(465 days)
In vitro test for the quantitative determination of lithium in human serum and plasma on Roche/Hitachi cobas c systems. Measurements of lithium are used as an aid in the management of patients taking lithium for the treatment of mental disturbances such as manic-depressive illness (bipolar disorder).
The cassette cobas c501 Lithium contains an in vitro diagnostic reagent system intended for use on Roche/Hitachi cobas c systems for the quantitative determination of lithium in human serum and plasma. The test principle is colorimetric.
The provided text describes a 510(k) submission for the cobas c501 Lithium test system. It outlines the device's intended use, its similarities and differences to a predicate device, and various performance characteristics. However, the document does not contain information typically associated with acceptance criteria or studies proving device performance for AI/ML-driven diagnostics, as none of the requested fields directly apply to this type of medical device.
The device described is an in vitro diagnostic reagent system for the quantitative determination of lithium in human serum and plasma, using a colorimetric test principle. This is a chemical assay, not an AI/ML-driven diagnostic device. Therefore, the concepts of "acceptance criteria" and "study that proves the device meets the acceptance criteria" in the context of AI/ML performance metrics (like sensitivity, specificity, AUC, and human reader improvement) are not applicable to this submission.
The document focuses on demonstrating substantial equivalence to a predicate device (COBAS INTEGRA ISE Direct) by comparing analytical performance characteristics relevant to chemical assays.
Given the nature of the device, I cannot provide the requested information. The document does not describe:
- A table of acceptance criteria and reported device performance in relation to AI/ML metrics. It provides analytical performance characteristics like precision, linearity, and interference.
- Sample size used for the test set and data provenance: While method comparison data is mentioned (e.g., Passing Bablok regression), the specific sample size and data provenance for demonstrating equivalence are not detailed in the provided text.
- Number of experts and qualifications for ground truth: Not applicable for a chemical assay.
- Adjudication method: Not applicable.
- Multi-reader multi-case (MRMC) comparative effectiveness study: Not applicable.
- Standalone (algorithm only) performance: Not applicable.
- Type of ground truth used (expert consensus, pathology, outcomes data): Not applicable in the AI/ML sense. The ground truth for a chemical assay would be reference methods (e.g., Atomic Absorption Spectroscopy as mentioned for traceability).
- Sample size for the training set: Not applicable as it's not an AI/ML model.
- How ground truth for the training set was established: Not applicable.
However, I can extract the analytical performance characteristics that are presented, which serve as evidence of the device's performance for this type of IVD.
Analytical Performance Characteristics of the cobas c501 Lithium (Modified Device)
While the typical "acceptance criteria" for AI/ML are not present, the following analytical performance characteristics are reported for the cobas c501 Lithium system, indicating its performance compared to the predicate and overall suitability:
| Performance Characteristic | Acceptance Criteria (Implicit via predicate comparison or industry standards for IVDs) | Reported Device Performance (cobas c501 Lithium) |
|---|---|---|
| Precision | Demonstrated precision comparable to or better than predicate. | Within run CV:1.7% @ 0.77 mmol/L1.0% @ 2.38 mmol/L1.9% @ 0.46 mmol/L1.2% @ 1.40 mmol/LTotal:2.2% @ 0.79 mmol/L1.3% @ 2.42 mmol/L2.3% @ 0.61 mmol/L1.6% @ 1.62 mmol/L |
| Endogenous Interferences | No significant interference at specified levels for common interferents. | Hemolysis: No significant interference up to H index of 1000Icterus: I index of 37 for conjugated and 43 for unconjugated bilirubinLipemia: L index of 2000 |
| Exogenous Interferences | No significant interference from common exogenous substances. | NH4Cl: 19.8 umol/LNaCl : 140 mmol/LKCl : 4 mmol/ LCaCl2: 2.4 mmol/LMgCl2: 0.9 mmol/LFeCl3: 1.04 mg/LCu (NO3)2: 1.15 mmol/LZnCl2: 1.07 mmol(none of these are in the physiological key interference range)In very rare cases gammopathy |
| Limit of Detection (LOD) | Clinically meaningful detection limit. | 0.05 mmol/L |
| Limit of Blank (LOB) | Defined blank. | 0.03 mmol/L |
| Measuring Range | Clinically relevant measurable range. | 0.05-3.00 mmol/LExtended measuring range: 0.05-6.00 mmol/L |
Study Information (as it pertains to this IVD):
The document mentions "Performance evaluation" was done for several characteristics, but does not provide details on specific study designs, sample sizes, or data provenance beyond what is implicit in standard IVD validation.
