six different automated blood-grouping systems were included in this three-phase, multi-site...

December 2003

NUMBER

MHRA 03067

Six automated blood grouping systems

Evaluation Report

Six different automated blood-grouping systems were included in this thre... http://dc393.4shared.com/doc/u6FIh4dr/preview.html#39

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WHAT YOU CAN EXPECT FROM MHRA EVALUATION REPORTS The Device Evaluation Service (DES) aims to provide independent and objective evaluations of medical devices available on the UK market. Specialist centres, mainly in NHS Trusts, do the evaluations under long-term contract to, and in accordance with protocols approved by, the MHRA. The evaluations are usually of a unit supplied by the manufacturer. We would expect this unit to be representative of the product on the market but cannot guarantee this. Prospective purchasers should satisfy themselves with respect to any modifications that might be made to the product type after MHRA’s evaluation. The reports are intended to supplement, not replace, information already available to prospective purchasers.

© Crown Copyright 2003 Apart from any fair dealing for the purposes of research or private

study, or criticism, or review, as permitted under the Copyright, Designs & Patents Act, 1988, this publication may only be reproduced, stored or transmitted in any form or by any means with the prior permission, in writing, of the Controller of Her Majesty's Stationery Office (HMSO).

Enquiries concerning reproduction outside those terms should be sent

to HMSO at the undermentioned address: The Copyright Unit Her Majesty’s Stationery Office, St Clements House, 2/16 Colgate NORWICH, NR3 1PD


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An evaluation of six automated

blood grouping systems

Clare Milkins Jenny White

United Kingdom National External Quality Assessment Scheme (Blood Transfusion Laboratory Practice) Watford General Hospital WATFORD WD18 8HB UK


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Contents

MHRA Evaluation Report: Six automated blood grouping systems

Summary 3 Introduction 9 Background 9 Aims 10 Limitations of the evaluation 10 Methods and protocols 13 Systems under evaluation 13 Phase 1 testing protocol 15 Phase 2 testing protocol 16 Phase 3 testing protocol 20 Description of systems 21 AutoVue 21 ID-GelStation 23 Tango 25 IBG MultiSampler 27 Sampler IIF 30 Qasar I 32 Individual instrument results 35 AutoVue 35 ID-GelStation 41 Tango 47 IBG MultiSampler 53 Sampler IIF 59 Qasar I 65 Phase 1 comparability data 71 Downtime 71 False positive and false negative antibody screens 73 Carryover 74 Controls 74 Phase 2 blood grouping comparability data 75 Methods and materials 75 Results 75 Phase 2 antibody screening comparability data 79 Materials and protocols 79 Results 79 Phase 3: manufacturers’ claims 81 Calibration and drift 81 Flexibility 82 Security 83 Throughput 84 Acknowledgements 85

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Contents

References 87 Appendix 89 Manufacturers’ comments 89 Examples of worksheets 95 How to obtain MHRA evaluation reports 113

MHRA Evaluation Report: Six automated blood grouping systems 2


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Summary

MHRA Evaluation Report: Six automated blood grouping systems

Six different automated blood-grouping systems were included in this three-phase, multi-site evaluation. During Phase 1 each participating site tested 3000 routine patient samples. During Phase 2, each tested aliquots of the same 30 whole blood samples for ABO and RhD and aliquots of the same 50 plasma samples for red cell antibodies. During Phase 3 a questionnaire was completed by each site and by the equipment manufacturers. Three of the systems, the AutoVue (utilising BioVue technology for blood grouping and antibody screening), the ID-GelStation (utilising DiaMed-ID technology for blood grouping and antibody screening) and the Tango (utilising Erytype technology for blood grouping and Solidscreen II for antibody screening) are fully automated systems. Generally, these systems offer the most security and require little input from laboratory staff. They offer no choice of technology and are more expensive than the semi-automated systems. The other three are semi-automated systems, namely the IBG MultiSampler [utilising Capture R solid phase technology for antibody screening at one site and in-house solid phase technology (SPAT) at the other], the DiaMed Sampler IIF (utilising DiaMed-ID technology for antibody screening) and the Qasar I (utilising DiaMed-ID technology for antibody screening). All of these sites utilised liquid phase microplate technology for blood grouping. Generally, these offer less security, but more flexibility with respect to choice of technology and consumables. The MultiSampler and the Qasar I can also be used for other applications such as ELISA assays, where such use has been properly validated by the assay manufacturer.

