PH 166 Clinical Chemistry Quality Management & Laboratory Safety PDF

PH 166: CLINICAL CHEMISTRY 1 Quality Management and Laboratory Safety Asst. Prof. Raycha Lei Concess M. Rama-Sabandal | January 27, 2025 Definition of Quality Control OUT...

PH 166: CLINICAL CHEMISTRY 1 Quality Management and Laboratory Safety Asst. Prof. Raycha Lei Concess M. Rama-Sabandal | January 27, 2025 Definition of Quality Control OUTLINE ​ Dictionary: A.​ Quality Control ○​ An aggregate of activities (such as design analysis and a.​ Quality inspection for defects) designed to ensure adequate i.​ Definition of Quality Control ii.​ Kinds of Quality Control quality, especially in manufactured products (for us, b.​ Quality Control in the Laboratory test results) i.​ Errors ○​ Process of looking at goods when they are being ii.​ Control Materials produced to make certain that all the goods are of the B.​ Quality Control Chart intended standard a.​ Levey-Jennings (LJ) Chart ​ ISO 9000 (Quality Management): i.​ Steps ii.​ Errors Observed ○​ The operational techniques and activities used to fulfill iii.​ Interpretation requirements for quality iv.​ Westgard Multirule System/ Control Rules ​ In short, quality control ensures that all the activities done v.​ Out of Control Values will produce accurate, reliable and timely results. C.​ Laboratory Workflow ​ Additional: a.​ Errors Arising During Pre-Analytic Phase ○​ Term used to describe the practical steps undertaken b.​ Errors Arising During Analytic Phase to ensure that errors in the analytical data are of a c.​ Errors Arising During Post-Analytic Phase d.​ Minimizing Errors magnitude appropriate for the use to which the data D.​ Laboratory Safety will be put a.​ Laboratory Hazards ​ The unavoidable errors made are quantified to i.​ Chemical Hazard enable a decision whether they are of an ii.​ Biological Hazard acceptable magnitude iii.​ Physical Hazard ​ Unacceptable errors are discovered so that iv.​ Ergonomic Hazard corrective action can be taken, and erroneous b.​ Controlling Laboratory Hazards i.​ Hierarchy of Controls data are not released ii.​ Personal Protective Equipment ​ In short, quality control must detect both random iii.​ Administrative Controls and systematic errors iv.​ Engineering Controls E.​ Review Questions Kinds of Quality Control F.​ References ​ Internal QC - INTRALAB quality control (within the lab) QUALITY CONTROL ○​ involves the in-house procedures for continuous monitoring of operations and systematic day-to-day QUALITY checking of the produced data to decide whether ​ A characteristic or feature of someone or something that these are reliable enough to be released makes it different from other things ​ External QC - INTERLAB quality control (across different ​ The degree of excellence of something, often a high laboratories) degree of it ○​ involves reference help from other laboratories and ​ Of a high standard; excellent characteristic participation in national and/or international ​ In service operations, quality is defined as: interlaboratory sample and data exchange programs ○​ Conformance with the requirements of users and (proficiency testing) customers ○​ Satisfaction of the needs and expectations of users QUALITY CONTROL IN THE LABORATORY and customers ​ A system of ensuring accuracy and precision in the ​ According to WHO, quality in a laboratory setting can be laboratory by including quality control reagents in every defined as accuracy, reliability and timeliness (ART) of series of measurements reported test results ​ A process of ensuring that analytical results are correct ○​ Accuracy: refers to the closeness of a measured by testing known samples that resemble patient samples value to a standard or known value ​ Involves the process of monitoring the characteristics ○​ Reliability: refers to the ability of correctly performing of the analytical processes and detects analytical a task or service over time (like precision) errors during testing, and ultimately prevent the reporting ○​ Timeliness: refers to provision of service at an of inaccurate patient test results appropriate or opportune moment in time ​ One component of the quality assurance system and is a ​ When making measurements, there is always some level part of the performance monitoring that occurs after a test of inaccuracy has been established ○​ The challenge is to reduce this as much as possible ​ The first step in establishing