(74 days)
The VALIDATE TDM Calibration Verification Test Set is used by trained laboratory professionals for the quantitative determination of linearity, calibration verification and verification of reportable range in automated, semi-automated, and manual clinical chemistry systems for the following analytes: acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, theophylline, tobramycin, valproic acid, and vancomycin.
VALIDATE TDM Calibration Verification Test Set contains purified chemicals in a human serum matrix. Multiple levels are provided to establish the relationship between theoretical operation and actual performance of each of the included analytes. Each set contains one bottle each of six (6) levels including zero. Each bottle contains 5 milliliters.
The provided text describes a 510(k) premarket notification for the "VALIDATE TDM Calibration Verification Test Set." The study presented is a comparison to predicate devices, demonstrating substantial equivalence rather than a study defining acceptance criteria for a new type of device performance.
Therefore, many of the requested categories (sample size for test/training sets, data provenance, number/qualifications of experts, adjudication method, MRMC study, standalone performance, type of ground truth, establishment of ground truth for training) are not applicable or not explicitly detailed in the context of this type of submission.
However, I can extract the acceptance criteria (implied by the comparison study) and the reported device performance.
Here's an analysis based on the provided document:
Acceptance Criteria and Study Details for VALIDATE TDM Calibration Verification Test Set
The device, "VALIDATE TDM Calibration Verification Test Set," is intended for in vitro diagnostic use for quantitatively verifying calibration, validating reportable ranges, and determining linearity for automated and manual chemistry systems for several analytes. The study presented aims to demonstrate substantial equivalence to predicate devices, namely "DOCUMENT TDM CAL-VER" and "Human serum spiked with salicylate."
The primary method to establish substantial equivalence is through linear regression analysis, comparing the performance of the VALIDATE TDM Calibration Verification Test Set with the predicate devices. The implicit acceptance criteria are that the correlation coefficients and regression equations for the new device should be comparable to or demonstrate substantial equivalence with the predicate devices.
1. A table of acceptance criteria and the reported device performance
For the purpose of this 510(k) submission, the "acceptance criteria" are implied by the comparison to predicate devices. A strong correlation coefficient (r-value close to 1) and a regression equation (Y = slope(X) + intercept) that indicates a close relationship between the test set and the predicate are considered evidence of substantial equivalence. While specific numerical thresholds for "acceptance" are not stated, the presented data is offered as proof of meeting this equivalence.
| Analyte | Reported VALIDATE TDM Correlation Coefficient (r) | Reported VALIDATE TDM Regression Equation (Y = slope(X) + intercept) | Predicate 1 (DOCUMENT TDM I CAL·VER) Correlation Coefficient (r) | Predicate 1 (DOCUMENT TDM I CAL·VER) Regression Equation (Y = slope(X) + intercept) | Predicate 2 (Spiked Human Serum) Correlation Coefficient (r) | Predicate 2 (Spiked Human Serum) Regression Equation (Y = slope(X) + intercept) |
|---|---|---|---|---|---|---|
| Acetaminophen | 0.9981 | 0.936x + 2.65 | 0.9974 | 0.8718x + 10.14 | N/A (Not compared to this predicate for this analyte) | N/A |
| Amikacin | 0.9940 | 1.099x - 0.79 | 0.9971 | 1.0469x - 0.4331 | N/A | N/A |
| Carbamazepine | 0.9989 | 1.009x - 0.01 | 0.9973 | 1.04x + 0.15 | N/A | N/A |
| Digoxin | 0.9976 | 1.026x - 0.01 | 0.9979 | 1.015x - 0.02 | N/A | N/A |
| Gentamicin | 0.9968 | 0.898x + 0.19 | 0.9939 | 0.8639x + 0.26 | N/A | N/A |
| Lidocaine | 0.9987 | 1.025x - 0.07 | 0.9970 | 1.0727x - 0.1567 | N/A | N/A |
| N-acetylprocainamide | 0.9975 | 0.995x + 0.01 | 0.9971 | 1.0363x - 0.42 | N/A | N/A |
| Phenobarbital | 0.9981 | 0.999x - 0.22 | 0.9974 | 0.9919x + 0.39 | N/A | N/A |
| Phenytoin | 0.9986 | 0.972x + 0.34 | 0.9990 | 1.0025x + 0.10 | N/A | N/A |
| Primidone | 0.9994 | 1.036x - 0.18 | 0.9993 | 0.9831x - 0.0014 | N/A | N/A |
| Procainamide | 0.9971 | 1.015x - 0.06 | 0.9965 | 1.1413x - 1.0 | N/A | N/A |
| Quinidine | 0.9994 | 1.043x - 0.05 | 0.9981 | 1.0541x - 0.08 | N/A | N/A |
| Salicylate | 0.9985 | 0.958x + 7.21 | N/A (Not compared to this predicate for this analyte) | N/A | 0.9916 | 0.902x + 17.99 |
| Theophylline | 0.9994 | 0.981x + 0.17 | 0.9992 | 0.9933x - 0.11 | N/A | N/A |
| Tobramycin | 0.9985 | 1.077x - 0.16 | 0.9935 | 0.9278x + 0.38 | N/A | N/A |
| Valproic acid | 0.9990 | 1.037x - 1.17 | 0.9983 | 1.0231x - 0.65 | N/A | N/A |
| Vancomycin | 0.9995 | 1.018x - 0.3 | 0.9920 | 0.9688x + 0.12 | N/A | N/A |
2. Sample size used for the test set and the data provenance
- Sample Size: The document states that each analyte was tested in triplicate for the linear regression analysis. The "test set" in this context refers to the measurements taken for each of the six levels provided in the VALIDATE TDM kit (plus potentially the comparable levels in the predicate devices).