The AutoVue, MultiSampler and Sampler IIF appeared to be mechanically reliable during Phase 1 of the evaluation. Neither AutoVue site reported any significant downtime. One MultiSampler site and one Sampler IIF each reported one episode of downtime; the former problem was resolved by the manufacturer via a modem connection, whilst the latter problem was resolved in-house with advice from the manufacturer. The ID-GelStation and Qasar I had problems requiring an engineer at both sites, but no downtime was recorded for faults that could be resolved in-house. The Tango appeared much less reliable at the first of the two sites completing Phase 1, with eight breakdowns, involving several parts of the system and requiring an engineer call-out. This site also recorded four episodes of downtime due to software problems but these were resolved in-house with advice from the company. The other Tango site recorded no episodes of downtime. This disparity in breakdown frequency is likely to be because the Tango at the first site was very new to the market and many of the problems experienced by this site had been rectified by the time that the second site performed Phase 1 of the evaluation. The number of failures to aspirate apparently acceptable samples measured another aspect of reliability. The ID-GelStation, MultiSampler, and Qasar I appeared extremely reliable in this respect. The AutoVue recognised a small number of pipetting failures of unknown cause, although two of these were not identified until the final volume check at the reading phase. The Tango

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Summary

again showed disparity between the two sites. The probe of the Sampler IIF at one site failed to reach the cells on several occasions due to the variety of sample tube types in use. This problem was rectified by newly developed software being installed by a service engineer. Barcode readers appeared to be very reliable, with just two failures noted by one of the Sampler IIF sites. Further details relating to reliability may be found in Phase 1 comparability data. The rate of false positive reactions recorded during Phase 1 was < 1% at all sites. The MultiSampler at site H (Capture R) recorded the highest level at 0.9%. The majority of these false positive tests were found to be negative on manual repeat, but some were not repeated. Given that this does not correlate with the level of < 0.1% recorded by site I (SPAT), it would appear that the false positives were at least partly due to the indirect antiglobulin test (IAT) technology, rather than the automation. The only false negative antibody screen recorded during Phase 1 was by the MultiSampler using Capture R.

There was only one false positive antibody screening result recorded for the 11 inert samples distributed in Phase 2. This false positive result was recorded by one of the sites utilising DiaMed technology on the Qasar I. During Phase 2, all sites tested aliquots from the same 30 whole blood samples. With the exception of three mixed field D types, there was only one incorrect interpretation made; the ID-GelStation (at one site) reported a result of ‘Discordant’ for ABO and ‘Positive’ for D type for the rr DAT positive sample, heavily coated with anti-c. The ID-card used did not include a reagent control well, hence the incorrect interpretation of D positive. However, this card was brought forward for review. The ID-GelStation (both sites) was the only instrument to detect the mixed field reaction in the 50:50 and 20:80 mixtures of D positive and D negative cells. The Tango, MultiSampler, Sampler IIF and Qasar I all showed a lack of reproducibility regarding the strength of reactions and interpretations recorded for the duplicate examples of weak D. The ID-GelStation was the only system to detect all antibodies of likely clinical significance at both testing sites. One of the Sampler IIF sites missed an example of anti-K, which was positive by manual testing using the same DiaMed technology. Similarly, one of the two Qasar I sites missed one example of anti-Fy

b that was positive by manual testing, using the same DiaMed technology. These would appear to be failures of automation rather than IAT technology. The IBG MultiSampler sites each missed one antibody of potential clinical significance (anti-Kp a by Capture R and anti-Fy a by SPAT), but these were also negative when tested manually using the same IAT technology, suggesting that the problem was with the IAT technology and not the automation. The AutoVue missed three antibodies at one site (two examples of anti-Fy b and one example of anti-D). These three sera gave negative



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Summary

reactions when tested by manual BioVue using the same reagent red cells, and two of the three gave weak positive reactions by the AutoVue, using the reagent red cells provided. These results suggest that the problem was with the IAT technology and/or the screening cells rather than the automation. Phase 2 testing was performed at only one of the two Tango sites, where three antibodies were missed, namely one example each of anti-C, anti-Fy a and anti-E. Repeat testing suggested that the anti-C was initially missed due to a failure in the automation, however, manual Solidscreen II was not performed. The other two failures may have been due to the Solidscreen II technology, the screening cells or a combination of both. Detection of three clinically insignificant cold reacting antibodies (anti-Le a

in duplicate and anti-P 1) was variable and probably dependent on IAT technology rather than automation. Overall, systems utilising solid phase technology were better at not detecting these unwanted antibodies, than those utilising column agglutination technology . Further details of sensitivity and specificity data may be found in Table 24, and later sections Phase 2 blood grouping comparability data and Phase 2 antibody screening comparability data. The fully automated systems offer excellent security. It is not possible to remove samples or reagents during processing, except in a controlled way and all barcodes are re-validated following a break in processing, thus preventing sample transposition errors. The AutoVue uses digital imaging to measure the final level of reactants in the column prior to reading, ensuring that any problems with aspirating samples, not detected at the pipetting stage, will be flagged before the results have been interpreted. This is an important feature, particularly where the IAT crossmatch is omitted from pre-transfusion testing and where antibody screening is only performed once on each patient sample. DiaMed stated in response to the questionnaires sent in Phase 3 that this feature is available in software version 3.06, however, this was not tested in the trial as only earlier software versions were available for use during Phase 1. The Tango has no level check of reactants in the well prior to washing. Any mis-sampling, undetected at the pipetting stage, may therefore remain unnoticed, potentially giving rise to a false negative antibody screen. Both the AutoVue and the ID GelStation analysers pierce the foil tops of the cards/cassettes, saving time, allowing on-board storage without danger of the columns drying out, reducing health and safety problems from waste and preventing the possibility of any cross contamination between columns.



