(198 days)
VALIDATE® Anemia Calibration Verification/Linearity Test Kit solutions are intended for in vitro diagnostic use in the quantitative determination of linearity, calibration and verification of reportable range for the following analytes: Ferritin Set: ferritin (FERR), Vitamin B12(VITB) and folate (FOL), on automated instrument systems. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling.
Each VALIDATE® Anemia Calibration Verification / Linearity Test Kit contains two analyte sets of purified chemicals in a human serum base. The kit includes a Ferritin set containing five liguid levels, 3.0mL each, and a Vitamin B12/Folate set containing five liquid levels, 4.0 mL each. The sets are provided to establish the relationship between theoretical and actual performance of the included analytes: Ferritin, Vitamin B12 and Folate. 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® Anemia Calibration Verification/Linearity Test Kit. This product is a quality control material, not a device that directly measures a patient's condition or relies on AI. Therefore, the common acceptance criteria and study designs typically associated with AI-powered medical devices (such as sensitivity, specificity, MRMC studies, and ground truth established by experts for a test set) are not applicable here.
Instead, the acceptance criteria and study detailed focus on the technical performance of the calibration verification/linearity kit itself, to ensure it provides accurate and linear results when used with automated instrument systems.
Here's an analysis based on the information provided, reinterpreting some categories to fit the context of a calibration verification kit:
1. Table of Acceptance Criteria and Reported Device Performance:
| Feature/Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Value Assignment | Levels 1-5 must meet specified Ferritin, Vitamin B12, and Folate targets. (Ranges determined by upper/lower detection limits; intermediate levels calculated based on equal dilutions following EP6-A guidelines). | All stated recovery values met internal pre-determined acceptance criteria. |
| Recovery Targets (Low/High Levels) | 90 to 110% of DOM value for product levels 2-5 during stability testing. | All product levels tested within the 90 to 110% of control acceptance criteria limits. |
| Freeze/Thaw Stability | Within 90 to 110% of control acceptance criteria limits. | Tested within the 90 to 110% of control acceptance criteria limits after 6 freeze/thaw events. |
| Shelf Life | Maintain stability for claim duration. | Set at 12 months based on real-time open vial studies (worst-case scenario). |
| Product Linearity | Demonstrated linearity on specified automated systems. | Product linearity performance was demonstrated for both automated systems (Roche® Cobas 6000 Chemistry Analyzer and Beckman-Coulter® Access II Immunochemistry Analyzer). |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: The number of individual test kit units or measurements used for "value assignment" and "stability" testing is not explicitly stated as a numerical sample size. It refers to testing on "Levels 1 through 5" of the kit. For stability, testing was done at "date of manufacture (DOM), followed by testing at specific intervals post manufacture" and "one month post-expiration." Freeze/thaw stability was assessed for "four (4) freeze/thaw events claim" and tested after "6 freeze/thaw events."
- Data Provenance: The studies were conducted internally by Maine Standards Company LLC. The text does not specify the country of origin of the raw data, but the company is based in the US. The studies appear to be prospective to validate the manufacturing and stability of the product.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications:
This question is not directly applicable in the typical sense of expert review for medical imaging or diagnostic algorithms. For this device, the "ground truth" or reference values are established by the manufacturing process itself:
- "Levels 1 and 5 are prepared independently by the addition of Ferritin, Vitamin B12 and Folate to a human serum base."
- "Intermediate 2, 3, and 4 are subsequently prepared from Levels 1 and 5 by equal part dilutions following EP6-A guidelines."
- The actual "ground truth" for the performance evaluation is the predetermined theoretical concentrations that the calibration verification kit levels should represent based on their formulation. The device's performance is then measured by how well instruments recover these known concentrations and demonstrate linearity.
There's no mention of external experts adjudicating results for the test set.
4. Adjudication Method for the Test Set:
Not applicable in the conventional sense. The test results are compared against internal, pre-determined acceptance criteria based on the known composition and expected behavior of the calibration verification material, and adherence to CLSI EP6-A guidelines.
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 is a quality control material intended for instrument calibration and linearity verification, not a diagnostic device that assists human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Not applicable. This device is used by automated analytical instruments (Roche Cobas, Beckman Access) to verify their performance. Its "standalone" performance means its inherent accuracy in representing known concentrations, which is what the "Value Assignment" and "Linearity" sections address. The analytical instruments are the "algorithm" in this context, and this device checks their accuracy.
