Verification and Validation Toolkit

• Printable Checklist for the Verification or Validation Process
• Method Verification Validation Plan Approval Checklist
• Verification Plan Template
• Verification Summary Report Template
• Validation Plan Template
• Validation Summary Report Template

• NGS Method Validation Plan Template (NGS Quality Initiative)
• NGS Method Validation Summary Report Template (NGS Quality Initiative)

• CLIA-compliant Analytical Method Validation Plan and Template FOR LRN-C Laboratories (APHL)
• Breakpoint Implementation Toolkit, CRO 2021 (APHL)
• Breakpoint Implementation Toolkit, MIC 2023 (CLSI)

• Bridging, Addendum and Extension Studies Template
• Reagent Comparison QC Studies Template
• Software Update SOP and Template

• Biological Risk Assessment for all New Assays Template

• Employee Training Verification Checklist Example
• Guidelines for Verification and Validation of Laboratory Methods (MN)
  
• Method Validation-Verification Summary Report Example (Fairfax County, VA)
• Method Verification Template Example (IN)
• Validation and Verification SOP Example (TX)
• Validation Plan Example (WA)
• Validation Summary Report Example (WA)
• Verification Plan Example (WA)

• Microbiology MALDI-TOF Validation Supplemental Checklist (New York CLEP)
  
• Microbiology NAAT Checklist (New York CLEP)

• Analytical Instrument Verification Example

The Clinical and Laboratory Standards Institute (CLSI) has complied a Harmonized Terminology Database of internationally accepted terminology used in laboratory sciences and related health organizations. This tool is publicly available to encourage broad acceptance and usage of internationally accepted terminology in the laboratory community.

Accuracy: An analytical performance measurement that assesses the ability of a method to produce correct results, as compared to a reference standard. Diagnostic sensitivity (known absence for target analyte) and diagnostic specificity (known presence of target analyte) are used.

Analytical Measurement Range: The range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment not part of the usual assay process.

Analytical Sensitivity (Limit of Detection): The lowest concentration, or amount of an analyte, that can be measured and distinguished from a blank (i.e., minimum detection limits).

Analytical Specificity (Interfering Substances): The ability of an instrument or test system to measure only the intended organism or substance. Tests the ability to discriminate between the target analyze and other related, but non-target analytes (i.e., cross-reactivity, interfering substances).

Coefficient of Variation (CV): A measure of relative precision. It is calculated as 100 times the standard deviation, divided by the mean, and expressed as a percentage.

Control—High Positive: A sample, preferably matrix-matched, to evaluate the ability of a laboratory to identify the target of interest near the upper limit of the reportable range, if applicable.

Control—Low Positive: A sample, preferably matrix-matched, to evaluate the ability of a laboratory test to identify the target of interest near the lower limit of the reportable range or near the cutoff.

Control—Negative: A sample, preferably matrix-matched, that lacks the target of interest and used to evaluate the ability of a test not to detect the target when it is not present.

Cutoff Value: In qualitative assays, the cutoff is defined as : the threshold above which the result is reported as positive and below which the result is reported as negative.

Direct Costs: Specific costs traceable to the test produced. These can be fixed or variable. Examples include supplies, reagents, consumables, labor, instrument costs, standards and controls.

Emergency Use Authorization (EUA): An EUA is a mechanism that the enables the FDA to facilitate the availability and use of medical countermeasures during declared public health emergencies.

False Negative: A negative result incorrectly ascribed to a positive sample.

False Positive: A positive result incorrectly ascribed to a negative sample.

FDA Approved: The device has been approved through the Premarket Approval process.

FDA Authorized: The device has been reviewed by FDA through the EUA mechanism.

FDA Cleared: The device has been cleared as a substantially equivalent device through Section 510(k) of the Food, Drug and Cosmetic Act.

FDA Modified: Any modification to an FDA approved or cleared test. The modification should be handled as a laboratory developed test.

Fixed Costs: A cost that remains constant regardless of workload and within a specific range of activity. Examples include Labor, rent, equipment depreciation, equipment/instrumentation.

Gold Standard: Any standardized clinical assessment, method, procedure, intervention or measurement of known validity and reliability which is generally taken to be the best available, against which new tests or results and protocols are compared.

