IMMAGE® Immunochemistry Systems IGMLC Reagent, when used in conjunction with IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for quantitative determination of immunoglobulin M in human serum or cerebrospinal fluid (CSF) by rate nephelometry.

CSF Cal (Cerebrospinal Fluid Protein Calibrator), when used in conjunction with Beckman Coulter Low Concentration Immunoglobulin A (IGALC) and Low Concentration Immunoglobulin M (IGMLC) reagents is intended for use on Immage for the calibration of these reagents.

Device Description

The IMMAGE System Low Concentration Immunoglobulin M (IGMLC) Reagent, when used in conjunction with IMMAGE Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator is intended for the quantitative determination of human Immunoglobulin M in serum and cerebrospinal fluid (CSF) by rate nephelometry.

The IMMAGE Immunochemistry System (cleared under K962294) is a high throughput, random access analyzer that uses rate nephelometry methodology to measure human immunoglobulin M concentration in serum and CSF samples. The IMMAGE Immunochemistry System automatically dilutes and delivers sample to the reaction cuvette along with reagents and other reaction constituents.

During the reaction, particle bound anti-IgM antibody binds to IgM molecules in the sample via an antigen-antibody reaction. This results in the formation of insoluble complexes causing an increase in light scatter. The rate of increase in light scattered from the particles suspended in solution is directly proportional to the concentration of immunoglobulin M in the sample.

The rate nephelometer measures the increase in the intensity of light scattered by particles suspended in a cuvette. The light source for the rate nephelometer is a 670 nm wavelength laser. The detector is placed at a 90° angle from the incident beam to measure light increase. At the end of the reaction, the system mathematically calculates the rate of change of the scatter signal.

AI/ML Overview

Here's an analysis of the acceptance criteria and study as requested, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Sample Type	Acceptance Criteria	Reported Device Performance	Result
Method Comparison
Slope	CSF	1.0 +/- 0.10	0.963	Pass
Intercept	CSF	< 0.075 mg/L	-0.133 mg/L	Pass
R	CSF	>= 0.95	0.997	Pass
Slope	Serum	1.0 +/- 0.10	1.048	Pass
Intercept	Serum	N/A	5.70	Pass
R	Serum	>= 0.95	0.997	Pass
Precision			(See detailed results below)	Pass
CSF1 Mean	CSF	N/A	0.196 mg/L	N/A
CSF1 Total CV	CSF	N/A	15.64%	N/A
CSF2 Mean	CSF	N/A	2.49 mg/L	N/A
CSF2 Total CV	CSF	N/A	2.85%	N/A
CSF3 Mean	CSF	N/A	8.81 mg/L	N/A
CSF3 Total CV	CSF	N/A	4.30%	N/A
Serum1 Mean	Serum	N/A	38.5 mg/L	N/A
Serum1 Total CV	Serum	N/A	10.84%	N/A
Serum2 Mean	Serum	N/A	1250.1 mg/L	N/A
Serum2 Total CV	Serum	N/A	2.85%	N/A
Serum3 Mean	Serum	N/A	1935.8 mg/L	N/A
Serum3 Total CV	Serum	N/A	3.28%	N/A

Note: The document only provides Acceptance Criteria for the Method Comparison study. Although detailed precision results are reported, explicit acceptance criteria for these were not stated in the provided text. The document generally states that "Equivalence is demonstrated through method comparison, linearity, and imprecision, and sensitivity experiments," implying the precision results were considered acceptable for demonstrating substantial equivalence.

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

Sample Size for Method Comparison: 80 for CSF and 80 for Serum.
Sample Size for Precision Study: Each of the 6 samples (3 CSF, 3 Serum) was tested 80 times ("N = 80"). This likely indicates 80 replicates per sample.
Data Provenance: Not explicitly stated. The document does not specify the country of origin of the data or whether it was retrospective or prospective.

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

This information is not provided in the document. The device is a quantitative immunoassay system, and the ground truth for such devices is typically established by reference methods or standards, not by expert interpretation. The term "ground truth" as it relates to expert consensus is usually applicable to diagnostic imaging or pathology, which is not the case here.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided in the document. Adjudication methods (e.g., 2+1, 3+1) are typically used in studies where human readers are interpreting images or clinical data, and their interpretations need to be reconciled to establish a consensus ground truth. This device is a fully automated immunoassay system that provides quantitative 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

This information is not provided and is not applicable to this device. An MRMC study with human readers assisting or being assisted by AI is relevant to diagnostic interpretation (e.g., radiology AI). This device is a laboratory instrument that quantifies immunoglobulin levels; it does not involve human interpretive reading in the same way.