a laboratory quality control ​ Health outcomes depend on the quality of the testing and program is to develop criteria for an acceptable reporting laboratory performance ​ If the quality of laboratory results and services is ○​ How accurate and precise should the laboratory compromised the following may happen: results be? ○​ Delay in delivering correct diagnosis ○​ What constitutes an acceptable analytical error? ○​ Unnecessary treatment ○​ Errors are detected, evaluated, reduced and ○​ Treatment complications subsequently controlled with the hope to control them. ○​ Additional and unnecessary diagnostic testing ○​ Increased cost in time and personnel effort #MagkabigkisBenteSais Group 2 | 1 of 9 ​ Accuracy: closeness of a measurement to its true value Provide a reference Traceable to Used to check ​ Precision: closeness of agreement among a set of results to determine international reliability of a test unknown reference materials system or a test concentrations or or methods, run to calibrate allowing for Bought from analytical comparable and central or reference instruments reliable results laboratories, Used to set or commercially calibrate an prepared, or can be instrument or kit made in-house Figure 1. Accuracy vs Precision. before testing is begun Run after Errors calibrating the Usually provided ​ Errors instrument and run by the ○​ non-conforming results with “statistical meaning” periodically during manufacturer of an testing ○​ inherent in the measurement process and cannot be instrument eliminated simply by repeating the experiment Usually have the ​ Random error same matrix as ○​ affects the precision of a test (reproducibility) patients’ samples ○​ Examples Important term/s: ​ bubbles in reagents or reagent lines Matrix: background components other than the analyte to be ​ instrument instability analyzed. Plasma, serum, urine, and CSF have different ​ have to make sure that instruments are doing matrices. fine ​ temperature variations ​ operator variability e.g. variation in pipetting ​ Systematic error ○​ RECALL: bias; there is a pattern involved ○​ causes inaccurate results that are consistently low or high ○​ Examples ​ change in reagent lot ​ Assay: set of things to be used for the test to be performed ​ Ex. if the reagent is changed due to a different manufacturer, it can greatly affect Figure 2. The Value of Control Materials. especially if the machine is not calibrated for that reagent ​ change in calibration ​ assigning the wrong calibrator values ​ reagents that were improperly prepared or are deteriorating ​ pipettor maintenance error (not adjusted correctly or misaligned) ​ a deteriorating photometric light source in the instrument ○​ All results may go in one direction, either low or high. Control Materials ​ Substances that contain an established amount of the Figure 3. Process of Assessing the Control Materials. substance being tested– the analyte ○​ Eg. A machine using a vial containing 100 mg glucose ​ Running controls in tests: should also produce 100 mg ○​ General steps ​ Tested at the same time and in the same way as patient ​ Obtain control material samples ​ Control Material is run 20 times over 30 days ○​ Patient sample and control sample should be tested at ​ Calculate mean and ±1,2,3 standard deviation the same time to ensure accurate results ○​ Check which run is “in control” or “out of control” ​ Controls should check both low values and high values ○​ Variability is a normal occurrence when a control is ○​ Control can either be abnormal high or abnormal low tested repeatedly but never both ○​ Inquire: Which variation is within acceptable range? ​ Used to validate reliability of the test system Table 1. Standards, Calibrators, Controls. QUALITY CONTROL CHART Standards Calibrators Controls ​ Graphically representing the data from running control Materials A substance with a A substance materials containing a known specific similar to ​ A widely used tool for applying such method of quality concentration of an concentration patients’ samples control in the laboratory analyte (similar matrix) that has an established concentration PH 166 | Quality Management and Laboratory Safety 2 of 9  LEVEY-JENNINGS (LJ) CHART ​ Most common ​ Separate control chart for each method being monitored ​ Separate charts for normal and abnormal controls ​ Mean and standard deviations (SDs) should be noted on the chart ​ Mean and SD are based on at least 20 measurements over 20 runs ​ Mean: the arithmetic average of results 5.