(105 days)
The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) 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 M in serum and cerebrospinal fluid by rate nephelometry.
The IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent and Cerebrospinal Fluid Calibrator are designed for optimal performance on the IMMAGE® Immunochemistry Systems. It is intended for the quantitative determination of immunoglobulin M in serum and cerebrospinal fluid.
Device Acceptance Criteria and Performance Study: Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent
This response describes the acceptance criteria and the study that proves the Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent meets these criteria, based on the provided K993547 Summary of Safety & Effectiveness.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined "acceptance criteria" in a typical quantitative format (e.g., "slope must be between X and Y"). Instead, it reports performance data for method comparison and imprecision studies, indicating that these results demonstrate "substantial equivalence" to existing commercial distribution test systems.
Therefore, the "acceptance criteria" are inferred from the reported performance characteristics that were deemed sufficient for demonstrating substantial equivalence. The reported device performance is directly from the provided text.
Inferred Acceptance Criteria based on Predicate Equivalence and Reported Performance:
| Performance Metric | Implied Acceptance Criteria (Demonstrates Substantial Equivalence and Acceptable Performance) | Reported Device Performance (IMMAGE IGMLC) |
|---|---|---|
| Serum Method Comparison | ||
| N | Sufficient sample size for statistical significance | 55 |
| Slope | Close to 1 (indicating proportional agreement with predicate) | 0.977 |
| Intercept | Close to 0 (indicating lack of constant bias with predicate) | 9.12 |
| Mean (IGMLC) | Comparable to predicate mean | 1039 mg/L |
| Mean (Predicate) | Comparable to IGMLC mean | 1054 mg/L |
| Correlation Coefficient | High (indicating strong linear relationship with predicate) | 0.988 |
| CSF Study Results (Qualitative equivalence focus) | ||
| N | Sufficient sample size for statistical significance | 51 (originally 51, then 45 for true positive, 6 for true negative) |
| Sensitivity % | High (indicating ability to correctly identify positive cases) | 100% |
| Specificity % | High (indicating ability to correctly identify negative cases and avoid false positives) | 89.5% (initial) / 100% (after adjustment or for a specific condition) |
| False Positives | Low (ideally 0) | 6 (initial) / 0 (after adjustment or for a specific condition) |
| False Negatives | Low (ideally 0) | 0 |
| Estimated Imprecision (Serum) | ||
| Within-Run % CV | Low (indicating good reproducibility within a single run) | Low: 3.2%, Mid: 1.7%, High: 1.8% |
| Total % CV | Low (indicating good overall reproducibility) | Low: 3.5%, Mid: 2.5%, High: 2.0% |
| Estimated Imprecision (CSF) | ||
| Within-Run % CV | Low (indicating good reproducibility within a single run) | Low: 5.2%, Mid: 2.0%, High: 2.1% |
| Total % CV | Low (indicating good overall reproducibility) | Low: 6.0%, Mid: 4.1%, High: 3.5% |
2. Sample Size Used for the Test Set and Data Provenance
- Serum Study (Method Comparison):
- Sample Size: N = 55
- Data Provenance: Not explicitly stated (e.g., country of origin). It is considered retrospective as it compares the new device's results to a predicate device's results on existing samples.
- CSF Study (Qualitative Evaluation):
- Sample Size: N = 51 (initial reported N for study), with further breakdown for "Test Positive" (51) and "Test Negative" (45+6=51).
- Data Provenance: Not explicitly stated (e.g., country of origin). It is considered retrospective as it evaluates an existing dataset or samples against a reference.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not mention the use of "experts" to establish ground truth in the context of radiologists or similar clinical reviewers.
For this type of in vitro diagnostic device (quantitative determination of immunoglobulin M), "ground truth" is typically established by:
- Serum Study: Comparison to a predicate device/method. The predicate device itself acts as the reference for comparison, implying its established accuracy.
- CSF Study: The reference for "positive" or "negative" status would likely be derived from the predicate method or a clinically accepted reference standard, not from human expert interpretation in the traditional sense. The document refers to "Test Positive" and "Test Negative," which implies a defined reference standard was used to classify samples.
Therefore, the concept of "number of experts" and their "qualifications" as it applies to image interpretation or clinical diagnosis by human experts is not directly applicable here.
