The Mono M Test is a qualitative enzyme immunoassay (EIA) that detects IgM antibodies to Paul-Bunnell heterophil, Epstein-Barr virus capsid antigen (EBV-VCA), and cytomegalovirus (CMV). When used in conjunction with Mono-G Test, it is as an aid in the serodiagnosis of infectious (EBV) mononucleosis and presumptive serodiagnosis of CMV mononucleosis-like syndrome.

This assay has not been FDA cleared or approved for the screening of blood or plasma donors. Performance with this device has not been established for either prenatal screening or newborn testing. Performance for this assay has not been established in a non-clinical laboratory environment (e.g., point of care testing).

Device Description

The product is an ELISA test method detecting heterophile, viral capsid antigen and cytomegalovirus IgM antibodies.

AI/ML Overview

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance (Table 5)
EBV Infectious Mononucleosis Sensitivity	High sensitivity required for diagnostic aid	98.8% (238/241) with Range 96-99.7%
EBV Infectious Mononucleosis Specificity	High specificity required for diagnostic aid	93% (42/45) with Range 93-99%
Mononucleosis Syndrome Sensitivity	High sensitivity required for diagnostic aid	98.7% (236/239) with Range 96-99.7%
Mononucleosis Syndrome Specificity	High specificity required for diagnostic aid	89% (42/47) with Range 77-96%
Precision (Qualitative Discrimination)	100% agreement for moderate and low antibody levels	100% for Heterophil (L1, L2), VCA IgM, CMV IgM (Table 6) and VCA IgG, EBNA IgG, CMV IgG (Table 7) for Moderate and Low levels, except for Toxoplasma IgG (85% at low)

Note: Explicit acceptance criteria are not stated in the provided text. The "Implicit" criteria are inferred from the context of a diagnostic aid device, which typically requires high sensitivity and specificity. The precision results, indicating 100% agreement in most cases, demonstrate excellent qualitative discrimination, which would be an implicit acceptance criterion.

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

Sample Size:
- EBV Performance (Combined Data - Table 3):
  - Negative: 42
  - Current: 33
  - Past/Recent: 204
  - Indeterminate: 16 (2+6+8)
  - Total (excluding Indeterminate for calculations in Table 5): 42 + 33 + 204 = 279 samples
- Overall Performance (Combined Data - Table 4):
  - Negative: 42
  - Current: 36
  - Past/Recent: 199
  - Indeterminate: 16 (2+6+8)
  - Total (excluding Indeterminate for calculations in Table 5): 42 + 36 + 199 = 277 samples
- Precision Test (Table 6 & 7): Varies by antibody level and analyte, ranging from 36 replicates to 144 replicates for different conditions.
Data Provenance: Prospective study. The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the study was conducted to support a U.S. market application. The study involved two sites (Site A and Site B).

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

The document does not provide information on the number of experts or their qualifications used to establish the "Reference Results" for the test set.

4. Adjudication Method for the Test Set

The document does not describe the adjudication method used for the test set.

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

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not mentioned. The device is an ELISA test for laboratory use, not an AI-assisted diagnostic imaging or interpretation system.

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

Yes, a standalone performance study was done. The ImmunoDOT Mono-M Test is an in vitro diagnostic (IVD) device (ELISA test) that generates results directly, which are then interpreted by laboratory personnel. The performance characteristics (sensitivity, specificity, precision) presented are for the device's standalone operation.

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

The ground truth for the performance study is referred to as "Reference Results" (Tables 1, 2, 3, 4). While the exact method for obtaining these reference results is not explicitly detailed, in the context of serodiagnosis for infectious diseases, these typically involve a combination of:

Confirmatory tests (e.g., Western blot, PCR)
Clinical diagnosis (symptoms, patient history)
Expert interpretation of other serological markers or a gold standard method for mononucleosis diagnosis.

Given the nature of the device, it is highly probable that the "Reference Results" represent a well-established serological or clinical gold standard for diagnosing mononucleosis.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of the study. This is typical for traditional in vitro diagnostic devices like ELISA assays, which do not typically involve machine learning or AI models with distinct training and test sets in the same way. The performance studies presented here are primarily for validation.

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

Not applicable, as a distinct training set (in the machine learning sense) and its ground truth establishment are not described for this device type.

Summary

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510(k) Summary

Contact	Bryan Kiehl
Address	GenBio15222-A Avenue of ScienceSan Diego, CA 92128
Telephone	(619) 592-9300 ext 309
FAX	(619) 592-9400
Email	Bryan@GenBio.com
Date:	17 September, 1998

DEVICE NAME	IMMUNODOT MONO M TEST
Common, usual, or classification name	Mononucleosis Test
Classification Number (if known)

Identification of the legally marketed device substantial equivalence is claimed: ImmunoDOT Infectious Mononucleosis Test, GenBio, San Diego, CA

Description of the new device:

The product is an ELISA test method detecting heterophile, viral capsid antigen and cytomegalovirus IgM antibodies.

