VALIDATE D-Dimer Calibration Verification / Linearity Test Kit

K170864 · Maine Standards Company, LLC · GGN · Jun 21, 2017 · Hematology

Device Facts

• Record ID: K170864
• Device Name: VALIDATE D-Dimer Calibration Verification / Linearity Test Kit
• Applicant: Maine Standards Company, LLC
• Product Code: GGN · Hematology
• Decision Date: Jun 21, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5425
• Device Class: Class 2

Indications for Use

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling.

Device Story

The device consists of a set of five liquid, ready-to-use human plasma-based solutions containing D-Dimer at varying concentrations. It is used in clinical laboratories by personnel to verify the linearity, calibration, and reportable range of quantitative D-Dimer assays on specific automated analyzers. The kit is manufactured with an equal relationship (equal deltas) between the five levels; Levels 1 and 5 are prepared independently, while Levels 2, 3, and 4 are derived via dilution. The healthcare provider runs the kit as a sample on the analyzer; the resulting recovery values are compared against expected targets to confirm system performance. This process helps ensure the accuracy of patient D-Dimer test results, supporting clinical decision-making for coagulation-related conditions.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated on Siemens Sysmex CS-2500 across multiple sites/days/operators (n=75 per level for reproducibility; n=240 per level for repeatability). All studies met pre-specified acceptance criteria. Linearity confirmed using statistical software per CLSI EP06-A. Stability validated for 4 freeze/thaw cycles and 2-month closed-vial shelf life.

Technological Characteristics

Liquid, ready-to-use human plasma-based matrix. Five-level set with equal concentration deltas. Storage: -10 to -25°C. Traceable to instrument-specific reagent calibrator curves. Designed for use on automated coagulation analyzers. No electronic components or software algorithms; relies on CLSI EP6-A guidelines for value assignment.

Indications for Use

Indicated for use by clinical laboratory personnel to verify linearity, calibration, and reportable range of D-Dimer quantitative assays on specified analyzers.

Regulatory Classification

Identification

A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.

Special Controls

*Classification.* Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Predicate Devices

• VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit (K152961)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K170864

B. Purpose for Submission:
To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Siemens Sysmex CS-2500® instrument system in combination with Siemens INNOVANCE® D-Dimer reagent.

C. Measurand:
D-Dimer

D. Type of Test:
Quantitative

E. Applicant:
Maine Standards Company LLC

F. Proprietary and Established Names:
VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit

G. Regulatory Information:
1. Regulation section:
21 CFR § 864.5425, Multipurpose system for in vitro coagulation studies
2. Classification:
Class II
3. Product code:
GGN – Plasma, Coagulation Control

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4. Panel:

Hematology (81)

H. Intended Use:

1. Intended use(s):

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling.

2. Indication(s) for use:

Same as intended use

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

Siemens Sysmex CS-2500® instrument system and Siemens INNOVANCE® D-Dimer reagent (K151259)

Diagnostica Stago STA-R® Evolution (K093001) and STA® - Liatest® D-Di (K162227)

Instrumentation Laboratory (IL) ACL TOP Family and HemosIL® D-Dimer HS assay (K160276)

I. Device Description:

The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to establish the relationship between theoretical and actual performance of the D-Dimer analyte. The kit includes five levels of D-Dimer analyte in a human plasma base matrix. VALIDATE® D-Dimer Calibration Verification/Linearity Test kit solutions are not intended for use as calibration materials.

J. Substantial Equivalence Information:

1. Predicate device name(s):

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit

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2. Predicate 510(k) number(s):

K152961

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate (K152961) |
| | VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit | VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit |
| Intended Use | For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. | Same |
| Analyte | D-Dimer | Same |
| Stability | Shelf -life: Until expiration date printed on labeling
Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles | Same |
| Matrix | Human plasma | Same |
| Number of Levels | 5 Levels | Same |
| Preparation | Liquid; Ready to Use | Same |
| Storage | -10 to -25°C | Same |

There is no difference between the subject device and the predicate.

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3; Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline –Third Edition

CLSI EP06-A; Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP25-A; Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline

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L. Test Principle:

The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is used for calibration verification and verification of the D-dimer measuring range of the INNOVANCE® D-Dimer reagent with the Siemens Sysmex CS-2500® instrument system. The kit includes five levels of D-dimer used to establish the relationship between theoretical and actual performance of the D-Dimer analyte quantitatively. The Level 1 D-Dimer is configured to contain the lowest level (lower limit) and Level 5 D-Dimer to contain the highest level (upper limit) of concentration of D-Dimer of the measuring range. The intermediate levels (Level 2, Level 3, and Level 4) are subsequently prepared from Level 1 and Level 5 by equal part dilutions following the CLSI EP06-A guideline to measure intermediate levels of the measuring range.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was evaluated on the Siemens Sysmex CS-2500® instrument system with the VALIDATE® D-Dimer Calibration Verification/Linearity Test kit. One lot of VALIDATE® D-Dimer (levels 1–5) was tested with one lot of Siemens INNOVANCE® D-Dimer reagent and quality controls on three instruments, across multiple sites, over five days, with one run per day of each level, five replicates per run, and a minimum of three operators. The study produced a total of 75 data points for each level. The reproducibility study met the pre-specified acceptance criteria. Results from the study are provided in the table below:

| Sample | Mean (mg/L FEU) | Repeatability | | Within-Laboratory | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV |
| Level 1 | 0.30 | 0.013 | 4.2% | 0.013 | 4.4% | 0.016 | 5.4% |
| Level 2 | 1.17 | 0.033 | 2.8% | 0.043 | 3.6% | 0.045 | 3.8% |
| Level 3 | 2.10 | 0.060 | 2.9% | 0.099 | 4.7% | 0.160 | 7.6% |
| Level 4 | 3.08 | 0.099 | 3.2% | 0.180 | 5.8% | 0.292 | 9.5% |
| Level 5 | 3.97 | 0.13 | 3.3% | 0.294 | 7.4% | 0.384 | 9.7% |

b. Precision/Repeatability:

