Bartels Clostridium difficile Toxin A Enzyme Immunoassay (EIA) is intended for the qualitative detection of Clostridium difficile Toxin A in human fecal specimens as an aid in the diagnosis of Clostridium difficile -associate diseases.

Device Description

The Bartels Clostridium difficile Toxin A EIA is a rapid method for the diagnosis of Clostridium difficile toxin A in human fecal samples, to be used as an aid in the detection of Clostridium difficile-associated disease. Microwell strips are coated with mouse IgG to Clostridium difficile toxin A, which selectively captures Clostridium difficile toxin A if present in a stool sample. Irrelevant specimen debris, including non-toxigenic strains of Clostridium difficile, is washed away. Rabbit immunoglobulins to Clostridium difficile toxin A and peroxidase-labeled goat anti-rabbit antibodies are added to the well concurrently in a coincubation step. During incubation, the rabbit anti- Clostridium difficile toxin A binds to captured toxin A. Peroxidase-labeled anti-rabbit antibodies bind to rabbit antitoxin, forming an antitoxin-conjugate complex. Unbound anti-toxin and conjugate are washed away. Solution 3 and Solution 4 are then added and color is produced if the antitoxin-conjugate complex, which possesses the enzyme for the substrate (HRP), is present. This color production is quantified spectrophotometrically and compared to negative and positive controls for determination of the presence of Clostridium difficile toxin A.

AI/ML Overview

The provided document (K990664) is a 510(k) summary for a modification to an existing device, the Bartels Clostridium difficile Toxin A Enzyme Immunoassay (EIA). The document primarily focuses on demonstrating substantial equivalence of the modified device to the previously cleared device (K913229) based on changes to the assay procedure (incubation times, temperature, and addition of a manual wash method), rather than presenting a full de novo study with detailed acceptance criteria and performance reports for the device's initial market clearance.

Therefore, the requested information, specifically detailed acceptance criteria and the comprehensive study that proves the device meets those criteria, is not fully available within this specific 510(k) modification document. This document mainly confirms that the methodological changes did not adversely affect the device's performance compared to the predicate device.

However, based on the information available and common regulatory practices for 510(k) modifications, I can infer and provide some relevant details:

Missing Information:

Detailed list of specific acceptance criteria (e.g., sensitivity, specificity thresholds) for the device's initial clearance.
The comprehensive study report that originally proved the device meets broad acceptance criteria. This document focuses on proving equivalence of a modified procedure.
Sample size and data provenance for the original clinical studies.
Number and qualifications of experts for the original ground truth.
Adjudication method for the original studies.
Whether an MRMC comparative effectiveness study was done for the original device.
Effect size of human readers improving with AI vs. without AI assistance (this is an immunoassay, not an AI-based diagnostic).
Sample size for the original training set (if applicable, for initial development).
How ground truth for the original training set was established.

Information that can be extracted or inferred from the provided modification document (K990664):

1. A table of acceptance criteria and the reported device performance

Since this is a 510(k) modification for procedural changes, the "acceptance criteria" here refer to demonstrating that the modified procedure performs equivalently to the predicate device whose performance was already established. The document states:

"INTRACEL has made no changes to the manufacturing process or quality control testing procedures for this product. The only changes relate to the incubation and washing conditions employed during performance of the immunoassay. The essential immunoreagents, underlying format and scientific principle remain the same with the improved product."

This implies that the key acceptance criterion for this modification was that the modified assay procedure did not negatively impact the established performance characteristics (sensitivity, specificity, precision, etc.) of the original Bartels C. difficile Toxin A EIA. The document does not list specific numerical performance metrics for the modified device, but rather refers to its equivalence to the predicate.

Acceptance Criteria (for the modified procedure)	Reported Device Performance (as implied by equivalence)
Performance of modified device is equivalent to predicate device (K913229)	No changes to essential immunoreagents, underlying format, and scientific principle. The modified procedure (reduced incubation time, new substrate incubation, added manual wash) is considered substantially equivalent to the predicate device.
	Performance characteristics (sensitivity, specificity, etc.) are maintained despite procedural changes.