7. The Type of Ground Truth Used:
The ground truth is based on:
- Known concentrations: The product is manufactured with specific, known concentrations of analytes (Ferritin, B12, Folate) at Levels 1 and 5.
- Dilution principles: Intermediate levels (2, 3, 4) are prepared by precise dilutions from Levels 1 and 5, following CLSI EP6-A guidelines, establishing their theoretical concentrations.
- Reference Standards: The product is described as "traceable to a reference standard based on the automated instrument platform it is used on." This implies a higher-level standard (e.g., NIST traceable or other internationally recognized standards) against which the instrument's calibrators are established, and by extension, this product helps verify that performance.
8. The Sample Size for the Training Set:
Not applicable. This is not a machine learning or AI device that requires a "training set." The product is a manufactured reagent with a defined chemical composition.
9. How the Ground Truth for the Training Set was Established:
Not applicable, as there is no "training set" for this type of device.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular fashion around a symbol. The symbol consists of a stylized caduceus-like design, with three human profiles facing right, representing health and human services.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
MAINE STANDARDS COMPANY LLC JAMES CHAMPLIN MANAGER, QA & RA 221 US ROUTE 1 CUMBERLAND FORESIDE, ME 04110
April 30, 2015
Re: K142964
Trade/Device Name: VALIDATE® Anemia Calibration Verification/ Linearity Test Kit Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJY Dated: April 1, 2015 Received: April 2, 2015
Dear James 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), 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" (21 CFR 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 yours,
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K142964
Device Name
VALIDATE® Anemia Calibration Verification/Linearity Test Kit
Indications for Use (Describe)
VALIDATE® Anemia Calibration Verification/Linearity Test Kit solutions are intended for in vitro diagnostic use in the quantitative determination of linearity, calibration and verification of reportable range for the following analytes: Ferritin Set: ferritin (FERR), Vitamin B12(VITB) and folate (FOL), on automated instrument systems. 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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
"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: K142964
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 Manager, Quality Assurance & Requlatory Affairs ichamplin@mainestandards.com 207-892-1300 Ext. 29 Telephone:
Date of Summary Preparation: April 24, 2015
B. Device Classification:
| Device classification name: | Quality control material (assayed and un-assayed)* | |
|---|---|---|
| Common name: | Calibration Verification / Linearity Test Kit | |
| Proprietary Name: | VALIDATE® Anemia Calibration Verification / Linearity Test Kit | |
| Review Panel: | Clinical Chemistry 75 | |
| Regulation Number: | 21 CFR 862.1660 | |
| Product Code: | JJY | |
| Regulatory Class: | Class I Reserved |
C. Predicate Device Identification:
VALIDATE® Ferritin Calibration Verification / Linearity Test Kit Maine Standards Company LLC, Cumberland Foreside, ME 04110. 510(k) Number: K133550
D. Candidate Device description: Each VALIDATE® Anemia Calibration Verification / Linearity Test Kit contains two analyte sets of purified chemicals in a human serum base. The kit includes a Ferritin set containing five liguid levels, 3.0mL each, and a Vitamin B12/Folate set containing five liquid levels, 4.0 mL each. The sets are provided to establish the relationship between theoretical and actual performance of the included analytes: Ferritin, Vitamin B12 and Folate. 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® Anemia Calibration Verification / Linearity Test Kit solutions are intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analytes: Ferritin Set: Ferritin (FERR), Vitamin B12 / Folate Set: Vitamin B12 (VIT B) and Folate (FOL), on automated instrument systems. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling.
{4}------------------------------------------------
F. Summary of Performance Data:
The performance of the new VALIDATE® Anemia Calibration Verification / Linearity Test Kit was compared to the predicate device K133550, VALIDATE® Ferritin Calibration Verification / Linearity Test Kit. Table 1 compares the technical characteristics of the new VALIDATE® Anemia Calibration Verification / Linearity Test Kit with those of the predicate VALIDATE® Ferritin Calibration Verification / Linearity Test Kit.
