K Number
K073487
Date Cleared
2008-02-11

(61 days)

Product Code
Regulation Number
866.5510
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

System reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on OLYMPUS analyzers. For in vitro diagnostic use.

Device Description

In this Olympus procedure:

  • When a sample is mixed with R1 buffer and R2 antiserum solution, human IgM reacts specifically with anti-human IgM antibodies to yield insoluble aggregates.
  • Immune complexes formed in solution scatter light in proportion to their size, shape and concentration.
  • Turbidimeters measure the reduction of incidence light due to reflection, absorption or scatter.
  • In the Olympus procedure, the decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution is as a result of complexes formed during the antigen-antibody reaction.
AI/ML Overview

The provided 510(k) summary describes a new Olympus IgM reagent (OSR6X173) and compares its performance to a predicate device. This document is a premarket notification for a diagnostic reagent, which falls under IVD (in vitro diagnostic) devices. For IVD devices, the "study" typically refers to analytical and clinical performance studies, not AI-specific studies like MRMC or standalone algorithm performance. Therefore, many of the requested items related to AI device performance (e.g., number of experts, adjudication methods, MRMC studies, standalone performance, training set details) are not directly applicable or reported in this type of submission.

Here's an analysis based on the provided text, focusing on the available information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a separate section. Instead, it presents performance characteristics of the new device and the predicate device side-by-side, implying that the new device's performance is acceptable if it is comparable to or better than the predicate. For the purpose of this analysis, I will treat the performance values of the predicate device and the new device as demonstrating acceptable performance through substantial equivalence.

Performance CharacteristicAcceptance Criteria (Predicate Device)Reported Device Performance (New Olympus IgM reagent OSR6X173)
Precision (Total CV%)
AU400/400eSample 1: 1.74%Sample 2: 1.18%Sample 3: 1.49%Sample 1: 4.03%Sample 2: 2.95%Sample 3: 2.60%
AU600/640/640eSample 1: 2.16%Sample 2: 1.48%Sample 3: 1.35% (for AU600)Sample 1: 1.5%Sample 2: 1.3% (for AU640/640e)Sample 1: 3.44%Sample 2: 3.29%Sample 3: 4.08%
AU2700/5400Sample 1: 2.49%Sample 2: 2.57%Sample 3: 3.07%Sample 1: 3.79%Sample 2: 3.31%Sample 3: 3.52%
Assay RangeNot explicitly stated, inferred from Method Comparison20-500 mg/dL
Hook Effect/ProzoneMay occur with highly elevated IgM samples > 3,500 mg/dL polyclonalMay occur with highly elevated IgM samples > 10,000 mg/dL polyclonal
Method Comparison (Linear Regression)Slope: 0.968Intercept: 0.6R: 0.998N: Not clearly stated in predicate table (appears truncated)Slope: 1.006Intercept: 2.8R: 1.000N: 107
Interfering Substances (Bilirubin)
AU400/400eInterference less than 2% up to 40 mg/dLInterference less than 4% up to 40 mg/dL
AU600/640/640eInterference less than 5% up to 40 mg/dLInterference less than 3% up to 40 mg/dL
AU2700/5400Interference less than 10% up to 40 mg/dLInterference less than 8% up to 40 mg/dL
Interfering Substances (Hemolysis)
AU400/400eInterference less than 2% up to 500 mg/dLInterference less than 4% up to 500 mg/dL
AU600/640/640eInterference less than 10% up to 500 mg/dLInterference less than 3% up to 500 mg/dL
AU2700/5400Interference less than 5% up to 500 mg/dLInterference less than 3% up to 500 mg/dL
Interfering Substances (Lipemia)
AU400/400eInterference less than 10% up to 300 mg/dLInterference less than 10% up to 300 mg/dL
AU600/640/640eInterference less than 10% up to 400 mg/dLInterference less than 10% up to 300 mg/dL
AU2700/5400Interference less than 10% up to 400 mg/dLInterference less than 10% up to 200 mg/dL
Interfering Substances (Ascorbic Acid)
AU400/400eInterference less than 2% up to 20 mg/dLNot Tested
AU600/640/640eInterference less than 1% up to 20 mg/dLNot Tested
AU2700/5400Interference less than 3% up to 20 mg/dLNot Tested
Functional SensitivityNot Specified< 20 mg/dL on AU400/400e, AU600/640/640e & AU2700/5400

Study Proving Device Meets Acceptance Criteria:

The study described is a comparative analysis against a legally marketed predicate device (Olympus (OSR6X46) IgM Reagent, K950900). The manufacturer carried out various analytical performance tests, including precision, assay range determination, prozone effect evaluation, method comparison (linear regression), and interference studies. The data presented demonstrates that the new device's analytical performance is substantially equivalent to the predicate device, or in some cases, improved (e.g., higher prozone limit).