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

Yes, this is a standalone device performance study. The IMMAGE® Immunochemistry System is an automated system designed to quantitatively determine human Immunoglobulin M levels. The studies described (method comparison, linearity, imprecision, sensitivity) assess the performance of the algorithm/instrument system itself, without human intervention in the primary measurement process.

7. The type of Ground Truth Used

The ground truth for the method comparison study was established by comparing the results of the modified device to the "current assay" (which is the predicate device, K993547). The clinical significance section also refers to established medical literature and standards. Specifically, for calibrator traceability, it mentions improved traceability to the international standard, ERM-DA-470(k)-IFCC. Therefore, the ground truth is based on:

Comparison to a legally marketed predicate device/current assay
Traceability to an international standard (for calibrator)

8. The Sample Size for the Training Set

This information is not provided in the document. The term "training set" is typically used in the context of machine learning or AI algorithm development. This submission describes a re-submission of an established immunoassay system with optimizations (e.g., reagent curve fit, analytical range, traceability). While there might have been internal studies or data used to refine these optimizations, the document does not refer to them as "training sets" in the AI sense, nor does it specify their size.

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

This information is not provided and is not directly applicable in the context of "training set" as understood in AI/ML. As mentioned above, the submission focuses on verifying the performance of an optimized immunoassay system against an existing predicate and international standards, rather than training a novel AI algorithm.

Summary

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510(k) SUMMARY

1.0 Submitted By:

Amanda Brown Regulatory Affairs Specialist Beckman Coulter, Inc. 250 S. Kraemer Boulevard M/S E1.2902 Brea, California 92821 Telephone: (714)961-6484 Email: abrown2@beckman.com

2.0 Date Submitted:

December 19, 2013

3.0 Device Name(s):

3.1 Proprietary Names

IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent IMMAGE® Immunochemistry System Cerebrospinal Fluid Protein Calibrator (CSF CAL)

3.2 Classification Name

Method, Nephelometric, Immunoglobulins (G, A, M) (21 CFR § 866.5510) [CFN]

Calibrator, multi-analyte mixture (21 CFR § 862.1150) [JIX]

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	DocketNumber
Beckman CoulterIMMAGE®ImmunochemistrySystem LowConcentrationImmunoglobulin M(IGMLC) Reagent	Beckman CoulterIMMAGE®Immunochemistry SystemLow ConcentrationImmunoglobulin M(IGMLC) Reagent	Beckman Coulter,Inc.	K993547
Beckman CoulterCerebrospinal FluidProtein Calibrator (CSFCAL)	Beckman CoulterCerebrospinal FluidProtein Calibrator (CSFCAL)

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5.0 Description:

6.0 Intended Use:

Clinical Siqnificance:

The concentration ratio of immunoglobulins in CSF and serum detects increased permeability of the blood-CSF barrier and intrathecal synthesis of immunoqlobulins. 1.2

The permeability of the blood-CSF barrier to plasma increases due to brain tumor, intracerebral hemorrhage, meningitis, encephalitis, and bacterial infections. The intrathecal synthesis of immunoglobulins is important in the diagnosis of diseases of the Central Nervous System (CNS) 3

European Neurology 1996; 36; 201-205 1.
ﻨ Journal of the Neurological Sciences 184 (2001) 101-122
Burtis, C. A., Ashwood, E. R., Tietz, Texbook of Clinical Chemistry, 3rd Edition, W. B. 3. Saunders, Philadelphia, PA (1999). '

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7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicate identified in Section 4.0 of this summary. Each modification was evaluated against the criteria for a Special 510(k) to insure that the particular change does not: (1) affect the intended use or (2) alter the fundamental scientific technology of the device.

