CONTROL OF ANALYTICAL VARIABLES

CONTROL OF ANALYTICAL VARIABLES

Analytical error contributes to 20-30% of total error. Many analytical variables must be controlled carefully to assure accurate measurements by analytical methods. Reliable analytical methods are obtained by a careful selection, evaluation, implementation, maintenance and control. Certain variables like water quality, calibration of analytical balances, calibration of volumetric glassware and pipettes, stability of electrical power and temperature of heating baths, refrigerators, freezers, and centrifuges should be monitored as they will affect analytical methods. The control of analytical variables includes,

Choice of analytical methodology – 

Before implementing the method, the overall performance of the method should be checked in the given setting. Those methods whose performance is satisfactory and that is cost effective must be used. Also the reagent stability for long time is desirable.

Reference material and calibration – 

The quality of calibrators and the calibration procedures used are major factors in determining the reliability of the analytical values. The highest quality methods, the definitive methods are to be used to validate reference method and primary reference material. The highest quality reference materials, namely primary reference materials should be used in the development and validation of reference method, calibration of definitive and reference methods, and the production of secondary reference materials. Reference methods should be used to validate field methods. Secondary reference material produced from reference method should be used to provide working calibrators for field methods and to assign values to control materials. Control materials are used only to monitor field methods. Method validation or external quality assurance of field method should be done by reference method and method validation of reference method should be done by definitive method.

Reference material (RM): A material or substance whose property are sufficiently homogenous and well established to be used for calibration of apparatus, assessment of method, or assigning values to materials.

Certified reference material (CRM): A Reference Material, accompanied by a certificate, whose property is certified by a procedure

Calibration material and/or calibrator: A material or device of known characteristics (e.g. concentration, activity, intensity, and reactivity) used to calibrate, graduate, or adjust a measurement procedure or to compare the response obtained with the response of a test specimen and/ or sample.

Control material: A device, solution, or preparation, or pooled collected from human or animal specimen or artificially derived material, intended for use in quality control process.

Documentation of analytical protocols: 

Reproducibility of the method should be maintained by maintaining written protocol or method and procedure manuals. These includes procedure name, clinical significance, principle of method, specimen requirement (volume, patient preparation, interference, minimum requirement for acceptance, criteria of rejection, etc), reagents and equipment’s (including standards along with suppliers, instruction for preparation), procedure (process of performing test, QC procedures, calculations), reference values (may be stratified, should include nature of population studies), comments (variable affecting test like pH temperature, effect of drugs, hazards, safety precautions, etc.), references (to literatures).

Monitoring technical competence: 

Proper training of laboratory personnel to achieve uniformity in technique is important. Personnel should be training for new method.

Inventory control of materials - 

Procedures is necessary to inventory materials and initiate orders when supplies are low. When materials are stable and changes in lot numbers cause problems, large stocks should be maintained. Adequate inventory should be maintained to allow time for additional shipment and testing of additional supplies. Along with the inventory management, the quality of materials purchases should be monitored when they are received like expiry date, adequate volume, control materials, manufactured date, storage condition, etc.

Control of analytical quality using stable control material and control charts

The performance of analytical methods is routinely monitored by analyzing specimens whose concentrations are known followed by comparing the observed values with the known values. The known values are usually represented by an interval of acceptable values, or upper and lower limits for control. When the observed values fall within the control limits, the analyst is assured that the analytical method is functioning properly. When the observed values fall outside the control limits, the analyst should be alerted to the possibility of problems in the analytical determination.

Control material: 

Specimens analyzed for QC purpose are called control materials. They must be stable, available in aliquots or vials. There should be little vial to vial variation so that differences between repeated measurements are attributed to the analytical method alone. The control material should preferably have the same matrix as the test specimens of interest (e.g., a protein matrix may be best when serum is the test material to be analyzed). 

Materials from human sources are preferred but due to some risk of hepatitis infection bovine materials offer a certain advantage in safety are readily available. The concentration of analyte should be in normal and abnormal ranges, corresponding to concentrations that are critical in the medical interpretation of the test results. These control material are supplied as liquid or lyophilized materials they are reconstituted by adding water or diluent solution. Assayed control materials come with a list of values for the concentrations that are expected for that material. Control material for internal quality control can be made by pooling serum samples, screen for presence of infective disease, adjusted to pH 7.1 by concentrated sulphuric acid, aliquot and freeze. Each day 1 vial is taken brought to room temperature and tested.