VALIDATE® D-Dimer Calibration Verification/ Linearity Test Kit

K162705 · Maine Standards Company, LLC · GGN · Jan 5, 2017 · Hematology

Device Facts

• Record ID: K162705
• Device Name: VALIDATE® D-Dimer Calibration Verification/ Linearity Test Kit
• Applicant: Maine Standards Company, LLC
• Product Code: GGN · Hematology
• Decision Date: Jan 5, 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

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit provides assayed quality control materials to verify quantitative performance of D-Dimer assays. Kit consists of five liquid levels of D-Dimer in human plasma-based matrix. Levels 1 and 5 are prepared by adding D-Dimer to human plasma; levels 2, 3, and 4 are prepared by equal-part dilutions of levels 1 and 5. Used in clinical laboratories by personnel to establish relationship between theoretical and actual assay performance on specific analyzers (e.g., Diagnostica Stago STA-R® Evolution). Output is a set of measured values compared against assigned concentrations to confirm linearity and reportable range. Benefits include ensuring accuracy and reliability of D-Dimer diagnostic testing.

Clinical Evidence

Bench testing only. Precision/reproducibility studies conducted over 20 days (single-site) and 5 days (multi-site) across three lots and multiple analyzers. Linearity confirmed using manual methods and Analyze-IT® software. Stability studies support 4-month shelf-life and 4 freeze/thaw cycles. No clinical data provided.

Technological Characteristics

Human plasma-based matrix; liquid, ready-to-use; 5-level set. Analyte: D-Dimer. Storage: -10 to -25°C. Connectivity: None (standalone test kit). Software: Uses Analyze-IT® linearity software for data analysis. Standards: CLSI EP05-A3, EP06-A, EP25-A.

Indications for Use

Indicated for use in clinical laboratory settings by laboratory personnel to perform quantitative determination of linearity, calibration verification, and verification of reportable range for D-Dimer 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:
K162705

B. Purpose for Submission:
To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di.

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
4. Panel:

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Hematology (81)

## H. Intended Use:

1. **Intended 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.

2. **Indication(s) for use:**

Same as Intended use

3. **Special conditions for use statement:**

For prescription use only

4. **Special instrument requirements:**

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

## I. Device Description:

The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL.

## J. Substantial Equivalence Information:

1. **Predicate device name:**

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit

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

K152961

3. **Comparison with predicate:**

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| Similarities | | |
| --- | --- | --- |
| Item | Device
VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit | Predicate
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: 4 months
Closed-vial: 9 months at -10 to -25°C
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 |

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 the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline

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

## L. Test Principle:

The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D-Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer.

## M. Performance Characteristics (if/when applicable):

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# 1. Analytical performance:

# a. Precision/Reproducibility:

To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1-5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, $\% \mathrm{CV}$ and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the predetermined acceptance criteria. Results from the study are provided in the table below.

