The Thermo BioStar® RSV OIA assay is an Optical ImmunoAssay (OIA) test for the qualitative, rapid detection of respiratory syncytial virus antigens (nucleoprotein) from nasal wash specimens. This test is intended for in vitro use to aid in the diagnosis of respiratory syncytial virus infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative 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 antigenantibody 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 surface retains the original gold color indicating a negative result.

AI/ML Overview

The provided text describes the RSV OIA® assay, a rapid test for Respiratory Syncytial Virus (RSV) antigens.

Here's an analysis of the acceptance criteria and study details:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined quantitative acceptance criteria (e.g., "The device must achieve a sensitivity of at least X%"). Instead, it presents performance metrics from the clinical studies. For the purpose of this analysis, we can infer that the reported performance was deemed acceptable for FDA clearance.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance	Comments
Reproducibility	High (e.g., minimal discordance)	95% overall reproducibility	Based on 8 discordant and 3 invalid results out of 162 tests.
Clinical Sensitivity	Adequate for intended use	86.2%	Compared to cell culture with fluorescent antibody staining.
Clinical Specificity	Adequate for intended use	86.2%	Compared to cell culture with fluorescent antibody staining.
Overall PPV	Adequate for intended use	67.1%	Not explicitly stated as acceptance criteria, but a reported outcome.
Overall NPV	Adequate for intended use	94.1%	Not explicitly stated as acceptance criteria, but a reported outcome.

2. Sample Size and Data Provenance

Test set sample size:
- Reproducibility study: 162 samples (9 blinded samples tested 3 times at 6 sites).
- Clinical Sensitivity and Specificity study: 241 nasal wash specimens were included in the data analysis (out of 267 enrolled patients).
Data provenance: Not explicitly stated, but the "two-site study in patients from emergency rooms and health clinics" and "four hospital laboratories and two physician office laboratories (POL)" suggest a prospective study design from clinical settings. The country of origin is not specified, but given the FDA submission, it's highly likely to be the USA.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number or qualifications of experts involved in establishing the initial ground truth (cell culture with fluorescent antibody staining). It only states that the comparison was made against "commercially available cell culture, with confirmation and typing by fluorescent antibody staining."

However, for secondary confirmation testing of specimens positive to OIA and negative to culture, "specific nucleic acid detection by PCR" was used. The expertise for performing and interpreting these methods is not detailed.

4. Adjudication Method for the Test Set

The document describes secondary confirmation testing for discordant results in the sensitivity and specificity study: "Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR." This implies a form of adjudication for discordant cases, where PCR acted as a tie-breaker or a higher-tier confirmation method for a specific subset of results. There is no mention of a traditional 2+1 or 3+1 expert review panel for the entire dataset.

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

There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study or any assessment of how human readers improve with or without AI assistance. The device is a diagnostic assay, not an AI-assisted diagnostic tool for human interpretation.

6. Standalone (Algorithm Only) Performance

Yes, the described performance of the RSV OIA assay is a standalone performance, as it is a diagnostic kit that provides a direct read-out (color change) and does not involve human interpretation beyond observing this change. The sensitivity and specificity figures represent the algorithm's (or assay's) performance.

7. Type of Ground Truth Used

The primary ground truth used for the clinical sensitivity and specificity study was:

Expert Consensus/Reference Method: "Commercially available cell culture, with confirmation and typing by fluorescent antibody staining."
Molecular Pathology (for discordant cases): "Specific nucleic acid detection by PCR" for secondary confirmation of specimens positive to OIA and negative to culture.

8. Sample Size for the Training Set

The document does not specify a separate training set or its sample size. This is typical for traditional in-vitro diagnostic (IVD) assays, where the device's design and parameters are often developed using internal R&D, and then validated with independent clinical studies. The concept of a distinct "training set" as understood in machine learning (ML) is not directly applicable or discussed here.

9. How Ground Truth for the Training Set Was Established

As no training set is explicitly mentioned, the method for establishing its ground truth is also not described. The development of the assay itself would have relied on established biological and chemical principles to detect RSV antigens, likely using purified antigens and characterized clinical samples during its optimization phase.

