The Bartels CINAkit™ CMV Antigenemia Test is intended for use as an aid in the diagnosis of Cytomegalovirus (CMV) infection by the rapid direct qualitative detection of CMV pp65 antigen in human blood leukocytes by indirect immunofluorescence (IF). This product is not intended to be used for testing (i.e. screening) blood or plasma donors.

Device Description

BARTELS CINAKIT CMV Antigenemia is an indirect immunofluorescence test that allows detection of Human Cytomegalovirus antigen in leukocytes from peripheral blood. The test uses a monoclonal antibody pool (1C3, AYM-1) which recognizes the 65-68kDa lower matrix structural phosphoprotein (pp) (protein kinase, pp65, present in the nucleus of cells. The antibody pool (blended antibodies) recognizes two epitopes on the protein. Leukocytes are prepared from whole blood by dextran sedimentation and centrifugation; slides are prepared, fixed in formalin and permeabilized on detergent (NP40). Staining is accomplished with primary murine monoclonal antibodies to the pp65 antigen and F(Ab-)2 fluorescein-conjugated anti-mouse immunoglobulin secondary antibody. The slides are read using a fluorescence microscope.

AI/ML Overview

This document describes the Bartels CINAkit CMV Antigenemia test, an immunoassay for the detection of CMV.

Here's a breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly based on demonstrating substantial equivalence to the predicate device, the BIOTEST CMV BRITE TEST Kit. The performance characteristics of both devices are directly compared.

Performance Characteristic	Acceptance Criteria (Predicate Device: Biotest CMV Brite)	Reported Device Performance (Bartels CINAkit CMV Antigenemia)
Sensitivity	82.86%	83% (95% CI: 70.4 - 95.3%)
Specificity	87.33%	89% (95% CI: 85.1 - 92.3%)
Accuracy	86.87%	88.06% (Implicit from Sensitivity and Specificity)

Note: The reported device performance for Bartels CINAkit CMV Antigenemia is presented in two places:

In Table 1, where it lists "Sensitivity: 82.86%, Specificity: 88.67%, Accuracy: 88.06%".
In the "Performance Characteristics 2." section, based on the clinical study, where it details "Sensitivity = 29/35 = 83% (95% Confidence interval = 70.4 - 95.3%)" and "Specificity = 266/300 = 89% (95% Confidence interval = 85.1 - 92.3%)". For the purpose of this table, the values from the clinical study are generally considered the primary performance claims. The values in Table 1 might represent initial expectations or a summary, but the detailed clinical study data provides the specific numbers that are directly supported.

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

Sample Size: 335 clinical specimens.
Data Provenance: The document does not explicitly state the country of origin. It refers to "clinical specimens" and a "clinical study" but does not specify if it was retrospective or prospective. Given the nature of medical device submissions, it's typically a prospective collection of real-world samples to validate performance, but this is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth and Qualifications

The ground truth was established by a "culture method," referred to as the "gold standard." This typically implies laboratory testing and interpretation by trained microbiologists or laboratory technicians rather than clinical experts (e.g., radiologists) in the context of imaging. The document does not specify the number of experts or their qualifications for interpreting the culture results.

4. Adjudication Method

Not applicable. The ground truth was established by a "gold standard" culture method, not through adjudication of expert opinions on the test specimens themselves.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly mentioned or performed. This is a diagnostic kit for laboratory use, not typically a device that involves multiple human readers interpreting images against an AI. The "comparison" mentioned is between the Bartels CINAkit and "Other CMV" (the predicate device) in terms of their performance against a gold standard, not a human-in-the-loop study with AI assistance.

6. Standalone Performance Study

Yes, a standalone performance study was clearly done. The Bartels CINAkit CMV Antigenemia device was evaluated by comparing its results against the "gold standard" culture method on 335 clinical specimens. The reported sensitivity and specificity are for the algorithm (kit) acting alone, without overt human-in-the-loop assistance for interpretation. The interpretation of the immunofluorescence slides by a fluorescence microscope would still involve a human reading the results of the kit-prepared slides.

7. Type of Ground Truth Used

Expert Consensus, Pathology, or Outcomes Data: The type of ground truth used was the culture method, which is explicitly stated as the "gold standard." This implies a microbiology laboratory culture result, which is considered highly reliable for detecting viral presence.

8. Sample Size for the Training Set

The document does not provide information about a separate training set. It describes a single "clinical study" involving 335 specimens for performance evaluation. For immunoassay kits like this, the development process might involve internal validation and optimization, but a distinct "training set" in the context of machine learning is not applicable here.

