The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGALC) Reagent, when used in conjunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin A in serum and cerebrospinal fluid by rate nephelometry.

Device Description

The IMMAGE® Low Concentration Immunoglobulin A (IGALC) Reagent and Cerebrospinal Fluid Calibrator are designed for optimal performance on the IMMAGE® Immunochemistry Systems. It is intended for the quantitative determination of immunoglobulin A in serum and cerebrospinal fluid.

AI/ML Overview

This is a premarket notification for new reagents and a calibrator for the Beckman Coulter IMMAGE Immunochemistry System, not a medical device in the typical sense of needing extensive clinical trials with human subjects. The acceptance criteria and performance data presented here are for the analytical performance of the diagnostic reagents.

Here's a breakdown of the requested information based on the provided document:

Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a separate section with numerical targets. Instead, it presents "Summary of Performance Data" including method comparison results (slope, intercept, correlation coefficient) and imprecision (CV%). The implicit acceptance criteria would be that these performance metrics demonstrate substantial equivalence to the predicate devices.

Here's the performance data as reported:

Method Comparison Data (Implicit Acceptance Criteria: Close to 1 for Slope, Close to 0 for Intercept, High Correlation Coefficient)

Test	N	Slope	Intercept	Mean (IGALC) mg/L	Mean (Predicate) mg/L	Correlation Coefficient
Serum: IMMAGE IGALC Reagent vs. IMMAGE IGA	50	0.973	91.02	2035	1999	0.984
CSF: IMMAGE IGALC Reagent vs. Behring N Latex IgA	50	1.056	0.56	6.59	5.72	0.991

Estimated IMMAGE System IGALC Reagent Imprecision (Serum) (Implicit Acceptance Criteria: Low %CV)

PRECISION	SAMPLE	N	MEAN (mg/L)	SD (mg/L)	% CV
Within-Run	Low	80	334	12.7	3.8
	Mid	80	1818	60.3	3.3
	High	80	2922	89.7	3.1
Total	Low	80	334	15.2	4.5
	Mid	80	1818	64.7	3.6
	High	80	2922	103.3	3.5

Estimated IMMAGE System IGALC Reagent Imprecision (CSF) (Implicit Acceptance Criteria: Low %CV)

PRECISION	SAMPLE	N	MEAN (mg/L)	SD (mg/L)	% CV
Within-Run	Low	80	5.06	0.188	3.7
	Mid	80	29.3	0.72	2.5
	High	80	59.8	2.29	3.8
Total	Low	80	5.06	0.208	4.1
	Mid	80	29.3	0.79	2.7
	High	80	59.8	2.70	4.5

1. A table of acceptance criteria and the reported device performance
See table above. As noted, the document doesn't explicitly state numerical acceptance criteria, but the presented data shows good correlation and low imprecision, which are typically the expected performance for analytical methods to demonstrate substantial equivalence.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size (Method Comparison): 50 samples for serum comparison, 50 samples for CSF comparison.
Sample Size (Imprecision): 80 samples for each of the low, mid, and high concentration levels for both serum and CSF imprecision studies (this implies 80 measurements were performed repeatedly on a single sample at each level to derive the SD and CV, not 80 unique patient samples).
Data Provenance: Not specified in the provided document. It is typical for such studies to be performed in a laboratory setting, often by the manufacturer or a contracted lab. The document does not indicate country of origin or whether the data was retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is an in vitro diagnostic (IVD) device for quantitative biochemical measurement, not an image-based diagnostic or clinical decision support system that would typically involve human experts for ground truth establishment.
The "ground truth" for the method comparison study is the measurement obtained from the predicate device.
For imprecision studies, the "ground truth" is the statistically derived mean value from repeated measurements.

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

Not applicable. This is an analytical performance study of an IVD reagent, not judgmental interpretation by human readers requiring adjudication.

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, not an AI-based diagnostic tool involving human readers or interpretation.

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

Yes, in a sense. The performance data presented (method comparison and imprecision) represents the "standalone" analytical performance of the IMMAGE system with the new reagents/calibrator, generating quantitative results. There is no human intervention in the result generation process itself, beyond operating the instrument and preparing samples.

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

Method Comparison: Measurements obtained from the legally marketed predicate device(s) were used as the reference or "ground truth" for comparison.
- For serum: IMMAGE Immunochemistry System Immunoglobulin A (IGA) Reagent (Beckman Instruments, Inc. K963868).
- For CSF: N Latex IgA Reagents (Behring Diagnostics, Inc. K952309).
Imprecision: The "ground truth" is based on the statistical mean of repeated measurements of samples at different concentration levels, indicating the inherent variability of the analytical method.

8. The sample size for the training set

The document does not explicitly mention a "training set" in the context of machine learning. For IVD reagents, development involves extensive R&D, formulation, and validation. The data presented here is the performance data used for regulatory submission. The predicate device data is effectively the "reference" against which the new device's performance is tested.

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

Not applicable in the context of a machine learning "training set". If referring to the development of the assay itself, the ground truth would involve established reference methods for IgA measurement and thorough biochemical characterization to ensure the reagent accurately detects and quantifies IgA. However, the document provided does not detail the reagent development process. For the purpose of showing substantial equivalence, the performance of the predicate device acts as the established comparison "ground truth."