​ Label the chart with the name of the test and the lot number of the control being used ​ Standard deviation – measurement of variation in a set of results Errors Observed ​ Trend - occurs when values gradually, but continually, move in one direction for six consecutive days; On the sixth occasion, this is determined to be a trend and results Steps are rejected. 1.​ Calculate the mean and SDs of 20 repeated measurements ○​ Main cause: deterioration of reagents, light source, or of the control value control material Figure 3. Trend ​ Shift – occurs when an abrupt change is followed by six or ​ more consecutive QC results that fall on one side of the ​ X̄ = 190.5, SD = 2.00 mean, but typically within 95% range as if clustered around ​ ± 1SD = 188.5, 192.5 a new mean. On the sixth occasion this is called a shift ​ ± 2SD = 186.5, 194.5 and results are rejected. ​ ± 3SD = 184.5, 196.5 ○​ Main cause: improper calibration of the instrument 2.​ Mean is shown by drawing a line horizontally in the middle of the graph Figure 4. Shift Interpretation 3.​ ± 1, 2 and 3 SDs are marked off at appropriate intervals ​ Using only 1 control (using LJ chart) and lines drawn horizontally on the graph ○​ If control value is within ±2 SD, run is considered “in control” ○​ If control value falls outside ±2 SD, run is considered “out of control” ​ Using 2 or more levels of control (low, normal or high) ○​ Apply Westgard Multirule system 4.​ Label the x-axis with days, runs or other intervals Figure 5. Flowchart for Westgard Multirule System. PH 166 | Quality Management and Laboratory Safety 3 of 9 Westgard Multirule System/ Control Rules ​ Do NOT simply repeat the testing without looking for sources of error and taking corrective action Table 2. Westgard Multirule System ​ Do NOT report patient results until problem is solved and Rule Interpretation Example controls indicate proper performance ​ To solve: 12S ➝ Warning rule ➝ One (1) control ○​ Refer to established policies and procedures for result exceeds the remedial action (standard operating procedures) mean ± 2SD ○​ Manufacturers provide guidelines that can be helpful ➝ Screening purposes ○​ Use any troubleshooting guides that are available ➝ If you only have this ○​ Possible problems to consider include: violation (with at least 2 ​ Degradation of reagents or kits levels of control), the run is still valid although, ​ Control material degradation Figure 6. 12S Rule Violation observation should be ​ Operator error heightened ​ Failure to follow manufacturer’s instructions ​ Outdated procedure manual 13S ➝ One (1) control ​ Equipment failure result exceeds the ​ Calibration error mean ±3SD ➝ Effective in LABORATORY WORKFLOW determining random error ​ Activities in the laboratory are precisely defined and more controllable as compared to other medical units Figure 7. 13S Rule Violation ​ Quality Control (QC) activities pioneered in the laboratory 22S ➝ Two (2) consecutive ​ Despite this, concern emerges from the high degree of control results exceed errors reported in literature either the mean ±2SD ○​ 1 error identified in every: ➝ Respond most often ​ 330 - 1100 events to systematic error ​ 900 - 2074 patients ➝ This will guide you ​ 214 - 8316 results how to troubleshoot the system ​ Divided into three (3) stages: ➝ If you have this ○​ Pre-Analytic Phase (e.g. Patient Preparation, Sample Figure 8. 22S Rule Violation violation, you have to Collection, Sample Receipt, Sample Transport) reject the results ○​ Analytic Phase (e.g. Quality Control Testing) ○​ Post-Analytic Phase (e.g. Reporting and Record R4S ➝ Range/difference Keeping) between the highest and lowest control results within an analytical run exceed 4SD ➝ Two (2) consecutive controls where one exceeds +2SD and the Figure 9. R4S Rule Violation next exceeds -2SD ➝ Respond most often to random error ➝ If you have this violation, you have to reject the results Figure 12. Types & Rates of Error in the 3 Stages of the Laboratory Testing 41S ➝ Four (4) consecutive Process. control results exceed either ±1SD ERRORS ARISING DURING PRE-ANALYTIC PHASE ➝ Respond to ​ Most errors happen in the Pre-analytic Phase systematic error ○​ Includes preparation, collection and transport ➝ If you have this violation, you have to ○​ Highest error rate (involves human handling) reject the results Figure 10. 