The BioStar® STREP B OIA® assay is an Optical ImmunoAssay (OIA) test for the rapid detection of group B streptococcal antigen directly from cervical and vaginal swabs from intrapartum maternity patients. The STREP B OIA assay is intended for use as an adjunct to culture, clinical observation and other information available to the physician.

Device Description

The STREP B OlA test involves the extraction of a carbohydrate antigen unique to group B Streptococi from the cervical or vaginal swab specimen and the subsequent use of Optical ImmunoAssay technology for the qualitative detection of this specific antigen. The Optical ImmunoAssay technology allows the direct visual detection of the physical change in optical thickness of molecular thing from the binding reactions between antibodies and antigens. The signal is generated by the reflection of light through the molecular thin films formed on an optical substrate. White light reflected through the molecular thin film results in a predominant visual background gold color. This color will not change unless the thickness of the optical molecular thin film is changed. When a liquid sample containing antigen from group B Streptococci is placed on the test surface, binding occurs between the antigen and immobilized antibody, causing an increased thickness in the molecular this reaction takes place, the optical path through the film is changed, causing a corresponding change in the gold color to purple/blue, thereby indicating a positive result. The change in optical thickness is due to the binding of specific antigen. If the antigen is not present in the sample, no binding takes place. The original molecular thickness remains unchanged and the test surface retains its original gold color, indicating a negative result. The clear endpoint and unequivocal results observed with the optical detection system lead to a very sensitive easily interpreted assay system.

AI/ML Overview

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the STREP B OIA® device:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of sensitivity and specificity targets. However, the study results are presented with 95% Confidence Intervals (CI), which implicitly define a range of acceptable performance. The performance is reported in comparison to "Lim Broth Culture" as the reference standard.

Performance Metric	Acceptance Criteria (Implied by 95% CI)	Reported Device Performance (STREP B OIA® vs. Lim Broth)
Sensitivity	56.7% - 70.5%	63.8%
Specificity	91.3% - 95.0%	93.3%

Note: The document also reports sensitivity for "TSA Culture to Lim Broth Culture" for comparison, which achieved a sensitivity of 60.8% (CI: 53.7-67.6%) and specificity of 99.6% (CI: 98.8-99.9%). This suggests that the STREP B OIA®'s performance falls within a similar range of what would be expected from a non-selective culture method compared to a selective broth culture.

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

Sample Size for Test Set: 947 samples (cervical and vaginal swabs).
Data Provenance: The study was a "prospective evaluation of clinical specimens taken from women." The country of origin is not explicitly stated, but the submission is to the FDA (USA), implying the study was likely conducted in the USA or adhering to US regulatory standards.

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

The ground truth was established by microbiological culture methods (Lim broth culture and TSA culture), not by human experts interpreting results. The document does not mention the number or qualifications of personnel performing these lab procedures.

4. Adjudication Method for the Test Set

No explicit adjudication method (like 2+1 or 3+1 consensus) was used, as the ground truth was determined by laboratory culture results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is a rapid diagnostic test intended for laboratory use, not typically requiring human reader interpretation in the same way as imaging studies. The study compared the device's performance to a laboratory reference standard.

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

Yes, this study represents a standalone performance evaluation of the STREP B OIA® device. The device itself produces a clear visual positive or negative result, which is then recorded. The performance metrics presented are based on the device's output compared to the reference standard, without any human interpretation of the device's optical changes being part of the reported performance.

7. The Type of Ground Truth Used

The primary ground truth used for establishing clinical performance was Lim broth culture, which is a selective broth culture method considered a more sensitive reference standard for Group B Strep detection compared to direct agar culture. The document also mentions comparison to "routine microbiological Trypticase Soy Agar with 5% Sheep Blood (TSA) culture media" as an initial step.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its size. In vitro diagnostic devices like the STREP B OIA® are typically developed and optimized by the manufacturer, and then clinical performance is assessed on a distinct set of samples. The study described in section H is referred to as a "clinical testing" or "clinical evaluation," implying it serves as the validation dataset.

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

Since no separate training set is explicitly mentioned, the method for establishing ground truth for the clinical evaluation (which serves as the basis for performance claims) was as follows:

Cervical and vaginal specimens were collected using dual swabs.
One swab was either:
- Plated directly onto TSA within 24 hours of collection.
- The pledget from the swab was placed in Lim broth, incubated, and then subcultured (10 ul) at 18-24 hours to a TSA plate.
All plates were incubated, and beta-hemolytic streptococcal colonies were selected and confirmed using a streptococcal group serotyping method.
Lim broth culture was identified as the reference standard against which the STREP B OIA®'s performance was compared.

