The Trinidad CH Vancomycin (Vanc) assay is for in vitro diagnostic use in the quantitative measurement of vancomycin in human serum or plasma on the Trinidad CH System. Vanc test results may be used in the diagnosis and treatment of vancomycin overdose and in monitoring levels of vancomycin to ensure appropriate therapy.

The Trinidad CH Drug 3 Calibrator (DRUG3 CAL) is intended for in vitro diagnostic use in the calibration of Vancomycin (Vanc) on the Trinidad CH System.

Device Description

The Trinidad CH Vancomycin (Vanc) assay is based on a homogeneous particle enhanced turbidimetric inhibition immunoassay (PETINIA) technique which uses a synthetic particle-vancomycin conjugate (PR) and monoclonal vancomycin specific antibody (Ab). Vancomycin present in the sample competes with vancomycin on the particles for available antibody, thereby decreasing the rate of aggregation. Hence, the rate of aggregation is inversely proportional to the concentration of vancomycin in the sample. The rate of aggregation is measured using bichromatic turbidimetric readings at 545 nm and 694 nm.

The Trinidad CH Drug 3 Calibrator (DRUG3 CAL) is a 5 level calibrator product prepared from bovine serum base product.

AI/ML Overview

The Siemens Healthcare Diagnostics Inc. Trinidad CH Vancomycin (Vanc) assay and Trinidad CH Drug 3 Calibrator (DRUG3 CAL) underwent several studies to establish their performance and substantial equivalence to predicate devices. Here's a breakdown based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a formal "acceptance criteria" table with pass/fail thresholds for all metrics. However, it presents the results of various performance studies which implicitly serve as evidence for meeting regulatory requirements for substantial equivalence. The "Acceptance Criteria" column below is inferred from the document's reporting of satisfactory results against established clinical laboratory guidelines (e.g., CLSI documents) or from comparisons to the predicate device.

Performance Metric	Acceptance Criteria (Inferred)	Reported Device Performance (Trinidad CH Vancomycin / DRUG3 CAL)
Detection Limit (LoB)	Demonstrated low limit of blank according to CLSI EP17-A2.	0.1 µg/mL
Detection Limit (LoD)	Demonstrated low limit of detection according to CLSI EP17-A2.	0.2 µg/mL
Limit of Quantitation (LoQ)	LoQ should support the claimed measuring interval (3.0 µg/mL) with a total error ≤ 20%.	2.8 µg/mL (measured), supporting a claim of 3.0 µg/mL with a total error ≤ 20%.
Linearity	Nonlinear coefficients are nonsignificant (all p values ≥ 0.05). If significant, allowable bias ≤ 0.5 µg/mL or 10%, whichever is greater.	Passed for all 10 levels across a range of 0.9 to 51.1 µg/mL. Absolute Bias ranged from -0.3 to 0.4 µg/mL, and % Bias ranged from -2.3% to 0.9%, all well within allowable bias limits.
Precision (Repeatability - SD)	Within acceptable variation for clinical assays (e.g., as per CLSI EP05-A3 guidelines).	Serum QC: 0.16 µg/mL (2.6% CV). Serum (11.2 µg/mL): 0.20 µg/mL (1.8% CV). Serum QC (17.5 µg/mL): 0.28 µg/mL (1.6% CV). Serum (32.7 µg/mL): 0.46 µg/mL (1.4% CV). Plasma (45.8 µg/mL): 0.78 µg/mL (1.7% CV).
Precision (Within-Lab - SD)	Within acceptable variation for clinical assays (e.g., as per CLSI EP05-A3 guidelines).	Serum QC: 0.18 µg/mL (2.7% CV). Serum (11.2 µg/mL): 0.23 µg/mL (2.0% CV). Serum QC (17.5 µg/mL): 0.35 µg/mL (2.0% CV). Serum (32.7 µg/mL): 0.67 µg/mL (2.0% CV). Plasma (45.8 µg/mL): 0.83 µg/mL (1.8% CV).
Interferences	Bias exceeding 10% is considered interference. No significant interference expected from common interfering substances at specified concentrations.	No interference detected at the following concentrations: Hemoglobin 600 mg/dL, Conjugated Bilirubin 20 mg/dL, Unconjugated Bilirubin 20 mg/dL, Lipemia (Intralipid) 1000 mg/dL. Note: Vancomycin crystalline degradation product (CDP-1) at 20 µg/mL showed cross-reactivity (21.0% at 0 µg/mL Vanc, 19.1% at 10 µg/mL Vanc).
Method Comparison (Serum)	Good agreement with predicate device (Dimension RxL VANC) when tested with patient samples (e.g., high correlation coefficient, low bias).	N=100, r = 0.997, Regression Equation: $y = 1.04x - 1.04 \frac{\text{µg}}{\text{mL}}$ for a sample interval of 4.4-48.1 µg/mL. (Demonstrated good agreement).
Matrix Equivalency (Plasma vs Serum)	Good agreement between plasma and serum samples across the assay's measuring interval (e.g., high correlation coefficient, low bias).	N=60, r = 0.990, Regression Equation: $y = 1.00x + 0.49 \mu g/mL$ for a sample interval of 4.0–43.3 µg/mL. (Demonstrated equivalency).