| Level 1 | Mean μg/mL FEU | Within-run | | Between-run | | Between-day | | Total | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| D-Dimer | Lot 1 | 0.44 | 0.080 | 18.5 | 0.000 | 0.0 | 0.027 | 6.2 | 0.086 | 19.5 |
| | Lot 2 | 0.46 | 0.055 | 11.8 | 0.015 | 3.2 | 0.030 | 6.5 | 0.064 | 13.8 |
| | Lot 3 | 0.46 | 0.057 | 12.6 | 0.043 | 9.4 | 0.045 | 9.8 | 0.085 | 18.6 |
| Level 2 | Mean μg/mL FEU | Within-run | | Between-run | | Between-day | | Total | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| D-Dimer | Lot 1 | 1.15 | 0.055 | 4.7 | 0.000 | 0.0 | 0.016 | 1.4 | 0.057 | 4.9 |
| | Lot 2 | 1.15 | 0.054 | 4.7 | 0.013 | 1.2 | 0.025 | 2.2 | 0.061 | 5.3 |
| | Lot 3 | 1.14 | 0.051 | 4.4 | 0.019 | 1.7 | 0.016 | 1.4 | 0.057 | 4.9 |
| Level 3 | Mean μg/mL FEU | Within-run | | Between-run | | Between-day | | Total | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| D-Dimer | Lot 1 | 1.88 | 0.059 | 3.1 | 0.024 | 1.3 | 0.000 | 0.0 | 0.064 | 3.4 |
| | Lot 2 | 1.92 | 0.042 | 2.2 | 0.000 | 0.0 | 0.036 | 1.9 | 0.055 | 2.9 |
| | Lot 3 | 1.88 | 0.060 | 3.2 | 0.000 | 0.0 | 0.041 | 2.2 | 0.072 | 3.9 |
| Level 4 | Mean μg/mL FEU | Within-run | | Between-run | | Between-day | | Total | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| D-Dimer | Lot 1 | 2.68 | 0.117 | 4.4 | 0.000 | 0.0 | 0.068 | 2.5 | 0.135 | 5.0 |
| | Lot 2 | 2.67 | 0.067 | 2.5 | 0.380 | 1.4 | 0.000 | 0.0 | 0.077 | 2.9 |
| | Lot 3 | 2.67 | 0.136 | 5.1 | 0.000 | 0.0 | 0.54 | 2.0 | 0.146 | 5.5 |
| Level 5 | Mean μg/mL FEU | Within-run | | Between-run | | Between-day | | Total | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| D-Dimer | Lot 1 | 3.53 | 0.171 | 4.8 | 0.000 | 0.0 | 0.000 | 0.0 | 0.171 | 4.8 |
| | Lot 2 | 3.56 | 0.168 | 4.7 | 0.000 | 0.0 | 0.077 | 2.2 | 0.185 | 5.2 |
| | Lot 3 | 3.56 | 0.080 | 2.2 | 0.058 | 1.6 | 0.051 | 1.4 | 0.111 | 3.1 |

To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers.

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| Level | Mean μg/mL FEU | Within-run | | Within-Laboratory | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV |
| Level 1 | 0.44 | 0.061 | 13.8% | 0.066 | 15.0% | 0.069 | 15.5% |
| Level 2 | 1.14 | 0.054 | 4.7% | 0.054 | 4.7% | 0.063 | 5.5% |
| Level 3 | 1.87 | 0.065 | 3.5% | 0.065 | 3.5% | 0.089 | 4.7% |
| Level 4 | 2.64 | 0.052 | 2.0% | 0.059 | 2.2% | 0.081 | 3.1% |
| Level 5 | 3.50 | 0.275 | 7.9% | 0.282 | 8.1% | 0.3 | 1.2% |

# b. Linearity/assay reportable range:

Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® linearity software. The D-dimer concentrations of each measured value of the five levels plotted vs. five assigned levels of concentration. The results provided appeared to be linear.

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

# Traceability:

Not applicable. An international reference preparation (IRP) is not available for D-dimer assays.

# Value Assignment

A linear relationship exists between levels 1 through 5 of each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit; level 1 being the lowest concentration and level 5 being the highest concentration. Levels 1 and 5 are prepared independently by the addition of D-dimer to a human plasma base. The D-dimer is prepared by Maine Standards from fresh frozen human plasma. Intermediate levels 2, 3, and 4 are subsequently prepared from levels 1 and 5 by equal part dilutions. Testing was performed for each level on five separate days, six replicates per day for a total of 30 replicates per level. Total percent coefficient of variation (%CV) was calculated for levels 1 and 5, and found to be within the predefined acceptance criteria. Typical mean recovery values for all levels for one representative lot tested using the STA® - Liatest D-Di reagent kit in combination with the STA-R® Evolution are presented in the table below.

| VALIDATE D-DIMER | Level 1 | Level 2 | Level 3 | Level 4 | Level 5 |
| --- | --- | --- | --- | --- | --- |
| D-dimer (μg/mL FEU) | 0.32 | 1.05 | 1.78 | 2.50 | 3.23 |

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# Shelf-life and Open-Vial Stability Testing

A real-time stability study was performed to support the shelf-life claim for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Stability was evaluated on the STA-R® Evolution using three lots of VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Acceptance criteria were found to be acceptable and support the shelf-life stability claim of 4 months from the date of manufacturing (DOM) when stored at -10 to -25°C.

A freeze/thaw stability assessment was also conducted to support the open-vial stability claim. Acceptance criteria were found to be acceptable to support four freeze/thaw events.

d. Detection limit:
Not applicable

e. Analytical specificity:
Not applicable

f. 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
b. Clinical specificity:
Not applicable

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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:
Not applicable.

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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