Summary

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8.0 510(k) SUMMARY (page 1 of 5)

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:

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

SUBMITTER'S NAME: BioStar, Inc.
ADDRESS: 6655 Lookout Rd. Boulder, CO 80301
TELEPHONE: (303) 530-3888 ext. 603 .
FAX: (303) 530-6601 .
CONTACT PERSON: Roger C. Briden ●
DATE 510(k) SUMMARY PREPARED: April 20, 1999 ●

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

TRADE OR PROPRIETARY NAME: STREP B OIA®
COMMON NAME: Group B Strep
CLASSIFICATION NAME: Antigens, All Groups, Streptococcus spp

C. Identification of legally marketed device to which we are claiming equivalence {{807.92(a)(3)[:

TRADE OR PROPRIETARY NAME: STREP B OIA® .
REGULATORY CLASS: Class I .
PRODUCT CODE: 83GTY .
. MANUFACTURER: BioStar, Inc.
510(k) NUMBER: K936112 .

Note: Performance of the STREP B OIA product was established versus Lim broth as the reference standard.

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

Principle of the Test:

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510(k) SUMMARY (page 2 of 5)

White light reflected through the molecular thin film results in a predominant visual background gold color. This color will not change unless the thickness of the optical molecular thin film is changed (Figure 1). When a liquid sample containing antigen from group B Streptococci is placed on the test surface, binding occurs between the antigen and immobilized antibody, causing an increased thickness in the molecular this reaction takes place, the optical path through the film is changed, causing a corresponding change in the gold color to purple/blue, thereby indicating a positive result. The change in optical thickness is due to the binding of specific antigen. If the antigen is not present in the sample, no binding takes place. The original molecular thickness remains unchanged and the test surface retains its original gold color, indicating a negative result. The clear endpoint and unequivocal results observed with the optical detection system lead to a very sensitive easily interpreted assay system.

Device Components:

The STREP B OIA test kit contains the following:

Extraction Tubes Reagent 1A, extraction reagent Reagent 1B, extraction reagent Reagent 2, neutralization reagent Reagent 3, Conjugate Reagent 4, wash solution Reagent 5, Substrate - Test Devices Positive Control Transfer Pipettes Swabs

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

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Biostar Strep B OIA 510(k) May 28. 1999

510(k) SUMMARY (page 3 of 5)

F. Technological characteristics [§807.92(a)(6)]:

There are no changes. This is the same device used to establish performance versus TSA culture in K936112 and versus Lim broth in this submission.

Technological Characteristic	Predicate Device (Strep B OIA®)	Our Device (STREP B OIA®)
Intended Use	The BioStar® Strep B OIA® assay is anOptical ImmunoAssay (OIA) test for therapid detection of Group B Streptococcalantigen directly from cervical and vaginalswabs from preterm and intrapartummaternity patients. The Strep B OIA isintended for use as an adjunct to culture,clinical observation and informationavailable to the physician.	The BioStar® STREP B OIA® assayis an Optical ImmunoAssay (OIA) testfor the rapid detection of group Bstreptococcal antigen directly fromcervical and vaginal swabs fromintrapartum maternity patients. TheSTREP B OIA assay is intended foruse as an adjunct to culture, clinicalobservation and other informationavailable to the physician.
Detection	Detects group B streptococcal antigen	Detects group B streptococcal antigen
Technology	OIA® Optical Immunoassay)	OIA® Optical Immunoassay)
Specimens Evaluated	Cervical / Vaginal swab	Cervical / Vaginal swab

G. Summary of nonclinical testing [§807.92(b)(1)]:

Only the clinical data has changed therefore the information provided here is what exists in the package insert ょ ………… for the cleared product.
" "Analytical Sensitivity:

LIMITS OF DETECTION

GBS cells of Subtypes Ia, Ib, II, III were grown on TSA / 5% sheep blood agar plates, harvested and diluted in saline. The diluted suspensions were enumerated by culture on TSA / 5% sheep blood agar plates. The following table presents the lowest concentration of each subtype giving a positive result in the assay.

Subtype	Strain	OIA Sensitivity(Cells / Assay)
Ia	CDC SS-880	$1.6X10^4$
Ib	CDC SS-884	$1.4X10^4$
Ic	CDC SS-1070	$1.6X10^4$
II	CDC SS-888	$8.7X10^3$
III	CDC SS-893	$7.7X10^3$

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Analytical Specificity (Cross Reactivity):

ANAL YTICAL SPECIFICITY (CROSS REACTIVITY)

To detectine the analytical specificity of the STREP B OIA test, the following organisms were grown in culture and tested at a concentration of at least 10' organisms test. Cell density was confirmed by plaing an aliquot of the suspension, growing the organism and counting the number of colonies formed. None of the organisms listed below gave a positive result in the STREP OIA test.

