The BD Directigen™ EZ RSV test is a rapid chromatographic immunoassay for the direct and qualitative detection of Respiratory Syncytial Virus (RSV) antigen in nasopharyngeal washes, nasopharyngeal aspirates, nasopharyngeal swabs, and nasopharyngeal swab/washes from patients suspected of having a viral respiratory infection. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in neonatal and pediatric patients under the age of 20. It is recommended that negative test results be confirmed by cell culture.

Device Description

The BD Directigen™ EZ RSV test is a chromatographic assay to qualitatively detect RSV antigen in samples extracted from respiratory specimens. When extracted specimens are added to the test device, RSV A and/or B antigens bind to anti-RSV conjugated to visualizing particles in the test strip. The antigenconjugate complex migrates across the test strip to the reaction area and is captured by the line of antibody on the membrane. A positive result is indicated by the appearance of two reddish purple lines in the read window, one line next to the Test "T" and the other next to the Control "C". The absence of a reddish purple line next to the "T" and the presence of a reddish purple line next to the "C" indicate a negative result. The test is considered uninterpretable if no visible reddish purple line is present next to the "C".

AI/ML Overview

The BD Directigen™ EZ RSV test is a rapid chromatographic immunoassay designed for the direct and qualitative detection of Respiratory Syncytial Virus (RSV) antigen. The acceptance criteria and performance data are summarized below, based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria values for the clinical performance metrics (sensitivity and specificity). Instead, it presents the device's performance compared to predicate methods and establishes "substantial equivalence." However, we can infer the achieved performance from the clinical study results.

Inferred Clinical Performance Acceptance Criteria and Reported Performance:

Performance Metric	Implied Acceptance Criteria (Achieved Performance)	Reported Device Performance (Overall)
Sensitivity (compared to culture)	Adequate for substantial equivalence	80%
Specificity (compared to culture)	Adequate for substantial equivalence	92%
Reproducibility	High consistency across sites	99.1%
Cross-Reactivity	No cross-reactivity with common microorganisms	None of 99 tested microorganisms showed cross-reactivity
Interfering Substances	No interference from common substances	None of tested substances showed interference
Limit of Detection (LOD)	Detectable at specified viral titers	Ranges from 4.05 X 10^2 to 7.03 X 10^3 TCID50 for different strains
Uninterpretable Rate	Low (ideally 0%)	0.0%

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

Sample Size for Clinical Test Set: 1176 specimens.
Data Provenance: The clinical study was a multicenter trial conducted during the 2001-2002 RSV season. The country of origin is not explicitly stated, but given the submission is to the U.S. FDA by Becton, Dickinson and Company (with a Maryland address), it is highly likely the data is from the United States. The study appears to be prospective as it evaluates current patients suspected of having RSV during a specific season.

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

The ground truth for the primary clinical performance comparison was viral cell culture and Direct Fluorescent Antibody (DFA) tests. These are laboratory-based diagnostic methods, not human expert consensus, for establishing true positives and negatives for RSV infection. Therefore, information on the "number of experts" or their "qualifications" in the traditional sense of interpreting images or clinical cases is not applicable here. The ground truth relies on the established accuracy and interpretation protocols of these comparators.

For discrepant resolution (culture negative, BD Directigen™ EZ RSV positive specimens), PCR testing was performed. Again, this is a laboratory test, not expert interpretation.

4. Adjudication Method for the Test Set

The primary adjudication method involved comparing the BD Directigen™ EZ RSV test results directly against viral cell culture. For specimens where the BD Directigen™ EZ RSV test was positive but cell culture was negative, PCR testing was used for further resolution. This can be considered a form of discrepant analysis or reference standard reconciliation.

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

This device is a rapid chromatographic immunoassay, not an AI-based imaging or interpretive device. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this product. The device itself provides a direct result.

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

Yes, the clinical performance study evaluated the standalone performance of the BD Directigen™ EZ RSV test. The device produces a direct qualitative result (positive, negative, or uninterpretable) that is read visually, but the device itself is the "algorithm only" in the sense that it performs the detection without human interpretive judgment of complex patterns.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical performance evaluation was viral cell culture. For discrepant results (culture negative, EZ RSV positive), PCR testing was used as a supplemental ground truth.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" in the context of device development. For an immunoassay like this, the development typically involves analytical testing (LOD, cross-reactivity, interference, etc.) and then clinical validation. There isn't a machine learning model that needs a training set in the conventional sense. The "training" of the assay involves optimizing reagent concentrations and manufacturing processes.

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

As explained above, a "training set" in the context of machine learning and its associated ground truth establishment is not applicable to this immunoassay device. The foundational data for optimizing the assay would come from analytical studies (e.g., testing known viral strains at various concentrations, known interfering substances).

