(93 days)
VALIDATE® Heparin 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 Heparin Anti-Xa activity on automated instruments in a clinical laboratory setting by laboratory personnel. The product is intended for use on the IL ACL TOP® analyzer.
Each VALIDATE® Heparin Calibration Verification / Linearity Test Kit contains one analyte set of Heparin 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 Heparin Anti-X activity. 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 text describes the performance data for the VALIDATE® Heparin Calibration Verification / Linearity Test Kit. Here's a breakdown of the acceptance criteria and study details based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state the numerical acceptance criteria for linearity, precision, or reproducibility in a table format. However, it indicates qualitative acceptance.
| Feature | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Linearity | Known relationship between levels (equal deltas) demonstrated. | "Product linearity performance was demonstrated for this automated system." |
| Precision | Met CV% acceptance criteria. | "All levels of the VALIDATE® Heparin kit met the CV% acceptance criteria on the IL ACL TOP 500® instrument system." |
| Reproducibility | Met CV% acceptance criteria. | "All levels of the VALIDATE® Heparin kit met the CV% acceptance criteria on the IL ACL TOP 500® instrument system." |
| Stability | 90 to 110% of DOM value. | "All product levels tested within the acceptance criteria limits after 2 freeze-thaw vial events." |
| Shelf Life | Support for extended stability claim. | "Stability of the VALIDATE® Heparin Calibration / Linearity Test Kit was set at 5 months based on available real-time stability studies. Real time stability studies are ongoing to support an extended stability claim." |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test: 80 replicates per kit level (5 levels, so 5 * 80 = 400 total replicates for precision across three lots of the VALIDATE® Heparin product).
- Reproducibility Test: 75 replicates per kit level (5 levels, so 5 * 75 = 375 total replicates for reproducibility for one lot of the VALIDATE® Heparin product).
- Stability Test: Four product lots were tested. The number of replicates per time point is not specified, but time points included "date of manufacture (DOM), followed by testing at specific intervals post manufacture."
- Freeze-thaw/open vial stress stability assessment: Not specified, but involved testing "All product levels."
- Data Provenance: The document states "All supporting data is retained on file at Maine Standards Company LLC." This suggests the data was generated internally by Maine Standards Company LLC. It is a prospective study as the testing was conducted to evaluate the performance of the new device. The country of origin is implicitly the USA (Maine Standards Company LLC is located in Maine, USA).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This device is an in vitro diagnostic (IVD) calibration verification/linearity test kit, not a device that relies on expert interpretation of results. Its performance is measured against established analytical targets and statistical criteria like CV% (Coefficient of Variation).
4. Adjudication Method for the Test Set
Not applicable. The performance is assessed based on quantitative measurements and meeting predefined statistical criteria (e.g., CV% limits, recovery percentages). There is no "ground truth" established through expert consensus requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging devices where multiple human readers interpret cases, and their performance with and without AI assistance is compared. This device is an IVD calibration product.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
The device itself is a test kit used on an automated instrument (IL ACL TOP 500® analyzer). Its "performance" is inherently standalone in that it is a measurement tool. The studies described (precision, reproducibility, linearity, stability) evaluate the performance of the physical test kit itself when run on the specified automated instrument without direct human interpretation of the analytical results beyond operating the instrument and collecting data.
7. The Type of Ground Truth Used
The "ground truth" for this device's performance is established by:
- Known concentrations: Levels 1 and 5 are prepared independently, and intermediate levels are prepared by equal part dilutions following CLSI EP6-A guidelines, establishing a known linear relationship and target concentrations.
- Reference Standards: The VALIDATE® Heparin kit is traceable through the IL HemosIL® calibrator to the 5th International WHO Standard 97/578 for UF heparin and the 2nd International WHO Standard 01/608 for LMW heparin. This establishes a "gold standard" for the analyte measurement.
- Statistical Performance Metrics: Meeting specified CV% acceptance criteria quantifies the precision and reproducibility against statistical norms.
- Recovery Targets: For stability, acceptance criteria are defined as 90 to 110% of the Date of Manufacture (DOM) value.
8. The Sample Size for the Training Set
Not applicable. This device is an IVD calibration verification/linearity test kit, not an AI/ML algorithm that requires a "training set."