41S Rule Variation ​ Incomplete laboratory request forms ○​ Comprises 2⁄3 of rejected samples 10X ➝ 10 consecutive ○​ Includes incomplete name, sex, age, etc. control results fall on ​ Wrong patient identification (e.g. mismatching of one side of the mean patients) ➝ Respond to ​ Wrong labeling of specimens (labeling done at the systematic error ➝ If you have this bedside) violation, you have to ​ Inadequate patient preparation reject the results Figure 11. 10X Rule Variation ○​ Recent intake of food, alcohol or drugs, smoking, exercise, stress may affect laboratory results Out of Control Values ​ Improper technique in specimen collection (e.g. ​ STOP testing Prolonged tourniquet application, IV infusion, etc.) ​ Identify and correct problem ​ Wrong specimen transport (e.g. Sample supposed to be ​ Repeat testing on patient samples and controls after placed inside purple top was stored in a red top tube) correction PH 166 | Quality Management and Laboratory Safety 4 of 9  ERRORS ARISING DURING ANALYTIC PHASE ○​ Ingestion Analytic Phase: actual testing and laboratory methods for ○​ Needle-sticks analytes and other specimens ○​ Through broken skin ​ Equipment malfunction ​ Adverse effects to health: ​ Sample mix up or interference ○​ Corrosive ​ Undetected failure in QC ○​ Allergens ​ Procedure NOT followed ○​ Irritants ○​ Asphyxiants ERRORS ARISING DURING POST-ANALYTIC PHASE ○​ Carcinogens Post-Analytic Phase: includes reporting of results and ○​ Mutagenic documentation for safekeeping ○​ Reproductive toxicants ​ Failure in reporting ○​ Systemic poisons ​ Erroneous validation of analytical data Biological Hazard ​ Improper data entry ​ Also known as biohazards ​ Excessive turn-around time ​ Refer to biological substances that pose a threat to health ○​ Turnaround time (TAT): Time taken to fulfill or complete ​ Sources: a request ○​ blood and body fluids ​ Key performance indicator of laboratory ○​ culture specimens performance ○​ body tissue and cadavers ​ Objective: minimize TAT since there are requests ○​ laboratory animals infected with pathogens needed to be done urgently ​ Routes of exposure: ○​ Skin puncture or injection MINIMIZING ERRORS ○​ Dermal absorption ​ Improved communication and collaboration between ○​ Ingestion laboratory and healthcare professionals ○​ Inhalation ○​ Formation of a “multidisciplinary team” ○​ Develop collaborative approaches to existing policies Physical Hazard ​ Ex. standardized labelling (PGH - electronic ​ Elements in the laboratory work environment that hold markers) potential to cause physical harm ​ Staff education and training ​ Examples: ​ Regular reporting and feedback ○​ Hot or Cold temperature ​ Strictly following protocols ○​ Poor illumination ○​ Setting criteria for rejection of samples ○​ Radiation ○​ Follow standards for transporting specimen ○​ Slips, trips and falls ​ Criteria for rejecting samples: ○​ Electrocution ○​ Unlabeled sample ○​ Compressed gas and cryogenic hazard ○​ Broken or leaking tube/container Ergonomic Hazard ○​ Insufficient patient information ○​ Sample label and patient name on the test request ​ When the type of work, body position and working form do not match conditions put strain on your body ○​ Hemolyzed sample (depending on test requested) ​ Repetitive motion injuries develop over time and occur ​ due to long tourniquet time when muscles and joints are stressed, tendons are ○​ Non-fasting samples, for tests that require fasting inflamed, nerves are pinched and the flow of blood is ○​ Sample collected in wrong tube/container restricted ○​ Inadequate volume for the quantity of preservative ​ Examples: ​ There are preservatives in each tube and an ○​ Poor lighting indicated bar. Some can be short filled but for ○​ Improperly adjusted workstations and chairs others it is nonnegotiable to fill it completely for ○​ Poor posture correct blood to additive ratio. ○​ Using too much force ○​ Insufficient quantity for the test requested ○​ Prolonged transport time or other poor handling CONTROLLING LABORATORY HAZARDS during transport Hierarchy of Controls ​ Implementation of new technology ○​ Patient identification system ○​ Computerized specimen labelling ○​ Automated releasing of results LABORATORY SAFETY LABORATORY HAZARDS Chemical Hazard ​ ​ Chemicals may have immediate, acute effects, as well as chronic effects that are often brought by long-term exposures ​ Includes