The Thermo BioStar® RSV OLA assay is an Optical ImmunoAssay test for the rapid and qualitative detection of respiratory syncytial virus (RSV) antigens (nucleoproteins) from nasal wash and nasopharyngeal swab specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative test results be confirmed by cell culture.

Device Description

The RSV OIA test involves the qualitative extraction and detection of protein antigens unique to RSV (nucleoprotein and fusion protein). The Optical ImmunoAssay technology enables the direct visual detection of a physical change in the optical thickness of molecular thin films. This change is a result of antigen-antibody binding on an optical surface (silicon wafer). When an extracted specimen is placed directly on the optical surface, the immobilized specific antibodies capture the antigen. After washing, the substrate is added, increasing the thickness (mass enhancement) of the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color change. Slight changes in optical thickness produce a distinct, visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the original gold color indicating a negative result.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the RSV OIA® device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds that needed to be met for regulatory clearance. Instead, it presents the achieved performance characteristics and compares them to a predicate device and historical standard method (viral culture). The implicit acceptance criterion seems to be demonstrating substantial equivalence to these established methods.

Metric	Acceptance Criteria (Implicit)	Reported Device Performance (Nasal Wash)	Reported Device Performance (Nasopharyngeal Swab)
Sensitivity	Substantially Equivalent to Cell Culture	86.8%	66.7%
Specificity	Substantially Equivalent to Cell Culture	83.2%	96.4%
Reproducibility	High consistency across sites	95% across all sites (151/159)	Not specified separately, assumed from overall

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

Sample Size for Test Set: A total of 414 nasalpharyngeal specimens were included in the data analysis from a multicenter study, with 77 specimens excluded.
Data Provenance: The data was collected from a multicenter study with "geographically diverse clinical sites," indicating it was conducted in multiple locations. The study was clinical, suggesting prospective or a mix of prospective and retrospective data collection, focused on symptomatic neonatal and pediatric patients. Specific countries are not mentioned.

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

The document states that the RSV OIA test was compared to "commercially available cell culture, with confirmation and typing by fluorescent antibody staining." It also mentions "Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR."

This suggests that the ground truth was established by:

Cell Culture: This is a laboratory standard, executed by trained laboratory personnel.
Fluorescent Antibody Staining: Performed as a confirmation and typing method, also by trained laboratory personnel.
PCR: Used for secondary confirmation, performed by trained laboratory personnel.

The document does not specify the number of individual experts who performed these ground truth assessments or their specific qualifications (e.g., "board-certified virologist with 10 years of experience"). However, the reliance on established laboratory methods implies qualified personnel.

4. Adjudication Method for the Test Set

The document describes a clear adjudication process for discrepant results:

"Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR."

This indicates a hierarchical adjudication method where PCR was used to resolve discrepancies between the OIA test and primary cell culture results.

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

No, the document does not describe a Multi-Reader Multi-Case (MRMC) comparative effectiveness study involving human readers with and without AI assistance. The device is a diagnostic assay (OIA), not an AI-powered image analysis or decision support tool for human readers.

6. Standalone (Algorithm Only) Performance Study

Yes, the described clinical studies evaluate the standalone performance of the RSV OIA assay. The sensitivity and specificity figures (86.8% and 83.2% for nasal wash; 66.7% and 96.4% for nasopharyngeal swab) represent the performance of the device itself against the established ground truth. There is no human-in-the-loop component mentioned for the device's diagnostic output.

7. Type of Ground Truth Used

The ground truth used was a combination of:

Laboratory Reference Standard: Commercially available cell culture.
Confirmatory Assays: Fluorescent antibody staining and specific nucleic acid detection by PCR.

This represents a strong form of ground truth based on established scientific and diagnostic methods.

8. Sample Size for the Training Set

The document does not provide information on a specific "training set" sample size. For an Optical ImmunoAssay (OIA) like the RSV OIA, the development process typically involves optimizing reagents and protocols during product development rather than training a machine learning algorithm on a distinct dataset. Clinical studies are performed for validation and performance assessment, not for "training" in the machine learning sense.

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

As there is no explicit mention of a "training set" in the context of machine learning, there is no description of how ground truth for such a set was established. Product development and optimization would rely on laboratory-based characterization against known positive and negative controls, and potentially early clinical samples, similar to the methods described for ground truth in point 7.

Summary

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510(k) SUMMARY (page 1 of 3) 8.0

JAN 1 4 2003

510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K023779

A. Safety and effectiveness information required per [§807.92(a)(1)]:

SUBMITTER'S NAME: Thermo BioStar, Inc. ●
ADDRESS: 331 South 104th Street .
TELEPHONE: (303) 530-3888 ext. 612 ●
FAX: (303) 581-6405 ●
CONTACT PERSON: John G. Adams ●
DATE 510(k) SUMMARY PREPARED: October, 2002 ●

B. Safety and effectiveness information required per [§807.92(a)(2)]:

TRADE OR PROPRIETARY NAME: RSV OIA® .
COMMON NAME: Respiratory Syncytial Virus assay ●
CLASSIFICATION NAME: Antigen, , CF (including CF Controls), Respiratory Syncytial Virus ●
C. Identification of legally marketed device to which we are comparing performance.

