Module 9 Notes:

Lab Operations:

Frameworks and Requirements -

- Quality Management System (QMS): Systematic process-oriented

approach to organize and meet quality objectives
- Quality Assurance (QA): Planned systematic activities to provide
confidence that requirements for quality will be met
- Quality Control (QC): Operational process control techniques to fulfill
quality requirements for regulatory requirements and accreditation

Quality assurance and QC are interrelated but different; QC has narrow focus
and is a reactive process – measurement of precision and reliability to
identify defects in a testing process

Quality assurance: provides confidence that quality requirements are being

met

QM: the totality of all functions involved in achieving quality

12 elements:

- Organization: defined roles and responsibilities of all individuals

working in lab
- Personnel: job qualifications, job descriptions, training and orientation
to work, competency assessment and continuing education
- Equipment: process from acquisition, installation, validation,
maintenance, calibration, troubleshooting, repairs and records
- Purchasing and inventory: managing supplies and reagents, inventory
- Process Control: QC, sample management, test method validation,
method verification, reagent acceptability
- Information Management: data security, confidentiality of records,
requisitions or lab test orders
- Documents & Records: creation, revisions approval, control of
documents and distribution of documents
- Records: collection, review, storage, and retention of many documents
- Occurrence management: identification, correction of non-formities,
complete resolution, investigations, implementation of corrective
actions, development of preventative measures
 - Process Improvement: monitoring of quality indicated or key
performance indicators across the entire flow of work from pre-
analytical, analytical, and post-analytical
- Customer service: customer’s needs are met, facility and safety in
work environment, transportation and waste management,
ergonomics, temperature management
- Regulatory Framework:
-

CLIA Quality Requirements:

- The lab must establish and follow written quality policies, procedures,
and a quality plan
- The lab must monitor and evaluate the overall quality of laboratory
systems and correct problems
- The lab must assess the effectiveness of the plan and corrective
actions taken to prevent recurrence of problems
- The lab must document systems quality assessment activities

CLIA Test Complexities Waived, Moderate, & High

- Knowledge
- Training and experience
- Reagents and material preparation
- Characteristics of operational steps
- Calibration, QC, and proficiency testing materials
 - Test system troubleshooting and maintenance
- Interpretation and judgment

- Most errors happen during pre-analytic phase

- About 10% of errors are lab related
- Number one cause of laboratory-related litigation is a post analytical
error

QC Sample:

- Used to ensure test system is performed correctly

- Run daily or more frequently if specified
- At least two concentrations
- Medical decision limits/critical performance limits
- Matrix matched: blood, urine, CSF, human/bovine
- Liquid vs lyophilized
- Evaluated daily by technical staff
- QC statistics calculated monthly (SD & CV) by designated qualified
personnel
- Corrective action required if out of control

Calibration Materials (Standards):

- Establishes relationship between test system & corresponding

concentrations
- Calibration verification: Confirms that current settings are valid
o Defined limits to accept or reject verification tests
- Run: Scheduled frequency
o Observed trend or shift or out of control QC
o Major maintenance
- Matrix matched
- Routine QC materials generally not suitable

Proficiency Testing (PT) Samples

- External quality assessment (graded)

- Participant’s performance is compared against pre-established criteria
via inter-laboratory comparisons
- Alternative performance assessment system at least semi-annually if
PT is not available commercially
o Split samples with another lab
 o Upgraded PT assessment
o Validation by chart review
o Defined criteria for acceptability
- Quality Control:
o QC samples with target values are inserted into the testing
process (same conditions as patient samples)
o Historical data used to define QC limits
o Control chart – evaluates change over time
o QC rules are established based on performance characteristics of
a test method
o Corrective action required when out of QC limits
- Precision: Reproducibility. Agreement between replicated
measurements on the same material; an indication of random error
- Accuracy: The closeness with which results agree with a known true
value
- Contributors to Imprecision:
o Measurement error
o Sample metering or pipetting error
o Reagent consistency (lot to lot)
o Reagent stability
o QC stability and variability
o Instrument drift
o Environmental effects (temperature)
o Calibration
- Levey-Jennings QC Chart:
o Randon errors: Statistical fluctuations (in either direction) in the
measured data due to the precision limitations
o Systematic errors: Reproducible inaccuracies that are
consistently in the same direction. Systematic errors are often
due to a problem that persists throughout the entire test system

- QC Strategy Rules:
o With 2 SD control limits, increased false positives (statistically
out 1/20)
o With 2 SD control limits: decreased false positives AND
decreased error detection

Patient Results Inaccurate:

- Investigation and Documentation:

 o Randon error of unknown origin

o Reconstitution/mixing of QC
o Deterioration/contamination of:
 QC
 Reagent
 Standard
- Corrective action must be documented:
o QC repeated and within control
o New vial of QC/Reagent/Standard prepared & run repeated

Calculation of Total Error, TE

- Bias = QC Mean – QC Target value

- TE = Bias + 2 SD
- TEa = Allowable bias + 2 SD
- TEa sets limits for the imprecision & bias that are tolerable in a single
test result
 - To meet quality requirements, TE must be less than total allowable
error (TEa)

Determination of Allowable Error – How good does a test need to be?