gases, vapors, liquids and aerosols (dusts, fibers, fumes, mists, fogs) ​ Routes of exposure: ○​ Inhalation ○​ Contact Figure 14. Hierarchy of Controls by OSHA Academy. PH 166 | Quality Management and Laboratory Safety 5 of 9  ​ Body protection ○​ Protects the body from splashes of chemicals, biohazard exposure, temperature extremes, potential impacts from tools, etc. ○​ E.g. Laboratory coats, coveralls, aprons, surgical gowns ​ Hand protection ○​ Protects the hands from chemical spills and splashes, biohazard contact and thermal protection. ○​ E.g. Gloves Figure 13. Hierarchy of Controls. Administrative Controls ​ Also called work practice controls ​ A concept/framework used in occupational health to ​ Changes in work procedures, such as: protect safety of workers. ○​ Written safety policies, rules, supervision, schedules, ​ Used to determine feasible and effective control and training (with the goal of reducing the duration, solutions to known hazards in the workplace. frequency, and severity of exposure to hazardous ​ Control method at the top of the pyramid is more chemicals or situations). effective and protective than those at the bottom. ​ Standardize hazard communication through: ​ The wider the area, the more effective it is in reducing ○​ Labels, symbols and pictograms harm (BSPH 2025). ○​ e.g. Global Harmonization System of Classifying and Labeling Chemicals (GHS) ELIMINATION ​ Availability of Material Safety Data Sheet (MSDS) for ​ Most effective method of controlling against the hazard. each chemical reagent which contains the following ​ It is more effective if you'll eliminate the hazard, but it is not information: possible. 1.​ Name of the chemical ​ Example: Physically removing the hazard 2.​ Manufacturer’s information 3.​ Hazardous ingredients/ identity information SUBSTITUTION 4.​ Physical/ Chemical characteristics ​ Can be done if hazard cannot be eliminated (since not 5.​ Fire and explosion hazard data everything can be removed). 6.​ Reactivity data ​ Example: Replacing the hazard 7.​ Health hazard data 8.​ Precautions for safe handling and use ENGINEERING CONTROLS 9.​ Control measure (varies by chemical) ​ Done if substitution cannot be carried out. ​ Use of signages ​ Measures and procedures that can isolate the person from the hazard. ​ Example: Fume hoods, biosafety cabinets ADMINISTRATIVE CONTROLS ​ Administrative tasks, policies, or guidelines that aim to change the way that people work. ​ Warnings are also part of the administrative controls. ​ Example: Standard Operating Procedures (SOPs), changing work practices, shifts/rotations. PERSONAL PROTECTIVE EQUIPMENT (PPE) ​ Least effective method of controlling hazards. ​ Protects workers with personal protective equipment ​ Example: lab gowns, masks, gloves, closed shoes, etc. Personal Protective Equipment ​ An equipment worn to minimize exposure to a variety of hazards. ​ It should be safe and reliable in design and construction; and comfortable, fit and clean when in use. ​ Proper use of PPE can make the difference between being safely covered and dangerously exposed. ​ Eye protection ○​ Protects eyes from chemical splashes from corrosive Figure 15. Examples of common signages in laboratories. substances, hot liquids, solvents or other hazardous solutions. ​ Universal precautions ○​ E.g. Protective glasses or goggles ○​ Recommendations designed and introduced by CDC ​ Face protection in 1987. ○​ Blocks large-particle droplets, splashes, sprays or ○​ Growing concern for occupational exposure to splatter of chemicals or solutions, keeping it from diseases based on epidemiologic evidence on the reaching the mouth and nose. transmission route of Hepatitis B virus (HBV) and ○​ E.g. Facemask Human Immunodeficiency Virus (HIV). PH 166 | Quality Management and Laboratory Safety 6 of 9  ​ Blood has been found to be the single most b.​ Mean and SD are based on at least 20 measurements important source of HIV and HBV. over 20 runs ​ “Treat all blood samples as potentially infectious c.​ It is the most common quality control chart for HIV, HBV and other blood borne pathogens.” d.​ All of the above ​ Stretching 5.​ Which of the following statement/s is/are FALSE ○​ To lessen injuries in the long run especially during regarding the Westgard Multirule System? repetitive motion (e.g. during pipetting) (BSPH 2025). I.​ Both 13S and R4S rule violations are similar when it comes to the type of error they respond to. II.