2. Sample Size Used for the Test Set and the Data Provenance

Detection Limit (LoB/LoD):
- LoB: 4 samples with no analyte tested (N=5) for 3 days, one run per day, 3 reagent lots. Total reps = 60 to determine rank for non-parametric approach.
- LoD: 4 low serum samples tested (N=5) for 3 days, one run per day, 3 reagent lots.
Limit of Quantitation (LoQ): 4 low serum samples processed on three reagent lots for three days, on one instrument. Total of 60 measurements per reagent lot, leading to a total of 180 determinations.
Linearity Study: 10 samples (prepared by mixing high and low concentration samples). Six replicates were measured for each sample.
Precision Studies: 80 replicates (n=2 replicates, two times a day for at least 20 days) for controls, serum, and plasma pools.
Interferences: Conducted using a "paired difference worst case scenario" approach with fresh sample pools containing low or high levels of vancomycin. Specific N not provided for individual interferents.
Method Comparison: 100 "remnant de-identified samples" (native, spiked, and diluted).
Matrix Equivalency: 60 matched samples (serum and lithium heparin plasma). Some samples were diluted or spiked.

Data Provenance:

All studies were "conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization personnel."
For the Method Comparison, "Remnant de-identified samples were tested. No patient history information was obtained on these samples." This suggests a retrospective data collection from a clinical laboratory or sample bank, likely within the US, given Siemens Healthcare Diagnostics is a US-based entity and the FDA submission is US-centric.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

The document does not explicitly mention the use of experts to establish a "ground truth" in the sense of clinical interpretation or diagnosis for the test sets.

For quantitative assays like this:

The "ground truth" for linearity, precision, and detection limits is based on the known concentrations of prepared standards or spiked samples.
For method comparison, the "ground truth" comes from the measurements generated by the predicate device.
The personnel conducting the study were "laboratory technicians with training similar to personnel who would conduct the tests in a hospital laboratory setting," and they were "trained on the operation of both the device and the predicate device." These individuals are not referred to as "experts" in the clinical sense of radiologists or pathologists, but rather as trained laboratory professionals.

4. Adjudication Method for the Test Set

Not applicable in the context described. Adjudication methods (like 2+1 or 3+1) are typically used for establishing ground truth in diagnostic studies involving subjective interpretation (e.g., image analysis by multiple radiologists). This submission describes performance studies for a quantitative measurement assay where the "ground truth" is either inherent to the sample preparation (e.g., spiked concentrations) or established by a reference method (the predicate device). No human interpretation requiring adjudication is mentioned.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted, nor is it applicable. MRMC studies evaluate the performance of human readers, often with or without AI assistance, on a set of cases, typically for diagnostic tasks like image interpretation. This submission is for an in vitro diagnostic assay that quantitatively measures vancomycin levels, not for an AI-powered diagnostic imaging device or a clinical decision support system that directly involves human "readers" interpreting cases.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