Staphylococcus aureus	Salmonella cholerarsuis
(Protein A Producer)	subspecies cholerarsuis
Staphylococcus aureus	serotype: typhimurium
Enterococcus faecalis	Gardnerella vaginalis
Staphylococcus epidermidis	Streptococcus Group A
Moraxella catarrhalis	Streptococcus Group F
Klebsiella pneumoniae	Eubacterium lentum
Pseudomonas aeruginosa	Streptococcus Group G
Escherichia coli	Haemophilus influenzae
Streptococcus pneumoniae	Streptococcus equi, ssp. equi
Lactobacillus fermentum	Acinetobacter calcoaceticus
Peptostreptococcus anaerobius	Candida glabrata
Proteus mirabilis	Neisseria gonorrhoeae
Salmonella cholerarsuis	Moraxella lacunata
subspecies cholerarsuis	Peptostreptococcus productu
serotype: minnesota	Candida albicans
Salmonella cholerarsuis
subspecies cholerarsuis

In addition, these organisms were cultured and tested and found to not interfere with the test.

HSV-I HSV-2 Trichomonas vaginalis

Interfering Substances:

The following substances have been tested and the STREP B OLA test methodology: urine, amniotic fluid, vaginal mucous and sheep blood agar.

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

The performance of the STREP B OIA assy was compared to that of routine microbiological Trypticase Soy Agar with 5% Sheep Blood (TSA) culture media and selective broth culture using Lim broth in a prospective evaluation of clinical specimens taken from women in the STREP B OLA test with Selective broth culture, cervical specimens were collected using standard techniques from 947 women using a dual swab (Duo-Transuber swabs-Medical Wire and Equipment Co., Spara, N). One swab was plated onto TSA within 24 hours of collection i im broth oversight. In addition, the pledget from the was placed in Lim broth, incubated and subcultured (10 ul) at 18-24 hours to a TSA plate. All plats were incubated in 5% C0 at 35-37°C. If beta-hemolytic streptococal colonies were selected and confirmed using a streptococal group serotyping method. The other swab was assayed in the STREP B OIA test within 24 hours of collection.

Of the 947 samples tested, 199 vere positive by Lim broth, 121 (60.8%) were also positive by direct agar culture. 127 (63.8%) of the Lim broth positive samples were positive by the OLA method. Of the 748 Lim broth culture regative by TSA and 698 (93.3%) were negative by the STREP B OIA test.

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510(k) SUMMARY (page 5 of 5)

The density of the GBS culture was judged by the TSA blood ager plate. Growin in the first quadman is graded in 11,14000 fco March 1, 1 third quadrant 3-t, and fourth quadesty data were available for 19912 (98.3%) TSA culture positives and 19/199 (59.8%) of cultures positive by Lim broth. The sensitivity of the STREP B OIA assay for the degrees of culture density is as follows:

Culture Density	% OIA Positive
4+	100% (31/31)
3+	88 % (30/34)
2+	83 % (15/18)
1+	67 % (24/36)
Broth Only	34 % (27/79)

Broth only results were for samples that were negative on direct BAP culture but positive by either swab or pledget broth.

COMPARISON of STREP B OIA to Lim Broth Culture 947 SAMPLES

	OIA
	+	-
Lim Broth+	127	72	Sensitivity = 63.8% CI (56.7-70.5%)*
Culture-	50	698	Specificity = 93.3% CI (91.3-95.0%)*

COMPARISON of TSA Culture to Lim Broth Culture 947 SAMPLES

	TSA Culture
	+	-
Lim BrothCulture	121	78	Sensitivity = 60.8% CI (53.7-67.6%)
	3	745	Specificity = 99.6% CI (98.8-99.9%)

95 % Confidence Interval

I. Conclusions from nonclinical / clinical testing {§807.92(b)(3)):

See sections G and H above.

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

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

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Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of a bird-like figure with three curved lines representing its wings or feathers. The overall design is simple and professional, conveying a sense of authority and trustworthiness.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 19 1999

Roger C. Briden, Ph.D. Director of Regulatory Affairs BioStar, Inc. 6655 Lookout Road Boulder, Colorado 80301

K991828 Re: Trade Name: Strep B OIA® Regulatory Class: I Product Code: GTY Dated: May 28, 1999 Received: May 28, 1999

Dear Dr. Briden:

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 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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Rage 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 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

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12.0 INDICATIONS FOR USE STATEMENT

INDICATIONS FOR USE STATEMENT

510(k) Number (if known):	K991828
Device Name:	STREP B OIA®

Indications For Use:

The BioStar® STREP B OLA® assay is an Optical ImmunoAssay (OTA) test for the rapid detection of group B streptococcal antigen directly from cervical and vaginal swabs from intrapartum maternity patients. The STREP B OIA assay is intended for use as an adjunct to culture, clinical observation and other information available to the physician.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

urols vision Sign Off) Division of Clinical Laboratory Devices K 99 1828 510(k) Number.

) Number K 9478

Over-The-Counter Use

Prescription Use (Per 21 CFR 801.109) (Optional Format 1-2-96)

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(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.