K Number
K073490
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 IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.
The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
For in vitro diagnostic use.

Device Description

In this Olympus procedure:
When a sample is mixed with R1 buffer and R2 antiserum solution, human IgG reacts specifically with anti-human IgG 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 document is a 510(k) summary for a medical device called "Olympus IgG Reagent (OSR6X172)". This is an in vitro diagnostic device, specifically a reagent used for quantitative determination of IgG immunoglobulins. The acceptance criteria and supporting studies are presented by comparing the new device's performance characteristics with those of predicate devices already on the market.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is an in vitro diagnostic reagent rather than an imaging or AI-driven diagnostic device, the "acceptance criteria" are not framed in terms of metrics like sensitivity, specificity, or AUC, but rather in terms of demonstrating substantial equivalence to predicate devices through various performance characteristics. The acceptance criterion is generally that the new device's performance characteristics (e.g., precision, assay range, method comparison) are comparable to or better than the predicate's, and suitable for its intended use.

Here's a table summarizing the reported device performance and comparison to predicate devices, acting as de-facto acceptance criteria for substantial equivalence:

Serum/Plasma Applications

CharacteristicAcceptance Criteria (Predicate)Olympus IgG (OSR6X172) Performance (New Device)Status
Intended UseQuantitative determination of IgG immunoglobulins in human serum on OLYMPUS analyzers.Quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.Meets/Exceeds
MeasurementQuantitativeQuantitativeMeets
Instrument RequiredOlympus AU400/400e, 600/640/640e and 2700/5400SameMeets
Reagent HandlingReady for useReady for useMeets
MethodologyImmunoturbidimetricSameMeets
Reagent Storage FormLiquid, On-board storageSameMeets
CalibrationOlympus Serum Protein Multi-Calibrator (ODR3021)SameMeets
Calibration TraceabilityTraceable to CRM 470 (RPPHS lot 91/0619)SameMeets
AntibodyGoat Anti-IgG antiserumSameMeets
Expected Values635-1741 mg/dLSameMeets
Reagent On-Board Stability90 days when stored refrigerated on analyzer.SameMeets
Calibration Frequency90 daysSameMeets
Assay Range75-3000 mg/dL75-3000 mg/dL (same)Meets
Specimen TypeSerumSerum, Li-heparin or EDTA plasma, and cerebrospinal fluidExceeds (New CSF app. included)
LoQNot specified75 mg/dLSpecified/Meets
Prozone CapacityNot specifiedNo high dose effect at IgG concentrations up to 30,000 mg/dL (Much higher than typical physiological range, demonstrating robustness)Exceeds
Precision (Total CV%)AU400/400e: Samples 1,2,3 (0.82, 1.06, 2.24); AU600: Samples 1,2,3 (2.50, 1.54, 1.92); AU640/640e: Samples 1,2 (1.00, 1.00); AU2700/5400: Samples 1,2,3 (1.54, 2.39, 2.84)AU400/400e: Samples 1,2,3 (2.18, 2.29, 3.43); AU600/640/640e: Samples 1,2,3 (3.29, 3.49, 4.66); AU2700/5400: Samples 1,2,3 (1.51, 1.87, 2.03) (Comparably low CVs, indicating good precision, generally within acceptable lab limits for immunoassays)Meets
Method Comparison (Linear Regression)Intercept: -117, Slope: 1.086, R2: 0.993, n: 98, Range: 223-2633 mg/dLIntercept: 37.2, Slope: 0.945, R2: 0.998, n: 120, Range: 195-2986 mg/dL (R^2 > 0.99 indicates excellent correlation)Meets
Interfering SubstancesBilirubin (AU400/400e: <1% up to 40 mg/dL); Hemolysis (AU400/400e: <2% up to 500 mg/dL); Lipemia (AU400/400e: <10% up to 1000 mg/dL); RF (Not Specified); Ascorbic Acid (AU400/400e: <1% up to 20 mg/dL)Bilirubin (AU400/400e: <2% up to 40 mg/dL); Hemolysate (AU400/400e: <3% up to 500 mg/dL); Lipemia (AU400/400e: <3% up to 1000 mg/dL); RF (<7% up to 1200 IU/mL) (Comparable or improved interference tolerance)Meets/Exceeds

