PICCOLO LACTATE TEST SYSTEM
Device Facts
| Record ID | K130113 |
|---|---|
| Device Name | PICCOLO LACTATE TEST SYSTEM |
| Applicant | Abaxis, Inc. |
| Product Code | KHP · Clinical Chemistry |
| Decision Date | Mar 11, 2013 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1450 |
| Device Class | Class 1 |
Indications for Use
The Piccolo® Lactate Test System (presently contained on the MetLac 12 Panel Reagent Disc) used with the Piccolo® xpress™ Chemistry Analyzer is intended to be used for the in vitro quantitative determination of lactate concentration in heparinized whole blood or heparinized plasma in a clinical laboratory setting or point-of-care location.
Device Story
The Piccolo Lactate Test System is an in vitro diagnostic device used with the Piccolo xpress Chemistry Analyzer. It processes lithium heparinized whole blood or plasma samples loaded into a MetLac 12 Panel Reagent Disc. The analyzer automatically meters the sample and diluent, mixes them, and delivers the mixture to reaction cuvettes containing dry reagent beads (Lactate Oxidase, Peroxidase, 4-AAP, and DHBSA). The system performs an enzymatic colorimetric assay at 37°C. The analyzer monitors the chemical reaction and calculates lactate concentration based on factory-calibrated lot-specific data provided via barcode. Used in clinical laboratories or point-of-care settings by professional operators, the system provides quantitative lactate results to assist clinicians in diagnosing lactate acidosis, monitoring tissue hypoxia, and identifying hyperlactatemia.
Clinical Evidence
No clinical trials were performed. Evidence consists of analytical bench testing: precision (N=80 for controls, N=40 for plasma, N=20 per POC site), linearity (R²=0.999), limit of detection (LoD=0.07 mmol/L), and interference studies. Method comparison against the predicate device using 126 patient samples showed high correlation (r=0.996) with a slope of 1.02 (linear regression). Reference range established using 130 healthy individuals.
Technological Characteristics
Single-use 8 cm diameter reagent disc; enzymatic colorimetric sensing principle; bichromatic measurement at 515 nm and 600 nm; lithium heparinized whole blood/plasma samples; factory-calibrated via bar-coded lot-specific data; internal quality control beads for fluidics, temperature, and sample delivery monitoring; standalone operation on Piccolo® xpress™ Chemistry Analyzer.
Indications for Use
Indicated for the diagnosis and treatment of lactic acidosis, monitoring tissue hypoxia, and diagnosis of hyperlactatemia in patients requiring lactate concentration measurement.
Regulatory Classification
Identification
A lactic acid test system is a device intended to measure lactic acid in whole blood and plasma. Lactic acid measurements that evaluate the acid-base status are used in the diagnosis and treatment of lactic acidosis (abnormally high acidity of the blood).
Predicate Devices
- i-STAT Lactate/LAC (K982071)
Related Devices
- K051108 — PICCOLO LACTATE DEPHYDROGENASE TEST SYSTEM · Abaxis, Inc. · Jul 8, 2005
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k130113
B. Purpose for Submission:
Addition of lactate analyte to Piccolo® MetLac 12 Panel Reagent Disc which contains eleven other previously cleared analytes
C. Measurand:
Lactate
D. Type of Test:
Quantitative, enzymatic colorimetric
E. Applicant:
Abaxis Inc.
F. Proprietary and Established Names:
Piccolo® Lactate Test System
G. Regulatory Information:
1. Regulation section:
21 CFR § 862.1450; Lactic acid test system
2. Classification:
Class I, meets limitations of exemptions per 21 CFR § 862.9 (c)(9)
3. Product code:
KHP; Lactic Acid, Enzymatic Method
4. Panel:
Clinical Chemistry (75)
H. Intended Use:
1. Intended use(s):
The Piccolo® Lactate Test System (presently contained on the MetLac 12 Panel Reagent Disc) used with the Piccolo® xpress™ Chemistry Analyzer is intended to be used for the in vitro quantitative determination of lactate concentration in heparinized whole blood or heparinized plasma in a clinical laboratory setting or point-of-care location.
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2. Indication(s) for use:
Lactate measurements are used in the diagnosis and treatment of lactic acidosis, monitoring tissue hypoxia, and diagnosis of hyperlactatemia.