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

As there is no distinct "training set" described in the context of a machine learning-based device, this question is not applicable. The performance evaluation study used the culture method as the gold standard for its 335 specimens.

Summary

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6.0 510(K) SUMMARY

Name of Device and Classification (A)

Tradename: Bartels CINAkit CMV Antigenemia

Classification: Cytomegalovirus indirect immunofluorescence assay that consists of antisera which has been classified as a Class II (Performance Standards) device, product code, 834N, (21 CFR 866.3175).

(B) Legally Marketed Device

BARTELS CINAKIT CMV Antigenemia claims substantial equivalance to the BIOTEST CMV BRITE TEST Kit (K951550), currently in commercial distribution by BIOTEST Diagnostics, Denville, New Jersey (USA).

Device Description (C)

Leukocytes are prepared from whole blood by dextran sedimentation and centrifugation; slides are prepared, fixed in formalin and permeabilized on detergent (NP40). Staining is accomplished with primary murine monoclonal antibodies to the pp65 antigen and F(Ab-)2 fluorescein-conjugated anti-mouse immunoglobulin secondary antibody. The slides are read using a fluorescence microscope.

The substantial equivalence claim between Bartels CINAkit CMV Antigenernia and Biotest CMV Brite Test is based on the attached comparison table (Table 1) and clinical study data

BARTELS CINAKIT CMV Antigenemia Method :

Isolation of peripheral blood leukocytes 1.
1. Preparation of cytospin slides
ತೆ. Fixation and permeabilization
1. Indirect immunofluorescence staining using anti CMV pp65
1. Interpretation of results

Leukocytes are isolated from whole blood by dextran sedimentation of erythrocytes and centrifugation of leukocytes followed by hypotonic lysis of residual erythrocytes with

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ammonium chloride. Slides are prepared fixed in formalin and permeabilized with detergent. Staining is accomplished with primary murine monoclonal antibodies to the pp65 antigen and F(Ab)2 fluorescein-conjugated anti-mouse immunoglobulin secondary antibody. The slides are read using a fluorescence microscope.

Immunofluorescence is the preferred method of staining. It has been reported that techniques used to block endogenous enzymatic activity (peroxidase or alkaline phosphatase) can destroy the antigen recognized in antigenemia. Bartels' blended antibody preparation targets different epitopes on the pp65 antigen and thus ensures avoidance of false negatives that may be caused by mutation of one of the epitopes recognized. This anti-pp65 preparation stains cells in positive samples.

(D) Intended Use

Bartels CINAkit CMV Antigenemia is intended for use as an aid in the diagnosis of Cytomegalovirus (CMV) infection by the rapid direct qualitative detection of CMV pp65 antigen in human blood leukocytes by indirect immunofluorescence (IF). This product is not intended to be used for testing (i.e. screening) blood or plasma donors.

(E) Comparison with the Predicate Device

TABLE 1

Product Name	Bartels CINAkit CMVAntigenemia	Biotest CMV Brite
Intended Use Statement	"Bartels CINAkit CMVAntigenemia is intended for use asan aid in the diagnosis ofCytomegalovirus (CMV) infectionby the rapid direct qualitativedetection of CMV pp65 antigen inhuman blood leukocytes by indirectimmunofluorescence (IF). Thisproduct is not intended to be usedfor testing (i.e. screening) blood orplasma donors."	"The Biotest CMV Brite Test Kit isintended for the qualitativedetection of Cytomegalovirus(CMV) lower matrix protein pp65by indirect immunofluorescenceusing microscopy in isolatedperipheral blood leukocytesobtained fromethylenediaminetetraacetic acid(EDTA) and heparin anticoagulatedhuman peripheral blood. Thedetection of CMV pp65 in humanperipheral blood cells aids in thediagnosis of acute or reactivatedCMV infection. This product is notFDA cleared (approved) for use intesting (i.e. screening) of blood orplasma donors."