​ The 41S rule violation commits random error on the fourth day of having invalid control results III.​ The 12S rule violation states that if one (1) control result exceeds the mean ± 2SD, then the results must be rejected. IV.​ Using the quality control chart, the main basis of rejecting the control results under the 10X rule violation is the mean. Figure 16. Stretching techniques. a.​ I and IV​ ​ ​ ​ c. Only I Engineering Controls b.​ II, III, and IV​ ​ ​ d. II and III ​ Methods that are built into the design of a plant, 6.​ Which of the following statements is correct? equipment or process to minimize the hazard. ​ Very reliable way to control worker exposures as long as First statement: The pre-analytic phase has the the controls are designed, used and maintained properly. highest error because it includes machine and human ​ Example: Fume Hood - a ventilation system that provides errors in preparation, collection and transport of protection against toxic fumes, vapors and dust samples. Second statement: When having out of control values, the best action to take is to stop the testing immediately, identify the problem, and repeat testing on patient samples and controls after correction without looking for sources of error. Third statement: Failure to detect invalid results using the quality control chart is a common error during the post-analytic phase of the laboratory testing process. Fourth statement: It is ideal to have an excessive turnaround time to ensure that a patient’s laboratory findings are all accurate and precise since these are Figure 17. Fume hood. critical in determining their real condition. REVIEW QUESTIONS a.​ The first and third statements are both correct while 1.​ What is the definition of quality in a laboratory setting the second and fourth statements are both false. according to WHO? b.​ Only one of the statements is true. a.​ Conformance with the requirements of users and c.​ Only the second statement is false. customers d.​ The first and second statements are both false while b.​ Accuracy, reliability, and timeliness of reported test the last two are both correct. results e.​ None of the statements is true. c.​ Excellent characteristic of a high standard d.​ Degree of excellence of something 7.​ Which of the following is an example of a physical hazard in the laboratory? 2.​ What is the primary goal of internal quality control in a a.​ Accidental ingestion of a toxic chemical laboratory? b.​ Exposure to bloodborne pathogens from a a.​ To compare results with other laboratories contaminated needle b.​ To participate in international interlaboratory programs c.​ Compressed gas and cryogenic hazard c.​ To determine whether the data are reliable enough to d.​ Developing an allergic reaction from prolonged be released to clients or patients chemical exposure d.​ To monitor long-term accuracy 8.​ What are the major contributing factors to repetitive 3.​ Which of the following control materials usually have strain injuries? the same matrix as patients’ samples? a.​ Position/posture, applied force, and frequency a.​ Standards of repetition b.​ Calibrators b.​ Inattention on the part of the laboratorian c.​ Controls c.​ Temperature and vibration d.​ Both a and b d.​ Fatigue, clumsiness, and lack of coordination 4.​ Which of the following is true about Levey-Jennings 9.​ Which of the following is an example of an (LJ) Chart? administrative control? a.​ Mean and standard deviations (SDs) should be noted a.​ Developing a new safety protocol on the chart b.​ Wearing gloves c.​ Replacing a hazardous chemical with a safer one PH 166 | Quality Management and Laboratory Safety 7 of 9  d.​ Using a biosafety cabinet 10.​ If a laboratory hazard cannot be eliminated, what is the next most effective control method to implement? a.​ Personal Protective Equipment (PPE) b.​ Administrative Controls c.​ Engineering Controls d.​ Substitution ANSWER KEY 1.​ B 6.​ E 2.​ C 7.​ C 3.​ B 8.​ A 4.​ D 9.​ A 5.​ D 10.​ D REFERENCES ​ Rama-Sabandal, R. (2025). Quality Management and Laboratory Safety [Slides]. https://drive.google.com/file/d/1JSzjbL12L9o9km_1fdepNUFha-M Y39Lf/view. ​ Bishop, M. L. (2020). Clinical chemistry: Principles, techniques, and correlations, Enhanced Edition. Jones & Bartlett Learning. PH 166 | Quality Management and Laboratory Safety 8 of 9  APPENDICES PH 166 | Quality Management and Laboratory Safety 9 of 9