(157 days)
System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU analyzers. The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
The device consists of two reagents: R1 buffer (Tris buffer pH 7.2, polyethylene glycol 6000) and R2 (goat anti-IgG antiserum). The reagents contain sodium azide as preservative.
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 then measure the reduction of incidence light due to reflection, absorption or scatter. In the AU 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.
The provided text describes a 510(k) premarket notification for a medical device called "IgG Regulation Number: 21 CFR 866.5510" (Trade/Device Name: IgG). This device is a system reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma, and cerebrospinal fluid on Beckman Coulter AU analyzers. The document details the comparison testing performed to demonstrate substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly present a "table of acceptance criteria" in the format of pass/fail thresholds. Instead, it compares the performance of the candidate device (IgG Reagent on DxC 700 AU Beckman Coulter Analyzers) to the predicate device (Olympus IgG Reagent (K073490) on AU400/400ᵉ/480, AU600/640/640ᵉ/680, and AU2700/5400/AU5800 Beckman Coulter Analyzers). The acceptance criterion is essentially that the candidate device's performance is "substantially equivalent" to the predicate, meaning it should perform at least as well as the predicate for key metrics.
Here's a table summarizing the comparison, with the predicate's performance serving as the de-facto acceptance criteria for equivalence:
| Feature | Predicate Device Performance (Acceptance Criteria for Equivalence) | Candidate Device Performance (Reported Performance) | Met? |
|---|---|---|---|
| Precision | |||
| Serum & Plasma | With-run: $\le$ ±3.5% mg/dLTotal: $\le$ ±6.0% mg/dL | Same | Yes (stated "Same") |
| CSF | With-run: $\le$ ±6.0% or ±0.4 mg/dLTotal: $\le$ ±7.5% or ±0.5mg/dL | Same | Yes (stated "Same") |
| Sensitivity (LoQ) | |||
| Serum & Plasma | 75 mg/dL | Same | Yes (stated "Same") |
| CSF | 2 mg/dL | Same | Yes (stated "Same") |
| Interference | |||
| Serum & Plasma | Bilirubin: Interference less than 3% up to 40 mg/dLHemolysis: Interference less than 3% up to 500 mg/dLLipemia: Interference less than 5% up to 1000 mg/dL IntralipidRF: Interference less than 7% up to 1200 IU/mL Rheumatoid Factor | SimilarThe criteria for No Significant Interference (NSI) is recovery within 10% of the initial value.Bilirubin: NSI up to 40 mg/dL BilirubinHemolysis: NSI up to 500 mg/dL HemolysateLipemia: NSI up to 1000 mg/dL IntralipidRF: NSI up to 1200 IU/mL Rheumatoid Factor | Yes (stated "Similar" and provided comparable NSI criteria) |
| CSF | Bilirubin: Interference less than 3% up to 40 mg/dLHemolysis: Interference less than 3% up to 500 mg/dLLipemia: Interference less than 5% up to 1000 mg/dL IntralipidRF: Interference less than 7% up to 1200 IU/mL Rheumatoid Factor | SimilarThe criteria for No Significant Interference (NSI) is recovery within 10% of the initial value.Bilirubin: NSI up to 40 mg/dL BilirubinHemolysis: NSI up to 500 mg/dL HemolysateLipemia: NSI up to 1000 mg/dL IntralipidRF: NSI up to 1200 IU/mL Rheumatoid Factor | Yes (stated "Similar" and provided comparable NSI criteria) |
| Analytic Range | Serum & Plasma: 75 – 3000 mg/dLCSF: 2 - 50 mg/dL | Same | Yes (stated "Same") |
| Onboard Stability | 90 Days | Same | Yes (stated "Same") |
| Calibration Stability | Serum & Plasma: 90 DaysCSF: 2 Days | Same | Yes (stated "Same") |
The study proving the device meets the acceptance criteria:
The study conducted is a comparative performance study between the candidate device and its predicate.
2. Sample size used for the test set and the data provenance
The document mentions "Comparison testing" was conducted, including "Method Comparison, Linearity, Sensitivity, Reference Interval, Interference, In use (On board) & Calibrator Stability, Precision, Prozone, Auto-dilution." However, it does not specify the sample sizes used for each of these tests.