This device is a standalone algorithm (an in vitro diagnostic assay) in the sense that its performance is measured directly and quantitatively on biological samples to determine vancomycin concentration. The "algorithm" here is the chemical reaction and measurement process (PETINIA technique) implemented on the Trinidad CH System, which then outputs a numerical value. There is no human "in-the-loop" interpretation component for the direct measurement itself; humans operate the instrument and interpret the final quantitative result. The performance data presented (linearity, precision, detection limits, method comparison) are effectively "standalone" performance metrics of the assay system.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for the studies varied by the specific test:

Detection Limits, LoQ, Linearity: Ground truth was established by known, prepared concentrations of vancomycin in control matrices (e.g., bovine serum base, spiked native serum).
Method Comparison: Ground truth was established by the measurements from the legally marketed predicate device (Dimension RxL VANC assay), which is considered an accepted method for vancomycin quantification.
Matrix Equivalency: Ground truth for comparison was the measurements from the new device itself on serum samples to compare against its performance on plasma from the same patient.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI algorithms. As this is a traditional in vitro diagnostic assay based on an immunoassay technique, it is developed and validated through laboratory experiments, not typically "trained" on a dataset in the way an AI algorithm would be. The experiments described (e.g., development of the assay, optimization of reagents, calibration) are analogous to the development phase, but not termed a "training set."

9. How the Ground Truth for the Training Set Was Established

As explained above, there isn't a "training set" in the AI sense for this type of IVD device. The development of such an assay involves:

Careful formulation of reagents (synthetic particle-vancomycin conjugate, monoclonal vancomycin specific antibody).
Optimization of reaction conditions and measurement parameters.
Calibration using highly characterized standards (like the Trinidad CH Drug 3 Calibrator, which is prepared from bovine serum base). The calibrators themselves would be assigned values based on precise preparation and analytical verification against reference methods or materials.

The "ground truth" during assay development would stem from known quantities of vancomycin standards and reference materials, used to ensure the assay accurately measures concentrations across its intended range.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 27, 2016

SIEMENS HEALTHCARE DIAGNOSTICS, INC. LAURA J. DUGGAN REGULATORY TECHNICAL SPECIALIST 500 GBC DRIVE, PO BOX 6101 MS 514 NEWARK, DE 19711 US

Re: K160202

Trade/Device Name: Trinidad CH Vancomycin (Vanc) Trinidad CH Drug 3 Calibrator (DRUG3 CAL) Regulation Number: 21 CFR 862.3950 Regulation Name: Vancomycin test system Regulatory Class: Class II Product Code: LEH, DLJ Dated: January 27, 2016 Received: January 28, 2016

Dear Ms. Duggan,

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

Courtney H. Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K160202

Device Name Trinidad CH Vancomycin (Vanc) Trinidad CH Drug 3 Calibrator (DRUG3 CAL)

Indications for Use (Describe)

The Trinidad CH Drug 3 Calibrator (DRUG3 CAL) is intended for in vitro diagnostic use in the calibration of Vancomycin (Vanc) on the Trinidad CH System.

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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510(K) SUMMARY

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.

ASSIGNED 510(K) NUMBER

The assigned 510(k) number is

APPLICANT AND DATE

Laura J. Duggan, Ph. D., RAC Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: laura.j.duggan@siemens.com Phone: 302-631-7654 Fax: 302-631-6299

March 29, 2016

MANUFACTURER

Siemens Healthcare Diagnostics Inc. 511 Benedict Ave Tarrytown, NY 10591 Registration Number: 2432235

REGULATORY INFORMATION

Regulatory Submission for the Trinidad CH Vancomycin (Vanc) and Trinidad CH Drug 3 Calibrator (DRUG3 CAL)

Common Name:	Clinical Toxicology Test Systems	Clinical Toxicology Test Systems
Proprietary Name:	Trinidad CH Vancomycin (Vanc)Assay	Trinidad CH Drug 3 Calibrator(DRUG3 CAL)
ClassificationName:	Vancomycin test system	Clinical Toxicology Calibrator
RegulationNumber:	21CFR862.3950	21CFR862.3200
Classification:	Class II	Class II
Product Code:	LEH	DLJ
Panel:	Toxicology	Toxicology
Predicate Device:	Vancomycin Flex ReagentCartridge (K963267)	Dimension Drug Calibrator II(K033809)

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DEVICE DESCRIPTION

TRINIDAD CH VANCOMYCIN (VANC)

Reaction Equation

Vancomycin + PR + Ab

PR-Ab complex + Vancomycin-Ab (scatters light at 545 nm)

..............................................................................................................................................................................

