1. CLSI EP23™—Laboratory Quality Control Based on Risk Management
James H. Nichols, PhD, DABCC, FACB
Chairholder
EP23 Document Development Committee
Professor of Clinical Pathology, Microbiology and Immunology
Vanderbilt University School of Medicine
Medical Director, Clinical Chemistry
Nashville, Tennessee, USA

2. Objectives Review key aspects of risk management.
Describe the various types of control processes.
Identify CLSI document EP23 as a resource for developing a laboratory quality control (QC) plan based on risk management.
Use CLSI document EP23 to develop a quality control plan (QCP) based on risk management for a simple, moderate complexity device.

3. Would you walk underneath this piano?
Risk
Would you walk underneath this piano?

4. Risk Management Risk management is not a new concept; laboratories:
Evaluate the performance of new devices.
Troubleshoot instrument problems.
Respond to physician complaints.
Estimate harm to a patient from incorrect results.
Take actions to prevent errors.
Risk management is a formal term for what clinical laboratories are already doing every day.

5. Risk Management Definition
Systematic application of management policies, procedures, and practices to the tasks of analyzing, evaluating, controlling, and monitoring risk (ISO 14971)

6. Risk Definition
Risk – the chance of suffering or encountering harm or loss (Webster's Dictionary and Thesaurus. Ashland, OH: Landall, Inc.; 1993).
Risk can be estimated through a combination of the probability of occurrence of harm and the severity of that harm (ISO/IEC Guide 51).
Risk, essentially, is the potential for an error to occur that could lead to patient/staff harm.

7. What could go wrong?

8. Sources of Laboratory Error
Environmental:
– Temperature
– Humidity
– Light intensity
– Altitude
Operator:
– Improper specimen preparation, handling
– Incorrect test interpretation
– Failure to follow test system instructions
Specimen:
– Bubbles
– Clots
– Incorrect tube additive
Analysis:
– Calibration factor incorrect
– Mechanical failure

9. Managing Risk With a Quality Control Process

10. Quality Control Advantages Disadvantages
QC monitors the end product (result) of the entire test system.
QC has target values: if assay recovers the target, then everything is assumed stable (ie, instrument, reagent, operator, sample).
Disadvantages
When a problem is detected, one must go back and reanalyze patients since the last “good” QC.
If results are released, then results may need to be corrected.
Need to get to fully automated analyzers that eliminate errors up front
Until that time, need a robust QC plan (QCP)

11. Types of Quality Control
“On-Board” or Analyzer QC – built-in device controls or system checks
Internal QC – laboratory-analyzed surrogate sample controls
External QC – blind proficiency survey
Other types of QC – control processes either engineered by a manufacturer or enacted by a laboratory to ensure result reliability

13. Quality Control Limitations
No single QC procedure can cover all devices, because the devices may differ.
QC practices developed over the years have provided laboratories with some degree of assurance that results are valid.
Newer devices have built-in electronic controls, and “on-board” chemical and biological controls.
QC information from the manufacturer increases the user’s understanding of device’s overall quality assurance requirements.
ISO. Clinical laboratory medicine – In vitro diagnostic medical devices – Validation of user quality control procedures by the manufacturer. ISO Geneva, Switzerland: International Organization for Standardization; 2004.

14. Laboratory- Manufacturer Partnership
Developing a quality plan surrounding a laboratory device requires a partnership between the manufacturer and the laboratory.
Some sources of error may be detected automatically by the device and prevented, while others may require the laboratory to take action, such as analyzing surrogate sample QC on receipt of new lots of reagents.
Clear communication of potential sources of error and delineation of laboratory and manufacturer roles for how to detect and prevent those risks is necessary.

15. Quality Control

16. CLSI Document EP23
Laboratory Quality Control Based on Risk Management; Approved Guideline (EP23-A™)
James H. Nichols, PhD, DABCC, FACB, Chairholder of the document development committee
EP23 describes good laboratory practice for developing a QCP based on the manufacturer’s risk mitigation information, applicable regulatory and accreditation requirements, and the individual health care and laboratory setting.

17. The Scenario
CLSI document EP23 provides guidance on developing an appropriate QCP that will:
– Save time and money.
– Use electronic and/or integrated QC features.
– Use other sources of QC information.
– Conform to one’s laboratory and clinical use of the test.

