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

Device Description

Each VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit contains one analyte set of D-Dimer in a human plasma base matrix. The kit includes a set containing five liquid levels, 3.0 mL each. The set is provided to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. Material of human origin used in the manufacture of this test kit was tested at the donor level using FDA approved methods and was found to be non-reactive for HBsAG and to antibodies to HCV and HIV-1/2.

AI/ML Overview

The provided text describes a 510(k) premarket notification for an in vitro diagnostic device, the VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit. This document does not pertain to an AI/ML medical device, but rather to a quality control material used for calibrating laboratory instruments.

Therefore, many of the requested criteria for describing an AI/ML device's acceptance criteria and study proving its performance (such as sample size for test/training sets, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone performance, etc.) are not applicable to this document.

However, I can extract information related to the device's performance validation as presented in the document:

Acceptance Criteria and Device Performance (for a Calibration Verification/Linearity Test Kit - Not an AI/ML Device)

1. Table of Acceptance Criteria and Reported Device Performance

The document describes performance in terms of precision/reproducibility and linearity, rather than typical AI metrics like sensitivity, specificity, or AUC. The "acceptance criteria" are implied by the statements that "All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Siemens CS-2500 instrument system." and that linearity testing was carried out. Specific numerical acceptance criteria for CV% are not explicitly stated in the provided text.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Precision/Reproducibility	All levels to meet pre-defined CV% acceptance criteria.	All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Siemens CS-2500 instrument system.
Linearity	The kit must demonstrate a linear relationship between levels for calibration verification and reportable range verification.	Linearity testing was carried out, and a linear relationship is stated to exist between each level. The product design relies on "equal deltas" as outlined in CLSI EP6-A.
Stability	Product must maintain performance within acceptance criteria over time and freeze-thaw cycles.	Shelf Life Claim: 9 months stability. All product levels tested within acceptance criteria limits after 6 freeze-thaw vial events.

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

Precision/Reproducibility Study:
- Sample Size (Replicates): 80 replicates per kit level for precision study; 75 replicates per kit level for reproducibility study.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implied to be from internal lab testing ("on the Siemens Sysmex CS-2500 instrument system" at "multi-site" for reproducibility). The studies are prospective in nature, as they involve active testing of the device.
Linearity Study:
- Sample Size: Not explicitly stated in terms of number of runs or replicates, beyond "Linearity testing was carried out."
- Data Provenance: Internal lab testing.

3. Number of Experts Used to Establish Ground Truth and Qualifications

Not applicable. This is a quality control material for an in vitro diagnostic test, not an AI/ML device that requires human expert annotation for ground truth. The "ground truth" (or target values) for this device is based on its intended concentration levels (Levels 1 through 5) and the expected linear relationship between them.

4. Adjudication Method for the Test Set

Not applicable. No human interpretation or qualitative assessment requiring adjudication is described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No. This type of study is relevant for AI/ML devices that assist human readers in image interpretation or similar tasks. This device is a quantitative control material.

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

Not applicable. This is a physical kit used to verify instrument performance, not a standalone algorithm. Its "performance" is its ability to reproducibly produce expected values and demonstrate linearity when run on an instrument.

7. The Type of Ground Truth Used

Internal Reference Standard / Expected Values: The "ground truth" for this device revolves around the predetermined concentrations of D-Dimer in each level (1-5) and their designed linear relationship.
- Level 1 and 5 are prepared independently with D-Dimer added to a human plasma base.
- Levels 2, 3, and 4 are subsequently prepared from Levels 1 and 5 by equal part dilutions following CLSI EP6-A guidelines.
- "Typical recovery values" are established by testing 30 replicates of Levels 1 and 5.
- The device is traceable to the instrument's (Siemens Sysmex CS-2500) calibrator curve (Innovance® reagent calibrator).

8. The Sample Size for the Training Set

Not applicable. This device is not an AI/ML model that undergoes "training" in the computational sense. Its formulation and design are based on established laboratory quality control guidelines (e.g., CLSI EP6-A).

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

Not applicable. See point 8. The "ground truth" for the development of the kit (i.e., establishing the target values and linearity across levels) is described by:
- Independent preparation of Levels 1 and 5.
- Subsequent preparation of Levels 2, 3, and 4 via equal part dilutions from Levels 1 and 5.
- Determination of "typical value ranges" and "typical recovery values" for Levels 1 and 5 through 30 replicates of testing.
- Adherence to CLSI EP6-A guidelines for linearity.

Summary

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

June 21, 2017

Maine Standards Company LLC James W. Champlin Director, QSHIE 221 US Route 1 Cumberland Foreside, ME 04110

Re: K170864

Trade/Device Name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: GGN Dated: March 22, 2017 Received: March 23, 2017

Dear Mr. Champlin:

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,

Leonthena R. Carrington -S

Lea Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

Form FDA 3881 (1/14) Attached

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Indications for Use

510(k) Number (if known)

Device Name

VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit.

Indications for Use (Describe)

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 being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92."

