9.3: Specific screening targets

9.3.1: HBsAg

• The UK specification for the minimum level of sensitivity for the performance of HBsAg screening is 0.2 IU/mL. This level of sensitivity can be demonstrated during assay evaluation/validation/verification through the use of a quality control calibrated to the World Health Organisation (WHO) International Standard. If the WHO International Standard is withdrawn or otherwise unavailable, an alternative quality control reagent can be used that must be validated for use by the UK Blood Service using that reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. This control must have a unitage of 0.2 IU/mL or less. If the unitage is not defined by the manufacturer it can be validated by at least one of the UK Blood Services. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.2: anti-HIV 1+2 or HIV 1+2 Ag/Ab combination

• Screening for both HIV p24 antigen and antibody to HIV 1+2+O in a combination assay is recommended as the serological screening approach for HIV within the UK Blood Services.
   
• The UK requirement for the minimum level of sensitivity for the performance of HIV 1+2 serological screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control calibrated to the WHO International Reference reagent. There is no specific requirement to demonstrate individual anit-HIV 2 or HIV p24 Ag reactivity. If the WHO International Reference reagent is withdrawn or otherwise unavailable, an alternative quality control reagent can be used that must be validated for use by the UK Blood Service using that reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

  9.3.3: anti-HCV

• The UK requirement for the minimum level of sensitivity for the performance of anti-HCV screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control calibrated to the WHO International Standard. In the absence of standardisation against a WHO International Standard, the reagent must be validated for use by the UK Blood Service using the reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.4: anti-HTLV I/II

• The UK requirement for the minimum level of sensitivity for the performance of anti-HTLV I/II screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control reagent calibrated to the WHO International Standard. In the absence of standardisation against a WHO International Standard, the quality control must be validated for use by the UK Blood Service using the reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.5: Syphilis antibody

• The UK requirement for the minimum level of sensitivity for the performance of syphilis (specific treponemal antibody) screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control reagent calibrated to the WHO International Standard. In the absence of standardisation against a WHO International Standard for enzyme immunoassays, the quality control must be validated for use by the UK Blood Service using the reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s and the additional quality control sample have satisfied the criteria laid down.

9.3.6: Malarial antibody

Donations collected from donors with an identified malarial risk may be released if the donation has been collected following the exclusion period set out in the JPAC Donor Selection Guidelines³ and malarial antibody is not detected on screening. These guidelines also identify specific situations when donations may be released if malarial antibody is detected and additional testing for malarial DNA is then performed and malarial DNA not detected, and situations when donations may be collected at a timepoint within the standard exclusion period.

• The UK requirement for the minimum level of sensitivity for the performance of malarial antibody (anti-P. falciparum/vivax as a minimum) screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control calibrated to the WHO International Reference reagent. If the WHO International Reference reagent is withdrawn or otherwise unavailable, an alternative quality control reagent can be used that must be validated for use by the UK Blood Service using that reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.7: T. cruzi antibody

The deferral criteria for donors from T. cruzi endemic areas are given in the JPAC Donor Selection Guidelines³. Donors at risk of T. cruzi must be tested for anti-T. cruzi and negative results obtained prior to the release of any donation for clinical use.

• The UK requirement for the minimum level of sensitivity for the performance of anti-T. cruzi screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control calibrated to the WHO International Standard. If the WHO International Standard is withdrawn or otherwise unavailable, an alternative quality control reagent can be used that must be validated for use by the UK Blood Service using that reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.8: anti-HBc

The exclusion period for blood donors who have had body piercing, which includes derma-rolling, ear and body piercing, permanent and semi-permanent make-up, tattooing, platelet rich plasma facial, ritual self-flagellation and acupuncture, are given in the JPAC Donor Selection Guidelines³.

All blood donors are to be screened for anti-HBc at their first donation or their donation after the introduction of anti-HBc screening. Anti-HBc screening to be repeated if a donor lapses (over 2 years) or has a new HBV risk. Tissue and stem cell donations have anti-HBc screening as a mandatory requirement at each donation.

• The UK requirement for the minimum level of sensitivity for the performance of anti-HBc screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control calibrated to the WHO International Standard. If the WHO International Standard is withdrawn or otherwise unavailable, an alternative quality control reagent can be used that must be validated for use by the UK Blood Service using that reagent.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.
   
• Blood donations which are confirmed positive for anti-HBc should be tested for anti-HBs; Tissue and stem cell donations found to be reactive for anti-HBc alone may not require additional anti-HBs testing (see section 9.3.10).

