1. The New EP23 ‒ Laboratory Quality Control Based on Risk Management, Approved Guideline
Luann Ochs, MS
Senior Vice President – Operations
Clinical and Laboratory Standards Institute

2. Objectives Describe the various types of control processes.
Identify CLSI document EP23-A as a resource for developing a laboratory quality control (QC) plan based on risk management.
Review key aspects of risk management.

3. Today’s Quality Control
Advantages
QC monitors the end product (result) of the entire test system.
QC has target values: if assay recovers target, then everything is assumed stable (instrument, reagent, operator, sample).
Disadvantages
When a problem is detected, one must go back and reanalyze patients since last “good” QC.
If results are released, then results may need to be corrected.
For Point of Care devices, does traditional QC work for every test?
Need to get to fully automated analyzers that eliminate errors up front
Until that time, need a robust QC plan (QCP) 3

4. 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 4

5. 5

6. 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. 6

7. 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, and helps the laboratory determine the right combination of tools: The Right QC

8. CLSI Document EP23
Laboratory Quality Control Based on Risk Management; Approved Guideline
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. 8

9. 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.

10. Post-implementation Monitoring
Developing a QCP
MEASURING SYSTEM INFORMATION
Medical
Requirements for
the Test Results
Regulatory and
Accreditation
Requirements
Test System Information
- Provided by the Manufacturer
- Obtained by the Laboratory
Information About
Health Care and
Test Site Setting
PROCESS
Risk Assessment
OUTPUT
Quality Control Plan
PROCESS
Post-implementation Monitoring

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

12. Developing a Process Map
Break down all phases of the test/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.

13. Process Map 13

14. Developing a Process Map (cont’d)
Compile this information.
A process map or a fishbone diagram is one example.

15. The Risk Assessment
Once the process map is created, examine it for places where errors could occur.
Five major areas:
Samples
Operator
Reagents
Laboratory environment
Measuring system

16. Key Process Steps
PREPARATION
Pre-analytical
Pre-examination
TESTING
Analytical
Examination
RESULT REPORTING
Post-analytical
Post-examination
Think about what steps can be taken to reduce errors “unrelated” to the actual testing of the sample.

17. 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.

18. Perform the Risk Assessment
“Risk Assessment” and “Risk Management” are formal terms for what you’re already doing.

19. 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. 19

20. Life is a Continual Risk Assessment
You assess risk every day,
all the time, usually without even thinking about it.

21. In the Laboratory
You do this every day!

22. Assess the Risk of Harm Due to Failures
Defective IVD: Hazard
Incorrect or
delayed
test result:
Hazard
Incorrect or
delayed
medical
treatment:
Hazardous
Situation
Injury or death:
Harm

23. 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 likelihood of that failure occurring, and the severity of consequences if it occurs.
Do this for each identified failure.
Use all of the information gathered in order to make these assessments.

24. Risk Assessment Worksheet

25. Frequency (1 – 5) Example (Sometimes called “Probability”)
Common Terms
Rating
Example (ISO 14971)
Practical Example
Frequent 5
≥ 1/1,000
More than 1x/week
Probable 4
< 1/1,000 and ≥1/10,000
Once every few months
Occasional 3
< 1/10,000 and ≥1/100,000
Once a year
Remote 2
< 1/100,000 and ≥1/1,000,000
Once every few years
Improbable 1
< 1/1,000,000 and ≥10,000,000
Unlikely to ever happen
The laboratory must decide – and it may be different for different tests!

26. Severity (1 – 5) Example Common Terms Rating Possible Description
(ISO 14971)
Catastrophic 5
Results in patient death
Critical 4
Results in permanent injury of life-threatening injury
Serious 3
Results in injury or impairment requiring professional medical intervention
Minor 2
Results in temporary injury or impairment not requiring professional medical intervention
Negligible 1
Inconvenience or temporary discomfort

27. Detectability (1 – 5)
What is the likelihood that the control process detects or prevents the failure?
Common Terms
Rating
Example
Low 5
Control is ineffective 4
Control less likely to detect the failure 3
Control may or may not detect the failure 2
Control almost always detects the failure
High 1
Control can detect the failure

28. Risk Acceptability Matrix

29. Criticality Multiply Frequency x Severity x Detectability
Example: Probable (4) x Catastrophic (5) x High likelihood to detect failure (1) = 20
Criticality
Result
Low
<10
Mid
10 – 20
High
>20
Higher criticality numbers must have quality control actions in place.

30. 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.

31. Monitor QCP 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.

32. Monitor QCP 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.

33. Summary 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.

34. EP23 Companion Products www.clsi.org
Implementation Workbook
Risk Assessment Worksheet
Plus – More fully worked examples coming soon