4. Adjudication Method for the Test Set
Not applicable. As described in point 3, the ground truth for these types of studies (method comparison, imprecision) is typically based on a predicate device/method or established quantitative benchmarks, not on human adjudication of subjective interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No. An MRMC comparative effectiveness study is not applicable to this type of in vitro diagnostic device (reagent for quantitative measurement). MRMC studies are typically used to assess the effectiveness of diagnostic imaging devices or algorithms that involve human interpretation of images or other complex data.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, in essence. The studies described are standalone performance evaluations of the IMMAGE® Immunochemistry System IGMLC Reagent and CSS CAL. The device itself performs the quantitative determination by "rate nephelometry," and the results are reported directly. There is no human "in-the-loop" interpretation step that the device is assisting (e.g., flagging areas on an image for a radiologist). The performance metrics (slope, intercept, correlation, sensitivity, specificity, imprecision) are all measures of the device's inherent analytical performance.
7. The Type of Ground Truth Used
- Serum Method Comparison: The ground truth was established by the predicate device/method (IMMAGE Immunochemistry Systems Immunoglobulin M (IGM) Reagent). The new device's measurements were compared against those obtained from the predicate.
- CSF Study: The ground truth for classifying "positive" or "negative" cases for the CSF study was likely based on a clinical reference standard or the predicate method's results for CSF analysis, if applicable. The details for this specific classification are not explicitly provided beyond the "Test Positive" and "Test Negative" categories.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or "training data" for this device. For in vitro diagnostic reagents like this, the development process might involve internal optimization and validation studies that could be considered analogous to training, but it's not typically reported in terms of a distinct "training set" like in machine learning applications. The studies reported here are for performance validation rather than model training.
9. How the Ground Truth for the Training Set was Established
As no specific "training set" is mentioned in the provided document, the method for establishing its ground truth is also not described.
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Image /page/0/Picture/2 description: The image shows the logo for Beckman Coulter. The logo consists of a circular graphic on the left and the company name on the right. The graphic is a stylized image of two curved lines within a circle. The text "BECKMAN COULTER" is written in bold, sans-serif font.
Summary of Safety & Effectiveness Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) 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):
3.1 Proprietary Names
Beckman Coulter IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) 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 SystemLow ConcentrationImmunoglobulin M(IGMLC) ReagentCerebrospinal FluidProtein Calibrator | IMMAGEImmunochemistrySystemsImmunoglobulin M(IGM) Reagent | BeckmanInstruments, Inc. | K963868 |
| CSF Predicate | Manufacturer | Docket Number | |
| Paragon®ImmunofixationElectrophoresis Reagent | BeckmanInstruments, Inc. | K823884 |
5.0 Description:
The IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent and Cerebrospinal Fluid Calibrator are designed for optimal performance on the IMMAGE® Immunochemistry Systems. It is intended for the quantitative determination of immunoglobulin M in serum and cerebrospinal fluid.
6.0 Intended Use:
The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) Reagent, when used in coniunction with Beckman Coulter's IMMAGE® Immunochemistry Systems and Cerebrospinal Fluid Protein Calibrator, is intended for the quantitative determination of human immunoglobulin M in serum and cerebrospinal fluid by rate nephelometry.
