PREMIER TOXINS A&B, MODEL 616096

K993914 · Meridian Diagnostics, Inc. · LLH · Dec 10, 1999 · Microbiology

Device Facts

• Record ID: K993914
• Device Name: PREMIER TOXINS A&B, MODEL 616096
• Applicant: Meridian Diagnostics, Inc.
• Product Code: LLH · Microbiology
• Decision Date: Dec 10, 1999
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.2660
• Device Class: Class 1

Indications for Use

Premier Toxins A&B is a qualitative enzyme immunoassay for the detection of Clostridium difficile toxin A and toxin B in stool from patients with antibiotic associated diarrhea. Premier Toxins A&B is intended for use as an aid in diagnosis of C. difficile associated disease.

Device Story

Premier Toxins A&B is an enzyme immunoassay (EIA) for qualitative detection of C. difficile toxins A and B in stool samples. Device utilizes breakaway microwells coated with toxin-specific monoclonal and polyclonal antibodies. Process involves adding diluted patient specimens and HRP-conjugated anti-toxin A and B polyclonal antibodies to wells. If toxins are present, HRP-conjugated antibody complexes form. After washing, substrate/chromagen (urea peroxide and tetramethylbenzidine) is added; bound conjugate converts substrate to blue color. Addition of stop solution turns color yellow. Healthcare providers interpret results visually or via spectrophotometry to aid in clinical diagnosis of C. difficile associated disease. Used in clinical laboratory settings.

Clinical Evidence

Clinical study at two US sites compared Premier Toxins A&B to cellular cytotoxicity assay. Total sample size: 573. Sensitivity: 94.7% (95% CI: 88.1-98.3%); Specificity: 97.3% (95% CI: 95.4-98.5%); Positive Predictive Value: 87.4%; Negative Predictive Value: 98.9%; Correlation: 96.9%. Reproducibility testing performed across various control levels.

Technological Characteristics

Microtiter well enzyme immunoassay. Components: toxin-specific monoclonal/polyclonal antibodies, HRP-conjugated antibodies, urea peroxide, tetramethylbenzidine. Detection principle: colorimetric enzymatic reaction. Manual/semi-automated laboratory workflow.

Indications for Use

Indicated for patients with antibiotic-associated diarrhea to aid in the diagnosis of Clostridium difficile associated disease.

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 Cytoclone A&B EIA (K911958)

Submission Summary (Full Text)

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Special 510(k): Device Modification Premier Toxins A&B

K993914

# Item II: 510(k) Summary

#### A. Contacts

Manufacturer: Meridian Diagnostics, Inc. 3471 River Hills Drive Cincinnati, OH 45244 Phone: [phone] FAX: [phone]

| FDA Registration Number: | 1524213 |
|-----------------------------|----------------------------------------------------------------------------------------------------------------------------------|
| Site Contact Person: | Allen Nickol, PhD<br>Senior Director Clinical & Regulatory Affairs & QA |
| Submission Contact Persons: | David H. Willis, PhD<br>Clinical & Regulatory Affairs<br>Allen Nickol, PhD<br>Senior Director Clinical & Regulatory Affairs & QA |

#### Date of Preparation B.

November 12, 1999

#### C. Name of Device and Classification

Name: Premier Toxins A&B Classification: "Reagents, Clostridium difficile toxin," Class I, LLH.

#### D. Legally Marketed Device

The predicate (previously cleared) device is the Premier Cytoclone A&B EIA, 510(k) number K911958. Concurrence date was 7/30/91.

#### E. Device Description

Premier Toxins A&B is an enzyme immunoassay for the direct detection of Clostridium difficile toxin A and toxin B in stool samples. Breakaway microwells are coated with toxin specific monoclonal and polyclonal antibodies. Diluted patient specimens and HRP-conjugated anti-toxin A and B polyclonal antibodies are added to microwells. If either toxin is present in the diluted patient samples, HRP-conjugated toxin polyclonal antibodies (specific for both toxins) complexes are formed which remain in the microwells after washing. After a final washing step, a substrate / chromagen (urea peroxide and tetramethylbenzidine) is added to the wells. Any bound conjugate converts the substrate / chromagen to a blue color. Addition of acid (Stop Solution) converts the blue to a vellow color.

