The ColorPAC™ Toxin A test is indicated for the qualitative detection of Clostridium difficile toxin A (enterntaxin) in stool specimens from patients used for the seefing C. difficile associated disease. The test can also be used for the confirmation of suspect colonies of toxigenic C. difficile from agar plates or BHI broth. The assay is intended for use as an aid in the diagnosis of C. difficile associated disease. The test is not indicated for asymptomatic adults or children. This device is not indicated for use in a point of care setting.

Device Description

The ColorPAC Toxin A test is comprised of a capture line consisting of C. difficile toxin A antibody immobilized on a chromatographic test strip which is contained within a test device. A specimen (stool, colonies, or BHI broth) is diluted with sample buffer and added to the sample well of the test device. The diluted sample wicks up the test strip by capillary action. Toxin A, if present, binds to the capture antibody at the test line as the specimen migrates across the test strip. The wash and remaining reagents are added to the reagent well of the test device. Upon addition of Detector A, toxin A antibody coated liposomes containing a pink dye migrate across the test strip and attach to the C. difficile toxin A antigen that was bound to the test strip in the previous step. Color formation is enhanced upon addition of a second liposome reagent, Detector B, that binds to the complex formed between Detector A and sample antigen at the test line. Following the final wash, the reactions are read visually. If toxin A antigen is detected in the patient specimen, a pink test line and a pink control line will appear, indicating a positive result. In the absence of toxin A, only the pink control line will appear, indicating a negative result. The result is uninterpretable if there is no pink control line or if the background obscures reading of the control line.

AI/ML Overview

The ColorPAC™ Toxin A device is a rapid chromatographic assay for the qualitative detection of Clostridium difficile toxin A (enterotoxin) in stool specimens and for the confirmation of suspect colonies of toxigenic C. difficile. The performance data presented focuses on comparing the device to the Cytotoxin B assay.

Here's a breakdown of the acceptance criteria and the study details:

1. Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" but presents performance metrics from the clinical studies. For comparison, we will use the results from the combined clinical study against the predicate device (Cytotoxin B assay) as the reported device performance.

Performance Metric	Acceptance Criteria (Implicit from predicate comparison)	Reported Device Performance (Combined Clinical Study vs. Cytotoxin B)
Sensitivity	Not explicitly stated but expected to be comparable to or better than predicate Cytotoxin B.	81% (95% CI: 72.4%, 87.3%)
Specificity	Not explicitly stated but expected to be comparable to or better than predicate Cytotoxin B.	97% (95% CI: 95.4%, 98.2%)

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

Sample Size: A total of 760 specimens were included in the combined clinical study for comparison with the Cytotoxin B assay (598 fresh and 162 frozen stool specimens).
Data Provenance: The study was conducted at geographically diverse areas of the United States. The data appears to be retrospective as it involved testing specimens against an established routine assay (Cytotoxin B).

3. Number of Experts and Qualifications:

The document does not specify the number of experts used to establish the ground truth nor their qualifications. The ground truth for the clinical study was established by comparing the ColorPAC™ Toxin A assay to each site's routine Cytotoxin B assay.

4. Adjudication Method:

The document does not describe any specific adjudication method (such as 2+1, 3+1). The comparison was made against the "routine cytotoxin B assay" at each site.

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

No MRMC study was mentioned in the provided text. The study design focused on comparing the ColorPAC™ Toxin A device against a predicate laboratory test (Cytotoxin B assay), not on human reader performance with or without AI assistance.

6. Standalone Performance:

Yes, the provided data reports the standalone performance of the ColorPAC™ Toxin A device against the Cytotoxin B assay. The sensitivity and specificity values listed above represent the performance of the device without human-in-the-loop assistance in interpreting the results once the test is run. The "read visually" step is inherent to the device's design, but the metrics are for the device's ability to detect the toxin.

7. Type of Ground Truth Used:

The ground truth for the clinical studies (comparing ColorPAC™ Toxin A to Cytotoxin B) was established by the Cytotoxin B assay. For the colony confirmation study, the "toxigenic status was determined by a cytotoxin B assay." This means the predicate device itself served as the reference standard for establishing the ground truth.

8. Sample Size for the Training Set:

The document does not provide details on a separate "training set" or its sample size. The performance data presented is likely derived from validation studies, with the clinical study representing a performance evaluation.

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

As no explicit "training set" is described, this information is not available. The development and validation of the ColorPAC™ Toxin A assay would have involved internal studies, likely using characterized samples, but these are not detailed as a distinct "training set" with ground truth establishment methods in this document.