18. Developing a QCP

19. The Quality Control Toolbox
Every QC tool has its strengths and weaknesses (there is no perfect QC tool).
Implement a combination of tools in order to properly control a test.
EP23 explains the strengths and weaknesses of the different QC processes.

20. Examples of Quality Control Tools
Intralaboratory QC
Interlaboratory QC
Integrated (built-in) QC
Measuring system function checks
Electronic system checks
Calibration checks
Repeat testing of patient samples
Monitoring aggregated patient results
Implausible values
Delta checks
Correlation of multiple analytes in same sample

21. What Could Go Wrong?

22. Gather Information for the Risk Assessment
Gather information from several sources:
– Regulatory and accreditation requirements
Clinical Laboratory Improvement Amendments Test/test system information
User’s manual, reagent package insert, literature
– Health care and testing site settings
Temperature conditions, operator training programs
– Medical requirements for the test results
Allowable performance specifications via physicians

23. Developing a Process Map
Break down all phases of the test or test system into steps, so that weak points can be identified.
Each step can be analyzed to find potential failure modes that could present significant risk to patients.
Process can then be further analyzed to see if controls can be put into place to avoid the failures.

24. Process Map

25. Key Process Steps
View the preexamination (preanalytical), examination (analytical), and postexamination (postanalytical) areas of the laboratory.
Think about what steps can be taken to reduce potential errors “unrelated” to the actual testing of the sample.

26. Where Is the Risk in the Process?
What could possibly go wrong?

27. Identify the Risks

28. Hazard or Risk Identification
Some areas to consider for weaknesses in the process:
Testing personnel training and competency
Reagent/calibrator/parts procurement and storage
Patient sample acceptability
System startup
System calibration
Loading and testing of patient samples
Proper device function
Test result review

29. Risk Assessment

30. Perform the Risk Assessment
Identify the potential failures and their causes.
– Review the process map, fishbone diagram, manufacturer’s instructions, etc.
Assess each potential failure.
Where a failure could occur, add an element to the QCP that will reduce the possibility of that failure, making residual risk acceptable.
– For some types of failures, the manufacturer’s information may already have a quality check in place.

31. Perform the Risk Assessment (cont’d)
Construct a table; see which types of errors are detected and which ones are not.
– If not detected, it must be included in the QCP.
For each possible failure, assess the possibility of that failure.
– Do this for each identified failure.
– Use all of the information gathered in order to make these assessments.

32. Assemble the Quality Control Plan
Use the information gathered earlier to assess all of the identified risks and their control measures.
Construct the QCP.
Include each of the identified QCP actions in the QCP.

33. What could go wrong?

34. Monitor Quality Control Plan for Effectiveness
Verify that the QCP that is put in place actually works.
Continue to monitor errors and control failures.
If an error occurs:
– Take the appropriate corrective action.
– Investigate the cause of the error.
– Once the cause is understood, evaluate whether any changes need to be made in the QCP.

35. Monitor Quality Control Plan for Effectiveness (cont’d)
Review any complaints that the laboratory receives from health care providers.
– These complaints may include pointing out another source of QC “failure” that must be addressed.
For patient safety, the QCP should be reviewed and monitored on an ongoing basis to ensure that the QCP is optimal.

36. Don’t Be Discouraged—Risk Management Is Documenting Much of What We Already Do!

37. Polling Question #1 What is a QCP?
The frequency of liquid controls for a test
A form that defines required specifications of materials from suppliers
A document that describes the practices, processes, and sequences of specified activities to control the quality of a particular measuring system
None of the above

38. A laboratory director wants to develop a QCP
The Scenario
A laboratory director wants to develop a QCP
– Incorporates the right QC processes for the specific test
– Uses adequate QC to control for their potential error sources
– Follows manufacturer’s instructions
A unit-use blood gas analyzer will be used as the example.

39. Developing a Quality Control Plan

40. Polling Question #2
Raise your hand if you are responsible for blood gas or electrolyte testing in your facility, or if you are a manufacturer or distributor of blood gas/electrolyte test systems.

41. Gather the Information

42. Blood Gas and Electrolytes
Generic unit-use blood gas/lytes analyzer in a same-day surgical center
Low volume: tests/day
Need for daily liquid QC uses two kits ($10 each) and adds to turnaround time (TAT).
Adoption of nontraditional QC through EP23 would improve cost, test, and labor efficiency.