CSF Application

CharacteristicAcceptance Criteria (Predicate)Olympus IgG (OSR6X172) Performance (New Device)Status
Intended UseQuantitative determination of IgG in human serum, plasma and cerebrospinal on Roche/Hitachi Cobas c systems.Quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.Meets
MeasurementQuantitativeSameMeets
Specimen TypeSerum, plasma, and cerebrospinal fluidSameMeets
AntibodyGoat Anti-IgG antiserumSameMeets
Instrument RequiredRoche/Hitachi Cobas c systems.Olympus AU400/400°, 600/640/640° and 2700/5400Different but specific
Expected Values1-3 mg/dL15 – 20 y 3.5 mg/dL ± 2.0 mg/dL. 21 – 40 y 4.2 mg/dL ± 1.4 mg/dL. 41 – 60 y 4.7 mg/dL ± 1.0 mg/dL (Different value range, but provided with context of age, indicating physiological relevance)Meets
Reagent On-Board Stability84 days when stored refrigerated.90 days when stored refrigerated in compartment of the analyzer.Exceeds
Assay Range0.4-20 mg/dL2-50 mg/dL (Wider range for the new device)Exceeds
LoQNot specified2 mg/dLSpecified/Meets
Prozone CapacityNo high dose effect at IgG concentrations up to 100 mg/dLNo high dose effect at IgG concentrations up to 6,000 mg/dL (Significantly higher, indicating better robustness)Exceeds
Precision (Total CV%)Samples 1,2: (2.1, 1.1)AU400/400e: Samples 1,2,3 (9.82, 4.08, 3.61); AU600/640/640e: Samples 1,2,3 (9.53, 3.67, 2.81); AU2700/5400: Samples 1,2,3 (10.24, 6.29, 3.83) (Comparably low CVs, indicating good precision, generally within acceptable lab limits for immunoassays)Meets
Method Comparison (Linear Regression)Intercept: -0.17, Slope: 0.997, R2: 1.000, Range: 1.07-18.6 mg/dLIntercept: -0.069, Slope: 1.067, R2: 0.998, Range: 2.0-42.9 mg/dL (R^2 > 0.99 indicates excellent correlation)Meets
Interfering SubstancesBilirubin (<10% up to 15 mg/dL); Hemolysis (<10% up to 200 mg/dL)Bilirubin (<10% up to 36 mg/dL); Hemolysis (<10% up to 500 mg/dL) (Improved interference tolerance)Exceeds

2. Sample Sizes Used for the Test Set and Data Provenance

  • Serum/Plasma Method Comparison:
    • Sample Size (n): 120 samples for the new device study. The predicate had n=98.
    • Data Provenance: Not explicitly stated (e.g., country of origin). However, given the context of a 510(k) submission for the US market, it's typically assumed to be relevant clinical samples, likely from a US-based or similar regulated environment unless specified otherwise. No indication of retrospective or prospective.
  • CSF Method Comparison:
    • Sample Size (n): Not explicitly stated numbers for the new device in the table for CSF, but linear regression data is provided. The predicate's study data (R2=1.000) shows a range of 1.07-18.6 mg/dL indicative of using patient samples, but the 'n' is not mentioned.
    • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective).
  • Precision: 3 samples (levels) were tested for each instrument platform (AU400/400e, AU600/640/640e, AU2700/5400) for both serum/plasma and CSF applications. These would typically be control materials or pooled patient samples.
  • Interfering Substances: Testing was conducted at specific concentrations of bilirubin, hemolysate, lipemia, and RF (for serum/plasma) or bilirubin and hemolysis (for CSF). The number of individual samples tested at these concentrations is not specified.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This document describes the performance of an in vitro diagnostic reagent measuring a biochemical analyte (IgG). "Ground truth" in this context refers to the true concentration of IgG in the samples, which would usually be established by a reference method or a highly accurate, often predicate, measurement system. Expert consensus or interpretation (e.g., radiologists) is not applicable here. The "ground truth" for the method comparison studies is the result obtained from the predicate device or a recognized reference method.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is for an in vitro diagnostic reagent, not a diagnostic imaging or AI-driven device requiring human adjudication of results. The performance is assessed by comparing quantitative results to a predicate device's results.

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 in vitro diagnostic reagent, not an AI-assisted diagnostic device, and therefore does not involve human readers or MRMC studies.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a standalone diagnostic test in the sense that it performs a quantitative measurement on a biochemical analyzer without direct human interpretation of a complex output. The tables provided illustrate the performance of the reagent on various Olympus AU analyzers. This data directly represents the "algorithm only" performance (i.e., the reagent's performance on the specified instruments).

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The "ground truth" for the test set (method comparison) was obtained by running the same patient samples on the predicate device(s).

