The role of quality management

In this video Ana and Dr Harper VanSteenhouse talk about the quality control and standards that can be used across a national laboratory network.

To ensure that laboratories provide accurate and reliable results and reduce the risk of errors, implementing a Quality management system (QMS) is important. However, in resource-constrained settings, most laboratories are not accredited and may only be partially implementing elements of a QMS. Introducing a new test, particularly under outbreak conditions, may therefore come with a high risk of errors. This step describes the key critical elements that laboratories should put in place to ensure quality results, particularly during COVID-19.

Quality control (QC) is a mechanism that monitors the analytical performance of the test when used with or as part of a test system. It may monitor the entire test system or only one aspect of the test. QC validates the competency of testing laboratories by assessing sample quality and monitoring test procedures, test kits, and instruments against established criteria. It also includes the review of PCR results and documentation of the validity of testing methods. Hence, QC is a multi-step process with certain checkpoints throughout the testing process: pre-analytical, analytical, and post-analytical stages. In general, “QC should be performed regularly to detect, evaluate, and correct errors due to test system failure, environmental conditions, or operator performance before reporting test results.”

QCs that are commonly employed for PCR testing include extraction negative control (checks contamination at extraction phase), extraction positive control (checks extraction process-reagents and equipment functionality), non-template control (checks contamination at PCR phase), positive template control(s) (check (s) limit of detection and robustness of the assay). Commercial QCs for positive controls are preferred; however, laboratories can use patient samples with known viral RNA concentration, preferably samples with low cycling threshold (Ct) values (25–30) for the target sequences of SARS-CoV-2. Nuclease-free water or viral transport medium can be used as the negative control. QC failures, for example, when a positive control turns out negative or a negative control turns out positive, invalidates the test results. The test must be repeated either from stored or newly collected samples after investigating and fixing the cause of the QC failure, such as contamination or degradation of samples, or expired reagents.

External Quality Assessment (EQA) is a process that allows laboratories to assess their performance by comparing their results with results from other laboratories within the network (testing and reference laboratories) via panel testing and retesting. EQA also includes the onsite evaluation to review the quality of the laboratory performance. EQA usually evaluates testing competency, the performance of the laboratories, reliability of the testing methods, and accuracy of the results reports, including follow-up for unacceptable EQA results with corrective action. One or more of the following three EQA methods can be applied to COVID-19 molecular testing laboratories.

Proficiency testing (PT) is when an external provider sends a set of SARS-CoV-2 positive and negative simulated clinical samples for testing in different laboratories and the results of all laboratories are analyzed, compared, and reported back to the participating laboratories. Laboratories should select PT providers with a track record in delivering PT panels within their region.

Retesting are samples that have been tested at one laboratory and are retested at another laboratory, allowing for inter-laboratory comparison. A laboratory’s first positive COVID-19 sample should be sent to another testing laboratory, preferably a national or a WHO reference laboratory. In the absence of PT, national COVID-19 laboratories should send five positive and ten negative samples, systematically selected, to WHO reference laboratories for retesting. Similarly, sub-national COVID-19 testing laboratories should send retesting samples to their national COVID-19 reference laboratory.

Onsite evaluation should be performed by experienced subject matter experts, who observe and assess the quality management systems of the COVID-19 testing laboratories across the three testing phases. Onsite evaluation includes Patient Management, Biosafety adherence, Quality control procedures, Staff competency, Sample collection procedures, Standardized testing policies, Documentation and maintenance of records. Onsite evaluation should be conducted at least annually, but preferably every three to six months.

For further information about quality management have a look at the material developed by the Africa Society for Laboratory Medicine and Africa Centres for Disease Control and Prevention available for download below.