Serum and lithium heparin plasma specimens may be used. The reagent is stored unopened at 2 - 8 °C and is stable for use on system for 30 days. Calibration is performed every 30 days for a reagent lot or every 7 days for an individual pack.

TRINIDAD CH DRUG3 CALIBRATOR (DRUG3 CAL)

The Trinidad CH Drug 3 Calibrator (DRUG3 CAL) is a 5 level calibrator product prepared from bovine serum base product. The product is stored at 2 - 8 °C. The Trinidad CH Drug 3 Calibrator is stable for 15 days at 2 – 8 °C after being opened and securely recapped.

INTENDED USE/INDICATIONS FOR USE

TRINIDAD CH VANCOMYCIN (VANC)

TRINIDAD CH DRUG3 CALIBRATOR (DRUG3 CAL)

The Trinidad CH Drug 3 Calibrator (DRUG3 CAL) is intended for in vitro diagnostic use in the calibration of Vancomycin (Vanc) on the Trinidad CH System.

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Below is a features comparison for the Trinidad CH system Vancomycin assay and the DRUG3 calibrator vs. their predicates:

Feature	Predicate Device:Dimension® VANC Flex®reagent Cartridge (K963267)	New Device:Trinidad CH Vancomycin(VANC)
Intended Use :	The VANC assay used on theDimension clinical chemistrysystem is an in vitrodiagnostic test intended tomeasure vancomycin, aglycopeptide antibiotic inhuman serum or plasma.	For in vitro diagnostic usein the quantitativemeasurement ofvancomycin in humanserum or plasma on theTrinidad CH System.
Indications for Use:	VANC test results may beused in the diagnosis andtreatment of vancomycinoverdose and in monitoringlevels of vancomycin toensure appropriate therapy.	Same
Device Technology:	Homogeneous particleenhanced turbidimetricinhibition immunoassay(PETINIA) technique	Same
Sample Type:	Serum/ Lithium Heparinplasma	Same
Therapeutic Interval:	Peak Intervals: Samples fromadult volunteers drawn twohours after the completion ofa 60 minute infusion ofvancomycin ranged from 18 –26 µg/mL.Samples drawn one hourafter the completion of a 60	Same

	minute vancomycin infusion ranged from 25 – 40 µg/mL. Samples drawn 30 minutes after the completion of a 60 minute infusion of vancomycin ranged from 30 – 40 µg/mL. Trough Intervals: Samples should be drawn just before the next dose. A trough interval of 5 - 10 µg/mL is recommended.
Standardization:	Traceable to United States Pharmacopeia (USP) standards.	Same
Calibration Frequency:	30 days	Same
Analytical Measuring Interval:	0.0 – 50.0 µg/mL	3.0–50.0 µg/mL
Interferences:	Bilirubin (Unconjugated) – 80 mg/dLLipemia (Intralipid®) – 200 mg/dLHemoglobin - 1000 mg/dL	Bilirubin (Conjugated & Unconjugated) – 20 mg/dLLipemia (Intralipid®) – 1000 mg/dLHemoglobin - 600 mg/dL
Calibrators:	Drug Calibrator II (K033809)	Drug 3 Calibrator

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Feature	Predicate Device:Dimension Drug CalibratorII (K033809)	New Device:Trinidad CH Drug 3Calibrator (DRUG3 CAL)
Calibrator Matrix:	Bovine Serum Base	Same
Calibrator Form:	Liquid	Same
Number of CalibratorLevels:	Five	Same

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Assay performance comparison results for the Trinidad CH Vancomycin (Vanc) with the Trinidad CH Drug 3 Calibrator were obtained by processing the appropriate body fluids. Summary statistics for each are provided. These data demonstrate substantial equivalency of the Trinidad CH Vancomvcin (Vanc) with the Trinidad CH Drug 3 Calibrator versus the predicate devices. The following data represent typical assay performance.

DETECTION LIMIT

The Limit of Blank (LoB) and Limit of Detection (LoD) were evaluated in accordance with CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation: Approved Guideline.

Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach.

LoB Rank Position = 0.5 +0.95*B, where B=total reps=60; Rank = 57.5

Trinidad CH Vancomycin (Vanc) - Limit of Detection Results
Limit	Protocol	Result
LoB	4 samples with no analyte(bovine serum base) weretested (N=5) for 3 days,one run per day, 3 reagentlots,	0.1 µg/mL
LoD	4 low serum samples weretested (N=5) for 3 days,one run per day, 3 reagentlots	0.2 µg/mL

The nonparametric approach described in EP17-A2 was followed to determine the Limit of Detection.

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The Limit of Quantitation (LoQ) for serum was determined as described in CLSI Document EP17-A2. Total Error is calculated using: TE = bias + 2 * SD.

Four low serum samples were processed on three reagent lots for three days, on one instrument for a total of 60 measurements per reagent lot. The measured LoQ was 2.8 ug/mL in support of the LoQ claim of 3.0 µg/mL based a total of 180 determinations with a total error of ≤ 20%.

LINEARITY STUDY

Linearity was evaluated with 10 samples which spanned the assay measuring interval. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A). The high sample was prepared by spiking native serum with purified vancomycin hydrochloride. The low sample was normal human serum. Six replicates were measured for each sample. The mean of these replicates was used for the calculations.

The assay was considered linear across the measuring interval if the nonlinear coefficients are nonsignificant (all p values are ≥ 0.05). If one or more of them are significant (p < 0.05), then the allowable bias is ≤ 0.5 µg/mL or 10%, whichever is greater.

Reagent Lot 1
Level	Lot 1 Expected(µg/mL)	Lot 1 Observed(µg/mL)	Predicted(µg/mL)	AbsoluteBias (µg/mL)	% Bias	AllowableBias (µg/mL)	Observed Bias ≤Allowable BiasPass/Fail
1	0.9	0.9	0.7	0.2	N/A	0.5	Pass
2	3.0	3.0	2.9	0.1	N/A	0.5	Pass
3	7.2	7.0	7.1	-0.1	N/A	0.5	Pass
4	13.5	13.1	13.4	-0.3	-2.3	0.7	Pass
5	19.7	19.7	19.7	0.0	-0.2	1.0	Pass
6	26.0	25.9	26.1	-0.2	-0.7	1.3	Pass
7	32.3	32.3	32.4	-0.1	-0.3	1.6	Pass
8	38.6	39.1	38.7	0.4	0.9	1.9	Pass
9	44.8	45.3	45.1	0.2	0.5	2.2	Pass
10	51.1	51.1	51.4	-0.3	-0.6	2.6	Pass

Vancomycin Linearity, results in µg/mL

PRECISION STUDIES

Precision testing was performed in accordance with CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline -

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Third Edition. Precision was tested n = 2 replicates, two times a day for at least 20 days for a total of 80 replicates with controls, serum and plasma pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3. The data are summarized in the following table.

SpecimenType	N	Meanµg/mL(µmol/L)	Repeatability		Within-Lab
			SDaµg/mL(µmol/L)	CVb(%)	SDaµg/mL(µmol/L)	CVb(%)
Serum QC	80	6.4 (4.4)	0.16 (0.11)	2.6	0.18 (0.12)	2.7
Serum	80	11.2 (7.7)	0.20 (0.14)	1.8	0.23 (0.16)	2.0
Serum QC	80	17.5 (12.1)	0.28 (0.19)	1.6	0.35 (0.24)	2.0
Serum	80	32.7 (22.6)	0.46 (0.32)	1.4	0.67 (0.46)	2.0
Plasma	80	45.8 (31.6)	0.78 (0.54)	1.7	0.83 (0.57)	1.8

ª SD = standard deviation

b CV = coefficient of variation

INTERFERENCES

CLSI EP7-A2 was followed for the interference testing. The interference study was conducted using a "paired difference worst case scenario" approach where these compounds were spiked into fresh sample pools containing either low or high levels of measurand in serum pools.

Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference. This study was conducted as needed for both serum pools.

Approximate Concentration (within 10%) of Analytes in Test Pools
Analyte	Matrix	Low	High
Vanc	Serum	10.0 µg/mL	40.0 µg/mL

No interference was detected at the following analyte concentrations.

