The CMV Brite™ Turbo Kit is intended for the qualitative detection of Cytomegalovirus (CMV) lower matrix protein pp65 by indirect immunofluorescence using microscopy in isolated peripheral blood leukocytes obtained from ethylenediaminetetraacetic acid (EDTA) or heparin anticoagulated human peripheral blood. The detection of CMV pp65 in human perpheral blood cells aids in the diagnosis of acute or reactivated CMV infection. This product is not FDA cleared (approved) for use in testing (i.e., screening) of blood or plasma donors.

Device Description

The CMV antigenemia assay has been developed using a cocktail of two monoclonal antibodies (C10/C11) directed against CMV lower matrix protein pp65(6). The assay uses the C10/C11 cocktail in an indirect immunofluorescence staining of cytospin preparations of peripheral blood leukocytes. The CMV Brite™ Turbo antigenemia assay is completed within two hours of blood collection which saves time and means a rapid answer for the clinician. The CMV Brite™ Turbo method consists of:

Direct lysis of peripheral blood erythrocytes a.
Preparation of cytospin slides b.
Fixation and permeabilization C.
Indirect immunofluorescence staining using monoclonal antibodies directed d. against CMV pp65 protein
Reading and evaluation of results e.
The first step in the CMV Brite™ Turbo method involves direct lysis of the peripheral blood erythrocytes(22). Following lysis the leukocytes are cytocentrifuged onto a slide, fixed and permeabilized to allow subsequent detection of CMV pp65 antigen. The presence of the CMV pp65 antigen is detected by the C10/C11 antibody cocktail and visualized by means of a specific secondary FITC-labeled antibody. CMV antigenpositive leukocytes exhibit homogeneous yellow-green polylobate nuclear staining when observed using a fluorescence microscope. The number of CMV antigen-positive cells are counted per duplicate stain.
The whole procedure can be performed in approximately 2 hours. The total analysis time has been shortened by performing direct erythrocyte lysis on whole blood and avoiding dextran sedimentation. Further time has been saved by shortening individual steps in the protocol so that the whole CMV antigenemia procedure has been reduced in time by more than 50%.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CMV Brite™ Turbo Kit, based on the provided text:

Acceptance Criteria and Reported Device Performance

The provided document specifically compares the CMV Brite™ Turbo Kit to its predicate device, the CMV Brite™ Test Kit, in terms of performance characteristics. The "acceptance criteria" are implied by the performance of the predicate device, which the new device aims to be "as safe, effective, and performs as well as."

Acceptance Criteria (implied by predicate device performance)	Reported Device Performance (CMV Brite™ Turbo)
Sensitivity: 91.0%	Sensitivity: 87.4%
Specificity: 99.5%	Specificity: 98.8%
Positive Predictive Value: 98.9%	Positive Predictive Value: 92.4%
Negative Predictive Value: 95.7%	Negative Predictive Value: 97.9%

Note: The document states, "The performance characteristics of the CMV Brite™ Turbo Kit are the same as those established for the CMV Brite™ Test Kit." However, the comparative table (Table 1) then lists slightly different numerical values for sensitivity, specificity, and predictive values. This might indicate that "the same" refers to generally comparable performance rather than identical numerical results, or that the table itself is the primary source of the "established" performance for the new device based on its own testing. For the purpose of this response, I'm listing the specific numbers presented in the table for the CMV Brite™ Turbo.

Study Details

Sample size used for the test set and the data provenance:
- Test Set Sample Size: The document does not explicitly state the sample size used for the test set.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing ground truth for the test set. The nature of the device (immunofluorescence staining read by microscopy) implies a human reader, but details about independent review or consensus are missing.
Adjudication method for the test set:
- The document does not describe any specific adjudication method (e.g., 2+1, 3+1, none) for the test set.
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 was not done. This device is a test kit for laboratory use, involving manual interpretation via fluorescence microscopy, not an AI-assisted diagnostic tool. Therefore, the concept of human readers improving with AI assistance is not applicable here.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- No, a standalone algorithm-only performance study was not done. This device is a manual laboratory test kit that requires human interpretation (microscopy of stained cells) to detect CMV pp65 antigen. It is not an algorithm or AI-driven system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The type of ground truth is not explicitly stated. Given the nature of CMV antigenemia testing, the ground truth would typically be established by clinical diagnosis of CMV infection, often supported by other laboratory methods (e.g., PCR, viral culture, or clinical outcomes), or by expert interpretation of the gold standard for CMV antigenemia. The document describes the new device being compared to a "legally marketed device" (CMV Brite™ Test Kit), implying the predicate device serves as a reference, but the ultimate ground truth for both is not detailed.
The sample size for the training set:
- The document does not mention a "training set" as this is not an machine learning/AI device. The studies described are for validating the performance of a wet laboratory assay.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" for this type of device.

Summary

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991650

510(k) SUMMARY OF INFORMATION RESPECTING SAFETY AND 11. EFFECTIVENESS

Name and Address of Submitter A.