Regarding data provenance: The document does not specify the country of origin of the data. It does not explicitly state whether the data was retrospective or prospective. Given the context of a 510(k) submission for an in vitro diagnostic device, the data would typically be generated in a controlled manner, likely through prospective experimental studies, to demonstrate performance characteristics.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable and not provided in the document. This device is an in-vitro diagnostic (IVD) for quantitative measurement of immunoglobulins. The "ground truth" for such devices is established through reference methods, calibrated materials, or highly accurate laboratory techniques, rather than expert consensus (e.g., radiological reads). The device measures a biomarker quantitatively, so the "truth" is the actual concentration of IgG, determined by a highly accurate measurement system.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not applicable and not provided. Adjudication methods like "2+1" or "3+1" are relevant for subjective interpretations (e.g., image reading) where multiple human readers might disagree, requiring a third or fourth reader to resolve discrepancies. For a quantitative IVD, the measurement itself is the "output," and its accuracy is assessed against a reference method or known concentration standards, not by human adjudication of its output.
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
This information is not applicable and not provided. An MRMC study is typically performed for AI or computer-aided detection/diagnosis (CAD) systems that assist human readers (e.g., radiologists interpreting images). This device is a lab assay system, not an AI system assisting human interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance data presented (Precision, Sensitivity, Interference, Analytical Range, Stability) for the "Candidate Device: IgG Reagent" are inherent performance characteristics of the assay system itself, irrespective of human intervention in the interpretation of the result. The device quantitatively determines IgG levels. The study assesses the accuracy, precision, and other analytical performance parameters of the device's measurement capability in a standalone fashion.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for this type of quantitative in-vitro diagnostic device would be established by:
- Reference materials/standards with known concentrations: Calibrators and controls with certified IgG concentrations are used to verify the accuracy and linearity of the measurement.
- Reference methods: Highly accurate and precise laboratory methods (e.g., isotope dilution mass spectrometry for some analytes, or established validated methods) that serve as the gold standard for measuring the analyte.
- Sample spiking: Adding known quantities of the analyte to samples to assess recovery.
While the document doesn't explicitly state the specific ground truth methods for each test, the standard practice for IVDs involves these types of analytical validation studies.
8. The sample size for the training set
This information is not applicable and not provided. This device is a chemical reagent and an assay system, not a machine learning or AI model that requires a "training set" in the computational sense. The device's performance is based on chemical reactions and optical detection, not learned patterns from data.
9. How the ground truth for the training set was established
This information is not applicable for the same reasons as #8. No "training set" in the AI/ML context exists for this type of device.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 9, 2017
Beckman Coulter, Inc. Geraldine Fuentespina Manager, Regulatory Affairs 250 S. Kraemer Blvd., Mail Stop E1.SE.01 Brea. CA 92821
Re: [510(k) Number] K162208 Trade/Device Name: IgG Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A. G. M. D. and E immunological test system Regulatory Class: Class II Product Code: CFN. JJE Dated: November 29, 2016 Received: November 30, 2016
Dear Ms. Fuentespina:
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
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21CFR 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,
Kelly Oliner -S
FOR.
Leonthena R. Carrington, MS, MBA, MT (ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health
Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K162208
Device Name IgG
Indications for Use (Describe)
System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU analyzers. The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
| 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) |
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1.0 Submitted By
Geraldine Fuentespina Manager, Regulatory Affairs Beckman Coulter, Inc. 250 S. Kraemer Blvd. Mail Stop: E1.SE.01 Brea, CA 92821 Telephone: (714) 961-3777 Fax: (714) 961-4234
2.0 Date of Preparation
6 January 2017
3.0 Device Name(s)
Proprietary Name: laG Common Name: laG Classification: Class II Classification Name: Immunoglobulins A, G, M, D, E Immunological Test System Product Codes: CFN Requlation Number: 21 CFR 866.5510
4.0 Predicate Device
| Candidate(s) | Predicate | Manufacturer |
|---|---|---|
| IgG | Olympus IgG Reagent(K073490) | Beckman Coulter,Inc. |
5.0 Device Description
The device consists of two reagents: R1 buffer (Tris buffer pH 7.2, polyethylene glycol 6000) and R2 (goat anti-IgG antiserum). The reagents contain sodium azide as preservative.
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 then measure the reduction of incidence light due to reflection, absorption or scatter. In the AU 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.
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6.0 Indications for Use
System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU 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.