3. Special conditions for use statement(s):
For prescription use only
4. Special instrument requirements:
Piccolo® xpress™ Chemistry Analyzer
I. Device Description:
The Piccolo® MetLac 12 Panel Reagent Disc (which contains the Piccolo® Lactate Test System) is designed for lithium heparinized whole blood and lithium heparinized plasma. The disc is an 8 cm diameter single-use device that contains chambers for reagents along the outer edge of the disc, chambers for the sample and diluent (sealed in diluent container in the center of the disc), and chambers for dilution of sample. Through capillary action and centrifugal force, the required quantity of sample and diluent are mixed, and the mixture is delivered to the reaction cuvettes along the disc perimeter. The diluted sample mixes with the reagent beads in the reaction chambers, initiating the chemical reactions that are colorimetrically monitored by the analyzer.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Abbott i-STAT Lactate/LAC
2. Predicate k number(s):
k982071
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Candidate device | Predicate device |
| Intended use | For in vitro quantitative determination of lactic acid/lactate concentration | same |
| Methodology | Enzymatic | same |
| Temperature of reaction | 37°C | same |
| Testing environment | Point-of-care and clinical laboratories | same |
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| Differences | | |
| --- | --- | --- |
| Item | Candidate device | Predicate device |
| Test principle | Colorimetric | Amperometric |
| Specimen type | Heparinized venous whole blood and heparinized plasma | Arterial, venous, or capillary whole blood (with or without heparin) |
| Reportable range | 0.30 to 9.99 mmol/L | 0.30 to 20.00 mmol/L |
| Calibration | Each disc is bar coded with factory-calibrated lot-specific data | Automatically calibrated during each analysis using on-board reagent |
| Reagents | Dry test-specific reagent beads and liquid diluent; reconstitution performed by analyzer. | Immobilized enzyme on a biosensor and liquid reagents. |
| Sample Size | Approximately 100 μL | 95 μL |
# K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline- Second Edition
- CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.
- CLSI EP7-A2: Interference Testing in Clinical Chemistry: Approved Guideline- Second Edition
- CLSI EP17-A: Protocol for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.
- CLSI EP9-A2-IR: Method of Comparison and Bias Estimation Using Patient Samples: Approved Guideline- Second Edition (Interim Revision)
- CLSI C28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline- Third Edition (corrected)
# L. Test Principle:
Lactate is oxidized by lactate oxidase (LOX) to pyruvate and hydrogen peroxide $(\mathrm{H}_2\mathrm{O}_2)$ . Peroxidase (horseradish) catalyzes the reaction of $\mathrm{H}_2\mathrm{O}_2$ , 4-amoniantipyrine (4-AAP), and 3,5-dichloro-2-hydroxybenzenesulfonic acid (DHBSA) into a red dye. The rate of formation of the dye is proportional to the lactate concentration in the sample. The reaction is measured bichromatically at $515~\mathrm{nm}$ and $600~\mathrm{nm}$ .
# M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision was evaluated per CLSI EP5-A2 using three commercially available human serum-based controls. Samples were run in duplicate on two instruments
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twice per day for five days at each of two sites. Data from both sites were combined to yield $\mathrm{N} = 80$ per control level. The results are summarized below (units = mmol/L):
| N=80 | Within Run | | | Total | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | %CV | Mean | SD | %CV |
| Control 1 | 1.62 | 0.03 | 1.8% | 1.62 | 0.04 | 2.2% |
| Control 2 | 3.63 | 0.05 | 1.5% | 3.63 | 0.08 | 2.3% |
| Control 3 | 6.99 | 0.18 | 2.6% | 6.99 | 0.36 | 5.2% |
The sponsor evaluated precision performance of two levels of heparinized plasma samples in house. The samples were run in duplicate on two instruments twice per day for five days. The results are summarized below (units = mmol/L):
| N=40 | Within Run | | | Total | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | %CV | Mean | SD | %CV |
| Plasma 1 | 0.86 | 0.02 | 1.9% | 0.86 | 0.02 | 1.9% |
| Plasma 2 | 6.22 | 0.20 | 3.2% | 6.22 | 0.20 | 3.2% |
The sponsor also identified three point-of-care (POC) sites and tested four whole blood samples at each POC site. The four whole blood samples contain two samples with normal lactate values and two samples with elevated lactate values. At each POC site, two operators tested every whole blood sample in ten replicates simultaneously on twenty analyzers. Data from both operators were combined to yield $\mathrm{N} = 20$ per sample per site. The results are summarized below (units = mmol/L):