	Company Name and Address:	Biotest Diagnostics Corporation66 Ford Road, Suite 131Denville, NJ 07834
	Telephone:	609-397-8511
	FAX:	609-397-8224
	Contact Person:	Patricia E. Bonness
B.	Device Names
	Proprietary Name:	CMV Brite™ Turbo Kit
	Common Name:	Cytomegalovirus Antigen Detection
	Classification Name:	Cytomegalovirus serological reagents
C.	Legally Marketed Device
	CMV Brite™ Test Kit (K951550)

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D. Device Description

Direct lysis of peripheral blood erythrocytes a.
Preparation of cytospin slides b.
Fixation and permeabilization C.
Indirect immunofluorescence staining using monoclonal antibodies directed d. against CMV pp65 protein
Reading and evaluation of results e.

The first step in the CMV Brite™ Turbo method involves direct lysis of the peripheral blood erythrocytes(22). Following lysis the leukocytes are cytocentrifuged onto a slide, fixed and permeabilized to allow subsequent detection of CMV pp65 antigen. The presence of the CMV pp65 antigen is detected by the C10/C11 antibody cocktail and visualized by means of a specific secondary FITC-labeled antibody. CMV antigenpositive leukocytes exhibit homogeneous yellow-green polylobate nuclear staining when observed using a fluorescence microscope. The number of CMV antigen-positive cells are counted per duplicate stain.

The whole procedure can be performed in approximately 2 hours. The total analysis time has been shortened by performing direct erythrocyte lysis on whole blood and avoiding dextran sedimentation. Further time has been saved by shortening individual steps in the protocol so that the whole CMV antigenemia procedure has been reduced in time by more than 50%.

Intended Use E.
The CMV Brite™ Turbo Kit is intended for the qualitative detection of Cytomegalovirus (CMV) lower matrix protein pp65 by indirect immunofluorescence using microscopy in isolated peripheral blood leukocytes obtained from ethylenediaminetetraacetic acid (EDTA) or heparin anticoagulated human peripheral blood. The detection of CMV pp65 in human perpheral blood cells aids in the diagnosis of acute or reactivated CMV infection. This product is not FDA cleared (approved) for use in testing (i.e., screening) of blood or plasma donors.

F. Comparison with Predicate Device

A summary comparison of the features of the CMV Brite™ Turbo Kit and CMV Brite™ Test Kit is provided in Table 1 on the following page:

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Table 1 Feature Comparison of the CMV Brite™ and CMV Brite™ Turbo Tests

	CMV Brite™	CMV Brite™ Turbo
Intended Use	Detection of CMV protein pp65 inperipheral leukocytes	Detection of CMV protein pp65 inperipheral leukocytes
Monoclonal Antibodies	Clones C10 and C11	Clones C10 and C11
Assay Method	Immunofluorescence Staining	Immunofluorescence Staining
Specimen: TypeMinimum vol	Heparin or EDTA5 - 7 ml	Heparin or EDTA3 - 5 ml
Preparation ofLeukocyte Suspension	Dextran sedimentation and lysis of redcells with NH₄Cl	Direct lysis of red cells with NH₄Cl
	Centrifugation: 10 min at 300 xg	Centrifugation: 2 min at 1000 xg
Cell Count Required(cells/ml)	$1.5 x 10^6$	$2 x 10^6$
Affixing Method	Cytospin Centrifugation	Cytospin Centrifugation
Fixation Time	10 minutes	5 minutes
Permeabilization Time	5 minutes	1 minute
Staining	0.002% Evans Blue	0.00075% Evans Blue
Incubation Time	30 minutes	20 minutes
Microscope	Immunofluorescence	Immunofluorescence
Controls	Positive & negative control slide (20)Leukocytes & SF9 Insect cells	Positive & negative control slide (5)Leukocytes & SF9 Insect cells
Sensitivity	91.0%	87.4%
Specificity	99.5%	98.8%
Positive PredictiveValue	98.9%	92.4%
Negative PredictiveValue	95.7%	97.9%
Kit Size	100 test	110 tests
Total Assay Time	5 hours	2 hours

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G. Performance Data

The performance characteristics of the CMV Brite™ Turbo Kit are the same as those established for the CMV Brite™ Test Kit.

H. Conclusions Drawn from the Studies
The conclusions drawn from the design control and validation studies demonstrate that the CMV Brite™ Turbo Kit is as safe, effective, and performs as well as the legally marketed device to which equivalence is claimed, the CMV Brite™ Test Kit.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is a stylized symbol that resembles a human figure in profile, with three overlapping shapes suggesting a head, body, and legs.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUL 1.2 1999

Patricia E. Bonness Official Correspondent Biotest Diagnostics Corporation 66 Ford Road, Suite 131 Denville, New Jersey 07834

Re: K991650 Trade Name: CMV Brite™ Turbo Kit Regulatory Class: II Product Code: LIN Dated: June 28, 1999 Received: July 1, 1999

Dear Ms. Bonness:

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 Ouality 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

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 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

510(k) Number (if known): _ K 991650

Device Name: ________________________________________________________________________________________________________________________________________________________________

Indications For Use:

The CMV Brite™ Turbo Kit is intended for use in the qualitative detection of Cytomegalovirus (CMV) lower matrix protein pp65 by indirect immunofluorescence using microscopy in isolated peripheral blood leukocytes obtained from ethylenediaminetreaacetic acid (EDTA) or heparin anticoagulated human peripheral blood. The detection of CMV pp65 in human peripheral blood cells aids in the diagnosis of acute or reactivated CMV infection. This product is not FDA cleared (approved) for use in testing (i.e., screening ) of blood or plasma donors.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois
(Division Sign off)

Division of Clin 510(k) Number

Prescription Use OR (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).