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of medical device.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 16, 2017
Maine Standards Company LLC Mr. James Champlin Director, QSHIE 221 US Route 1 Cumberland Foreside, Maine 04110
Re: K163498
Trade/Device Name: Validate® Heparin 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: February 14, 2017 Received: February 15, 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
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as set forth in the quality systems (OS) 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/ResourcesforYou/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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| 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) | K163498 |
|---|---|
| Device Name | VALIDATE® Heparin Calibration Verification / Linearity Test Kit |
| Indications for Use (Describe) | VALIDATE® Heparin 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 Heparin Anti-Xa activity on automated instruments in a clinical laboratory setting by laboratory personnel. The product is intended for use on the IL ACL TOP® analyzer. |
| 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: K163498
A. Submitter: Maine Standards Company LLC 221 US Route 1 Cumberland Foreside, ME 04110 Telephone: 207-892-1300 Fax: 207-892-2266
Contact Person: James Champlin Director, QSHIE jchamplin@mainestandards.com Telephone: 207-892-1300 Ext. 29
Date of Summary Preparation: February 14, 2017
B. Device Classification:
| Device classification name: | Plasma, Coagulation Control |
|---|---|
| Common name: | Calibration Verification / Linearity Test Kit |
| Proprietary Name: | VALIDATE® Heparin Calibration Verification / Linearity Test |
| Kit | |
| Review Panel: | Hematology (81) |
| Regulation Number: | 21 CFR 864.5425 |
| Product Code: | GGN |
| Regulatory Class: | Class II |
C. Predicate Device Identification:
K090209, HemosIL® Liquid LMW/UF Heparin Controls, Instrumentation Laboratory
D. Candidate Device description: Each VALIDATE® Heparin Calibration Verification / Linearity Test Kit contains one analyte set of Heparin 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 Heparin Anti-X activity. 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® Heparin 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 Heparin Anti-Xa activity on automated instruments in a clinical laboratory setting by laboratory personnel. The product is intended for use on the IL ACL TOP 500® analyzer.
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F. Summary of Performance Data:
The performance of the new VALIDATE® Heparin Calibration Verification / Linearity Test Kit was compared to the predicate device k09209, HemosIL® Liquid LMW/UF Heparin Controls.
Table 1 summarizes the comparison of the new VALIDATE® Heparin Calibration Verification / Linearity Test Kit device to the predicate device.
| New DeviceVALIDATE® Heparin CalibrationVerification / Linearity Test Kit | Predicate (k09209)HemosIL® Liquid LMW/UFHeparin Controls | |
|---|---|---|
| Similarities | ||
| Intended Use | For in vitro diagnostic use withHemosIL® reagents on the ILACL TOP 500 instrument | Same |
| Test Kit | Assayed quality control | Same |
| Matrix | Human plasma base | Same |
| Number of Levels | 5 levels | Same |
| FDA product Code | GGN | Same |
| Differences | ||
| Analytes | Heparin Anti-Xa activity | LMW/UFH Heparin |
Table 1 - Comparison to Predicate
Value Assignment
VALIDATE® Heparin 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 Heparin to a human plasma base matrix. Levels 1 through 5 must meet specified Heparin Anti-Xa 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 Heparin Anti-Xa. 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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| Set | ||||||||
|---|---|---|---|---|---|---|---|---|
| Levels | ||||||||
| Instrument | Analyte | Units | 1 | 2 | 3 | 4 | 5 | |
| IL ACL TOP 500® | HeparinAnti-Xa | IU/mL | 0.11 | 0.52 | 0.94 | 1.36 | 1.77 |
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 calibration material.
Precision/Reproducibility
Precision was evaluated on the Instrumentation Laboratory (IL) IL ACL TOP 500® instrument system with the VALIDATE® Heparin product following the product package insert instructions. Three lots of VALIDATE® Heparin product were tested with one lot of IL HemosIL® Liguid Anti-Xa reagent and quality controls on one IL ACL TOP 500® 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® Heparin kit met the CV% acceptance criteria on the IL ACL TOP 500® instrument system.
Reproducibility was evaluated on the IL ACL TOP 500® instrument system with the VALIDATE® Heparin kit containing 5 levels following the product package insert instructions. One lot of VALIDATE® Heparin Calibration Verification / Linearity Test Kit was tested with one lot of IL Heparin HemosIL® 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® Heparin kit met the CV% acceptance criteria on the IL ACL TOP 500® instrument system.
Traceability
This product is traceable to a reference standard based on the automated instrument platform it is used on. The traceability of this product will be established per the respective end user automated instrument method calibrator traceability reference statement. The VALIDATE® Heparin kit is traceable through the IL HemosIL® calibrator to the 5th International WHO Standard 97/578 for UF heparin and the 2nd International WHO Standard 01/608 for LMW heparin.
Stability
Stability testing on four product lots was performed using the IL ACL TOP 500® instrument system. The study testing time points included date of manufacture (DOM), followed by testing at specific intervals post manufacture. Acceptance criteria are defined as 90 to 110% of DOM value.
A freeze-thaw/open vial stress stability assessment was also conducted in support of the product package insert two (2) freeze-thaw open vial events claim. All product levels tested within the acceptance criteria limits after 2 freeze-thaw vial events.
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Shelf Life Claim: Stability of the VALIDATE® Heparin Calibration / Linearity Test Kit was set at 5 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® Heparin Calibration Verification / Linearity Test Kits on the Instrumentation Laboratory IL ACL TOP 500® coagulation instrument. Product linearity performance was demonstrated for this automated system. 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® Heparin Calibration Verification / Linearity Test Kit behaves substantially equivalent to the predicate device, K090209, HemosIL® Liquid LMW/UF Heparin Controls.
§ 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.