| N=20 | Site 1 | | | Site 2 | | | Site 3 | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Mean | SD | %CV | Mean | SD | %CV | Mean | SD | %CV |
| Normal lactate sample | 0.71 | 0.02 | 2.7% | 1.01 | 0.03 | 2.5% | 0.88 | 0.03 | 3.8% |
| Normal lactate sample | 1.51 | 0.03 | 2.0% | 1.10 | 0.03 | 2.7% | 1.08 | 0.03 | 3.2% |
| Elevated lactate sample | 4.15 | 0.15 | 3.5% | 5.89 | 0.25 | 4.2% | 5.89 | 0.20 | 3.3% |
| Elevated lactate sample | 4.63 | 0.15 | 3.1% | 6.28 | 0.24 | 3.9% | 7.76 | 0.27 | 3.5% |
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b. Linearity/assay reportable range:
A human plasma pool spiked with lactate was diluted to produce eleven lactate levels of samples ranging from 0.19 to 10.55 mmol/L. Each sample was assayed in quadruplicate on four different analyzers. Results are summarized below using the first replicate of the data from one analyzer.
| Slope | 1.016 |
| --- | --- |
| Intercept | -0.023 |
| R² | 0.999 |
The reportable range of this device for lactate measurements is 0.3 to 9.99 mmol/L.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The reagent discs are calibrated at the manufacturer using 6-8 human lactate pools that are spiked with lactate covering the reportable range of the assay. The calibrator lactate values are assigned by a commercially available method, whose calibration was traceable to a commercially available standard sodium L-lactate. The pools are then analyzed on the Piccolo® xpress™ analyzer to determine the enzymatic rate at each level, and a linear regression calibration line is calculated with the slope and intercept serving as the calibration factors. The calibration information is bar-encoded on each reagent disc. No user calibration is required.
Quality control beads are included on each reagent disk and automatically run with each assay. The information from this quality control analysis is stored with the test results and can be printed by the user. This is the internal build-in control to check fluidics, spectrophotometer, temperature, and sufficient sample delivery. In addition, sponsor recommends user to test quality controls according the federal, state, and local regulations in the labeling.
The shelf life of the lactate assay is 12 months when stored at 2-8°C. Stability protocols and acceptance criteria for real time stability study for lactate system were reviewed and considered acceptable.
d. Detection limit:
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Detection (LoQ) were determined based on CLSI guideline EP17-A as described below:
Limit of Blank (LoB):
A saline blank sample was assayed sixty times on one day (three times on each of twenty analyzers). The results were ordered according to their values and the 95th percentile of the zero-level samples concentration level was deemed as LoB level. The sponsor claimed the LoB = 0.02 mmol/L.
Limit of Detection (LoD):
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Six low level samples, including 5 samples prepared by diluting a normal human plasma pool (lowest non-zero lactate calibrator) with saline, and one normal human plasma pool, were assayed sixty times each on one day (three times on each of twenty analyzers per sample). The low level samples were examined to see where 5% or fewer of the observed measurements were below LoB. The sponsor claimed the LoD = 0.07 mmol/L.
Limit of Detection (LoQ):
The LoQ was determined as the concentration that displayed a total error (TE) of 20% (TE = %bias + 2*%CV). The sponsor claimed the LoQ = 0.11 mmol/L. The LoQ value supports the sponsor's claimed measuring range of 0.3 – 9.99 mmol/L.
e. Analytical specificity:
To evaluate potential endogenous interference, two levels of lactate plasma pools were spiked to prepare at least four test pools containing different levels of the potential endogenous interferents. Four replicates of each pool were assayed on four different analyzers and compared to the control pool. The sponsor defined non significant interference if the bias between control pool and test pool was within ± 10%. Below are the levels of the endogenous substances that exhibit ≤10% interference.
| endogenous substance | Level with ≤10% interference (mg/dL) |
| --- | --- |
| Hemoglobin | 500* |
| Bilirubin | 15* |
| Triglycerides | 3000* |
| Glucose | 700 |
| Uric Acid | 30 |
*Samples with values above these levels will be reported as “HEM”, “LIP”, or “ICT” on the result card, respectively.