Summary

{0}------------------------------------------------

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

SEP 1 3 2002

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: K021172

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

SUBMITTER'S NAME: Thermo BioStar, Inc. .
ADDRESS: 331 South 104th Street, Louisville, CO 80027 .
TELEPHONE: (303) 530-3888 ext. 612 ●
. FAX: (303) 581-6405
CONTACT PERSON: John G. Adams
DATE 510(k) SUMMARY PREPARED: April, 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: AB FLU OIA Regulatory Class: I Manufacturer: Thermo BioStar K981651 510(k) Number:

Clinical application:

Trade or Proprietary Name: Directigen Respiratory Syncytial Virus Test Kit Regulatory Class: T Manufacturer: Becton Dickinson 510(k) Number: K882629

Historical Reference Method:

Viral Culture

E. Intended use of device [§807.92(a)(5)]:

{1}------------------------------------------------

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

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

Principle of the Test:

DEVICE COMPARISON:

Device Technology:

The RSV OIA assay is similar to the FLU OIA assay 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 respiratory infections. ●
Both assays can provide results in less than 20 minutes. ●
. Both assavs are qualitative.

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

RSV OIA assay detects an antigen unique to respiratory syncytial virus. ●
RSV OIA assay specimen types are limited to nasal wash specimens, and do not include throat . specimens.

Device clinical application:

The RSV OIA assay is similar to the Directigen Respiratory Syncytial Virus Test in that:

Both assays are rapid diagnostic tests that detect RSV antigen ●
Both assays can provide results in less than 20 minutes .
Both assays are qualitative. ●
. Both assays utilize visual detection for confirmation of reactivity.

The RSV OIA assay differs from the Directigen Respiratory Syncytial Virus Test in that:

Directigen employs an immunomembrane filter , OIA utilizes molecular thin film technology ●
. Reaction results with OIA can provide a permanent record; Directigen results disperse and fade after a finite time.

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 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.

{2}------------------------------------------------

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 two-site study in patients from emergency rooms and health clinics.

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 (n=162). Samples consisted of negative, low and moderate levels of RSV antigen, and the Kit positive 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. There were a total of 8 discordant results and 3 invalid results determining an overall reproducibility of 95%.

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 267 patients were enrolled into the clinical study. A total of 241 nasal wash specimens were included in the data analysis, with 26 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 86.2% respectively. Overall PPV and NPV for the clinical specimens were 67.1% and 94.1% respectively.

1. 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.

{3}------------------------------------------------

Image /page/3/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" arranged around the perimeter. Inside the circle is a stylized symbol of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 1 3 2002

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

Re: K021172

Trade/Device Name: RSV OIA® Test Kit Regulation Number: 21 CFR 866.3480 Regulation Name: Respiratory Syncytial Virus Serological Reagents Regulatory Class: Class I Product Code: GOG Dated: August 8, 2002 Received: August 13, 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. Iisting 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{4}------------------------------------------------

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 regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Butman

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

{5}------------------------------------------------

510(k) Number (if known): K021172

Device Name: Thermo BioStar RSV OIA

Indications For Use: The Thermo BioStar™ RSV OIA® assay is an Optical Immunoassay (OIA) test for the qualitative, rapid detection of respiratory syncytial virus antigens (nucleoprotein and fusion protein) from nasal wash specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of respiratory syncytial virus 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)

Feededinte. Paolo

(Division Sign-Off) for D.R. DuBois

Division of Clinical Laboratory Devices

510(k) Number K021172

(Optional Format 3-10-98)

Prescription Use Only.

Regulation Number and Section

§ 866.3405 Poliovirus serological reagents.

(a)
Identification. Poliovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to poliovirus in serum. Additionally, some of these reagents consist of poliovirus antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify polioviruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of poliomyelitis (polio) and provides epidemiological information on this disease. Poliomyelitis is an acute infectious disease which in its serious form affects the central nervous system resulting in atrophy (wasting away) of groups of muscles, ending in contraction and permanent deformity.(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.