- Sample size for test set and data provenance: Not explicitly stated for specific performance studies. The method comparison data includes parameters like Passing Bablok regression (y = 1.037x + 0.004, $\tau$ = 0.940) and Linear regression (y = 1.044x -0.000, r = 0.995) which imply a comparison study with an unspecified number of samples. The data provenance (e.g., country of origin, retrospective/prospective) is not provided.
- Number of experts and qualifications for ground truth: Not applicable for a chemical assay. The ground truth for this device would be established by reference methods.
- Adjudication method: Not applicable.
- Multi-reader multi-case (MRMC) comparative effectiveness study: Not applicable.
- Standalone performance: The performance characteristics listed (precision, interference, limits) represent the standalone analytical performance of the device. This is the equivalent of "algorithm only" performance for a chemical assay.
- Type of ground truth: For analytical performance testing, the ground truth would be established by validated reference methods or materials (e.g., Atomic Absorption Spectroscopy for traceability, or gravimetrically prepared reference materials for calibrators).
- Sample size for the training set: Not applicable, as this is not an AI/ML device.
- How the ground truth for the training set was established: Not applicable.
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510(k) Summary – cobas c501 Lithium
MAR 2 1 2008
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence |
|---|---|
| Submitter name, address, contact | Roche Diagnostics 9115 Hague Rd Indianapolis IN 46250 (317) 521-3723 |
| Contact person: Theresa Ambrose Bush | |
| Date prepared: January 14, 2008 | |
| Device Name | Proprietary name: Lithium |
| Common name: LI | |
| Classification name: Lithium | |
| Device Description | The cassette cobas c501 Lithium contains an in vitro diagnostic reagent system intended for use on Roche/Hitachi cobas c systems for the quantitative determination of lithium in human serum and plasma. |
| The test principle is colorimetric. | |
| Intended use | In vitro test for the quantitative determination of lithium in human serum and plasma on Roche/Hitachi cobas c systems. |
| Predicate Device | We claim substantial equivalence to the COBAS INTEGRA ISE Direct cleared as K963627 |
| Substantial equivalency - Similarities | The table below indicates the similarities between the modified Lithium test and its predicate device (COBAS INTEGRA ISE Direct, K963627). |
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| Feature | Predicate device: ISE Direct(K963627) | Modified device: Lithium |
|---|---|---|
| General | ||
| Intended Use/Indications forUse | The ISE module of the COBASINTEGRA systems is intended foruse for the quantitativedetermination of sodium, potassium,chloride and lithium concentrationsin undiluted serum and plasma usingion-selective electrodes. | In vitro test for the quantitativedetermination of lithium in humanserum and plasma onRoche/Hitachi cobas c systems. |
| Specimen type | Serum and plasma | Same |
| Test principle | ||
| Referencemethod | Ion-selective electrodes usingundiluted specimens (ISE Direct) | Colorimetric test |
| Reagent information | ||
| Stability - shelflife and on-board | 1 day at 15 to 25° C7 days at 4° Cstable at -20 ° C | 1 day at 15 to 25° C7 days at 2-8° C6 months at (-15) to (-25) ° C |
| Calibrator | ISE Solutions 1, 2 and 3ISE Calibrator Direct5 hrs (main calibration) | C.f.a.s.After 24 hrs, reagent pack change,reagent lot change |
| Every sample (one-point calibration) | ||
| Quality control | Precinorm U and Precipath U | Precinorm U and Precipath UPrecinorm U plus and Precipath U |
| Traceability | Gravimetrically traceable to highpurity inorganic reference material | Atomic Absorption Spectroscopy |
| Performance characteristics | ||
| Expected values(literaturereference) | Therapeutic concentration: 0.6-1.2mmol/LToxic concentration:>2.0 mmol/L | Same |