- Medical usefulness
- Biologic variation
- Clinical decision requirements
- Interlaboratory testing variation (PT)
- Published recommendations

Laboratory Test Validation:

- The laboratory must define the performance specifications required for

each assay and follow a defined process to produce objective evidence
that a test performs as intended
- Validation activities must be performed at the same location and in the
same conditions as where patient testing is done
o Required for tests not approved/cleared by the FDA
o Modified FDA-approved tests
o Laboratory-developed test (LTDs)
o High complexity tests
- Establish (validate) specifications:
o Accuracy (bias): systematic error
o Precision: random error
o Analytical sensitivity (limit of detection)
o Analytical specificity (interferences)
o Correlation with a comparison method
o Reportable range (AMR & CCR)
o Define QC and PT procedures
o Reference range – pediatric blood cell count
o Specimen requirements & analyte stability
- Simpler process to demonstrate that a test’s performance
specifications are consistent with a manufacturer’s claims
- If a test is validated on one instrument, accuracy can be verified on
duplicate instruments
- Verification of a validated test when an instrument is moved to a new
environment
- Verification of accuracy, precision, sensitivity, specificity, reportable
range of previously validated test
 - Manufacturer or literature data may be used to determine reference
range
- If an instrument is moved, a significant distance such as transporting it
in a truck under high temperatures across a town, loaded on and off
the truck and then set up in a new environment, it requires
revalidation.

Document Control & Retention:

- Documents must be readily available to lab personnel

- Documents locked in a cabinet is not a good example of document
control
- When technical procedures are updated, modified, or changed in any
way, the previous versions must be retained for defined periods
- A policy is required to define the individuals that are authorized to
write the procedures or policies that author them, who is authorized to
make modifications

Analytical Procedure:

- Title, purpose or principle, specimen requirements, process flowchart

or table, step by step procedure instructions, quality control, reagents
and materials, related documents, references, author, approval
signatures, dates: effective, last reviewed, revised

Sources of Pre-Analytical Error Specimen Collection

- Specimen quality: there needs to be written criteria for acceptance and

or rejection of specimens – Ex: avoid clotting specimens by gently
rotating 8-10 times. If vigorously shake, can cause hemolysis
- Contamination from IV lines
- Skin not prepared appropriately, specimens collected for blood cultures
can be contaminated with skin
- Specimen needs to be appropriately labeled with the patient name and
other identification

Specimen Quality/Rejection Criteria

- Unacceptable (test-dependent):
o Wrong container
o Underfilled
o Quantity not sufficient (QNS) - drawing from children
o Clotted – tube not rotated properly
 o Hemolyzed – pulling back on hard syringe
o Unlabeled/mislabeled
o Stored at wrong temperature
o Untimely processing (too old)
o Contaminated

Phlebotomy – Order of Draw

- Varies – blood cultures

- Light blue – sodium citrate
- Red – clot activator
- Gold – SST
- Light Green – Lithium heparin
- Dark Green – Sodium heparin
- Lavender – EDTA
- Gray – Sodium fluoride
- Yellow – ACD Solution

Laboratory Safety:

- Protective Measures: Engineering controls, administrative controls,

work practices, PPE
- Biological safety cabinets
- Sharps containers, chemical safety, biologic safety policies, and
procedures
- Ergonomic program to prevent ergonomic injuries
- Evacuation plan, dress code to ensure employees are protected

Biological/Infection Control Avoid Exposure:

- Bloodborne pathogens
- Standard precautions – wearing personal protective equipment
- Biosafety levels – engineering controls. Ex: fungal culture, viral culture,
ebola testing labs
- Eyewash – in case of accidental splash
- Exposure (direct contact, invasive contact, airborne)
- Decontamination
- Hand hygiene
- Sharps disposal – no manual manipulation of needles
- Red bags (non-sharps regulated waste)
- Decontamination
PPE: Gloves, gowns, masks, eye protection, selected based on the hazard to
the worker, properly fitted, worn, removed & disposed, maintained and
replaced according to the specifications, not modified

Fire Safety:

- Class A: ordinary combustible materials like paper wood

- Class B: Flammable liquids and gases
- Class C: electrical equipment
- Class D: combustible materials
- RACE: remove occupants, activate alarm, confine the fire
(extinguisher), evacuate of extinguish, PASS: pull the pin, aim nozzle
at the base of fire, squeeze the trigger, sweeping over fire

Personnel:

- Adequate number of staff and the effectiveness of training and

competence assessment program directly affects the laboratory’s
ability to meet its quality goals and objectives

Competency Assessment:

- Confirms a person’s ability to use his or her skill and knowledge to

perform assigned duties correctly
- Must be performed for testing personnel for each test or test system
that an individual is authorized to perform
o Assessment must be performed before reporting patient results
o Semi-annually during the first year of testing then annually
o When methodology or instruments are changed
o When new test platforms are introduced
o Newly hired, transferred or promoted personnel
o When an employee demonstrates repeated performance issues
o Must be documented and assessed by qualified staff

Six Elements at the Minimum:

- Direct observation (handling, preparation, processing, testing)

- Monitoring the recording and reporting of testing
- Review of intermediate test results or worksheets, QC, PT results, and
preventative maintenance records
- Direct observation of performance of instrument maintenance and
function checks
- Assessment of problem solving skills
- Assessment of test performance using previously tested specimens,
blind specimens, and external proficiency samples
- Why perform competency assessment? It’s a regulatory requirement
and these requirements can, in the US, vary, based on state
requirements and various accrediting organizations.
- Improves quality by identifying:
o Non-standard work practices
o Short cuts developed by personnel
o Loss of familiarity with processes of SOPs
o Reliance of memory instead of using documented procedure