The assigned 510(k) number is: K170864

A. Submitter:

Maine Standards Company LLC 221 US Route 1 Cumberland Foreside, ME 04110 207-892-1300 Telephone: Fax: 207-892-2266

Contact Person: James Champlin Director, QSHIE jim.champlin@lgcgroup.com 207-892-1300 Ext. 29 Telephone:

Date of Summary Preparation: June 16, 2017

B. Device Classification:

Device classification name: Plasma, Coagulation Control Common name: Calibration Verification / Linearity Test Kit VALIDATE® D-Dimer Calibration Verification / Linearity Test Proprietary Name: Kit Review Panel: Hematology (81) 21 CFR 864.5425 Requlation Number: Product Code: GGN Regulatory Class: Class II

C. Predicate Device Identification:

VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit. Maine Standards Company LLC, Cumberland Foreside, ME 04110 K152961

D. Candidate Device description: Each VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit contains one analyte set of D-Dimer in a human plasma base matrix. The kit includes a set containing five liquid levels, 3.0 mL each. The set is provided to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. Material of human origin used in the manufacture of this test kit was tested at the donor level using FDA approved methods and was found to be non-reactive for HBsAG and to antibodies to HCV and HIV-1/2.

E. 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.

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F. Summary of Performance Data:

The performance of the new VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit was compared to the predicate device K152961, VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit.

Table 1 compares the technical characteristics of the new VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit with those of the predicate.

	New Device	Predicate (K152961)
	VALIDATE® D-Dimer Calibration	VALIDATE® D-Dimer Calibration
	Verification / Linearity Test Kit	Verification / Linearity Test Kit
	Similarities	Similarities
Test Kit	Calibration Verification/LinearityTest Kit	Same
Intended Use	For in vitro diagnostic use in thequantitative determination oflinearity, calibration verificationand verification of reportablerange in automated instrumentsystems	Same
Analytes	D-Dimer	Same
Stability	Until expiration date	Same
Matrix	Human plasma base	Same
Number of Levels	5 levels	Same
Preparation	Liquid, ready to use	Same
Storage	-10 to -25°C	Same

Table 1 - Technical Comparison to Predicate

Value Assignment

VALIDATE® D-Dimer Calibration Verification / Linearity Test Kits are manufactured such that an equal relationship exists among Levels 1 through 5; Level 1 being the lowest concentration and Level 5 being the highest. Levels 1 and 5 are prepared independently by the addition of D-Dimer to a human plasma base matrix. Levels 1 through 5 must meet specified D-Dimer target ranges at all stages of testing.

Specific recovery targets for Levels 1 through 5 are determined by the upper and lower detection limits for D-Dimer. Intermediate Levels 2, 3, and 4 are subsequently prepared from Levels 1 and 5 by equal part dilutions following EP6-A guidelines. Typical value ranges are provided in the package insert.

Typical recovery values, presented in Table 2, were established for Level 1 and Level 5 by testing 30 replicates, with values for Mid-Levels 2, 3, and 4 calculated based on an equal distance (delta) between levels.

The product is designed for laboratories to satisfy the requirements for calibration verification and verification of the systems reportable range as specified in the current CLIA regulations section 493.1255.

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Table 2 - Typical Recovery Values

Set
Instrument	Analyte	Units	Levels
			1	2	3	4	5
Siemens SysmexCS-2500®	D-Dimer	mg/L FEU	0.30	1.19	2.08	2.97	3.86

A linear relationship exists between each level in a kit. The quantitative determination of linearity, calibration verification, and verification of reportable range relies on the known relationship between each of the levels of the product, in this case equal deltas, as outlined in the CLSI EP6-A referenced standard.

This kit is not intended for use as a calibration material.

Precision/Reproducibility

Precision was evaluated on the Siemens Sysmex CS-2500 instrument system with the VALIDATE® D-Dimer product following the product package insert instructions. Three lots of VALIDATE® D-Dimer product were tested with one lot of Siemens Innovance® D-Dimer reagent and quality controls on the Siemens CS-2500 instrument system over 20 days, 2 runs per day, 2 replicates per run for Level 1 through Level 5 with a minimum of two operators to obtain a total of eighty (80) replicates per kit Level. All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Siemens CS-2500 instrument system.

Reproducibility was evaluated on the Siemens Sysmex CS-2500 instrument system with the VALIDATE® D-Dimer kit containing 5 levels following the product package insert instructions. One lot of VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit was tested with one lot of Siemens Innovance® D-Dimer reagent and quality controls on three instruments, multi-site, over 5 days, with 1 run per day of Levels 1-5, 5 replicates per run and a minimum of three operators to obtain seventy-five (75) replicates per kit level. All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Siemens CS-2500 instrument system.

Traceability

This device is traceable to a reference standard based on the automated instrument. platform it is used on. The traceability of our product will be established per the respective end user automated instrument calibrator traceability reference statement. For the Siemens Sysmex CS-2500 the device is traceable to the Innovance® reagent calibrator curve.

Stability

Stability testing was performed using the Siemens Sysmex CS-2500 instrument system. The study testing time points included date of manufacture (DOM), followed by testing at specific intervals post manufacture.

A freeze-thaw vial stability assessment was also conducted in support of the product package insert four (4) freeze-thaw open vial events claim. All product levels tested within the acceptance criteria limits after 6 freeze-thaw vial events.

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Shelf Life Claim: Stability of the VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit was set at 9 months based on available real-time stability studies. Real time stability studies are ongoing to support an extended stability claim. The recommended storage temperature is -10 to -25°C. All supporting data is retained on file at Maine Standards Company LLC.

Linearity:

Linearity testing was carried out with the new device VALIDATE® D-Dimer Calibration Verification / Linearity Test Kits on the Siemens Sysmex CS-2500 instrument. All supporting data is retained on file at Maine Standards Company LLC.

G. Conclusion:

Based upon the purpose of the device, the descriptions and labeling of the predicate device, the VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit behaves substantially equivalent to the predicate for the quantitative determination of linearity, calibration verification and verification of reportable range for the D-Dimer analyte. The product is substantially equivalent to the predicate device, K152961.

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
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.(b)
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.