 (20-52); AmpliScreen, 126 (67-311); AmpliScreen with NucliSens Extractor, 37 (23-69), and NucliSens QL assay, 123 (51-566). HIV RNA genotype E panels were detected with equal sensitivity as HIV RNA genotype B panels. In the Gen-Probe TMA assay, the 50-percent detection limits on HIV RNA type B and type E were 3.6 (2.6-5.0) and 3.9 (2.4-5.8) geq per mL, respectively. The HCV RNA genotype 1 and 3 standards were detected with equal sensitivity. CONCLUSION: The differences in sensitivity between NAT assays can be explained by the input of isolated viral nucleic acid in the amplification reactions. The FDA requirements for sensitivity of NAT blood screening assays can be met by the Gen-probe TMA, as well as by the AmpliScreen assays, particularly when combined with the NucliSens Extractor.

[Development of an alternative method to the monkey neurovirulence test for oral poliovirus vaccines]

Each oral poliovirus vaccine lot contains attenuated and small amounts of wildtype viruses. Vaccines containing more than a certain limit of wildtype viruses may cause a vaccine associated poliomyelitis. To provide safe vaccines for humans, each newly manufactured vaccine lot is tested in the monkey neurovirulence test. A certain point mutation on the poliovirus genome has been shown to be responsible for the attenuated phenotype of the vaccine virus. We developed a quantitative PCR method to determine the wildtype proportion at position 472 of poliovirus type 3 genome. This method possibly can be used as an alternative for the monkey neurovirulence test.