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#### Intended Use Statement F.

Premier Toxins A&B is a qualitative enzyme immunoassay for the detection of Clostridium difficile toxin A and toxin B in stool from patients with antibiotic associated diarrhea. Premier Toxins A&B is intended for use as an aid in diagnosis of C. difficile associated disease.

## Description of the Technology of the Modified Device Compared to G. Cleared Device

Both devices are microtiter well enzyme immunoassays that involve capture of C. difficile toxins A and B by antibody attached to microtiter wells. Detection is accomplished in both assays using HRP-conjugated antibody. In both assays color change is affected using urea peroxide and tetramethylbenzidine. The differences in protocol and materials do not reflect any fundamental change in technology.

The performance of Premier Toxins A&B was evaluated in a clinical study performed at two sites in the United States. The kit was compared to the cellular cytotoxicity assay .

| Premier<br>Toxins A&B Results | Cytotoxin Result:<br>Site 1 | | Cytotoxin Result:<br>Site 2 | | Cytotoxin Result:<br>All Sites | |
|-------------------------------|-----------------------------|------------|-----------------------------|------------|--------------------------------|------------|
| | Pos | Neg | Pos | Neg | Pos | Neg |
| Pos | 55 | 7 | 35 | 6 | 90 | 13 |
| Neg | 3 | 257 | 2 | 208 | 5 | 465 |
| Performance Statistic | Value | 95% CI | Value | 95% CI | Value | 95% CI |
| Sensitivity | 94.8% | 85.6-98.9% | 94.6% | 81.8-99.3% | 94.7% | 88.1-98.3% |
| Specificity | 97.3% | 94.6-98.9% | 97.2% | 94.0-99.0% | 97.3% | 95.4-98.5% |
| Positive Predictive Value | 88.7% | 78.1-95.3% | 85.4% | 70.8-94.4% | 87.4% | 81.0-93.8% |
| Negative Predictive Value | 98.8% | 96.7-99.8% | 99.0% | 96.6-99.9% | 98.9% | 97.5-99.7% |
| Correlation | 96.9% | 94.4-98.5% | 96.8% | 93.8-98.6% | 96.9% | 95.1-98.1% |

### H. Reproducibility

| Souce of Variance | Positive<br>Control | Negative<br>Control | High<br>Positive | Medium<br>Positive | Low Positive | Negative |
|-------------------|---------------------|---------------------|------------------|--------------------|--------------|----------|
| Mean Absorbance | 2.010 | 0.013 | 2.250 | 1.146 | 0.280 | 0.009 |
| Within Run CV | 4.1% | 24.5% | 7.3% | 6.9% | 15.9% | 28.9% |
| Between Run CV | 7.0% | 16.2% | 6.2% | 13.9% | 14.6% | 31.7% |

### I. Cross-Reactivity

The Premier Toxins A&B test did not cross-react with other known pathogenic bacteria and viruses. Positive reactions were noted with two strains of C. sordellii known to produce the HT and LT homologues to toxins A and B, respectively.

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DEC I 0 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

David H. Willis, Ph.D. Manager, Clinical and Regulatory Affairs Meridian Diagnostics, Inc. 3471 River Hills Drive Cincinnati, Ohio 45244

K993914 Re: Trade Name: Premier Toxins A&B Regulatory Class: I Product Code: LLH Dated: November 16, 1999 Received: November 17, 1999

Dear Dr. Willis:

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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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 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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# Item III: Indications of Use Statement

1993914 510(k) Number (if known):

Device Name: Premier Toxins A&B

Indications For Use:

Premier Toxins A&B is a qualitative enzyme immunoassay for the detection of Clostridium difficile toxin A and toxin B in stool from patients with antibiotic associated diarrhea. Premier Toxins A&B is intended for use as an aid in diagnosis of C. difficile associated disease.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

510(k) Number

Prescription Use
(Per 21 CFR 801.109)

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Over-The-Counter Use (Optional Format 1-2-96)