Interferent Concentration

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Hemoglobin 600 mg/dL
Conjugated Bilirubin 20 mg/dL
Unconjugated Bilirubin 20 mg/dL
Lipemia (Intralipid) 1000 mg/dL

Vancomvcin crystalline degradation product (CDP-1) at 20 ug/mL demonstrates cross-reactivity at 0 and 10 ug/mL Vanc of 21.0% and 19.1% respectively.

METHOD COMPARISON

The predicate device selected for the method comparison study was the Dimension RxL VANC assay cleared under K963267. Remnant de-identified samples were tested. No patient history information was obtained on these samples. Inclusion/exclusion data criteria are not applicable. The study included native, spiked, and diluted samples to properly span the assay intervals.

These studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization personnel. The personnel conducting the study were laboratory technicians with training similar to personnel who would conduct the tests in a hospital laboratory setting. They were trained on the operation of both the device and the predicate device. A split sample method comparison, following EP09-A3, demonstrated good agreement between the Trinidad CH Vancomycin (Vanc) and the predicate Dimension RxL VANC assay with patient samples.

The results across the full assay intervals were analyzed by Deming regression. One replicate of each sample was tested and used in the analysis.

Specimen Type	Comparison Assay (x)	N	r	Regression Equation	Sample Interval
Serum	Dimension® RxL VANC	100	0.997	$y = 1.04x - 1.04 \frac{\text{µg}}{\text{mL}}$	$4.4-48.1 \frac{\text{µg}}{\text{mL}}$

MATRIX EQUIVALENCY

Serum and lithium heparin plasma equivalency was demonstrated by testing sixty matched samples. Some samples were diluted with water or spiked with vancomycin to obtain samples spanning the assay measuring intervals. The table below summarizes the Deming linear regression statistics. The results across the full assay intervals were analyzed by Deming regression. One replicate of each sample was tested and used in the analysis.

Specimen Type	Comparison Assay (x)	N	r	Regression Equation	Sample Interval
Plasma(Lithium heparin)	Trinidad CH Vanc –Serum	60	0.990	$y = 1.00x + 0.49 \mu g/mL$	4.0–43.3 μg/mL

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THERAPEUTIC INTERVAL

The therapeutic intervals are cited from the literature 12-1

There is great disparity in vancomycin therapeutic intervals, especially with peak therapeutic intervals. Factors that might affect peak therapeutic intervals include dosage regimen and timing of sample collection.

Vancomycin levels in renal dialysis patients, burn patients and intravenous drug abusers should be closely monitored.

Peak Intervals: Samples from adult volunteers drawn two hours after the completion of a 60 minute infusion of vancomycin ranged from 18 - 26 µg/mL.

Samples drawn one hour after the completion of a 60 minute vancomycin infusion ranged from 25 - 40 µg/mL.

Samples drawn 30 minutes after the completion of a 60 minute infusion of vancomycin ranged from 30 - 40 µg/mL.

Trough Intervals: Samples should be drawn just before the next dose. A trough intervals of 5 - 10 µg/mL is recommended.

Note: The physician must ultimately determine the most appropriate vancomycin therapeutic interval for each patient.

Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Biology, Fourth Edition, Elsevier Saunders, St. Louis, MO; pp. 1253 (clinical significance), pp. 2315 (reference values).
Finn AL, Taylor WJ. Individualizing Drug Therapy, Practical Applications of Drug Monitoring, New York: Gross, Townsend, Frank, Inc., 1981: 87-108.

CONCLUSION

The Trinidad CH Vancomycin (Vanc) and the Trinidad CH Drug 3 Calibrator are substantially equivalent to the Dimension® VANC Flex® reagent Cartridge and the Dimension Drug Calibrator II in principle and performance based on the similarity of device designs and function demonstrated through method comparison and other performance attributes.

Regulation Number and Section

§ 862.3950 Vancomycin test system.

(a)
Identification. A vancomycin test system is a device intended to measure vancomycin, an antibiotic drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of vancomycin overdose and in monitoring the level of vancomycin to ensure appropriate therapy.(b)
Classification. Class II.