CDTOX A OIA

K991829 · Biostar, Inc. · LLH · Nov 2, 1999 · Microbiology

Device Facts

• Record ID: K991829
• Device Name: CDTOX A OIA
• Applicant: Biostar, Inc.
• Product Code: LLH · Microbiology
• Decision Date: Nov 2, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.2660
• Device Class: Class 1

Indications for Use

The BioStar® CdTOX A OlA assay is an Optical ImmunoAssay test for the rapid qualitative detection of Clostridium difficile Toxin A in human fecal samples from patients suspected of having Clostridium difficile associated disease (CDAD). This test is intended for in vitro diagnostic use as an aid in the diagnosis of CDAD.

Device Story

CdTOX A OIA is an in vitro diagnostic test for qualitative detection of Clostridium difficile Toxin A in human fecal samples. Principle of operation: Optical ImmunoAssay (OIA) technology; antigen-antibody binding on a silicon wafer surface; mass enhancement via substrate addition increases molecular thin film thickness; change in optical thickness alters reflected light path; visually perceived as color change (purple spot on gold background). Used in clinical laboratories; performed by laboratory personnel. Output is a visual colorimetric result; aids clinicians in diagnosing CDAD. Benefits patients by providing rapid detection of C. difficile toxin.

Clinical Evidence

Clinical evaluation included 874 specimens compared against Premier EIA and cytotoxicity assay (CTA). Sensitivity 77.3%, specificity 93.8%, concordance 91.0% vs CTA. Concordance between CdTOX A OIA and Premier EIA was 95.0%. Reproducibility studies at multiple hospital and physician office labs showed 94.4% to 97.8% agreement.

Technological Characteristics

Optical ImmunoAssay (OIA) on silicon wafer surface. Manual test kit includes reaction tubes, conjugate, wash solution, substrate, test devices, controls, pipettes, and sampling brushes. Qualitative visual readout. No electronic components or software.

Indications for Use

Indicated for rapid qualitative detection of Clostridium difficile Toxin A in human fecal samples from patients suspected of having Clostridium difficile associated disease (CDAD).

Regulatory Classification

Identification

A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.

Predicate Devices

• PREMIER™ C. difficile Toxin A (K903456)

Submission Summary (Full Text)

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# NOV - 2 1999

8.0 510(k) SUMMARY (page 1 of 4)

# 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: _ K991829

A. Safety and effectiveness information required per [5807.92(a)(1)]:

- SUBMITTER'S NAME: BioStar, Inc. .
- ADDRESS: 6655 Lookout Rd. Boulder, CO 80301 .
- TELEPHONE: [phone] ext. 659 .
- . FAX: [phone]
- CONTACT PERSON: Curtis A. Carlson .
- DATE 510(k) SUMMARY PREPARED: May 28, 1999; revised October 27, 1999. ●

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

- TRADE OR PROPRIETARY NAME: CATOX A OLA® .
- . COMMON NAME: C. difficile Toxin A Assay
- CLASSIFICATION NAME: Direct Antigen Detection Assay, Clostridium difficile .

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

- TRADE OR PROPRIETARY NAME: PREMIER™ C. difficile Toxin A ●
- . REGULATORY CLASS: Class I
- PRODUCT CODE: 83LLH .
- MANUFACTURER: Meridian Diagnostics, Inc. .
- 510(k) NUMBER: K903456 ●

Note: Performance of the CdTOX A OIA product was also established versus cytotoxicity assay.

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

## Principle of the Test:

The CdTOX A OIA test involves the qualitative detection of the enterctoxin (Toxin A) produced by Clostridium difficile. The Optical Immuno Assay technology enables the direction of a physical change in the optical thickness of molecular this change is a result of antigen-antibody binding on an optical surface (silicon wafer). When a sample containing Toxin A (antigen) from Clostridium difficile is placed directly on the optical surface, the immobilized specific antibody captures 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 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.

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Biostar CdTOX A OLA 510(k) Summary. Revised October 27, 1999

### 8.0 510(k) SUMMARY (page 2 of 4)

### Device Components:

The CdTOX A OLA test kit contains the following:

Reaction Tubes Reagent 1: Conjugate Wash Solution Substrate Test Devices Positive Control Negative Control Transfer Pipettes Sampling Brushes

- E. Intended use of device [§807.92(a)(5)]:
The BioStar® CdTOX A OlA assay is an Optical ImmunoAssay test for the rapid qualitative detection of Clostridium difficile Toxin A in human fecal samples from patients suspected of having Clostridium difficile associated disease (CDAD). This test is intended for in vitro diagnostic use as an aid in the diagnosis of CDAD.

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

| Technological Characteristic | Predicate Device (Premier TM Toxin A) | Our Device (CdTOX A OLA) |
|------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The PremierTM C. difficile Toxin A assay is<br>an Enzyme Immunoassay for the Detection<br>of C. difficile Toxin A in Stool Specimen. | The BioStar® CdTOX A OIA assay is<br>an Optical ImmunoAssay test for the<br>rapid qualitative detection of<br><i>Clostridium difficile</i> Toxin A in<br>human fecal samples from patients<br>suspected of having <i>Clostridium<br/>difficile</i> associated disease (CDAD).<br>This test is intended for <i>in vitro</i><br>diagnostic use as an aid in the<br>diagnosis of CDAD. |
| Detection | Detects <i>C. difficile</i> Toxin A | Detects <i>C. difficile</i> Toxin A |
| Technology | Enzyme Immunoassay (EIA) Microwell | Optical Immunoassay (OIA) |
| Specimens Evaluated | Stool | Stool |

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### 8.0 510(k) SUMMARY (page 3 of 4)

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

#### Analytical Sensitivity:

The analytical sensitivity was determined by adding known concentrations of Toxin A to five specimens each of liquid, semi-solid, and solid stools. Seeded specimens were tested in duplicate by the CdTOX A OfA test. Results are summarized in the table below.