| Method comparison | ||
| Methodcomparison | Passing Bablok: y = 1.037x + 0.004$\tau$ = 0.940 | |
| Linear regression: y = 1.044x -0.000r = 0.995 | ||
| Feature | Predicate device: ISE Direct(K963627) | Modified device: Lithium |
| Test principle | ||
| Referencemethod | Ion-selective electrodes usingundiluted specimens (ISE Direct) | Colorimetric test |
| Performance characteristics | ||
| Precision | Within run CV:2.5% @ 4.4 mmol/L0.81% @ 1.9 mmol/LTotal:3.4% @ 0.443 mmol/L2.5% @ 33.2 mmol/L | Within run CV:1.7% @ 0.77 mmol/L1.0% @ 2.38 mmol/L1.9% @ 0.46 mmol/L1.2% @ 1.40 mmol/LTotal:2.2% @ 0.79 mmol/L1.3% @ 2.42 mmol/L2.3% @ 0.61 mmol/L1.6% @ 1.62 mmol/L |
| Endogenousinterferences | Hemolysis: levels higher than 1 g/Lincrease lithium concentrationssignificantly | No significant interference up to:Hemolysis: H index of 1000 |
| Icterus no significant interferences | Icterus: I index of 37 for conjugatedand 43 for unconjugated bilirubin | |
| Lipemia: highly lipemic specimensmay interfere with ISE fluiddetection causing the flag NOFLUID | Lipemia: L index of 2000 | |
| ExogenousInterferences | Phenylpropamine andpseudoephedrine interfere with themembrane of the lithium electrode. | NH4Cl: 19.8 umol/LNaCl : 140 mmol/LKCl : 4 mmol/ LCaCl2: 2.4 mmol/LMgCl2: 0.9 mmol/LFeCl3: 1.04 mg/LCu (NO3)2: 1.15 mmol/LZnCl2: 1.07 mmol(none of these are in thephysiological key interferencerange)In very rare cases gammopathy |
| Limit ofDetection (perCLSI EP17) | Not stated | 0.05 mmol/L |
| Limit of Blank | Not stated | 0.03 mmol/L |
| Measuring range | 0.1-4 mmol/L | 0.05-3.00 mmol/LExtended measuring range: 0.05-6.00 mmol/L |
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Substantial The table below indicates the differences between the modified Lithium test
and its predicate device (COBAS INTEGRA ISE Direct, K963627). equivalency – Differences
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Performance evaluation
The cobas c501 test system was evaluated for several performance characteristics.
In addition, the traceability, value assignment process, and stability of the lithium analyte within the c.f.a.s. calibrator are described.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with outstretched wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the bird.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Roche Diagnostics Corp. c/o Dr. Theresa Ambrose Bush Regulatory Affairs Principal 9115 Hague Road Indianapolis. IN 46250
MAR 2 1 2008
Re: K063684 Trade/Device Name: Lithium Test System Regulation Number: 21 CFR 862.3560 Regulation Name: Lithium test system Regulatory Class: Class II Product Code: NDW, JIX Dated: March 7, 2008 Received: March 14, 2008
Dear Dr. Bush:
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 (QS) regulation (21 CFR Part 820).
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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 vour 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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Jéan M. Cooper, M.S., 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
510(k) Number (if known):
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Device Name: Lithium test system
Indications For Use:
In vitro test for the quantitative determination of lithium in human serum and plasma on Roche/Hitachi cobas c systems. Measurements of lithium are used as an aid in the management of patients taking lithium for the treatment of mental disturbances such as manic-depressive illness (bipolar disorder).
Prescription Use XXXX (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
063684
§ 862.3560 Lithium test system.
(a)
Identification. A lithium test system is a device intended to measure lithium (from the drug lithium carbonate) in serum or plasma. Measurements of lithium are used to assure that the proper drug dosage is administered in the treatment of patients with mental disturbances, such as manic-depressive illness (bipolar disorder).(b)
Classification. Class II.