(99 days)
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.
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 liguid 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.
The provided document describes the FDA 510(k) summary for the VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit (K162705). This device is an assayed quality control material, not an AI-powered diagnostic device. Therefore, the specific questions related to AI performance, such as multi-reader multi-case studies, human reader improvement with AI assistance, and AI-specific ground truth, are not directly applicable.
However, I can extract information related to the acceptance criteria and the studies performed for this device based on the provided text.
Acceptance Criteria and Reported Device Performance
The core acceptance criterion for this device, a calibration verification/linearity test kit, is its ability to demonstrate linearity between specified levels and to perform consistently with a predicate device. The performance is primarily evaluated through precision/reproducibility studies and linearity testing.
Table 1: Acceptance Criteria (Implicit) and Reported Performance
| Feature/Study | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | CV% for all levels should meet established criteria on the Stago STA-R® instrument system. (Specific CV% targets not explicitly stated, but standard for such devices.) | Precision: All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Stago STA-R® instrument system. Reproducibility: All levels of the VALIDATE® D-Dimer kit met the CV% acceptance criteria on the Stago STA® instrument system (across multiple instruments, sites, and operators). |
| Linearity | A linear relationship must exist between each level in the kit, and the device should demonstrate quantitative determination of linearity, calibration verification, and verification of reportable range as outlined in CLSI EP6-A. | Linearity testing was carried out, and the device demonstrated the quantitative determination of linearity, calibration verification, and verification of reportable range for the D-Dimer analyte. All supporting data is retained on file. |
| Value Assignment (Levels) | Levels 1-5 must meet specified D-Dimer target ranges, with Levels 2, 3, and 4 prepared by equal part dilutions of Levels 1 and 5 (following EP6-A guidelines), maintaining an equal 'delta' between levels. Specific recovery targets were determined by upper and lower detection limits. | Levels 1-5 had typical value ranges provided (Table A1 shows example values). Level 1 and 5 values were established by testing 30 replicates. Mid-Levels 2, 3, and 4 were calculated based on an equal distance (delta) between levels. |
| Stability (Shelf Life) | The product must maintain its performance within acceptance criteria over the claimed shelf life and during freeze-thaw cycles. | Shelf Life Claim: 4 months (real-time studies ongoing for extension). All product levels tested within acceptance criteria limits after 6 freeze-thaw open vial events. Recommended storage: -10 to -25°C. |
| Substantial Equivalence | The device must be demonstrated to be substantially equivalent to the predicate device (K152961) in terms of intended use, analytes, stability, matrix, number of levels, preparation, storage, and overall performance. | The new device was found to be substantially equivalent to the predicate device (K152961) based on technical characteristics and performance data for quantitative determination of linearity, calibration verification, and verification of reportable range. |
Study Details:
2. Sample sizes used for the test set and the data provenance:
- Precision Study (Test Set 1):
- Sample Size: 80 replicates per kit level (for Levels 1 through 5). Total 400 replicates (5 levels * 80 reps).
- Methodology: 3 lots of devices, 1 lot of reagent and quality controls, tested over 20 days, 2 runs per day, 2 replicates per run.
- Provenance: Data appears to be prospective, collected specifically for this submission. Country of origin is not explicitly stated but implied to be within the US given the submission to the FDA. The testing was done on a Stago STA-R® Evolution instrument system.
- Reproducibility Study (Test Set 2):
- Sample Size: 75 replicates per kit level (for Levels 1 through 5). Total 375 replicates (5 levels * 75 reps).
- Methodology: 1 lot of device, 1 lot of reagent and quality controls, tested on 3 instruments, multi-site, over 5 days, 1 run per day, 5 replicates per run.
- Provenance: Data appears to be prospective, collected specifically for this submission. Multi-site indicates varied data sources geographically, likely within the US. The testing was done on a Stago STA® instrument system.
- Value Assignment (Levels 1 & 5) (Test Set 3):
- Sample Size: 30 replicates for Level 1 and Level 5.
- Methodology: Testing was performed to establish typical recovery values.
- Provenance: Not explicitly stated, but part of the manufacturing and quality control process.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable: This device is a quantitative control material for D-Dimer, not an AI or diagnostic imaging device that requires human expert interpretation for ground truth. The "ground truth" for this device's performance is its measured concentration and its linearity, verified against instrument performance and established industry standards (e.g., CLSI EP6-A).
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not Applicable: As this is a quantitative control material, there is no subjective interpretation requiring adjudication by experts. The "adjudication" is based on objective statistical analysis (e.g., CV% calculation) of the measured values.
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:
- Not Applicable: This device is not an AI-powered diagnostic system. It is a calibration and linearity verification kit.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not Applicable: This device does not involve an algorithm being tested in a standalone capacity. Its performance is intrinsically tied to human laboratory personnel using it on an analytical instrument.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for this device essentially comes from:
- Expected Quantitative Values: The known, manufactured concentrations of D-Dimer at each level (Levels 1 and 5 prepared independently, Levels 2, 3, and 4 derived from equal part dilutions).