## Limit of Detection by Stool Type

| Toxin A Seeded Matrix | Limit of Detection (ng/g) |
|-----------------------|---------------------------|
| Buffer Control | 3 |
| Liquid Stool | 3-8 |
| Semi-Solid Stool | 4-8 |
| Formed Stool | 3-5 |

#### Analytical Specificity (Cross Reactivity):

To determine the analytical specificity of the CdTOX A OIA test, microorganisms were grown on the appropriate media and suspended to a concentration of approximately 1.0 X 10 cfu/mL or greater and tested in the absence and presence of Toxin A near the lower limit of detection of the assay. . Cryptosporidium parvum and Giardia lamblia were rested at 1.25 X 10° cysts reactivity or interference was observed.

#### Interfering Substances:

Interference testing was performed to determine the effect of substances which might be encountered in the collection of specimens. Whole blood, Red Blood Cells (RBC), White Blood Cells (WBC), mucous (25mg/g), and barium sulfate (58% w/w suspension) were tested and did not interfere with the CdTOX A OLA test. All assays were run per the procedure described in the package insert.

#### Sample/Toxin Stability

Toxin stability in liquid, semi-solid, and formed stool was judged by spiking Toxin A (Lee Laboratories) at levels near the analytical sensitivity of the assay and testing at the specified times. Spiked samples were initially held at room temperature for 2 hours then transferred to 2-8℃ storage. These results show that over the sample consistency types tested, the toxin is sufficiently stable to allow detection in samples handled as recommended in the package insert.

#### Stool Consistency Reactivity:

The reactivity of stools with liquid, semi-solid, or formed consistency was evaluated using the OdTOX A OIA test and microwell EIA test. The positivity rates were similar for the two assays across all three types of stool specimens. All of the specimens in the clinical performance evaluation of the CdTOX A OLA rest were submitted for C. difficile testing on the basis of clinical history of the patient, not the consistency of the specimen. Test results are illustrated in the table below.

## Reactivity Data From Four Clinical Sites

#### Stool Consistency

| | Liquid (445) | Semi-solid (298) | Formed (80) |
|---------------|--------------|------------------|-------------|
| CdTOX A OIA + | 42 (9%) | 54 (18%) | 21 (26%) |
| EIA + | 51 (11%) | 50 (17%) | 19 (24%) |

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#### 8.0 510(k) SUMMARY (page 4 of 4)

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

Reproducibility testing was conducted using a stool marix at three hospital laboratories. Ten blinded samples were tested at each site at three separate times. Samples consisted of negative, low, and moderate levels of C. difficile Toxin A. The concentration of toxin in the low samples was less than 2-fold over the minimum detectable limit. The overall reproducibility was 94.4% (85/90). An additional study was done using artificial stool matrix. Comparable samples were prepared and tested at four hospital laboratories and three physician office laboratories (POLs). Overall reproducibility in this study was 97.6% (205/210); at the hospitals, 97.5% (117/120) at the POLs, 97.8% (88/90).

#### Clincal Sensitivity and Specificity

A sudy comparing the CdTOX A OIA test and a commercial microwell immunoassay, the Premier EIA, to cytotoxicity assay (CTA) was performed at a central hospital lab. The sensitivity, specificity, and concordance of the CdTOX A OIA test was 77.3%, 93.8%, and 91.0% respectively. The sensitivity, specificity, and concordance of the Premier ELA test was 81.8%, 92.0%, and 90.3% respectively.

The CdTOX A OIA test was evaluated versus the Premier EIA at four clinical trial sites (central hospital labs) located in the Southwest, Mid-Atlantic and East Coast regions of the United States. A total of 874 specimens from patients suspected of having or with a history of CDAD were evaluated by the CdTOX A OLA test and the Premier ELA. Of these, 823 gave unequivocal results using the BlA method. Concordance between the Cd TOX A OlA test and the Premier EIA test was 95.0% (98+/+, 684 -/-); discordance was 5.0% (19 +/-, 22 -/+).

- I. Conclusions from nonclinical / clinical testing [§807.92(b)(3)]:
The results of the above described internal and external studies demonstrate that the CdTOX A OLA test is as safe and effective as the cleared predicate device.

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

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

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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 features a stylized eagle with three lines forming its body and two wavy lines representing its legs. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.

NOV - 2 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Curtis A. Carlson, Ph.D. Director, Regulatory Affairs BioStar, Inc. 6655 Lookout Road Boulder, Colorado 80301

Re: K991829 Trade Name: CdTOX A OIA® Test Kit Regulatory Class: I Product Code: LLH Dated: October 7, 1999 Received: October 8, 1999

Dear Dr. Carlson:

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 (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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely vours.

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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## INDICATIONS FOR USE STATEMENT

#### INDICATIONS FOR USE STATEMENT

| 510(k) Number (if known): | K991829 |
|---------------------------|--------------|
| Device Name: | CdTOX A OIA® |

Indications For Use:

The BioStar® CdTOX A OlA assay is an Optical ImmunoAssay test for the rapid qualitative detection of Clostridium difficile Toxin A in human fecal samples from patients suspected of having Clostridium difficile associated disease (CDAD). This test is intended for in vitro diagnostic use as an aid in the diagnosis of CDAD.

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

Concurrence of CDRH, Qffice of Device Evaluation (ODE)

Woody Dubois

(Division Sign-Off) Division of Clinical Laboratory Devices K991829 510(k) Number _

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)