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Summary

The semi-automated systems have fewer security features than the fully automated systems, leading to an increased possibility of human error:

all use barcodes to identify samples, cards/cassettes and plates, but with the exception of the Qasar I, it is possible to remove two samples (or cards/cassettes/plates) and replace them the wrong way round without the system alerting the user to the mistake. The IBG MultiSampler does have a facility to re-check all of the sample barcodes at the end of each run, but the customer has to request that this facility be installed

•

•

• •

the Qasar I does not control the reagents with barcodes, with the consequence that reagents could be misplaced without the user being alerted none has a final level check on reactants the Qasar I does not have a clot detector, so sampling could fail without the user being alerted.

With the exception of the Qasar I, it is possible to remove a sample from all of the analysers for urgent manual testing, without compromising the remainder of the samples being processed. There is minimal or no delay with most of the systems, however there could be a delay of up to ten minutes with the Tango. However, the Tango does have the facility to allow an on-board sample to ‘queue jump’ by being re-prioritised as urgent. The IBG MultiSampler and the Qasar I can be used for any manufacturer validated column or microplate technology, although use of Capture R increases the level of automation attained on the MultiSampler. The Sampler IIF can be used with liquid phase microplates, but can only utilise DiaMed cards for antiglobulin testing.

All of the systems can accept a fairly wide range of sample tubes, the Sampler IIF and the Qasar I having the most restrictions with regard to acceptable dimensions. With the exception of the Qasar I, different sized sample tubes can be mixed within a batch, though not necessarily within a single rack. With the exception of the Sampler IIF, users can design their own test profiles. There are, however, already 300 profiles integrated in the Sampler IIF software. The manufacturers of the ID-GelStation and the MultiSampler do not encourage users to design their own and all of the manufacturers will write new profiles as required. The fully automated systems all allow a mixture of test profiles to be loaded simultaneously, although the ID- GelStation processes them sequentially rather than simultaneously. This feature, combined with a bi-directional interface (written for all systems except the Sampler IIF), allows the user to select profiles dependent on patient type or the presence of historical data. The AutoVue is the fastest of the three fully automated systems, processing a single sample for blood group and antibody screen in 20 minutes compared with 33 minutes for the ID-GelStation and Tango. Although these can all be used in trickle feed mode, in practice they are likely to be used for small batches, the size of which may depend on the technology and type of sample carriers used. Times taken to process greater numbers of samples are shown in Table 32.



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Document OutlineClare MilkinsAimsSystems under evaluationTable 1: Simple non-manipulated groups

GroupO D positive

Table 2: Complex or manipulated groupsO mixed field D

Service contractsElectrical requirementsTango

SpecificationsEnvironmental conditionsElectrical requirements

CostService contracts

��Environmental conditions

Environmental conditionsCostService contractsCostService contracts

AutoVueTable 4: Summary of local practice

ThroughputCalibrationStart-up and daily maintenanceTrainingSkill levelsHealth and safety

ID GelStation (formerly WADiana Compact)DowntimePipetting errors

AnalyteFalse positive antibody screensFalse negative antibody screen

FlexibilityThroughputCalibrationStart-up and daily maintenanceInterfacingTrainingSkill levels

TangoDowntimePipetting errorsSite G experienced problems with aspiration of samples on 11 occasions. Nine of these were due to probe damage and the two others were of unknown cause.There were no pipetting errors at site F. See Table 23 for comparability data.Phase 1 serology

Undetermined groups and screensAnalyte

False positive antibody screensFalse negative antibody screens

CarryoverFlexibilityThroughputCalibrationStart-up and routine maintenanceInterfacingTrainingSkill levelsHealth and safety

IBG MultiSamplerSite I

Software versionAHG type

Manipulation of reagents?DowntimePipetting errorsPhase 1 serology


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False positive antibody screensFalse negative antibody screen

CarryoverScreensThroughputCalibrationStart-up and routine maintenanceInterfacingSkill levelsHealth and safety

Sampler IIFAntenatal

DowntimePipetting errorsPhase 1 serology

Site JFalse positive antibody screensFalse negative antibody screens

CarryoverScreensSecurityFlexibilityThroughputStart-up and routine maintenanceInterfacingTrainingSkill levelsHealth and safety

Qasar ISite L

Software versionHaematology/oncology

DowntimePipetting errors

Phase 1 serologyUndetermined groups and screens

AnalyteFalse positive antibody screensFalse negative antibody screen

CarryoverScreensThroughputCalibrationStart-up and routine maintenanceInterfacingTrainingSkill levelsHealth and safetySite Code

BAutoVueC

ID GelStationResults

Results for complex or manipulated groupsWeak DSamples 6, 19 and 27 were all classed as weak D, with 19 and 27 being from the same donation. Interpretation of weak D will depend on the affinity of theanti-D reagent used, the method of reading, the sensitivity setting of the camera and the user-defin

InstrumentAutoVue

LSampler IIFQasar 1

Requirement for in-house calibrationAutoVue

Possible to adjust sensitivity of the cameraParameter

Can be used as trickle feed analyserMax. batch size if applicable

Minimum STAT ABO/D type onlyMDA.DOWNTIME.1


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