9.3.9: anti-HCMV

• The UK requirement for the minimum level of sensitivity for the performance of anti-HCMV screening is that a positive result should be obtained during assay evaluation/validation/verification with a quality control reagent calibrated to the WHO International Standard. In the absence of standardisation against a WHO International Standard, the quality control must be validated for use by the UK Blood Service using the material.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro, assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.10: anti-HBs

• The UK requirement for the minimum level of sensitivity for the performance of anti-HBs testing is that a positive result should be obtained during assay evaluation/validation/verification with a quality control reagent calibrated to the WHO International Standard. In the absence of standardisation against a WHO International Standard, the quality control must be validated for use by the UK Blood Service using the material.
   
• In addition to the assay manufacturer’s controls a quality control suitable for the purposes of monitoring the performance of in-vitro assays must be included at least once in each series of tests to demonstrate acceptable sensitivity of the test method. Where available, the quality control should be CE or UKCA marked. The quality control must be manufactured by a different manufacturer to that of the assay.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down.

9.3.11: Hepatitis C virus RNA

• The UK requirement for the minimum level of sensitivity for the performance of HCV RNA screening is 5000 IU/mL in an individual donation.
   
• The assay must include a specific internal control for each sample tested.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and any additional quality control sample have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.12: Hepatitis B virus DNA

• There is currently no specific UK requirement for the minimum level of sensitivity for the performance of HBV DNA screening.
   
• The assay must include a specific internal control for each sample tested.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s and any additional quality control samples have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.13: Human immunodeficiency virus RNA

• There is currently no specific UK requirement for the minimum level of sensitivity for the performance of HIV RNA screening.
   
• The assay must include a specific internal control for each sample tested.
   
• The assay must utilise two separate targets within the HIV genome to minimise any risk of failure of detection due to sequence changes in the primer or probe binding regions.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and any additional quality control sample have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.14: Hepatitis E virus RNA

• There is currently no specific UK requirement for the minimum level of sensitivity for the performance of HEV RNA screening.
   
• The assay must include a specific internal control for each sample tested.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and any additional quality control sample have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.15: West Nile virus RNA

The exclusion criteria for donors from a WNV risk area is given in the JPAC Donor Selection Guidelines³. These guidelines specify some situations where donations may only be released if a test for WNV RNA is negative. WNV RNA screening can be performed on donations provided by donors within the exclusion period and the donations released if WNV RNA negative.

• There is currently no specific UK requirement for the minimum level of sensitivity for the performance of WNV NAT.
   
• The assay must include a specific internal control for each sample tested.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and any additional quality control sample have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.16: Other infectious agents

The JPAC Donor Selection Guidelines³ may identify other infectious agents and specify some situations when screening may be applied in addition to donor deferral. In such situations any screening performed must:

• use assays specifically evaluated and validated for the screening of the donation type.
   
• identify and utilise an independent quality control in each series of tests in addition to the manufacturer’s assay controls.
   
• ensure that the results of the assay manufacturer’s controls and the additional quality control sample have satisfied the criteria laid down prior to release of the result.

9.3.17: Additional screening of plasma intended for fractionation

All plasma pools intended for the manufacture of medicines are subjected to microbiological screening as described in the current European Pharmacopoeia Monograph on Human Plasma for Fractionation. Dependent on which product the plasma pool is being used to produce, to limit the viral burden in-process screening of the first homogenous plasma pool for both hepatitis A Virus (HAV) RNA and human parvovirus B19 (B19V) DNA is performed. A maximum level for B19 DNA has been defined in the European Pharmacopoeia, but not for HAV RNA.

There is no mandatory requirement to screen donations for HAV and Human B19V, although UK Blood services may elect to screen donations in minipools to reduce the risk of discard of larger plasma pools.

9.3.17.1: Human parvovirus B19 DNA

• There is currently no specific UK requirement for the minimum level of sensitivity for the performance of human B19V DNA screening. If screening is performed in minipools, UK Blood Services must ensure that human B19V DNA can be detected at a level that will ensure less than 10⁴ IU/mL of B19V DNA in the homogenous plasma pool.
   
• The assay must include a specific internal control for each test performed.
   
• No series of tests should be considered acceptable unless the manufacturer’s QC requirements in the IFU have been met, and the results of any additional quality control samples used have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

9.3.17.2: Hepatitis A virus RNA

There is currently no specific UK requirement for the minimum level of sensitivity for the performance of HAV NAT. If screening is performed in minipools, UK Blood Services must ensure that HAV RNA can be detected at a level that will ensure a negative HAV NAT in the homogenous plasma pool.

• The assay must include a specific internal control for each test performed.
   
• No series of tests should be considered acceptable unless the result of the assay manufacturer’s controls and the results of any additional quality control sample used have satisfied the criteria laid down.
   
• If an additional quality control is run on each series of tests, it should be a CE or UKCA marked quality control where available and suitable for the purposes of monitoring the performance of in-vitro assays and manufactured by a different manufacturer to that of the assay.

 

Note – International Standards or Reference Reagents do not need to be CE or UKCA marked.