What is Quality Control in the modern clinical laboratory?
Quality Control (QC) refers to procedures for monitoring work processes, detecting problems and making corrections prior to delivery of products or services. Statistical QC is a major procedure for monitoring the analytical performance of Clinical Laboratory testing processes.
Laboratory QC is focused on ensuring that patient test results reported by clinical laboratories are accurate. Laboratory QC is designed to detect, reduce and correct deficiencies in a laboratory's internal analytical process which generate patient test results prior to their release and in order to improve the quality of the results reported by the laboratory. QC is a measure of precision, or how well the measurement system reproduces the same result over time and under varying operating conditions.
Laboratory QC materials, such as Multichem, are usually run at defined intervals and when there are changes in the laboratory such as after an instrument is serviced, when reagent lots are changed, after calibration or whenever patient results seem inappropriate. The performance of analytical methods can be monitored by analysing specimens (QC Material) whose concentrations are known, then comparing the observed values (Test Results) to the known values. The known values are usually represented by a range of acceptable values, or upper or lower limits for control (control limits). When the observed values fall within the control limits, this should assure the laboratory personnel that the analytical method is working properly. When the observed values fall outside the control limits, the laboratory personnel should be alerted to the possibility of problems in the analytical results. The known specimens that are analysed for quality control purposes are called “quality control materials”.
Quality control materials should approximate the same matrix as patient specimens, taking into account properties such as viscosity, turbidity, composition, stability and colour. Control matrices are currently available that represent serum/plasma, urine, whole blood, and spinal fluid. They should be simple to use, with minimal vial to vial variability, because variability could be misinterpreted as systematic error in the method or instrument. Quality control materials should be stable for long periods of time and available in large enough quantities from a single batch to last at least 1 year. Quality control materials are available in liquid stable or lyophilised formats. Liquid stable control materials are more convenient than lyophilized control materials because they do not have to be reconstituted minimising pipetting error.
When selecting commercial quality control materials, there are several aspects to be considered. Two or three different control materials should be selected to provide concentrations which monitor assay performance at different medical decision concentrations and/or at critical concentrations (medical and/or performance). This will enable laboratory personnel to estimate random error at critical levels of the method during stable operation. Control materials designed by one manufacturer to have a certain relationship between analyte concentrations can be used to gain additional information regarding linearity and accuracy.
Quality control material can be described as assayed or unassayed. Assayed control material is manufactured with a list of target values and upper and lower limits (control ranges) for all analytes listed in the material. Values may be specified for several of the common analytical methods. While the stated assay values are useful in selecting control materials, the control ranges are provided only as a guideline until the laboratory has established its own statistical limits. Assayed controls are generally more expensive than unassayed controls due to the cost incurred with the manufacturer value-assignment process.
Caution has to be exercised by laboratory personnel when using control materials supplied by the instrument manufacturer. It is recommended and advisable to use control materials made by companies other than instrument manufacturers to provide independent assurance that methods are performing properly. Such control material is commonly referred to as “third party” quality control material. The term “third party” is used to describe quality control materials that help provide an independent assessment of a diagnostic device or method, and is not optimised for any specific instrument or reagent system. Third party control materials are manufactured independently of the test system calibrators and reagents. Such control materials generally begin with a human base matrix that helps provide a material analogous to a patient sample.
Third party quality control materials have distinct advantages over quality control materials that are linked into reagent/calibrator/analyser systems in that these ‘system’ controls are designed for use only on their own test systems, but more importantly, system controls are often manufactured from the same materials as the calibrators. Consequently, the control may mimic the calibrator, making it less sensitive to changes in device performance. This can lead to acceptance of patient test results with analytical error that could be medically important, potentially leading to unnecessary or inappropriate treatments and unwanted outcomes. Often times, a laboratory using an instrument manufacturer or in-kit control may receive a different control lot with each new reagent lot. This does not provide the laboratory with the benefits of long-term QC monitoring.
Third party controls with longer shelf life allow the use of the same lot of control over multiple changes of reagent and calibrator lot numbers. To achieve this, each laboratory should ensure continuous supply for the shelf life of any control material which is viewed as a "critical to quality" factor. This will in turn create a quality environment that will facilitate the following:
- Reduced cross over studies with significant positive impact on cost and efficiencies
- A stable set of reference values for an extended period of time
- The ability to detect shifts that can occur with new reagents and calibrators
- Provides increased compliance with the international standard ISO15189
Multichem® controls are third party liquid ready controls, with a shelf life up to 30 months. Feedback from clinical laboratory opinion currently indicates a minimum requirement of 1 year uninterrupted availability of the same lot of control material. Optimum efficiencies for control material end users is maximised if the same control lot number is available to the end of the in-use control shelf life.