- Data Provenance: Not explicitly stated (e.g., country of origin, specific lab). The study uses "preproduction lots" of the VALIDATE TDM Calibration Verification Test Set, and compares them to commercially available predicate devices. It is inherent in this type of submission that the data is internal to the manufacturer (Maine Standards Company) or a contract lab.
- Retrospective/Prospective: The study itself is prospective in nature, as it involves testing the new device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. "Ground truth" in this context refers to the assigned values of the calibration verification materials. These are established through manufacturing processes (spiking known concentrations into a matrix) and analytical testing, not typically by expert interpretation in the same way, for example, a radiologist might establish ground truth for an image. The "accuracy" of these assigned values is assumed to be part of the quality control for in vitro diagnostic reagents.
4. Adjudication method for the test set
Not applicable. This is not a study involving human interpretation of results requiring adjudication.
5. If a multi-reader, multi-case (MRMC) comparative effectiveness study was done
No, this was not an MRMC study. This device is an in vitro diagnostic reagent, not an imaging AI or diagnostic algorithm that would typically involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This refers to the performance of an IVD reagent in an automated system, which is inherently "standalone" in its analytical function (i.e., the chemical reaction and measurement, not requiring human interpretation of results generation in the way an AI algorithm might). The study tests the performance of the reagent on the "VITROS instrument system."
7. The type of ground truth used
The "ground truth" for calibration verification materials is the known, theoretical concentration of each analyte at each level. This is established during the manufacturing process by precisely adding known quantities of highly purified analytes to a human serum matrix. The performance of the device is then measured against these expected theoretical values, and its linearity is assessed.
8. The sample size for the training set
Not applicable. This device is a diagnostic reagent, not an AI/ML algorithm that requires a "training set" in the computational sense. Its performance relies on the biochemical properties and concentrations of its components.
9. How the ground truth for the training set was established
Not applicable, as there is no training set in the AI/ML context.
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Image /page/0/Picture/0 description: The image shows the logo for Maine Standards Company LLC. The word "maine" is on the top left, with a line going through it. The word "standards" is on the bottom right, and the words "COMPANY LLC" are below it in smaller letters.
FEB 2 7 2004
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: _ < 03387
| Submitter: | Maine Standards Company |
|---|---|
| Address: | 765 Roosevelt TrailWindham, ME 04062 |
| Telephone: | 207-892-1300 |
| Fax: | 207-892-2266 |
| Contact: | Christine Beach, Mgr. RA/QA |
December 11, 2003 Summary prepared on:
| Proprietary Name: | VALIDATE TDM Calibration Verification Test Set |
|---|---|
| Common Name: | Calibration Verification |
| Classification Name: | Calibrator, Multi-Analyte |
Predicate Devices:
-
- DOCUMENT TDM | CAL-VER. K913309. manufactured by CASCO NERL Diagnostics.
-
- Human serum spiked with salicylate
Device description: VALIDATE TDM Calibration Verification Test Set contains purified chemicals in a human serum matrix. Multiple levels are provided to establish the relationship between theoretical operation and actual performance of each of the included analytes. Each set contains one bottle each of six (6) levels including zero. Each bottle contains 5 milliliters.
Intended use: VALIDATE TDM Calibration Verification Test Set is intended for in vitro diagnostic use for quantitatively verifying calibration, validating reportable ranges, and determining linearity for automated and manual chemistry systems for the following seventeen analytes: acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, tobramycin, valproic acid, and vancomycin.
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Comparison of VALIDATE TDM Calibration Verification Test Set to the predicate devices:
Table 1 compares characteristics of the VALIDATE TDM Calibration Verification Test Set with those of the DOCUMENT TDM I CAL•VER.