- Industry Standards: Adherence to guidelines like CLSI EP6-A for linearity and calibration verification.
- Instrument Reference Standard: Traceability to the Stago LiaTest calibrator on the Stago STA-R® Evolution instrument system.
8. The sample size for the training set:
- Not Applicable in the context of machine learning model training. For a calibration verification kit, the concept of a "training set" doesn't apply in the same way. The device's characteristics are designed and controlled during manufacturing based on established analytical chemistry principles and instrument performance specifications.
9. How the ground truth for the training set was established:
- Not Applicable in the context of machine learning. The "ground truth" for the various levels of the calibration kit is established during its manufacturing process. Levels 1 and 5 are prepared independently by adding D-Dimer to a human plasma base matrix to target specific concentrations. Levels 2, 3, and 4 are then prepared from these by equal part dilutions according to EP6-A guidelines, ensuring a known linear relationship (equal delta) between all five levels. This forms the basis of the expected "truth" for validating linearity and calibration on user instruments.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 5, 2017
Maine Standards Company LLC Mr. James Champlin Manager, Quality Assurance & Regulatory Affairs 221 US Route 1 Cumberland Foreside, Maine 04110
Re: K162705
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: January 4, 2017 Received: January 5, 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
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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 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
Leonthena R. 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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| Form Approved: OMB No. 0910-0120 |
|---|
| Expiration Date: January 31, 2017 |
| See PRA Statement below. |
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Indications for Use
| 510(k) Number (if known) | K162705 |
|---|---|
| Device Name | VALIDATE D-Dimer Calibration Verification / Linearity Test Kit |
| Indications for Use (Describe) | 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. |
| 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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| FORM FDA 3881 (8/14) | Page 1 of 1 |
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PSC Publishing Services (301) 443-6740 EF
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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: K162705
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 Manager, Quality Assurance & Regulatory Affairs ichamplin@mainestandards.com Telephone: 207-892-1300 Ext. 29
Date of Summary Preparation: December 23, 2016
B. Device Classification:
| Device classification name: | Plasma, Coagulation Control |
|---|---|
| Common name: | Calibration Verification / Linearity Test Kit |
| Proprietary Name: | VALIDATE® D-Dimer Calibration Verification / Linearity TestKit |
| Review Panel: | Hematology (81) |
| Regulation Number: | 21 CFR 864.5425 |
| 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 liguid 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 / 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.
| Table 1 - Technical Comparison to Predicate | ||
|---|---|---|
| New DeviceVALIDATE® D-Dimer CalibrationVerification / Linearity Test Kit | Predicate (K152961)VALIDATE® D-Dimer CalibrationVerification / Linearity Test Kit | |
| Similarities | ||
| Test Kit | Calibration Verification/LinearityTest Kit | Same |
| Intended Use | VALIDATE® D-Dimer CalibrationVerification / Linearity Test Kitsolutions are an assayed qualitycontrol materials intended for in vitro diagnostic use in thequantitative determination oflinearity, calibration verificationand verification of reportablerange for the following analyte:D-Dimer in a clinical laboratorysetting by laboratory personnel.The product is intended for usewith quantitative assays on theindicated analyzers specified inthe labeling. | 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 |
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 1, 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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| ableA1 | |
|---|---|
| ---------------- | -- |
| Set | ||||||||
|---|---|---|---|---|---|---|---|---|
| Levels | ||||||||
| Instrument | Analyte | Units | 1 | 2 | 3 | 4 | 5 | |
| Stago STA-R® | D-Dimer | ug/mL FEU | 0.32 | 1.05 | 1.78 | 2.50 | 3.23 |
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 Stago STA-R® Evolution 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 Stago Liatest D-Dimer reagent and quality controls on the Stago STA-R® 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 Stago STA-R® instrument system.
Reproducibility was evaluated on the Stago STA® 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 Stago LiaTest D-Dimer reagent and quality controls on three instruments, multi-site, over 5 days, with 1 run per day of Level 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 Stago STA® instrument system.
Traceability
This product is traceable to a reference standard based on the automated instrument platform it is used on. The traceability of our product was established on the Stago STA-R® Evolution instrument system and is traceable to the Stago LiaTest calibrator.
Stability
Stability testing was performed using the Stago STA-R® Evolution 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.
Shelf Life Claim: Stability of the VALIDATE® D-Dimer Calibration / Linearity Test Kit was set at 4 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.
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Linearity:
Linearity testing was carried out with the new device VALIDATE® D-Dimer Calibration Verification / Linearity Test Kits on the Stago STA-R® Evolution coagulation 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
§ 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.