| Table 1 - Technical Comparison to Predicate | ||
|---|---|---|
| New Device | Predicate (K133550) | |
| VALIDATE® Anemia CalibrationVerification / Linearity Test Kit | VALIDATE® Ferritin CalibrationVerification / Linearity Test Kit | |
| Similarities | ||
| Test Kit | Calibration Verification Test Kit | Same |
| Intended Use | For in vitro diagnostic use in thequantitative determination oflinearity, calibration verificationand verification of reportablerange in automated instrumentsystems | Same |
| Preparation | Liquid, ready to use | Same |
| Stability | Until expiration date | Same |
| Storage | -10 to -25°C | Same |
| Matrix | Human serum base | Same |
| Number of Levels | 5 levels | Same |
| Differences | ||
| Analytes | Ferritin, Vitamin B12 and Folate | Ferritin |
| Packaging | 3.0 mL each level Ferritin Set4.0 mL each level Vitamin B12/Folate Set | 3.0 mL each level |
Table 1 - Technical Comparison to Predicate
Value Assignment
VALIDATE® Anemia 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 Ferritin, Vitamin B12 and Folate to a human serum base. The VALIDATE® Anemia Calibration Verification / Linearity Test Kit was tested on the Roche Cobas and Beckman Access analyzers to confirm adeguate recovery across all levels. Levels 1 through 5 must meet specified Ferritin, Vitamin B12 and Folate targes at all stages of testing.
Specific recovery targets for Levels 1 through 5 are determined by the upper and lower detection limits for each analyte. Intermediate 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. All stated recovery values met internal pre-determined acceptance criteria.
Typical recovery values for Low Levels and High Levels, established via an internal protocol, are presented in Table 1. Typical values for Mid-Levels are calculated based on an equal distance (delta) between levels. Any level result showing no value is above the method's reportable range. Due to the analytical differences of immunoassays on different instrument systems, these ranges are to be used as a guide only. Expected target values may change depending on instrumentation and methodology.
{5}------------------------------------------------
| Table1I | |
|---|---|
| ----------------- | -- |
| Ferritin Set | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Levels | |||||||||
| Instrument | Analyte | Units | 1 | 2 | 3 | 4 | 5 | ||
| BeckmanAccess/Dxl | FERR | ng/mL | 1.9 | 348 | 694 | 1,040 | 1,386 | ||
| RocheCobas/Elecsys | FERR | ng/mL | 3.0 | 465 | 926 | 1,388 | 1,850 | ||
| Vitamin B12 / Folate Set | |||||||||
| Levels | |||||||||
| Instrument | Analyte | Units | 1 | 2 | 3 | 4 | 5 | ||
| BeckmanAccess/DxI | VIT B12 | pg/mL | 68 | 462 | 855 | 1,248 | N/A | ||
| RocheCobas/Elecsys | VIT B12 | pg/mL | 83 | 515 | 947 | 1,380 | 1,812 | ||
| BeckmanAccess/Dxl | FOL | ng/mL | 1.1 | 4 | 7 | 10 | 13 |
The quantitative determination of linearity, calibration, 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 EP6A referenced standard) not on an expected value.
Traceability
This product 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.
Stability
Stability testing was performed using the Beckman Coulter® Access II and Roche COBAS 6000 instrument systems. The study testing time points included date of manufacture (DOM), followed by testing at specific intervals post manufacture. The last testing event is one month post-expiration. Acceptance criteria are defined as 90 to 110% of DOM value for product levels 2-5.
A freeze/thaw stability assessment was also conducted in support of the product package insert four (4) freeze/thaw events claim. All product levels tested within the 90 to 110% of control acceptance criteria limits after 6 freeze/thaw events.
Shelf Life Claim: Stability of the VALIDATE® Anemia Calibration Verification / Linearity Test Kit was set at 12 months based on real-time open vial studies as a worst case scenario. The recommended storage temperature is -10 to -25°C. All supporting data is retained on file at Maine Standards Company LLC.
{6}------------------------------------------------
Linearity:
Linearity testing was carried out with the candidate device VALIDATE® Anemia Calibration Verification / Linearity Test Kits using a Roche® Cobas 6000 Chemistry Analyzer and Beckman-Coulter® Access II Immunochemistry Analyzer. Product linearity performance was demonstrated for both automated systems. All supporting data for all three analytes 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® Anemia Calibration Verification / Linearity Test Kit behaves substantially equivalent to the predicate for the evaluation of calibration verification, verification of reportable range. The product is substantially equivalent to the predicate device K133550.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.