| Catalog # | VALIDATE TDM CalibrationVerification Test Set | DOCUMENTTDMCAL•VER |
|---|---|---|
| 126 | For in vitro diagnostic use inquantitatively verifying calibration,validating reportable ranges, anddetermining linearity in automated,semi-automated and manualchemistry systems | For in vitro diagnostic use in thequantitative determination oflinearity in manual, automated andsemi-automated chemistrysystems. |
| Analytes | acetaminophen, amikacin,carbamazepine, digoxin, gentamicin,lidocaine, N-acetylprocainamide,phenobarbital, phenytoin, primidone,procainamide, quinidine, salicylate,theophylline, tobramycin, valproic acid,and vancomycin | acetaminophen, amikacin,carbamazepine, chloramphenicol,disopyramide, ethosuximide, digoxin,gentamicin, lidocaine,N-acetylprocainamide, phenobarbital,phenytoin, primidone, procainamide,quinidine, theophylline, tobramycin,valproic acid, and vancomycin |
| Matrix | human serum | human serum |
| Number ofLevels | 6 | 8 |
| Preparation | Liquid, ready to use | Liquid, ready to use |
| Packaging | 5.0 mL each level | 5.0 mL each level |
| Stability | Until expiration | Until expiration |
| Storage | 2 to 8°C | 2 to 8°C |
TABLE 1. Comparison of Products
The performance of VALIDATE TDM Calibration Test Set solutions on the VITROS instrument system as compared to DOCUMENT TDM I CAL.aVER and human serum spiked with salicylate has been shown to be substantially equivalent using preproduction lots of VALIDATE TDM Calibration Verification Test Set. The results of correlation comparisons between the VALIDATE TDM Calibration Test Set and the predicate devices are presented in Table 2.
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| VALIDATE®TDM | DOCUMENT®TDM ICAL·VER | |||
|---|---|---|---|---|
| Calibration Verification Test Set | ||||
| Analyte | Correlation Coefficient(r) | Regression EquationY = slope(X) + intercept | Correlation Coefficient(r) | Regression EquationY = slope(X) + intercept |
| ACET | 0.9981 | 0.936x + 2.65 | 0.9974 | 0.8718x + 10.14 |
| AMI | 0.9940 | 1.099x - 0.79 | 0.9971 | 1.0469x - 0.4331 |
| CARB | 0.9989 | 1.009x - 0.01 | 0.9973 | 1.04x + 0.15 |
| DIG | 0.9976 | 1.026x - 0.01 | 0.9979 | 1.015x - 0.02 |
| GENT | 0.9968 | 0.898x + 0.19 | 0.9939 | 0.8639x + 0.26 |
| LIDO | 0.9987 | 1.025x - 0.07 | 0.997 | 1.0727x - 0.1567 |
| NAPA | 0.9975 | 0.995x + 0.01 | 0.9971 | 1.0363x - 0.42 |
| PHENO | 0.9981 | 0.999x - 0.22 | 0.9974 | 0.9919x + 0.39 |
| PHENY | 0.9986 | 0.972x + 0.34 | 0.999 | 1.0025x + 0.10 |
| PRIM | 0.9994 | 1.036x - 0.18 | 0.9993 | 0.9831x - 0.0014 |
| PROC | 0.9971 | 1.015x - 0.06 | 0.9965 | 1.1413x - 1.0 |
| QUIN | 0.9994 | 1.043x - 0.05 | 0.9981 | 1.0541x - 0.08 |
| THEO | 0.9994 | 0.981x + 0.17 | 0.9992 | 0.9933x - 0.11 |
| TOB | 0.9985 | 1.077x - 0.16 | 0.9935 | 0.9278x + 0.38 |
| VPA | 0.999 | 1.037x - 1.17 | 0.9983 | 1.0231x - 0.65 |
| VANC | 0.9995 | 1.018x - 0.3 | 0.992 | 0.9688x + 0.12 |
| TABLE 2. Linear Regression Statistical Comparison of VALIDATE TDM | ||||
|---|---|---|---|---|
| Calibration Verification Test Set to the predicate devices. |
| VALIDATETDMCalibration Verification Test Set | Spiked Human Serum | |||
|---|---|---|---|---|
| Analyte | Correlation Coefficient(r) | Regression EquationY = slope(X) + intercept | Correlation Coefficient(r) | Regression EquationY = slope(X) + intercept |
| SALI | 0.9985 | $0.958x + 7.21$ | 0.9916 | $0.902x + 17.99$ |
Summary:
Linear regression analysis was carried out on recovered values for each analyte. Each analyte was tested in triplicate. The VALIDATE TDM Calibration Verification Test Set has been shown to be functionally equivalent for calibration verification and linearity assessment to DOCUMENT TDM I CAL•VER and human serum spiked with salicylate.
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, stacked on top of each other, resembling a bird-like shape.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FEB 27 2004
Ms. Christine V. Beach Manager, QA/RA Maine Standards Co. 765 Roosevelt Trail Suite 9A Windham, ME 04062
Re: K033879
Trade/Device Name: Validate® TDM Calibration Verification Test Set Regulation Number: 21 CFR 862.3200 Regulation Name: Clinical toxicology calibrator Regulatory Class: Class II Product Code: DKB Dated: December 11, 2003 Received: December 16, 2003
Dear Ms. Beach:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).
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Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours.
Jean M. Cooper, MS, DVM.
Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
510(k) Number: K033871
Device Name: Validate® TDM Calibration Verification Test Set
Indications for Use:
The VALIDATE TDM Calibration Verification Test Set is used by trained laboratory professionals for the quantitative determination of linearity, calibration verification and verification of reportable range in automated, semi-automated, and manual clinical chemistry systems for the following analytes: acetaminophen, amikacin, carbamazepine, digoxin, gentamicin, lidocaine, N-acetylprocainamide, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, theophylline, tobramycin, valproic acid, and vancomycin.
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
5704k K033879
§ 862.3200 Clinical toxicology calibrator.
(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.