2. Sample size used for the test set and the data provenance:

  • Test Set Sample Size:
    • Method Comparison: N = 107 (for linear regression). This represents 107 human serum/plasma samples analyzed.
    • Precision: The table lists 3 samples for each instrument type (AU400/400e, AU600/640/640e, AU2700/5400). It's implied that these samples were run multiple times to calculate the Total CV%.
    • Interfering Substances: The exact number of samples for each interference study is not specified, but the data indicates the upper limit of interferent concentration at which interference remained below a specified threshold.
  • Data Provenance: The document states the intended use is for "human serum and plasma." The country of origin for the data is not specified in this summary. The studies appear to be prospective analytical performance evaluations performed by the manufacturer as part of the 510(k) submission.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This is not applicable for this type of IVD device. The ground truth for IgM measurement is established through quantitative laboratory methods, not by expert interpretation in an AI context. The predicate device's measurements serve as the reference for method comparison.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not applicable. Adjudication methods are relevant for subjective interpretations (e.g., radiology reads) where discrepancies between experts need to be resolved. This device measures a quantitative analyte.

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 an IVD reagent and not an AI-assisted diagnostic imaging or interpretation device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

This is not an AI algorithm. The device is a chemical reagent used in a laboratory analyzer. Its performance is inherently "standalone" in the sense that it directly measures IgM concentration, without human interpretive input for the measurement itself, but operated by laboratory personnel.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" a.k.a. reference method for the quantitative determination of IgM in the method comparison study is the predicate device (Olympus (OSR6X46) IgM Reagent, K950900), which is a legally marketed and presumably validated method for IgM quantification. The calibrator traceability is to the International Reference Preparation CRM470, which serves as a metrological standard.

8. The sample size for the training set:

Not applicable. This is not an AI device that requires a training set. The "training" for such a system would involve validating the chemical formulation and assay parameters through analytical studies.

9. How the ground truth for the training set was established:

Not applicable, as there is no training set in the context of an AI device. The development of the reagent involves chemical formulation and optimization, with performance verified against established analytical standards and reference methods.

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510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance
with the requirements of SMDA 1990 and 21 CFR 807.92.
1990 and 21 CC (CCC

The assigned 510(k) number is:K073486
-----------------------------------------
1. Submitter name, address, contactOlympus America Inc.3500 Corporate ParkwayCenter Valley, PA 18034
U.S. Telephone:469-230-0959
U.S. Fax:972-317-7861
Contact Person:Stephanie G. Donnelly
Date Prepared:December 11, 2007

FEB 11 2008

2. Device name
Proprietary Name:Olympus IgM reagent (OSR6X173)
Common Name:IgM reagent
Classification Name:IgM (mu chain specific), antigen, antiserum, control.
3. Predicate device
Reagent:Olympus (OSR6X46) IgM Reagent Submitted K950900
4. Device descriptionIn this Olympus procedure:
  • When a sample is mixed with R1 buffer and R2 antiserum solution, human IgM reacts specifically with anti-human IgM antibodies to yield insoluble aggregates.
  • Immune complexes formed in solution scatter light in proportion to their size, shape and concentration.
  • Turbidimeters measure the reduction of incidence light due to reflection, absorption or scatter.
  • In the Olympus procedure, the decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution is as a result of complexes formed during the antigen-antibody reaction.
5. Intended useSystem reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on OLYMPUS analyzers.For in vitro diagnostic use.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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The following Tables compare the new Olympus IgM (OSR6X173) reagent
with the predicate device outlined in point 3 above.

Similarities
ItemOlympus IgM (OSR6X173) reagentPredicate System
Intended UseSystem reagent for the quantitativedetermination of IgM immunoglobulinsin human serum and plasma onOLYMPUS analyzers.System reagent for the quantitativedetermination of IgM immunoglobulinsin human serum on OLYMPUSanalyzers.
InstrumentOlympus AU400/400°, 600/640/640°and 2700/5400Same
MeasurementQuantitativeSame
Reagent handlingReady for useSame
AssayMethodology/OperatingPrincipleImmunoturbidimetricSame
AntibodyGoat anti-IgM antiserumSame
Reagent storage formLiquidOn-board storageSame
On-Board Stability90 daysSame
CalibratorOlympus Serum Protein Mulit-Calibrator (ODR3021)Same
Calibrator TraceabilityThis method is traceable to theInternational Reference PreparationCRM470 (US designation RPPHS lot91/06/19)Same
Calibration Frequency90 daysSame
Expected Values45-281 mg/dLSame
Differences
ItemOlympus IgM (OSR6X173) reagentPredicate System
Specimen TypeSerum and plasma: Li-heparin andEDTA plasmaSerum