43. Blood Gas and Electrolytes
Portable clinical analyzer for in vitro quantification of various analytes in whole blood
Analyzers and cartridges should be used by healthcare professionals trained to use the system according to the facility’s policies and procedures.

44. Blood Gas and Electrolytes
System consists of:
Portable clinical analyzer
Test cartridges sealed in foil pouch for protection during storage
Quality assurance materials
Control solutions
Calibration verification set
Data Management System
Server class computer
Data management software
Wireless connectivity and LIS/HIS interfaces
Device
Device
Device
Device

45. Blood Gas and Electrolytes
Unit use cartridge contains all components to perform the testing
– Calibrating solution
Reagents
Sample handling system
Sensors
Analyzer automatically controls all steps of the testing process:
Fluid movement
Calibration
Reagent mixing
Thermal control

46. Cartridge Operations
Cartridges are standardized to plasma core lab methods using multi-point calibration curves stored in the device memory that are stable over many lots
Upon insertion, a calibrant solution in the cartridge is passed across the sensors.
Signals produced by the sensor’s responses to calibrant are measured – A one-point calibration adjusts the offset of stored multi-point calibration curve.
Analyzer then moves sample over sensors, and the signal of the sensor responses to the sample are measured off the adjusted calibration curve

47. Polling Question #3
What types of quality control processes can help laboratories manage their risk of errors for a blood gas/electrolyte test system?
Liquid quality control samples
Manufacturer checks and simulated internal electronic controls
Staff training and competency
All of the above

48. Internal Control Processes
Simulated internal QC - diagnostic check of the edge connector, internal electronics, and analyte circuitry.
Internal QC simulates electronic signals produced by the sensors during a cartridge test.
An isolated region of the internal circuit board sends a range of simulated sensor signals through the cartridge measurement channels
Range of signals encompasses entire linear range expected from blood analytes
Next, conductivity out of the connector pins is measured, insuring no contamination is present in the edge connector which would interfere with the test.
Signal measurements must fall within strict predetermined thresholds to pass.

49. Quality Control Recommendations
Internal Simulated QC:
Automatically performed by device every 8 hrs
If significant change in analyzer temp (cold to hot)
Whenever performance of device in question
Liquid QC:
Each shipment of cartridges
New lots of cartridges
If cartridges experience temperature shift >8°C (15°F)
Periodically as required by facility policies
Temperature Verification
Monitored continuously during each patient test, but verification cartridge available and recommended annually, or as required by facility policy

50. Identify Weak Steps for Hazards or Risk of Error
Create a Process Map
Identify Weak Steps for
Hazards or Risk of Error

51. Polling Question #4
What are some common sources of error for a blood gas/electrolyte test system?
Shipping and storage temperature of cartridges
Operator technique
Device failure
All of the above

52. Finding the Failure Points Hazard Identification

53. Process Map: Finding the Failure Points
Work from the current package insert
Test order – electronic or hardcopy
Test collection
Incorrect collection – bubbles, sample exposure to air
Wrong tube type – calcium titrated, heparinized BG tubes
Indirect phlebotomy – line draw contamination
Undermixing/overmixing – sample clots, hemolysis
Analytic delay – glucose, BG, pH, iCa, etc.
Analysis
Wrong sample volume loaded onto cartridge
Incorrect procedure, timing, result interpretation
Expired reagent
Reagent exposure during shipment
Degradation during storage
Infection Control
Result reporting errors

54. Conduct a Risk Assessment
Identify Control Processes for Each Hazard That Maintain Risk at a Clinically Acceptable Level

55. Blood Gas and Electrolytes Risk Assessment
Refer to Appendix A, CLSI document EP18 for a more comprehensive list of error sources.
Work from the manufacturer’s current package insert.
Samples
Physician order – POCT possible w/o order, need written or electronic physician order before commencing test.
Wrong tube type – train to use BG syringes/tubes
Line contamination – train on preferred collection and techniques if catheter collection is only option
Sample mixing – analyzer has clot detection, but will not detect hemolysis - train on proper mixing technique
Analytic delay – YES – train to analyze immediately, no longer than mins of collection