Intended Use of New Device:

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Similarities and/or differences

ITEM	PREDICATE DEVICE	NEW DEVICE
Methodology	ELISA	ELISA
Specimen Type	Serum	Serum
Test Objective	Mononucleosis Serology	Mononucleosis Serology
Product type, e.g.,calibrator, control, kit	Kit	Kit
Intended Use	Mononucleosis Serodiagnosis	Mononucleosis Serodiagnosis
Other	EBV, CMV and toxoplasmainfections. IgG and IgM aredetected within one assay.	EBV, CMV and toxoplasmainfections. IgG and IgM aredetected separately butreported together.

Relative Performance

A prospective study was performed to assess assay performance. Site A information based on profile comparison is presented in Table 1. Site B information is shown in Table 2 and the combined data can be seen in Table 3.

	Reference Results
ImmunoDOT	Negative	Current	Past/Recent
Negative	33	0	1
Current	2	23	1
Past/Recent	0	1	112
Indeterminate	0	6	7

Table 1: Site A EBV Performance

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	Reference Results
ImmunoDOT	Negative	Current	Past/Recent
Negative	9	0	0
Current	1	10	1
Past/Recent	0	0	92
Indeterminate	2	0	1

Table 2: Site B EBV Performance

Table 3: EBV Performance Summary

	Reference Results
ImmunoDOT	Negative	Current	Past/Recent
Negative	42	0	1
Current	3	33	2
Past/Recent	0	1	204
Indeterminate	2	6	8

There was no toxoplasma IM cases identified during the prospective trial period. Two CMV mononucleosis cases at Site A and three CMV mononucleosis cases at Site B were observed. Three of the five sera from presumptive CMV mononucleosis cases were positive according to reference results. These CMV results are included in Table 4 as ImmunoDOT current positives and summarize overall ImmunoDOT performance.

ImmunoDOT	Negative	Current	Past/Recent
Negative	42	0	1
Current	5	36	2
Past/Recent	0	1	199
Indeterminate	2	6	8

Table 4: Overall Performance Summary

Using the above information, assay performance characteristics are shown in Table 5. Indeterminate results are not used for the calculations.

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	Sensitivity	SensitivityRange	Specificity	SpecificityRange
EBV Infectious Mononucleosis	98.8% (238/241)	96-99.7%	93% (42/45)	93-99%
Mononucleosis Syndrome	98.7% (236/239)	96-99.7%	89% (42/47)	77-96%

Table 5: Performance Characteristics

r a a

The intensity of the dot is directly related to precision. The darkest dots are most reliable while weaker reactions are proportionately less reliable. Site A and Site B laboratories were supplied masked specimens containing mixtures of the various analytes. Therefore, not all analytes tested the same number of replicates. Testing was conducted in triplicate each day. Tests were performed on six different days. The results are shown below. The results (Tables 12 and 13) show adequate qualitative discrimination for each analyte.

Table 6: ImmunoDOT Mono M Precision Results

Antibody Level	Level 1	Level 2	VCA IgM	CMV IgM
	Heterophil	Heterophil
Moderate	100%	100%	100%	100%
	(36/36)	(36/36)	(36/36)	(72/72)
Low	100%	100%	100%	100%
	(108/108)	(108/108)	(72/72)	(144/144)

Table 7: ImmunoDOT Mono G Precision Results

Antibody Level	VCA IgG	EBNA IgG	CMV IgG	Toxoplasma IgG
Moderate	100%(144/144)	100%(36/36)	100%(144/144)	100%(72/72)
Low	100%(72/72)	100%(144/144)	100%(72/72)	85%(122/144)

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Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird-like figure.

SEP 2 2 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Bryan L. Kiehl, Ph.D. Vice President GenBio 15222 Avenue of Science, Suite A San Diego, California 92128

Re : K974244/S2 Trade Name: ImmunoDOT Mono-M Regulatory Class: I Product Code: LSE Dated: July 7, 1998 Received: July 8, 1998

Dear Dr. Kiehl:

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 reqistration, listing of devices, qood 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 Requlations, 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, of growisi or other Federal laws or regulations. " receive and

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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 requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 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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Indications for Use

510(k) Number (if known):

Device Name: ImmunoDOT Mono-M

Indications for Use:

The Mono M Test is a qualitative enzyme immunoassay (EIA) that detects IdM antibodies to Paul-Bunnell heterophil, Epstein-Barr virus capsid antigen (EBV-VCA), and cytomegalovirus (CMV). When used in conjunction with Mono-G Test, it is as an aid in the serodiagnosis of infectious (EBV) mononucleosis and presumptive serodiagnosis of CMV mononucleosis-like syndrome.

(Please do not write below this line - Continue on another page if needed) Concurrence of CDRH, Office of Device Evaluation (ODE)

Wordy Dubois

Regulation Number and Section

§ 866.3235 Epstein-Barr virus serological reagents.

(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).