Mailing Address: 200 S. Kraemer Boulevard P.O. Box 8000 Brea, CA 92822-8000
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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
| IMMAGE System | Aspect/Characteristic | Comments |
|---|---|---|
| IMMAGE System IGMLC Reagent | Intended use | Same asPredicatedevice |
| Rate nephelometry method | ||
| Antibody is goat antihuman IgM | ||
| Cerebrospinal Fluid Protein Calibrator | Single level calibrator | |
| SIMILARITIES to the CSF PREDICATE | ||
| IMMAGE System | Aspect/Characteristic | Comments |
| IMMAGE System IGMLC | Intended use | Same as predicate device |
| Reagent | Serum and CSF are acceptable sample types | |
| Antibody is goat antihuman IgM | ||
| Cerebrospinal Fluid ProteinCalibrator | Single level calibrator | N/A |
| Protein is of human serum originadded to human urine base | Predicate hasno calibrator |
DIFFERENCES from the SERUM PREDICATE
| IMMAGE System | Aspect/Characteristic | Comments |
|---|---|---|
| IMMAGE SystemIGMLC Reagent | Serum or CSF as sample type | Predicate cleared for serum only |
| CSF CAL | CSF CAL Cerebrospinal FluidCalibrator is a single level,human urine base, azidepreserved liquid | Predicate calibrator is a singlelevel, human serum based, azidepreserved liquid |
DIFFERENCES from the CSF PREDICATE
| IMMAGE System | Aspect/Characteristic | Comments |
|---|---|---|
| IMMAGE SystemIGMLC Reagent | IMMAGE System IGMLC isa rate nephelometric reactionat a controlled 37°C | Predicate is a gel immunofixationelectrophoresis at roomtemperature |
| IMMAGE SystemIGMLC Reagent | IMMAGE System providesquantitative result based oncalibration curve | Qualitative result based on visualcomparison to known controls |
| IMMAGE SystemIGMLC Reagent | Sample may be loadedand/or run neat without pre-analysis concentration | Sample concentration typicallyrequired prior to IFE analysis |
| CSF CAL | Single level calibrator | Predicate has no calibrator |
Beckman Coulter, Inc. IMMAGE® Low Concentration Immunoglobulin M (IGMLC) Reagent Filename: igmlcSSE2.doc
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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 and imprecision experiments.
| Serum Study Results | CSF Study Results | ||
|---|---|---|---|
| N | 55 | N | 51 51 |
| Slope | 0.977 | Test Positive | 51 45 |
| Intercept | 9.12 | Test Negative | 0 6 |
| Mean (IGMLC) mg/L | 1039 | False Positives | 6 0 |
| Mean (predicate) mg/L | 1054 | False Negative | 0 0 |
| Correlation Coefficient | 0.988 | Sensitivity % | 100 100 |
| Specificity % | 89.5 100 | ||
| % sensitivity = (N/(N + false negative))*100 | |||
| % specificity = (N/(N + false positive))*100 |
Method Comparisons
Estimated IMMAGE System IGMLC Reagent Imprecision (Serum)
| PRECISION | SAMPLE | N | MEAN (mg/L) | SD (mg/L) | % CV |
|---|---|---|---|---|---|
| Within-Run | Low | 80 | 173 | 5.4 | 3.2 |
| Within-Run | Mid | 80 | 869 | 14.6 | 1.7 |
| Within-Run | High | 80 | 1779 | 31.8 | 1.8 |
| Total | Low | 80 | 173 | 6.1 | 3.5 |
| Total | Mid | 80 | 869 | 21.8 | 2.5 |
| Total | High | 80 | 1779 | 35.5 | 2.0 |
Estimated IMMAGE System IGALC Reagent Imprecision (CSF)
| PRECISION | SAMPLE | N | MEAN (mg/L) | SD (mg/L) | % CV |
|---|---|---|---|---|---|
| Within-Run | Low | 80 | 0.536 | 0.0279 | 5.2 |
| Within-Run | Mid | 80 | 4.77 | 0.096 | 2.0 |
| Within-Run | High | 80 | 8.61 | 0.182 | 2.1 |
| Total | Low | 80 | 0.536 | 0.0320 | 6.0 |
| Total | Mid | 80 | 4.77 | 0.197 | 4.1 |
| Total | High | 80 | 8.61 | 0.299 | 3.5 |
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 M (IGMLC) Reagent Filename: igmlcSSE.doc
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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing right, with flowing lines representing hair or clothing.
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: K993547
Trade Name: IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) 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 (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS 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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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 Putman
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 _
510(k) Number (if known): Not yot assigned
Device Name:
IMMAGE® Immunochemistry System
Low Concentration Immunoglobulin M (IGMLC) Reagent
Beckman Coulter™ Cerebrospinal Fluid Protein Calibrator (CSF CAL)
Indications for Use:
The IMMAGE® Immunochemistry System Low Concentration Immunoglobulin M (IGMLC) 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 M in serum and cerebrospinal fluid by rate nephelometry.
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 hemorrhage, 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 II.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
| 510(k) Number | K993547 |
|---|---|
| --------------- | --------- |
| Prescription Use (per 21 CFR 801.109) | ✓ | OR | Over-the-Counter Use |
|---|---|---|---|
| Optional Format 1-2-96 |
§ 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).