56. Blood Gas and Electrolytes Risk Assessment (cont’d)
Operator
Operator lock-out – prevents use of analyzer by untrained operators
Sample volume detection – Analyzer detects inadequate sample volume and prevents overloading.
Incorrect procedure, timing, result interpretation – analysis and result interpretation fully automated, clotted sample or bubbles will be detected by analyzer.
Expired reagents – cartridges are bar-coded with lot number and expiration date, analyzer prevents use past expiration
Wireless Connectivity – data management automates reporting of result provided patient properly identified, train on proper patient ID, use barcoded wristbands
Infection control – train to clean and disinfect after each use

57. Blood Gas and Electrolytes Risk Assessment
Reagents
Test exposure outside specifications (eg, temperature, humidity) during shipment – analyze liquid QC with each shipment
Lot-to-lot variability – analyze liquid QC with each lot
Liquid QC degradation – monitor refrigerator (2 to 8°C), bring to room temperature at least 30 minutes before use, discard within 30 days of opening bottle
Degradation during storage – monitor storage conditions, room temp for 2 years). If refrigerated, bring to room temperature at least 30 minutes before use, (analyze liquid QC due to temp change). What about other QC frequency?

58. Polling Question #5
How should laboratories determine the optimal frequency of liquid quality controls?
Refer to the manufacturer’s package insert recommendations
Identify local and regional regulatory requirements
Conduct a risk assessment
All of the above

59. Liquid Quality Control Frequency
Minimum – follow manufacturer recommendations and regulatory requirements (CLIA for BG analysis – one QC sample q 8 hr, two levels q 24 hrs, one QC w/ each pt sample unless calibration every 30 mins)
Manufacturer recommends liquid QC with each
Shipment
New lot
Significant change in cartridge temperature (>8°C)
Whenever question of test system performance
Options for determining liquid QC frequency
Peer publications – verify what others are already doing
Develop QC rules based on six-sigma of test system
Verify in your facility:
analyze 2 levels each day for several weeks, then reduce to every few days, weekly or monthly after more experience with test system
QC-lockout assists with compliance

60. Blood Gas and Electrolytes Risk Assessment (cont’d)
Environment
Incorrect collection – train staff anaerobic phlebotomy
Compliance with documentation – risk bases on prior issues with other testing noted at this location (refrigerator monitoring, QC documentation, etc.)
Clinical Application
Immediate medical decisions – test results used to manage critical patients, higher risk since only one chance to get right result!
Sample not stable – analyze immediately, presents higher risk since can’t be repeated!

61. Summarize the
Quality Control Plan

62. Blood Gas and Electrolytes Quality Control Plan
Analyze liquid QC.
Each new shipment*
Start of a new lot*
After significant change in cartridge temperature (>8°C) *
Whenever uncertainty about analyzer performance*
Monthly (based on facility verification and experience with test)
Note: Simulated multi-level quality control automatic every 8 hours and internal calibration with each test cartridge **
Use checklist to document training/competency.
Test only when electronic or written physician order
Proper patient identification
Use BG syringes/tubes for specimen collection
Arterial BG collection (preferred), or line draws as required
Use anaerobic technique
Mix specimens appropriately and analyze immediately
Monitor refrigerator and room temperatures
Clean and disinfect analyzers after each use *
(* Manufacturer recommendations) (** Mandated by accreditation regulations)

63. What should a laboratory do once a QCP is drafted?
Polling Question #6
What should a laboratory do once a QCP is drafted?
Have a party; the laboratory has now proved the quality of its test.
Nothing; once developed, the QCP is the end of the risk management process.
Monitor its QCP for effectiveness, and modify the plan as needed.
None of the above.

64. Monitor for Failure/Errors and Modify Quality Control Plan as Needed
Implement the
Quality Control Plan
Monitor for Failure/Errors and Modify Quality Control Plan as Needed

65. Quality Control Plan Implementation: BG/Electrolyte Monitors
Frequency of analyzer error codes
Liquid QC failure rates
Frequency of specimen issues – hemolysis, clots, or other problems
Number of physician complaints: results that don’t match clinical situation
Any other unexpected error

66. Risk Management will help you learn about your processes and weaknesses

67. Summary
Risk management is something laboratories are already doing. EP23 simply formalizes this.
A QCP is necessary for result quality, and each QCP is unique.
A QCP is the industry standard. It depends upon the extent to which the device’s features achieve their intended purpose in union with the laboratory’s expectation for ensuring quality results.
Once implemented, the QCP is monitored for effectiveness and modified as needed to maintain risk at a clinically acceptable level.

68. Now that you’ve survived this…