Quality control (QC) procedures are key in the medical laboratory, to provide reliable patient results and do the utmost to ensure patient safety. The relationship between the reliability of a result and the analytical process has been understood since the early days in the laboratory, and requires additional consideration and attention. This article focuses on the use of independent quality control material and why it is so important to help safeguard patient safety in laboratory medicine.
Quality control is the issue most discussed and focused on in laboratory medicine, and various QC procedures have been developed. Most diagnostic companies recommend using their own QC material to evaluate the performance of the system – the combination of reagent, calibrator, and instrument – as specified in the instructions for use (IFUs). This QC material is usually optimized for the combination mentioned above. If all QC procedures in the production of the reagent, calibrator and QC material went well, the laboratory would be on the safe side, however, there are often issues with transportation, laboratory conditions or stability that may lead to problems.
Medical laboratories do their utmost to follow the IFU and QC regulations, to deliver highly reliable patient results. Occasionally, dependent on the applicable regulations, they might have to participate in a proficiency testing (PT) program to find out how the laboratory performs in comparison with its peers or, if available, against the reference method values of the PT QC material.
The Benefits of Choosing an Independent QC Material
The advantages of choosing an independent, rather than the manufacturer’s, QC material is best illustrated by real-world examples.
A laboratory received a phone call from a clinician saying that its calcium test results have been too low for some days and do not meet the clinical picture. Initially, the laboratory examined its QC results for the last couple of days to determine whether any critical QC event had occurred. Next, the patient moving average was calculated over a period of time. It became clear that there had been a significant shift in patient results since the calcium method was last calibrated. Consequently, incorrect results had been released, an event that should never happen.
So, why was the issue not detected sooner when QC material was analyzed daily? Both the QC material and calibrator set were lyophilized, and the pipette used to add the solvent to dissolve them was not dispensing the correct volume. As the same error was transferred to both materials, it was not possible to detect the issue based solely on the QC material results. If the laboratory had used a liquid – rather than lyophilized – QC material the error would have been discovered immediately.
The QC material is optimized for the particular reagent lot and calibrator currently in use. A new reagent lot is received, which the laboratory calibration checks for acceptable performance using its in-kit QC material. While changing to a new lot does not usually show any effect on the in-kit QC material, patient results may behave differently and therefore a lot-to-lot check is necessary. This phenomena has already been reported (1-7), and the Clinical and Laboratory Standards Institute (CLSI) provides a document (8) to guide laboratories through doing a calibration check in this situation.
A diagnostic company announced an urgent field safety notice regarding a product recall (9), with immediate action required, because:
- a performance shift in the assay had the potential to generate falsely elevated results on patient samples;
- results generated with the affected lots might demonstrate a positive shift relative to those generated with previous combinations of reagent and/or calibrator lots;
- the issue might also impact the established reference ranges;
- the magnitude of shift averaged approximately 13 to 45 %;
- the in-kit controls did not detect the shift.
The recall could have resulted in approximately 40,000 inaccurate laboratory tests reported by 18 laboratories from the impacted area.
In this instance, the company offered an in-kit QC material for the product concerned. In-kit QC materials are produced by the manufacturer of the reagent, calibrator, and instrument for checking the system performance. There is a high risk that the calibrator and QC material are made from the same source and therefore optimized to work well together. It is rare that this combination of materials will detect any kind of error. This is where independent QC materials derived from a different source have an advantage, as they are designed to detect errors that may be overlooked by the in-kit control.
The optimal way to produce highly reliable patient results is for laboratories to establish a proper scheme and use an additional QC material from a source that is independent from the manufacturer of the reagent, calibrator, and instrument.
To optimize the QC procedure, laboratories should consider using a QC material comprising a large number of analytes. The advantages and cost savings of using such materials was evaluated in the Microcoat study (10) which demonstrated a decrease in waste and the amount of storage space required, a reduction in preparation and handling time, and lower dead volume while maintaining good performance. Finally, the advantages and disadvantages of using independent QC material are clearly described in a recently published paper (11).
This article is sponsored by LGC Clinical Diagnostics. To reach out, email [email protected], or call 800.377.9684.
- Solsvik AE, Kristoffersen AH, Sandberg S, Gidske G, Vegard Stavelin A, Eikeland J, et al. A national surveillance program for evaluating new reagent lots in medical laboratories. Clin Chem Lab Med 2022;60:351-60. https://doi.org/10.1515/cclm-2021-1262
- van Schrojentein Lantman, M, Cubukcu, HC, Panteghini, M, Bernabeu, AF, Milinkovic, N, Mesko, BP, et al. An approach for determining allowable between reagent lot variation. Clin Chem Lab Med 2022;60:681-8. https://doi.org/10.1515/cclm-2022-0083.
- Miller WG, Erek A, Cunningham TD, Oladipo O, Scott MG, Johnson RE. Commutability limitations influence quality control results with different reagent lots. Clin Chem 2011;57:76-83.
- Algeciras-Schimnich A, Bruns DE, Boyd JC, Bryant SC, La Fortune KA, Grebe SK. Failure of current laboratory protocols to detect lot-to-lot reagent differences: findings and possible solutions. Clin Chem 2013;59:1187-94. https://doi.org/10.1373/clinchem.2013.205070
- Kim HS, Kang HJ, Whang DH, Lee SG, Park MJ, Park JY, Lee KM. Analysis of reagent lot-to-lot comparability tests in five immunoassay items. Ann Clin Lab Sci 2012;42:165-73.
- Ambade V, Misra P, Vashum Y, Sharma M, Mukherjee B, Bhatia K, et al. Analysis of short-term variation and long-term drift during reagent kit lot change in an NABL accredited clinical biochemistry laboratory. J Med Biochem 2021;40:92-8. https://doi.org/10.5937/jomb0-25597
- Plebani M, Zaninotto M. Lot-to-lot variation: no longer a neglected issue. Clin Chem Lab Med 2022;60:645-646. https://doi.org/10.1515/cclm-2022-0128
- Clinical and Laboratory Standards Institute. EP26A: user evaluation of between-reagent lot variation; 2013. Available from: https://clsi.org/standards/products/method-evaluation/documents/ep/26/
- Lima-Oliveira G, Lippi G, Salvagno GL, Brocco G, Guidi GC. In vitro diagnostic company recalls and medical laboratory practices: an Italian case. Biochem Med 2015;25:273-8. http://dx.doi.org/10.11613/BM.2015.028
- Microcoat study whitepaper. Study on file at Technopath Clinical Diagnostics, available on request.
- Sonntag O. Independent quality control and its importance: Are you dependent? Trillium Diagnostik 2019;17:156-7. https://www.trillium.de/zeitschriften/trillium-diagnostik/ausgaben-2019/td-heft-42019/in-vitro-diagnostik/unabhaengige-qualitaetskontrolle-und-ihre-bedeutung-sind-sie-etwa-abhaengig/independent-quality-control-and-its-importance-are-you-dependent.html
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