Device Technology:

Trade or Proprietary Name: Regulatory Class: Manufacturer: 510(k) Number:

RSV OIA test kit I Thermo BioStar K021172

Historical Reference Method:

Viral Culture

Intended use of device [§807.92(a)(5)]: F.
The Thermo BioStar® RSV OLA assay is an Optical ImmunoAssay test for the rapid and qualitative detection of respiratory syncytial virus (RSV) antigens (nucleoproteins) from nasal wash and nasopharyngeal swab specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative test results be confirmed by cell culture.

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8.0 510(k) SUMMARY (page 2 of 3)

D. Description of device [§807.92(a)(4)]:

Principle of the Test:

the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color change. Slight changes in optical thickness produce a distinct, visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the original gold color indicating a negative result .

DEVICE COMPARISON:

Device Technology:

The RSV OIA assay addressed in this submission is identical to the RSV OIA assay previously cleared in that:

Both assays are rapid diagnostic tests that utilize Optical ImmunoAssay technology ●
Both assays are used to detect and identify antigen proteins specific to RSV infections. ●
Both assays can provide results in less than 20 minutes. ●
Both assays are qualitative. ●

The RSV OIA assay differs from the currently marketed RSV OIA assay in that:

The original RSV OIA assay (K021172) specimen types are limited to nasal wash specimens, and do not include nasopharyngeal swab specimens.

Comparison to historical standard method:

The RSV OIA assay is similar to culture methods in that:

Both assays are used to detect and identify respiratory syncytial virus. .
Both assays can detect the RSV virus from nasal wash and nasopharyngeal swab specimens. .
Both assays are qualitative .

The RSV OIA assay differs with traditional culture methods in that:

RSV OIA assay detects an antigen unique to the respiratory syncytial virus while the traditional culture . methods detect the whole living organism.
. RSV OIA assay can provide results in less than 20 minutes, in contrast to culture methods that can take in excess of 48 hours.

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8.0 510(k) SUMMARY (page 3 of 3)

SUMMARY OF PERFORMANCE DATA:

CLINICAL STUDIES

Performance characteristics for the RSV OIA assay were initially established in a multicenter study with geographically diverse clinical sites.

H. Summary of clinical testing [§807.92(b)(2)]:

Reproducibility

Reproducibility testing was conducted at four hospital laboratories and two physician office laboratories (POL). Nine blinded samples were tested at each site at three separate times. The samples consisted of negative, low and moderate levels of RSV antigen, and the Kit positive and negative controls. These samples were prepared in buffered protein solution, and were spiked onto swabs for analysis. The reproducibility study included both the swab extraction and OIA testing of the antigen associated with RSV.

There were no significant differences in performance among the sites. Overall reproducibility for the sample panel was 95% across all sites (151/159).

Clinical Sensitivity and Specificity

A study was conducted comparing the RSV OIA test to commercially available cell culture, with confirmation and typing by fluorescent antibody staining. Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR . A total of 491 patients were enrolled into the multicenter study. A total of 414 nasalpharyngeal specimens were included in the data analysis, with 77 specimens excluded.

The RSV OIA assay was evaluated versus cell culture with confirmation and typing by fluorescent antibody staining. Sensitivity and specificity for symptomatic patients was 86.8% and 83.2% respectively for nasal wash specimens. Sensitivity and specificity for symptomatic patients and nasopharyngeal swas 66.7% and 96.4% respectively.

Conclusions from nonclinical / clinical testing [§807.92(b)(3)]:

Analytical testing was performed on both microbial and viral panels to assess specificity and cross reactivity.

Whole blood and several types of over the counter (OTC) products were evaluated to assess the potential for interference.

The results of the above described internal and external studies demonstrated that the RSV OIA test is as safe and effective as the comparative devices.

J. Additional information [§807.92(d)]:

No additional information has been requested by FDA at this time.

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Image /page/3/Picture/1 description: The image is a 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 to the right, stacked on top of each other.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 1 4 2003

Mr. John G. Adams Regulatory Affairs Thermo BioStar 331 South 104th Street Louisville, CO 80027

K023779 Re: Trade/Device Name: RSV OIA® Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory Syncytial Virus Serological Reagents Regulatory Class: Class I Product Code: GQG Dated: November 8, 2002 Received: November 12, 2002

Dear Mr. Adams:

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 Putman

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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INDICATIONS FOR USE STATEMENT 12.0

INDICATIONS FOR USE STATEMENT

Koa3779 510(k) Number (if known): RSV OIA® Device Name:

Indications For Use:

The Thermo BioStar® RSV OIA assay is an Optical ImmunoAssay test for the rapid and qualitative detection of respiratory syncytial virus (RSV) antigens (nucleoproteins and fusion proteins) from nasal wash and nasopharyngeal swab specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative test results be confirmed by cell culture.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Freddie W. Poole

Over-The-Counter Use

(Optional Format 1-2-96)

(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number _K 02

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.