To evaluate potential exogenous interference, 41 drugs were spiked into two levels of lactate plasma pools. The un-spiked plasma pool served as the control pool. The control pool and each interferent pool were tested in quadruplicate on four analyzers. The sponsor defined non significant interference if the bias between control pool and test pool was within ± 10%.
The following table summarized the 39 substances that showed non significant interference at the highest concentration tested:
| Substance | Highest Concentration Tested (mg/dL) |
| --- | --- |
| Acetaminophen | 100 |
| Acetoacetate | 102 |
| Acetylsalicylic acid | 50 |
| Ampicillin | 30 |
| Ascorbic Acid | 3 |
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| Bromide | 30 |
| --- | --- |
| Caffeine | 10 |
| Cephalothin (Keflin) | 400 |
| Chloramphenicol | 100 |
| Cimetidine | 16 |
| Digoxin | 5 |
| D-lactate | 45 |
| Epinephrine | 1 |
| Erythromycin | 10 |
| Glutathione | 30 |
| Glycolic acid | 7.6 |
| Hydrochlorothiazide | 7.5 |
| Hydroxyurea | 0.7 |
| Ibuprofen | 50 |
| Isoniazide | 4 |
| Ketoprofen | 50 |
| Lidocaine | 1 |
| Metformin | 500 |
| Methicillin | 100 |
| Methotrexate | 0.5 |
| Metronidazole | 5 |
| Nafcillin | 1 |
| Nitrofurantoin | 20 |
| Oxacillin | 1 |
| Oxaloacetate | 132 |
| Penicillin G | 100 |
| Phenytoin (5,5-Diphenylhydantion) | 3 |
| Proline | 4 |
| Pyruvate | 44 |
| Rifampin | 0.5 |
| Salicylic Acid | 50 |
| Sulfadiazine | 150 |
| Sulfanilamide | 50 |
| Theophylline | 20 |
The sponsor states that dopamine and L-dopa demonstrate interference, and includes the following information in the device's labeling:
| Substance | Concentration (mg/dL) | % interference |
| --- | --- | --- |
| Dopamine | 13 | 85% decrease |
| | 0.52 | <10% decrease |
| L-dopa | 5 | 49% decrease |
| | 0.5 | <10% decrease |
f. Assay cut-off: Not applicable
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2. Comparison studies:
a. Method comparison with predicate device:
The sponsor performed method comparison study at a POC site using 126 unaltered heparinized whole blood patient samples. In order to obtain samples with high lactate results, seven samples were allowed to sit at room temperature for glycolysis process to occur to raise lactate levels. A total of four Piccolo xpress analyzers were used for the study. Each sample was tested on the predicate and on one of the four Piccolo® xpress™ analyzers. Both linear and Deming regression analysis was performed for comparison. Summary data is as follows (Piccolo® range = 0.30 – 9.88 mmol/L, Predicate range = 0.42 – 9.85 mmol/L).
| N=126 | Linear Regression | Deming Regression |
| --- | --- | --- |
| Slope (95% CI) | 1.02 (1.01 to 1.04) | 1.03 (0.99 to 1.06) |
| Intercept (95% CI) | 0.13 (0.07 to 0.19) | 0.06 (-0.01 to 0.14) |
| Correlation coefficient | 0.996 | 0.996 |
b. Matrix comparison:
Lithium heparin is the only acceptable anti-coagulant for the lactate assay. Either whole blood or plasma sample may be used for the test.
Lithium heparinized whole blood and plasma (processed from the whole blood samples) were collected from 10 individuals and tested in replicates of four on eight Piccolo® xpress™ analyzers. Samples range tested from 0.68 to 9.81 mmol/L. Deming regression analysis was performed and regression yielded: Y= 1.01X + 0.071, R²= 0.997.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable.
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
The sponsor established the reference range for the Piccolo® Lactate system using venous lithium heparin whole blood samples collected from 130 apparently healthy individuals (47% male; 53% female). The reference range was defined by the limits of the central 95% of values tested.
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Reference range: 0.53 – 2.10 mmol/L
**N. Proposed Labeling:**
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
**O. Conclusion:**
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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