Summary

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K980185

JU 17 1998

SUMMARY OF SAFETY AND EFFECTIVENESS

SUBMITTED BY:

Colleen Rohrbeck Becton Dickinson Microbiology Systems 7 Loveton Circle Sparks, MD 21152

NAME OF DEVICE:

Trade Name:	ColorPAC™ Toxin A
Common Name/Description:	Reagents, Clostridium difficile Toxin

PREDICATE DEVICE:

Cytotoxin B

DEVICE DESCRIPTION:

INTENDED USE: ColorPAC™ Toxin A is a rapid chromatographic assay for the qualitative detection of Clostrictium difficile toxin A (enterotoxin) in stool specimens from patients suspected of having C. difficile associated disease. The test can also be used for the confirmation of suspect colonies of toxigenic C. difficile from agar plates or BHI broth. This assay is intended for use as an aid in the diagnosis of C. difficile associated disease.

KIT CONTENTS:

The following components are included in the ColorPAC™ Toxin A Test kit.

Reagent 1	(30 ml)	Sample Buffer: Buffered saline with a mucolyticagent, 1% detergent.
Reagent W	(2.3 ml)	Wash Reagent: Buffered saline solution withbovine protein stabilizer, 0.1 % detergent.
Reagent 2	(1.5 ml)	Detector A: Rabbit C. difficile toxin A antibodycoated liposomes.
Reagent 3	(1.5 ml)	Detector B: Rabbit antibody coated liposomesspecific for Detector Reagent A.

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Control +	(1.0 ml)	Positive Control: Buffered saline solution withbovine protein stabilizer, inactivated C. difficiletoxin A.
Control -	(1.0 ml)	Negative Control: Buffered saline solution withbovine protein stabilizer.
		Reagents and controls each contain 0.2%sodium azide (preservative)
30 Test Devices		Each containing a test strip coated withmonoclonal C. difficile toxin A antibody and C.difficile toxin A.

30 SQ-EASY™ Tubes and Filter Tips, 30 Applicator Sticks, 30 Transfer Pipets, 1 Dropper Rod

PRINCIPLE OF PROCEDURE: The ColorPAC Toxin A test is comprised of a capture line consisting of C. difficile toxin A antibody immobilized on a chromatographic test strip which is contained within a test device. A specimen (stool, colonies, or BHI broth) is diluted with sample buffer and added to the sample well of the test device. The diluted sample wicks up the test strip by capillary action. Toxin A, if present, binds to the capture antibody at the test line as the specimen migrates across the test strip. The wash and remaining reagents are added to the reagent well of the test device.

Upon addition of Detector A, toxin A antibody coated liposomes containing a pink dye migrate across the test strip and attach to the C. difficile toxin A antigen that was bound to the test strip in the previous step. Color formation is enhanced upon addition of a second liposome reagent, Detector B, that binds to the complex formed between Detector A and sample antigen at the test line. Following the final wash, the reactions are read visually. If toxin A antigen is detected in the patient specimen, a pink test line and a pink control line will appear, indicating a positive result. In the absence of toxin A, only the pink control line will appear, indicating a negative result. The result is uninterpretable if there is no pink control line or if the background obscures reading of the control line.

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PERFORMANCE DATA:

ANALYTICAL STUDIES:

Cross-Reactivity 1.
The ColorPAC™ Toxin A test was evaluated for cross reactivity by The ColorPACT® Toxin A tost wateria, yeast, viruses and parasites) into toxin A positive and toxin A negative stool specimens to a final concentration of 107-10° CFUlmi for bacteria and yeast, 1082- - 1082 Concentration of 10 -10 -10 -10 - 10 - narasites/ml. The only organism shown to I City of the viruses and 10 penic isolate of Clostridium sordellii (VPI a oss-leact was a highly toxigente is Cowan strain ATCC 12598, which 9040). The Staphyloooooo aan cross reactivity. In addition, Escherichia produces protein A, and 43895 which produce Shiga-like toxins, did not show any cross reactivity.

2. Limit of Detection

The analytical sensitivity of the ColorPAC Toxin A test was performed by The analytical sensitivity of a lo of toxin A into 5 speciments each of liquid, seemi-solid, and solid stools. Seeded specimens were tested in triplicate. The limit of detection range for liquid, semi-solid, and solid stool specimens was 1.4-5.2, 1.6-18.7, 3.2-22.6 ng/ml, respectively.