Summary

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K022133

510(k) SUMMARY

DEC 1 0 2002

SUBMITTED BY:	BECTON, DICKINSON AND COMPANY7 LOVETON CIRCLESPARKS, MD 21152Phone: 410-316-4988Fax: 410-316-4499
CONTACT NAME:	Colleen A. Kistler, Regulatory Affairs Specialist
DATE PREPARED:	June 28, 2002
DEVICE TRADE NAME:	BD Directigen TM EZ RSV
DEVICE COMMON NAME:	Antigen, CF, respiratory syncytial virus
DEVICE CLASSIFICATION:	21 CFR§866.3480
PREDICATE DEVICES:	Cell CultureDirect Fluorescent Antibody (DFA)Directigen TM RSV (K882629)

INTENDED USE:

The BD Directigen™ EZ RSV test is a rapid chromatographic immunoassay for the direct and qualitative detection of Respiratory Syncytial Virus (RSV) antigen in nasopharyngeal washes, nasopharyngeal aspirates, nasopharyngeal swabs, nasopharyngeal swab/washes, lower respiratory specimens (sputum, tracheal aspirates and bronchoalveolar layage), and other swabs (pharyngeal, lower nasal, nose/throat) from patients suspected of having a viral respiratory infection.

DEVICE DESCRIPTION:

The BD Directigen™ EZ RSV test is a chromatographic assay to qualitatively detect RSV antigen in samples extracted from respiratory specimens. When extracted specimens are added to the test device, RSV A and/or B antigens bind to the antibody-colloidal gold conjugate in the test strip forming an antigenantibody complex. This complex migrates across the test strip to the reaction area and is captured by the line of RSV antibody on the membrane. Excess conjugate binds to a second line of inactivated RSV antigen that serves as a functional control. A positive result is indicated by the appearance of two reddish purple lines in the read window, one line next to the Test "T" and the other next to the Control "C". The absence of a reddish purple line next to the "T" and the presence of a reddish purple line next to the "C" indicate a negative result. The test is considered uninterpretable is no visible reddish purple line is present next to the "C".

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DEVICE COMPARISON:

The BD Directigen™ EZ RSV was compared to viral cell culture, direct fluorescent antibody (DFA) tests, and the Directigen™ RSV test. Although there are some differences between the BD Directigen™ EZ RSV test and the predicate devices, these differences do not present new issues of safety and effectiveness. The impact of these differences on the safety and effectiveness of the BD Directigen™ EZ RSV test was assessed using accepted scientific methods.

SUMMARY OF PERFORMANCE DATA:

Analytical Sensitivity

The limit of detection (LOD) for the BD Directigen™ EZ RSV test was established for a total of five RSV strains; two RSV A and three RSV B strains.

Viral Strain	Viral Type	LOD (TCID50)
RSV (Long)	A	3.95 X 103
RSV (A-2)	A	5.95 X 103
RSV (9320)	B	4.05 X 102
RSV (Washington)	B	7.03 X 103
RSV (Wild)	B	5.56 X 102

Cross Reactivity

A panel of 99 microorganisms (including bacteria, yeasts and viruses) were cultured and tested at appropriate concentrations in triplicate with the BD Directigen™ EZ RSV test. None of the microorganisms tested in the panel were shown to cross react with the BD Directigen™ EZ RSV test.

Interfering Substances

A variety of substances were tested with the BD Directigen™ EZ RSV test at concentration levels comparable to or greater than levels that may be present in patient respiratory samples. Substances tested included blood, mouthwashes, throat drops, nasal sprays, cold medications and prescription medications. Each substance was tested in triplicate. None of the substances evaluated were shown to interfere with the performance of the BD Directigen™ EZ RSV test.

Reproducibility

The reproducibility of the BD Directigen EZ RSV test was evaluated at three sites. The overall reproducibility for the BD Directigen RSV EZ test was 99.1%.

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Clinical Performance:

The overall sensitivity and specificity of the BD Directigen™ EZ RSV test for RSV when compared to culture were 80% and 92%, respectively. The performance characteristics of the BD Directigen™ EZ RSV as compared to cell culture for each specimen type are shown in Table 1.

	Culture/ EZ					Discrepant ResolutionforCulture - / EZ +Specimens
Specimen Type	n	+/+	-/+	+/-	-/-	Sensitivity (%)(95% CI)	Specificity (%)(95% CI)	# PCR tested	# PCR +
NasopharyngealWash	358	130	30	20	178	86.780.2 - 91.6	85.680.1 - 90.1	30	22
NasopharyngealAspirate	405	90	24	27	264	76.968.2 - 84.2	91.787.6 - 94.6	182	12
NasopharyngealSwab/Wash	162	28	6	11	117	71.855.1 - 85.0	95.189.7 – 98.2	6	2
NasopharyngealSwab	286	20	20	10	236	66.747.2 - 82.7	92.288.2 - 95.2	20	11
Other Swabs1	73	3	1	1	68	75.019.4 - 99.4	98.692.2 - 99.9	03	0
LowerRespiratory	51	5	1	1	44	83.335.9 - 99.6	97.888.2 - 99.9	1	0

Table 1: Summary of the Performance of the BD Directigen EZ RSV (EZ) Test Compared to Culture for all Specimen Types

(+) = RSV positive (-) = RSV negative (#) = number

1 Refer to Limitations of the Procedure for additional information on these specimen types

2 Two specimens not submitted for PCR testing; four specimens had insufficient quantity for PCR testing 3 One specimen not submitted for PCR testing

There were 82 specimens that were culture negative, BD Directigen™ EZ RSV test positive. PCR testing was performed on 75 of the 82 specimens; a total of 47 of the 75 specimens were positive by PCR. The uninterpretable rate for the BD Directigen™ EZ RSV test was 0.0%.