High Complexity: The most complex testing category assigned to a test by the FDA, based on seven scored criteria. CLIA requirements for laboratories will vary based on the assigned complexity of a test with more stringent requirements for high complexity testing.

Indirect Costs: Any cost that is not assigned to the direct production of a test but contributes to the adequate provision of the work environment. Examples include supervisory salaries, quality assurance, education, travel, administrative costs, building maintenance, security and training.

Individualized Quality Control Plan (IQCP): The Clinical Laboratory Improvement Amendments (CLIA) Quality Control (QC) procedure for an alternate QC option allowed by 42CFR493.1250. The guidance and concepts for IQCP are a formal representation and compilation of many things laboratories already do to ensure quality test results. IQCP permits the laboratory to customize its QC plan according to test method and use, environment, and personnel competency while providing for equivalent quality testing.

Laboratory-developed Test: Test developed wholly, or in part, by the performing laboratory. This may include analyte specific reagents (ASR) or adoption of another laboratory's LDT or non-cleared or approved test.

Limit of Detection (LoD): In quantitative and qualitative measurement procedures, the lowest concentration of analyte that can be consistently detected (typically, in ≥ 95% of samples tested under routine medical laboratory conditions and in a defined type of sample).

Matrix Effect: The influence of sample property independent of analyte presence.

Negative Predictive Value (NPP): The probability that a negative result accurately indicates the absence of the analyte or specific disease.

Positive Predictive Value (PPV): The probability that a positive result accurately indicates that the analyte or specific disease is present.

Precision: An analytical performance measurement that assesses the closeness of agreement between independent results of measurements obtained under stipulated conditions. Assesses the inherent random error of a test system to determine how close two or more repeated measurements are to each other, regardless of accuracy.

Premarket Approval (PMA) Process: This is the FDA process of scientific and regulatory review to evaluation the safety and effectiveness of Class III Medical Devices.

Premarket Notification 510(k): Before marketing a device in the US intended for human use that does not require a PMA must submit a 510(k) to FDA (unless otherwise exempt).

Reference Range: The typical result (qualitative) or range of values (quantitative) expected in a non-diseased population that do not have the condition for which the test is performed, including variation due to type of specimen and demographic variables such as age and sex, as applicable.

Reportable Range: The span of test result values over which the laboratory can establish or verify the accuracy of the instrument or test system measurement response. For a qualitative test, the reportable range could be the limit of detection, the cutoff value, or the 95% confidence interval.

True Negative: A negative result that correctly reflects the condition of a sample.

True Positive: A positive result that correctly reflects the condition of a sample.

Validation: The process used to confirm with objective evidence that a laboratory-developed test (LDT) or modified FDA-cleared or approved test method or instrument system delivers reliable results for the intended application.

Variable Costs: A cost that varies with changes in test volume. Examples include reagents and consumables. Labor costs can sometimes be variable when significant increases or decreases in test volume occur, but typically labor will be a fixed cost.

Verification: The one-time process by which a laboratory determines that an unmodified FDA-cleared or approved test performs according to the manufacturer's specifications when used as directed.

AMR: Analytical Measurement Range

ANSI: American National Standards Institute

ASR: Analyte Specific Reagents

CAP: College of American Pathologists

CFU: Colony Forming Units

CLIA: Clinical Laboratory Improvement Amendments

CLSI: Clinical and Laboratory Standards Institute

CoA: CLIA Certificate of Accreditation

CoC: CLIA Certificate of Compliance

CV: Coefficient of Variation

EUA: Emergency Use Authorization

FDA: US Food and Drug Administration

FSIS: USDA Food Safety and Inspection Service

HL7: Health Level 7 standards for electronic transfer of data

IFU: Instructions for Use

IQCP: Individualized Quality Control Plan

ISO: International Organization for Standardization

LIS: Laboratory Information System

LoD: Limit of Detection

MSDS: Material Safety Data Sheet

PPE: Personal Protective Equipment

PPV: Positive Predictive Value

PT: Proficiency Testing

QAO: Quality Assurance Officer

QC: Quality Control

RF: Relative Fluorescence

TCID50: Median Tissue Culture Infectious Dose

TNI: The NELAC Institute

USDA: US Department of Agriculture