§ 493.1218 - Standard; Control procedures.

Control procedures are performed on a routine basis to monitor the stability of the method or test system; control and calibration materials provide a means to indirectly assess the accuracy and precision of patient test results. Control procedures must be performed as defined in this section unless otherwise specified in §§ 493.1223 through 493.1285 of this subpart.

(a) For each device cleared by the FDA as meeting certain CLIA requirements for quality control, the laboratory must, at a minimum, follow the manufacturer's instructions for control procedures. In addition, the laboratory must meet the requirements under paragraphs (c) through (e) of this section and, as applicable, paragraph (f) of this section.

(b) For each device, as specified in either § 493.1202 (a) or (b) or § 493.1203(a), the laboratory must evaluate instrument and reagent stability and operator variance in determining the number, type, and frequency of testing calibration or control materials and establish criteria for acceptability used to monitor test performance during a run of patient specimen(s). A run is an interval within which the accuracy and precision of a testing system is expected to be stable, but cannot be greater than 24 hours or less than the frequency recommended by the manufacturer. For each procedure, the laboratory must monitor test performance using calibration materials or control materials or a combination thereof.

(1) For qualitative tests, the laboratory must include a positive and negative control with each run of patient specimens.

(2) For quantitative tests, the laboratory must include at least two samples of different concentrations of either calibration materials, control materials, or a combination thereof with the frequency determined in § 493.1218(b), but not less frequently than once each run of patient specimens.

(3) For electrophoretic determinations—

(i) At least one control sample must be used in each electrophoretic cell; and

(ii) The control sample must contain fractions representative of those routinely reported in patient specimens.

(4) Each day of use, the laboratory must evaluate the detection phase of direct antigen systems using an appropriate positive and negative control material (organism or antigen extract). When direct antigen systems include an extraction phase, the system must be checked each day of use using a positive organism.

(5) If calibration materials and control materials are not available, the laboratory must have an alternative mechanism to assure the validity of patient test results.

(c) Control samples must be tested in the same manner as patient specimens.

(d) When calibration or control materials are used, statistical parameters (e.g., mean and standard deviation) for each lot number of calibration material and each lot of control material must be determined through repetitive testing.

(1) The stated values of an assayed control material may be used as the target values provided the stated values correspond to the methodology and instrumentation employed by the laboratory and are verified by the laboratory.

(2) Statistical parameters for unassayed materials must be established over time by the laboratory through concurrent testing with calibration materials or control materials having previously determined statistical parameters.

(e) Control results must meet the laboratory's criteria for acceptability prior to reporting patient test results.

(f) Reagent and supply checks. (1) The laboratory must check each batch or shipment of reagents, discs, stains, antisera and identification systems (systems using two or more substrates) when prepared or opened for positive and negative reactivity, as well as graded reactivity if applicable.

(2) Each day of use (unless otherwise specified in this subpart), the laboratory must test staining materials for intended reactivity to ensure predictable staining characteristics.

(3) The laboratory must check fluorescent stains for positive and negative reactivity each time of use (unless otherwise specified in this subpart).

(4) The laboratory must check each batch or shipment of media for sterility, if it is intended to be sterile, and sterility is required for testing. Media must also be checked for its ability to support growth, and as appropriate, selectivity/inhibition and/or biochemical response. The laboratory may use manufacturer's control checks of media provided the manufacturer's product insert specifies that the manufacturer's quality control checks meet the National Committee for Clinical Laboratory Standards (NCCLS) for media quality control. The laboratory must document that the physical characteristics of the media are not compromised and report any deterioration in the media to the manufacturer. The laboratory must follow the manufacturer's specifications for using the media and be responsible for the test results.

Note:

A batch of media (solid, semi-solid, or liquid) consists of all tubes, plates, or containers of the same medium prepared at the same time and in the same laboratory; or, if received from an outside source or commercial supplier, consists of all of the plates, tubes or containers of the same medium that have the same lot numbers and are received in a single shipment.