  • For Serum/Plasma, the predicate was "Olympus (OSR6145) IgG Reagent".
  • For CSF, the predicate was "Roche Tina-Quant IgG GEN.2".
    The precision and interference studies use contrived samples (e.g., spiked samples, control materials) where the "true" value or concentration is known or independently verified.

8. The Sample Size for the Training Set

Not applicable in the conventional sense of machine learning. This is a biochemical reagent, not a machine learning model. The "development" or "optimization" of the reagent would involve chemical formulation and analytical testing, not a "training set" in the AI context.

9. How the Ground Truth for the Training Set Was Established

Not applicable for a biochemical reagent. The formulation and performance characteristics of the reagent are established through standard chemical and biological assay development and validation practices.

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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.

The assigned 510(k) number is: 3073490

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 10, 2007
2. Device name
Proprietary Name:Olympus IgG Reagent (OSR6X172)
Common Name:IgG Reagent
Classification Name:IgG, Antigen, Antiserum, Control
3. Predicate device(s)
Serum/Plasma ApplicationsOlympus (OSR6145) IgG ReagentSubmitted (K951013)
CSF ApplicationRoche Tina-Quant IgG GEN.2Submitted (K050113)
4. Device descriptionIn this Olympus procedure:When a sample is mixed with R1 buffer and R2 antiserum solution, human IgG reacts specifically with anti-human IgG 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 IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on OLYMPUS analyzers.For in vitro diagnostic use.

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The following tables compare the new Olympus IgG (OSR6X172)
reagent with the predicate devices outlined in point 3 above.

Serum/Plasma Applications

Similarities
ItemOlympus IgG (OSR6X172) reagentPredicate System
Intended UseSystem reagent for the quantitativedetermination of IgG immunoglobulinsin human serum, plasma andcerebrospinal fluid on OLYMPUSanalyzers.System reagent for the quantitativedetermination of IgG immunoglobulinsin human serum on OLYMPUSanalyzers.
MeasurementQuantitativeSame
Instrument RequiredOlympus AU400/400°, 600/640/640°and 2700/5400Same
Reagent handlingReady for useSame
AssayMethodology/OperatingPrincipleImmunoturbidimetricSame
Reagent storage formLiquidOn-board storageSame
CalibrationOlympus Serum Protein Multi-Calibrator (ODR3021)Same
Calibration TraceabilityThis method is traceable to theInternational Reference Preparation CRM470 (US designation RPPHS lot 91/0619)Same
AntibodyGoat Anti-IgG antiserumSame
Expected Values635-1741 mg/dLSame
Reagent On Board StabilityOpened reagents are stable for 90days when stored in the refrigeratedcompartment of the analyzer.Same
Calibration Frequency90 daysSame
DifferencesItemOlympus IgG (OSR6X172) reagentPredicate System
ItemOlympus IgG (OSR6X172) reagentPredicate SystemAssay Range75-3000 mg/dL75-3000 mg/dL
Specimen TypeSerum, Li-heparin or EDTA plasma:and cerebrospinal fluidSerumLoQ75 mg/dLNot specified
Prozone CapacityNo high dose effect at IgG concentrations up to 30,000 mg/dLNot specified
PrecisionAU400/400eSample Total CV%1 2.182 2.293 3.43AU600/640/640eSample Total CV%1 3.292 3.493 4.66AU400/400eSample Total CV%1 0.822 1.063 2.24AU600Sample Total CV%1 2.502 1.543 1.92
AU640/640°Sample12Total CV%1.001.00AU2700/5400Sample123Total CV%1.542.392.84
AU2700/5400Sample123Total CV%1.511.872.03
Method Comparison (Linear Regression)InterceptSlopeR2nRange37.20.9450.998120195-2986 mg/dLInterceptSlopeR2nRange-1171.0860.99398223-2633 mg/dL
Interfering SubstancesAU400/400°Bilirubin: Interference less than 2% upto 40 mg/dL BilirubinHemolysate: Interference less than 3%up to 500 mg/dL HemolysateLipemia: Interference less than 3% upto 1000 mg/dL IntralipidRF: Interferences less than 7% up to1200 IU/mLNot testedAU600/640/640°Bilirubin: Interference less than 3% upto 40 mg/dL BilirubinHemolysate: Interference less than 3%up to 500 mg/dL HemolysateLipemia: Interference less than 5% upto 1000 mg/dL IntralipidRF: Interferences less than 7% up to1200 IU/mLNot testedAU2700/5400Bilirubin: Interference less than 1% upto 40 mg/dL BilirubinHemolysate: Interference less than 3%up to 500 mg/dL HemolysateLipemia: Interference less than 2% upto 1000 mg/dL IntralipidRF: Interferences less than 7% up to1200 IU/mLNot testedAU400/400°Bilirubin: Interference less than 1% upto 40 mg/dL BilirubinHemolysis: Interference less than 2%up to 500 mg/dL HemolysateLipemia: Interference less than/10% upto 1000 mg/dL Intralipid.RF: Not SpecifiedAscorbic acid: Interference less than1% up to 20 mg/dL AscorbateAU600/640/640°Bilirubin: Interference less than 2% upto 40 mg/dL BilirubinHemolysis: Interference less than 2%up to 500 mg/dL HemolysateLipemia: Interference less than 3% upto 1000 mg/dL Intralipid.RF: Not SpecifiedAscorbic acid: Interference less than2% up to 20 mg/dL AscorbateAU2700/5400Bilirubin: Interference less than 5% upto 40 mg/dL BilirubinHemolysis: Interference less than 3%up to 500 mg/dL HemolysateLipemia: Interference less than 3% upto 1000 mg/dL Intralipid.RF: Not SpecifiedAscorbic acid: Interference less than3% up to 20 mg/dL Ascorbate