Similarities
IMMAGEIGMLCReagent	Intended UseReagent formulationCalibrator formulationTechnologyMethodologyKit configurationSpecimen typesStabilityReference IntervalPrecision specificationInterferences
Differences
IMMAGEIGMLCReagent	Reagent curve fit optimizationSensitivity	Additional standards added to the low end of the curve.Current:CSF: 0.3 mg/LSerum: 64.8 mg/L	New:0.15 mg/L32.4 mg/L
	Calibratortraceability	Improved traceability to the international standard,ERM-DA-470(k)-IFCC.
	AnalyticalRange	Current:CSF 0.3-10 mg/LSerum 64.8-2160 mg/L	New:0.15 - 10 mg/L32.4 - 2160 mg/L
	ImprecisionValue	Included CSF typical imprecision with samplemean concentration between 0.15-0.30 mg/L andupdated low end serum sample with meanconcentration between 32.4-64.8 mg/L
	Equivalency	Current:CSF: Concordance to IFE method (obsolete)Serum: Comparison to IGM assayNew:CSF: Comparison to current assaySerum: Comparison to current assay

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8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, linearity, and imprecision, and sensitivity experiments.

Sample Type	AcceptanceCriteria	N	R	Slope	Intercept	Result
CSF	Slope: 1.0 +/- 0.10Intercept: < 0.075mg/LR: ≥0.95	80	0.997	0.963	-0.133	Pass
Serum	Slope: 1.0 +/- 0.10Intercept: N/AR: ≥ 0.95	80	0.997	1.048	5.70	Pass

Method Comparison Study Results

Precision Study Results
Sample	N	Mean(mg/L)	Within-RunPrecisionSD / %CV	Between RunPrecisionSD / %CV	Between DayPrecisionSD / %CV	TotalPrecisionSD / %CV
CSF1	80	0.196	0.03 mg/L16.55%	0 mg/L0%	0.01 mg/L4.57%	0.03 mg/L15.64%
CSF2	80	2.49	0.05 mg/L2.07%	0.06 mg/L2.22%	0 mg/L0%	0.07 mg/L2.85%
CSF3	80	8.81	0.29 mg/L3.25%	0.29 mg/L3.32%	0 mg/L0%	0.38 mg/L4.30%
Serum 1	80	38.5	3.84 mg/L9.99%	0.69 mg/L1.80%	1.46 mg/L3.81%	4.17 mg/L10.84%
Serum2	80	1250.1	28.87 mg/L2.31%	21.33 mg/L1.71%	0 mg/L0%	35.59 mg/L2.85%
Serum3	80	1935.8	55.23 mg/L2.85%	29.58 mg/L1.53%	10.23 mg/L0.53%	63.48 mg/L3.28%

OLLI D

Conclusion:

As summarized, the modification to the iMMAGE IGMLC Reagent is substantially equivalent to the originally cleared product (K993547). Substantial equivalence has been demonstrated through performance to verify 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.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 7, 2014

BECKMAN COULTER. INC. C/O MS. AMANDA BROWN REGULATORY AFFAIRS SPECIALIST 250 S. KRAEMER BLVD M/S E1.2902 BREA, CA 92821

Re: K130122

Trade/Device Name: IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent IMMAGE® Immunochemistry Systems CSF-CAL Cerebrospinal Fluid Protein Calibrator

Regulation Number: 21 CFR § 866.5510 Regulation Name: Immunoglobulins A, G, M, D, and E immunological test system Regulatory Class: II Product Code: CFN, JIX Dated: December 2, 2013 Received: December 3, 2013

Dear Ms. Brown:

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

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Page 2 - Ms. Amanda Brown

comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the 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 Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Maria.M.Chan -S

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K130122

Device Name

IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent

Indications for Use (Describe)

IMMAGE® Immunochemistry Systems IGMLC Reagent, when used in conjunction with IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for quantitative determination of Immunoglobulin M (IGMLC) in human serum or cerebrospinal fluid (CSF) by rate nephelometry.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Image /page/6/Picture/13 description: The image shows the name "Elizabeth FDA Stafford -S" in a bold, sans-serif font. The word "Elizabeth" is on the left, followed by the letters "FDA" in a decorative, stylized font. The name "Stafford" is to the right of "FDA", and the letter "S" is on the far right.

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K130122

Device Name

IMMAGE® Immunochemistry Systems CSF-CAL Cerebrospinal Fluid Protein Calibrator

Indications for Use (Describe)

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Image /page/7/Picture/13 description: The image shows the name "Elizabeth A Stafford -S" in black font. The "A" is stylized with a pattern inside the letter. The text is horizontally oriented and appears to be a signature or nameplate.

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

Regulation Number and Section

§ 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).