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Target Population	Individuals suspected of acute or reactivated CMV infection.	Individuals suspected of acute or reactivated CMV infection.
Design/format	Indirect immunofluorescence assay (IFA)	Indirect immunofluorescence assay (IFA)
Materials	Cocktail (2) of murine monoclonal antibodies (CINA pool, 1C3/AYM-1) against lower matrix structural phospoprotein (pp65), FITC-conjugated secondary polyclonal antibody, Evans Blue counterstain, dextran solution, erythrocyte lysing reagents, fixative, sample diluents, and mounting fluid.	Cocktail (2) of murine monoclonal antibodies (C10/C11) against lower matrix structural phospoprotein (pp65), FITC-conjugated secondary polyclonal antibody, Evans Blue counterstain, dextran solution, erythrocyte lysing reagents, fixative, sample diluents, and mounting fluid.
Performance Characteristics	Sensitivity: 82.86%Specificity: 88.67%Accuracy: 88.06%	Sensitivity: 82.86%Specificity: 87.33%Accuracy: 86.87%
Risk to patient	No unique issues of safety or effectiveness.
Specimen Type	Anticoagulated [EDTA, heparin, or Adenine Citrate Dextrose (ACD)] human venous blood.	Anticoagulated (EDTA, heparin) human venous blood.
Analyte	CMV lower matrix structural phospoprotein (pp65)	CMV lower matrix structural phospoprotein (pp65)
Controls	Optional Positive and Negative Intracel CMV Control Slides (B1029-81B) not included in kit.	Positive and Negative Control Slides (20 per 100 test lab)Leukocytes and SF9 Insect cells
Kit Size	100 Tests	100 Tests
Cell Count Required	$2 x 10^5$ cells	$1.5 x 10^5$ cells

(F) Performance Data

】-Cross Reactivity

Bartels CINAkit CMV Antigenemia has been tested against the following viruses and has shown no cross-reactivity :

Human Immunodeficiency Virus (HIV) - Virion (Switzerland) Human Herpes Simplex Virus Type 1 (HSV-1) strain McIntyre (HHV-1) Human Herpes Simplex Virus Type 2 (HSV-2) strain M.S. (HHV-2) Varicella Zoster Virus (VZV) strain ATCC VR586 (HHV-3) Epstein-Barr Virus (EBV) strain B95.8 (HHV-4)

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Herpesvirus Type 6 (HHV-6) A variant strain TAN Herpesvirus Type 6 (HHV-6) B variant strain HST Influenza A - Puerto Rico/8/34 strain Influenza B - Russia/69 strain Parainfluenza Type I - C35 strain Parainfluenza Type II -Greer strain Parainfluenza Type III -Russia/69 strain or S.B. strain Adenovirus -Type 3 GB strain Respiratory Syncytial Virus - Long VR26 strain

Each of the aforementioned 14 viruses was found to be negative by immunofluorescence using the CINAkit reagents. However, positive control antibodies produced staining of +3 to +4 for its corresponding slide. It can be concluded that the Bartels CINAkit CMV monoclonal antibodies are highly specific for CMV.

Note: Absence of cross-reactivity against Echovirus 11 and 30 has not been established

Performance Characteristics 2.

Bartels CINAkit CMV Antigenemia was compared to CMV virus detection by the culture method using human peripheral blood leukocytes. Three hundred thirty-five (335) clinical specimens were evaluated in comparison to the culture method. In the same study, the performance of a comparable commercial CMV Antigementia test ("Other CMV") was also was compared to CMV virus detection by culture using human peripheral blood leukocytes from the same specimens. The performance data for the two Antigenemia tests, using the culture method as the "gold standard", are presented below.

Antigenemia Method/Result	Culture (+)n=35	Culture (-)n=300
Bartels CINAkit CMV (+) n=63	29	34
Bartels CINAkit CMV (-) n=272	6	266
Other CMV (+) n=67	29	38
Other CMV (-) n=268	6	262

TABLE 2

Total n = 335

The performance characteristics for Bartels CINAkit CMV Antigeneraia, using the culture method as the "gold standard", are as follows:

Sensitivity = 29/35 = 83% (95% Confidence interval = 70.4 - 95.3%) Specificity = 266/300 = 89% (95% Confidence interval = 85.1 - 92.3%)

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Bartels CINAkit CMV Antigenemia 510(k) Premarket Notification

Conclusion (G)
Bartels Cina kit CMV Antigenemia is substantially equivalent to the predicate device, Biotest CMV Brite.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing right, with flowing lines representing hair or clothing.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 4 1998

Fedora Daye Contreras, MPH Regulatory Affairs Associate Intracel 1330 Piccard Drive Rockville, MD 20850

Re: K982311 Trade Name: Bartels CINAkit CMV Antigenemia Regulatory Class: II Product Code: GQH Dated: October 2, 1998 Received: October 2, 1998

Dear Ms. Knapp:

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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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

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" (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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

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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510(k) Number (if known): j

Device Name: Bartels CINAkit™ CMV Antigenemia Test

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

pratory Devices 510(k) Number

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use_

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.3175 Cytomegalovirus serological reagents.

(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).