Summary

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K99 3549

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Summary of Safety & Effectiveness Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGALC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

1.0 Submitted By:

Richard T. Ross Staff Regulatory Specialist, Product Submissions Beckman Coulter, Inc. 200 South Kraemer Blvd., W-104 Brea, California 92822-8000 Telephone: (714) 961-4912 FAX: (714) 961-4123

2.0 Date Submitted:

01 October 1999

3.0 Device Name(s):

Proprietary Names 3.1

Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGALC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

3.2 Classification Name

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

4.0 Predicate Device(s):

IMMAGE System	Serum Predicate	Manufacturer	Docket Number
IMMAGE System LowConcentrationImmunoglobulin A (IGALC)Reagent	IMMAGEImmunochemistrySystemImmunoglobulin A(IGA) Reagent	BeckmanInstruments,Inc.	K963868
Cerebrospinal Fluid ProteinCalibrator
	CSF Predicate	Manufacturer	Docket Number
	N Latex IgA Reagents	BehringDiagnostics,Inc*	K952309

*Westwood, MA 02090

5.0 Description:

Mailing Address: 200 S. Kraemer Boulevard P.O. Box 8000 Brea, CA 92822-8000

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6.0 Intended Use:

The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGMAC) Reagent, when used in conjunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin A in serum and cerebrospinal fluid by rate nephelometry.

7.0 Comparison to Predicate(s):

The following tables show similarities and differences between the predicate identified in Section 4.0 of this summary.

SIMILARITIES to the SERUM PREDICATE

SIMILARITIES to the SERUM PREDICATE
IMMAGE System	Aspect/Characteristic	Comments
IMMAGE System IGALC Reagent	Intended useRate nephelometry methodAntibody is goat antihuman IgA	Same asPredicatedevice
Cerebrospinal Fluid Protein Calibrator	Single level calibrator
SIMILARITIES to the CSF PREDICATE
IMMAGE System	Aspect/Characteristic	Comments
IMMAGE System IGALCReagent	Intended use and serum and CSF areacceptable sample typesReagent storage at 2°C to 8°C	Same as predicatedevice
IMMAGE Cerebrospinal FluidProtein Calibrator	Protein is of human serum originContains azide as a preservative
DIFFERENCES from the SERUM PREDICATE
IMMAGE System	Aspect/Characteristic	Comments
IMMAGE SystemIGALC Reagent	Serum or CSF as sample type	Predicate cleared for serum only
IMMAGECerebrospinal FluidProtein Calibrator	CSF CAL Cerebrospinal FluidCalibrator is a single level, humanurine base, azide preserved liquid	Predicate calibrator is a singlelevel, human serum based, azidepreserved liquid
DIFFERENCES from the CSF PREDICATE
IMMAGE System	Aspect/Characteristic	Comments
IMMAGE System IGALCReagent	IMMAGE System IGALC reactionis at a controlled 37°CAntibody source for IMMAGEIGALC is goatIMMAGE Reagent is liquid stable	Behring N Latex IgA reaction is atroom temperatureAntiserum source for Behring NLatex Reagent is rabbitBehring Reagent is lyophilized
IMMAGE Cerebrospinal	IMMAGE Cerebrospinal Fluid	Behring N IgA Standard is

8.0

Summary of Performance Data:

Fluid Protein Calibrator

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 and imprecision experiments.

Ivophilized

Beckman Coulter, Inc. IMMAGE® Low Concentration Immunoglobulin A (IGALC) Reagent Filename: igalcSSE.doc

Calibrator is liquid

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	IMMAGE IGALC ReagentSerumIMMAGE IGA	CSFBehring N Latex IgA
N	50	50
Slope	0.973	1.056
Intercept	91.02	0.56
Mean (IGALC) mg/L	2035	6.59
Mean (predicate) mg/L	1999	5.72
Correlation Coefficient	0.984	0.991

Estimated IMMAGE System IGALC Reagent Imprecision (Serum)

PRECISION	SAMPLE	N	MEAN (mg/L)	SD (mg/L)	% CV
Within-Run	Low	80	334	12.7	3.8
	Mid	80	1818	60.3	3.3
	High	80	2922	89.7	3.1
Total	Low	80	334	15.2	4.5
	Mid	80	1818	64.7	3.6
	High	80	2922	103.3	3.5

Estimated IMMAGE System IGALC Reagent Imprecision (CSF)

PRECISION	SAMPLE	N	MEAN(mg/L)	SD(mg/L)	% CV
Within-Run	Low	80	5.06	0.188	3.7
	Mid	80	29.3	0.72	2.5
	High	80	59.8	2.29	3.8
Total	Low	80	5.06	0.208	4.1
	Mid	80	29.3	0.79	2.7
	High	80	59.8	2.70	4.5

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

Beckman Coulter, Inc. IMMAGE® Low Concentration Immunoglobulin A (IGALC) Reagent Filename: igalcSSE.doc

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Image /page/3/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a circular design with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract emblem resembling an eagle or bird in flight, composed of three curved lines.

FEB 1 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Richard T. Ross Staff Regulatory Specialist Beckman Coulter, Inc. 200 S. Kraemer Boulevard, W-104 P.O. Box 8000 Brea, California 92622-8000

Re: K993549

Trade Name: IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGALC) Reagent Beckman Coulter " Cerebrospinal Fluid Protein Calibrator (CSF CAL) Regulatory Class: II Product Code: CFN Dated: December 20, 1999 Received: December 21, 1999

Dear Mr. Ross:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

This letter will allow you to begin marketing your device as described in your 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 your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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page of

99.354 510(k) Number (if known): Not yet assic

Device Name:

IMMAGE® Immunochemistry System Low Concentration Immunoglobulin A (IGALC) Reagent Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)

Indications for Use:

Clinical Significance:

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

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

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

(b) Classification. Class I I.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE-QN ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)
Signature
(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number	4995549
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Prescription Use (per 21 CFR 801.109)
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Over-the-Counter Use
Optional Format 1-2-96

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).