Interfering Substances 3.
The evaluation of interfering substances was performed by seeding substances that may be present in stool specimens from patients substarious a lat may be provins associated disease. ColorPAC Toxin A test results are not affected by ampicillin, cephalexin, metronidazole, vancomycin, barium sulfate, laxatives, blood, and antidiarrheal medications.
Stability of Stool Specimens with Known Amounts of Toxin A 4.
Multiple freeze thaw cycles (up to three) had no significant effect on the assay. A subset of clinical trial samples that were tested at one site demonstrated that specimens can be stored up to 72 hours at 2-8°C . If specimens are to be tested after 72 hours, they should be frozen at -70°C immediately upon receipt in the laboratory. Specimens may be frozen up to 2 months.

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CLINICAL STUDIES:

ColorPAC Toxin A vs. Cytotoxin B 1.

The performance of the ColorPAC™ Toxin A test was determined in The performance of the Color Ao - Cannotest medical content . The sites were located in geographically diverse areas of the United States. A
sites were located in geographically diverse areas of the United with sites were located in geographically diversions from patients with total of 598 fresh and 162 frozen stocked disease were tested. Each site intigl its routine cytotoxin B assay to ColorPAC Toxin A. Results of this initial
its routine cytotoxin B assay to ColorPAC Toxin of this initial its routine cylotoxin D docuy to site are summarized below.

Site	No.	ColorPACToxin A	Positive	Negative		95%ConfidenceIntervals
1	240	Positive	28	6	Sensitivity 82%	(65.5%,93.2%)
		Negative	6	200	Specificity 97%	(93.8%,98.9%)
2	135	Positive	18	1	Sensitivity 90%	(68.3%,98.8%)
		Negative	2	114	Specificity 99%	(95.3%,99.9%)
3	207	Positive	21	11	Sensitivity 81%	(60.7%,93.5%)
		Negative	5	170	Specificity 94%	(89.4%,96.9%)
4	178	Positive	29	1	Sensitivity 74%	(57.9%,87.0%)
		Negative	10	138	Specificity 99%	(96.1%,100%)
Combined	760	Positive	96	19	Sensitivity 81%	(72.4%,87.3%)
		Negative	23	622	Specificity 97%	(95.4%,98.2%)

13n

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Reproducibility: 2.

Reproducibility of the ColorPAC Toxin A test was evaluated by testing stool panels consisting of three levels of toxin A and a toxin A negative stool panels Consisting of through were tested in triplicate on each of antigen Control. Billious specifical trial sites. ColorPAC Toxin A
three days at each of four different clinical trial situsiity three days at back of loar and inter assay reproducibility.

Colony Confirmation: 3.

A study was conducted to evaluate the ColorPAC™ Toxin A test A study was concident to evalual confirmation from suspected colony
performance for providing culture confirmation schoological va accr performance for providing strains of C. difficile using selective agar,
growth for toxin producing strains of C. difficile using broth . A tatal grown for toxin producing strains of O. Chilision (BH), broth. A fotal of 111
anaerobic blood agar, and Brain Heart Infusion (BH), broth, a ff. differily vore anaerobic blood agar, and Drain Houseteristics of C. difficile were
clinical isolates that morphological characteristics of C. difficile were cirflical (Solates that mor moring the ColorPAC Toxin A test. After identification of the colonies by biochemical methods, toxiganic status was determined by a cytotoxin B assay. Results from this initial was dotennino each medium are summarized below.

Media Type	No.Specimens	Sensitivity95% ConfidenceIntervals	Specificity95% ConfidenceIntervals
BHI Broth	111	95% (84.9%,98.8%)	93% (82.7%,98.0%)
Selective Agar	111	95% (84.9%, 98.8%)	93% (82.7%,98.0%)
Anaerobic BloodAgar	111	89% (77.7%,95.9%)	95% (85.1%,98.9%)

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Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

July 17 1998

Colleen Rohrbeck Regulatory Affairs Associate Becton Dickinson Becton Dickinson Microbiology Systems 7 Loveton Circle Sparks, Maryland 21152

K980185 Re: Trade Name: ColorPAC™ Toxin A Regulatory Class: I Product Code: LLH Dated: May 13, 1998 Received: May 14, 1998

Dear Ms. Rohrbeck:

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 (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 Nutman

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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Page 1 of 1

510(k) Number (if known):

K980185

Device Name:

ColorPAC™ Toxin A

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	980185

Prescriptive Use	X
(Per 21CFR 801.109)

Over-the-Counter-Use
----------------------

odiff.ind.rev.	(Optimal Format 1-2-96)
----------------	-------------------------

Regulation Number and Section

§ 866.2660 Microorganism differentiation and identification device.

(a)
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.(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.