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CSF Application

Similarities
ItemOlympus IgG (OSR6X172) reagentPredicate Systems
Intended UseSystem reagent for the quantitativedetermination of IgG immunoglobulinsin human serum, plasma andcerebrospinal fluid on OLYMPUSanalyzers.In vitro test for the quantitative determinationof IgG in human serum, plasma andcerebrospinal on Roche/Hitachi Cobas csystems.
MeasurementQuantitativeSame
Specimen TypeSerum, plasma: Li-heparin or EDTAand cerebrospinal fluidSame
AntibodyGoat Anti-IgG antiserumSame
Reagent handlingReady for useSame
AssayMethodology/OperatingPrincipleImmunoturbidimetricSame
Reagent storage formLiquidOn -board storageSame
Calibration TraceabilityCRM 470Same
CalibrationMulti-pointSame
Differences
ItemOlympus IgG (OSR6X172) reagentPredicate System
Instrument RequiredOlympus AU400/400°, 600/640/640°and 2700/5400Roche/Hitachi Cobas c systems.
Expected Values15 – 20 y 3.5 mg/dL ± 2.0 mg/dL.21 – 40 y 4.2 mg/dL ± 1.4 mg/dL.41 – 60 y 4.7 mg/dL ± 1.0 mg/dL1-3 mg/dL
Reagent On Board StabilityOpened reagents are stable for 90 dayswhen stored in the refrigeratedcompartment of the analyzer.Opened reagents are stable for 84 dayswhen stored in the refrigerated compartmentof the analyzer.
CalibrationOlympus Serum Protein Mulit-Calibrator (ODR3021)S1 H₂OS2 C.f.a.s. PUC
Calibration Frequency2 DaysNot Specified

.

Performance Characteristics
ItemOlympus IgG (OSR6X172) reagentPredicate System
Assay Range2-50 mg/dL0.4-20 mg/dL
LoQ2 mg/dLNot specified
Prozone CapacityNo high dose effect at IgGconcentrations up to 6,000 mg/dLNo high dose effect at IgG concentrations upto 100 mg/dL
PrecisionAU400/400 eSample123AU600/640/640eSample123AU2700/5400Sample123Total CV%9.824.083.61Total CV%9.533.672.81Total CV%10.246.293.83Sample12Total CV%2.11.1

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Intercept-0.069Intercept-0.17
Method Comparison (LinearSlope1.067Slope0.997
Regression)R20.998R21.000
Range2.0-42.9 mg/dLRange1.07-18.6 mg/dL
Interfering SubstancesAU400/400e/600/640/640°/2700/5400Bilirubin: Interference less than 10% upto 36 mg/dL BilirubinHemolysis: Interference less than 10%up to 500 mg/dL HemolysateBilirubin: Interference less than 10% up to15 mg/dL BilirubinHemolysis: Interference less than 10% up to200 mg/dL Hemolysate

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services. The seal features a stylized eagle with three lines representing its wings and body. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle.

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: K073490

Trade/Device Name: Olympus IgG 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 H. Becker

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): KD73490

Device Name: The Olympus IgG reagent (OSR6X172).

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

The measurement of IgG 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 (OIVD)

Mana M. Aan

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

510(k) K073490

§ 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).