7.0 Comparison to the Predicate
The formulation of the candidate IgG reagent and the predicate IgG reagent are identical. The following tables show the similarities and differences between the predicate device.
| Feature | Predicate Device: IgG Reagent (K073490) | Candidate Device: IgG Reagent |
|---|---|---|
| Item Number | IgG (OSR6X172) reagent | Same |
| Intended Use | System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU analyzers | Same |
| Measurement | Quantitative | Same |
| Instrument Required | AU400/400ᵉ/480,AU600/640/640ᵉ/680 andAU2700/5400/AU5800Beckman Coulter Analyzers | AU400/400ᵉ/480,/640/640ᵉ/680,AU2700/5400/AU5800 andDxC 700 AU BeckmanCoulter Analyzers. |
| Methodology | Immunoturbidimetric | Same |
| Antibody | Goat anti-IgG | Same |
| Reagent form and storage | Liquid, on-board storage | Same |
| Specimen Type | Serum, EDTA or Lithium heparin plasma, and cerebrospinal fluid | Same |
| Calibrator | Serum Protein Multi-Calibrator (Cat # ODR3021) | Same |
| Onboard Stability | 90 Days | Same |
| Calibration Stability | Serum & Plasma90 Days | Same |
| CSF2 Days | Same | |
| Analytic Range | Serum & Plasma75 – 3000 mg/dL | Same |
| CSF2 - 50 mg/dL | Same |
Table 7.0 - IgG Predicate Device Comparison Table
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| Feature | Predicate Device:IgG Reagent(K073490) | Candidate Device:IgG Reagent | |
|---|---|---|---|
| Precision | Serum &Plasma | With-run:$\le$ ±3.5% mg/dLTotal:$\le$ ±6.0% mg/dL | Same |
| CSF | With-run:$\le$ ±6.0% or ±0.4 mg/dLTotal:$\le$ ±7.5% or ±0.5mg/dL | Same | |
| Sensitivity | Serum &Plasma | LoQ:75 mg/dL | Same |
| CSF | LoQ:2 mg/dL | Same | |
| Interference | Serum &Plasma | Bilirubin: Interference lessthan 3% up to 40 mg/dLBilirubinHemolysis: Interference lessthan 3% up to 500 mg/dLHemolysateLipemia: Interference lessthan 5% up to 1000 mg/dLIntralipidRF: Interference less than7% up to 1200 IU/mLRheumatoidFactor | SimilarThe criteria for NoSignificant Interference(NSI) is recovery within 10%of the initial value.Bilirubin: NSI up to 40mg/dL BilirubinHemolysis: NSI up to 500mg/dL HemolysateLipemia: NSI up to 1000mg/dL IntralipidRF: NSI up to 1200 IU/mLRheumatoidFactor |
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| Feature | Predicate Device:IgG Reagent(K073490) | Candidate Device:IgG Reagent |
|---|---|---|
| CSF | Bilirubin: Interference lessthan 3% up to 40 mg/dLBilirubin | SimilarThe criteria for NoSignificant Interference(NSI) is recovery within 10%of the initial value. |
| Hemolysis: Interference lessthan 3% up to 500 mg/dLHemolysate | Bilirubin: NSI up to 40mg/dL Bilirubin | |
| Lipemia: Interference lessthan 5% up to 1000 mg/dLIntralipid | Hemolysis: NSI up to 500mg/dL Hemolysate | |
| RF: Interference less than7% up to 1200 IU/mLRheumatoidFactor | Lipemia: NSI up to 1000mg/dL IntralipidRF: NSI up to 1200 IU/mLRheumatoidFactor |
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8.0 Comparison testing
IgG assay was selected as the representative immunoturbidimetry assay for the DxC 700 AU Clinical Chemistry Analyzer. In order to demonstrate the comparability between the predicate device, AU5800 and the candidate device, DxC 700 AU, the following performance testing was conducted on the IgG Assay:
- Method Comparison Linearity Sensitivity Reference Interval Interference In use (On board) & Calibrator Stability Precision Prozone Auto-dilution
All other immunoturbidimetric reagent applications will be validated using risk management, design controls, and FDA's Guidance for Industry and FDA staff -Replacement Reagent and Instrument Family Policy. The core validation principles are linearity, method comparison, precision, sensitivity, interference, reference interval, prozone tolerance and on-board/calibration frequency studies. Reference ranges will be verified.
9.0 Summary of Performance Data
The data contained in the Premarket Notification supports the substantial equivalence of the IqG reagent to the predicate IgG reagent already in commercial distribution. Equivalence is demonstrated through method comparison, linearity, imprecision and sensitivity experiments.
10.0 Conclusion
The IqG Reagent on the DxC 700 AU Clinical Chemistry Analyzer is identical in design and composition as the IgG Reagent on AU Systems cleared under K073490. Method comparison, linearity, sensitivity, reference interval, interference, precision, prozone, stability testing demonstrates that the assay performance is substantially equivalent between the candidate system and the predicate.
Substantial equivalence of the immunoturbidimetric assays has been demonstrated through performance of IgG. Performance testing conducted verifies that the device functions as intended and that design specifications have been satisfied.
This 510(k) summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.
§ 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).