To evaluate repeatability and within-laboratory precision, three lots of VALIDATE® D-Dimer Calibration Verification/Linearity Test kit (levels 1–5) were tested with one lot of Siemens INNOVANCE® D-Dimer reagent and quality controls at one site on one Siemens Sysmex CS-2500® instrument system. The study was performed over 20 operating days, two runs per day, and two replicates per run with a minimum of two operators to obtain a total of 240 replicates for each level. The repeatability study met the pre-determined acceptance criteria. Results from the study are summarized in the table below:

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| Sample | N | Mean (mg/L FEU) | Within-Run | | Between-Run | | Between-Day | | Between-Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Level 1 | 240 | 0.29 | 0.012 | 4.1% | 0.001 | 0.5% | 0.005 | 1.6% | 0.006 | 2.0% | 0.014 | 4.9% |
| Level 2 | 240 | 1.19 | 0.042 | 3.6% | 0.000 | 0.0% | 0.053 | 4.5% | 0.000 | 0.0% | 0.068 | 5.7% |
| Level 3 | 240 | 2.07 | 0.068 | 3.3% | 0.029 | 1.4% | 0.049 | 2.4% | 0.000 | 0.0% | 0.089 | 4.3% |
| Level 4 | 240 | 3.02 | 0.139 | 4.6% | 0.087 | 2.9% | 0.119 | 4.0% | 0.000 | 0.0% | 0.203 | 6.7% |
| Level 5 | 240 | 4.01 | 0.183 | 4.6% | 0.131 | 3.3% | 0.156 | 3.9% | 0.000 | 0.0% | 0.274 | 6.8% |

c. Linearity/assay reportable range:

Linearity was determined using three lots of the VALIDATE® D-Dimer Calibration Verification/Linearity Test kit on the Siemens Sysmex CS-2500® instrument. Linearity performance was confirmed for the D-Dimer analyte using statistical software. The D-dimer concentrations of each measured value of the five levels were plotted vs. five assigned levels of concentration. The results were determined to be linear.

d. Traceability, Stability, Expected values (controls, calibrators, or methods):

Stability:

Open Vial (Freeze/Thaw) Stability

A freeze/thaw vial stability assessment was performed to support the open vial stability claim. Three lots of the VALIDATE® D-Dimer Calibration Verification/Linearity Test kit were tested on a Siemens Sysmex CS-2500® instrument. The study demonstrated that each level of VALIDATE® D-Dimer is stable after four freeze/thaw events when stored at -10 to $-25^{\circ}\mathrm{C}$ . The study met the pre-determined acceptance criteria.

Closed Vial Stability Study

Real-time stability testing was performed using three lots of VALIDATE® D-Dimer Calibration Verification/Linearity Test kit on a Siemens Sysmex CS-2500® instrument. Results from the VALIDATE® D-Dimer meet acceptance criteria out to a 2 month time point from the date of manufacture (DOM) when stored at -10 to $-25^{\circ}\mathrm{C}$ . A 2 month expiry date is supported by current stability data. Real-time stability testing is ongoing. Stability data is being maintained to extend the stability claim of the VALIDATE® D-Dimer Calibration Verification/Linearity Test kit.

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Expected Values:

# Value Assignment/Recovery Data

Value assignment for the VALIDATE® D-Dimer Calibration Verification/Linearity Test kit is established by testing Level 1 (lowest concentration) and Level 5 (highest concentration) of VALIDATE® D-Dimer to generate 30 replicates on one Siemens Sysmex CS-2500® instrument. The value assignments for the intermediate levels are calculated based on an equal distance (delta) between levels. Levels 1 and 5 are prepared independently by the addition of D-dimer to a human plasma base matrix. Intermediate Levels 2, 3, and 4 are subsequently prepared from Levels 1 and 5 by equal part dilutions following CLSI EP06-A. The value assignment study met the predetermined acceptance criteria. Typical recovery target values for all five levels are presented in the table below:

| Instrument | Analyte | Levels (mg/L FEU) | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | 1 | 2 | 3 | 4 | 5 |
| Sysmex CS-2500® | D-Dimer | 0.30 | 1.19 | 2.08 | 2.97 | 3.86 |

e. Detection limit:

Not applicable

f. Analytical specificity:

Not applicable

g. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

Not applicable

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

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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 VALIDATE® D-Dimer Calibration Verification/Linearity Test kit is manufactured such that a linear relationship exists among Levels 1 through 5. Actual expected values will be included in the kit lot Certificate of Analysis sheet for each Level 1 and Level 5. The values for mid-levels are calculated based on an equal distance (delta) between levels.

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.