ItemPerformance CharacteristicsOlympus IgM (OSR6X173) reagentPredicate System
PrecisionAU400/400eSampleAU400/400eSample
123123
Total CV%Total CV%
4.032.952.601.741.181.49
AU600/640/640eSampleAU600Sample
123123
Total CV%Total CV%
3.443.294.082.161.481.35
AU640/640eSample
12
Total CV%
1.51.3

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AU2700/5400AU2700/5400
SampleTotal CV%SampleTotal CV%
3.79112.49
23.3122.57
Assay Range33.5220-500 mg/dL33.07
Hook effect may occur with highly elevatedSameHook effect may occur with highly elevated
ProzoneIgM samples > 10, 000 mg/dL polyclonalIgM samples > 3, 500 mg/dL polyclonal
Slope1.006Slope0.968
Method Comparison (LinearIntercept2.8Intercept0.6
Regression)R1.000R0.998
N107ക്കZ
Interfering Substances22-468 mg/dLRangeAU400/4006Range24-497 mg/dLAU400/4008
Bilirubin: Interference less than 4% up toBilirubin: Interference less than 2% up to 40
40 mg/dL Bilirubinmg/dL Bilirubin
Hemolysis: Interference less than 4% up toHemolysis: Interference less than 2% up to
500 mg/dL Hemolysate500 mg/dL Hemolysate
Lipemia: Interference less than 10% up toLipemia: Interference less than 10% up to
300 mg/dL Intralipid300 mg/dL Intralipid
Not TestedAscorbic Acid: Interference less than 2% upto 20 mg/dL Ascorbate
AU600/640/640°AU600/640/640
Bilirubin: Interference less than 3% up toBilirubin: Interference less than 5% up to 40
40 mg/dL Bilirubinmg/dL Bilirubin
Hemolysis: Interference less than 3% up toHemolysis: Interference less than 10% up to
500 mg/dL HemolysateLipemia: Interference less than 10% up to500 mg/dL Hemolysate
300 mg/dL IntralipidLipemia: Interference less than 10% up to400 mg/dL Intralipid
Not TestedAscorbic Acid: Interference less than 1% up
to 20 mg/dL Ascorbate
AU2700/5400AU2700/5400
Bilirubin: Interference less than 8% up to40 mg/dL BilirubinBilirubin: Interference less than 10% up to
Hemolysis: Interference less than 3% up to40 mg/dL BilirubinHemolysis: Interference less than 5% up to
500 mg/dL Hemolysate500 mg/dL Hemolysate
Lipemia: Interference less than 10% up toLipemia: İnterference less than 10% up to
200 mg/dL. Intralipid400 mg/dL Intralipid
Not TestedAscorbic Acid: Interference less than 3% up
Function Sensitivity< 20 mg/dL on AU400/4008to 20 mg/dL Ascorbate
AU600/640/640° & AU2700/5400Not Specified
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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of a human figure embracing a sphere. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the emblem.

Public Health Service

FEB 11 2008

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Olympus America, Inc. c/o Ms. Stephanie Donnelly Regulatory Affairs/Quality Assurance Manager Olympus Life Science Research Europa GmbH Lismeehan, O, Callaghan's Mills Co. Claire, Ireland.

Re: K073487

Trade/Device Name: Olympus IgM reagent Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, E immunological test systems Regulatory Class: Class II Product Code: CFN Dated: December 11, 2007 Received: December 12, 2007

Dear Ms. Donnelly:

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 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The

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Page 2 --

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 (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Robert Becker J

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known):

Device Name: Olympus IgM reagent (OSR6X173)

Indication For Use: System reagent for the quantitative determination of IgM immunoglobulins in human serum and plasma on OLYMPUS analyzers.

The spectrum of abnormalities in serum immunoglobulin concentrations is broad. Abnormal concentrations range from a virtual absence of one or more of the three major classes of immunoglobulin (IgA, IgG, and IgM) to polyclonal increases in one or more immunoglobulins. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

For in vitro diagnostic use.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use __________ (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

m cland

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K073487

§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.

(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).