Overall performance of the BD Directigen™ EZ RSV test is substantially equivalent' to viral cell culture and DFA tests that were in use prior to May 28, 1976 and to the BD Directigen™ RSV test.

1 The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without premarket approval or reclassification. A determination of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, with three intertwined snakes forming a triple helix. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

2003 FEB 3

Ms. Colleen Kistler Regulatory Affairs BD Diagnostic Systems Becton, Dickenson and Company 7 Loveton Circle Sparks, MD 21152

Re: K022133

Trade/Device Name: BD Directigen™ EZ RSV Kit Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory Syncytial Virus Serological Reagents Regulatory Class: Class I Product Code: GQG Dated: September 23, 2002 Received: September 24, 2002

Dear Ms. Kistler:

This letter corrects our substantially equivalent letter of December 10, 2002, regarding the BD Directigen™ EZ RSV Kit. The revised Indications for use and 510(k) summary are enclosed.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer 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 Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number (if known):

BD Directigen™ EZ RSV Test Device Name:

Indications for Use:

The BD Directigen™ EZ RSV test is a rapid chromatographic immunoassay for the direct and qualitative detection of Respiratory Syncytial Virus (RSV) antigen in nasopharyngeal washes, nasopharyngeal aspirates, nasopharyngeal swabs, and nasopharyngeal swab/washes from patients suspected of having a viral . respiratory infection. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in neonatal and pediatric patients under the age of 20. It is recommended that negative test results be confirmed by cell culture.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Freddie M. Poole

vision Sign-Division of Clinical Laboratory Devices

510(k) Number KD22133

For Prescription Use ✓

(Optional Format 3-10-98)

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510(k) SUMMARY

SUBMITTED BY:	BECTON, DICKINSON AND COMPANY7 LOVETON CIRCLESPARKS, MD 21152
Phone:	410-316-4988
Fax:	410-316-4499
CONTACT NAME:	Colleen A. Kistler, Regulatory Affairs Specialist
DATE PREPARED:	December 10, 2002
DEVICE TRADE NAME:	BD Directigen™ EZ RSV
DEVICE COMMON NAME:	Antigen, CF, respiratory syncytial virus
DEVICE CLASSIFICATION:	21 CFR§866.3480
PREDICATE DEVICES:	Cell CultureDirect Fluorescent Antibody (DFA)Directigen™ RSV (K882629)

INTENDED USE:

DEVICE DESCRIPTION:

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"C" indicate a negative result. The test is considered uninterpretable if no visible reddish purple line is present next to the "C".

DEVICE COMPARISON:

SUMMARY OF PERFORMANCE DATA:

Several analytical studies and a clinical study were performed to establish the performance characteristics of the assay.

Analytical Studies: The limit of detection (LOD) for the BD Directigen™ EZ RSV test was established for two RSV A and three RSV B strains. A panel of 99 microorganisms (including bacteria, yeasts and viruses) were cultured and tested at appropriate concentrations in triplicate with the BD Directigen™ EZ RSV test. A variety of substances were tested with the BD Directigen™ EZ RSV test at concentration levels comparable to or greater than levels that may be present in patient respiratory samples. Substances tested included blood, mouthwashes. throat drops, nasal sprays, cold medications and prescription medications. Each substance was tested in triplicate. The reproducibility of the BD Directigen EZ RSV test was evaluated at three sites.

Clinical Study: A total of 1176 specimens, consisting of nasopharyngeal washes, nasopharyngeal aspirates, nasopharyngeal swabs, and nasopharyngeal swab/washes from patients suspected of having RSV were evaluated with the BD Directigen EZ RSV test in a multicenter trial during the 2001-2002 RSV season.

Based on the results of the analytical and clinical studies, the performance of the BD Directigen™ EZ RSV test is substantially equivalent¹ to viral cell culture and DFA tests that were in use prior to Mav 28, 1976 and to the BD Directigen™ RSV test.

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notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

Regulation Number and Section

§ 866.3480 Respiratory syncytial virus serological reagents.

(a)
Identification. Respiratory syncytial virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to respiratory syncytial virus in serum. Additionally, some of these reagents consist of respiratory syncytial virus antisera conjugated with a fluorescent dye (immunofluorescent reagents) and used to identify respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of respiratory syncytial virus infections and provides epidemiological information on diseases caused by these viruses. Respiratory syncytial viruses cause a number of respiratory tract infections, including the common cold, pharyngitis, and infantile bronchopneumonia.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.