2. Sample size used for the test set and the data provenance (country of origin of the data, retrospective or prospective)

The document does not explicitly state these details for this specific modification. It implies that the changes were validated through internal testing to confirm equivalence. Usually, for procedural changes in a 510(k) modification, manufacturers would perform comparative studies using clinical samples to show that results are consistent between the old and new procedures. However, the details of such a study (sample size, provenance, retrospective/prospective nature) are not provided in this summary.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document. For an immunoassay like this, the "ground truth" would typically come from a gold standard diagnostic method (e.g., toxigenic culture or a highly validated PCR method) rather than expert consensus on images.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not specified in the document.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. This device is an Enzyme Immunoassay (EIA) for detecting Clostridium difficile Toxin A, not an AI-based diagnostic or imaging device requiring human reader interpretation. Therefore, the concept of "human readers improving with AI vs. without AI assistance" is not applicable here.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, this is a standalone diagnostic test. The Bartels Clostridium difficile Toxin A EIA is an in vitro diagnostic device; its performance is assessed based on its ability to detect the toxin in fecal samples, without human intervention required for its analytical performance beyond running the assay and interpreting the quantitative spectrophotometric result against controls.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The document itself does not specify the method for establishing ground truth. However, for a test detecting Clostridium difficile Toxin A, the typical ground truth in clinical validation studies would involve:

Culture for toxigenic C. difficile strains (cytotoxigenic culture): Considered the gold standard for many years.
Molecular methods (e.g., PCR for toxin genes): Increasingly used as a gold standard.
Correlation with clinical outcomes: While not a direct "ground truth" for the presence of toxin, association with clinical disease is crucial for medical devices.

8. The sample size for the training set

This document does not provide details on a "training set" as it relates to machine learning models. For an immunoassay, developmental testing would involve numerous samples, but these are typically not referred to as a "training set" in the context of device regulatory submissions.

9. How the ground truth for the training set was established

Not applicable/not specified for an immunoassay in this context.

Summary

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Image /page/0/Picture/0 description: The image shows the date 3/3/99 and the text "Bartels Clostridium difficile Toxin A EIA Special 510(k) Modification". The date is written in a handwritten style, with the year 1999 abbreviated to 99. The text below the date describes a medical product or test, likely related to Clostridium difficile toxin A.

K990664 000017
Confidential

510(K) SUMMARY

CONTACTS A.

MANUFACTURING SITE:

Candice DiDominick Compliance Manager INTRACEL Corporation 2005 NW Sammamish Road, Suite 107 Issaquah, Washington 98027

Phone: (425) 392-2992 ext. 638 Fax: (425) 557-1894

INTRACEL -ROCKVILLE

Cecilia Matos-Rosa Regulatory Compliance INTRACEL Corporation 1330 Piccard Drive Rockville, MD 20850

Phone: (301) 258-5200 ext. 1124 (301) 977-3229 Fax:

NAME OF DEVICE AND CLASSIFICATION B.

Bartels PRIMA System™ Clostridium difficile Toxin A Enzyme Immunoassay (EIA).

Trade/Proprietary Name:

PRIMA System – old Bartels ELISA - new

Device Class:

Class I

510(k): K913229

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C. LEGALLY MARKETED DEVICE

Bartels Clostridium difficile Toxin A EIA claims substantial equivalence to Bartels PRIMA System Clostridium difficile Toxin A EIA (K913229), currently in commercial distribution by INTRACEL, Corporation, Issaquah, WA (USA).

DEVICE DESCRIPTION: D.

INTENDED USE STATEMENT E.

DESCRIPTION OF MODIFIED DEVICE COMPARED TO CLEARED F. DEVICE

INTRACEL has made no changes to the manufacturing process or quality control testing procedures for this product. The only changes relate to the incubation and washing conditions employed during performance of the immunoassay. The essential immunoreagents, underlying format and scientific principle remain the same with the improved product.

The following changes have been made for the kit assay procedure:

1 . In the FDA cleared kit, the specimen is incubated in the antibodycoated well for 90 minutes at 37° C. In the improved format, the specimen is now incubated for only 30 minutes at 37° C.

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1. In the FDA cleared kit, the product insert only specifies the use of an automated microwell washer after sample and conjugate incubation steps. In the improved format, the wash can also be conducted using a manual method. The manual wash procedure is being incorporated into the procedure in reaction to actual use conditions by the customers. The total number of washes remains at 4 for both procedures.
1. In the FDA cleared kit, the colorimetric substrate is incubated for 15 minutes at ambient temperature. In the improved assay procedure, the substrate is incubated for 30 minutes at 37℃.

To summarize, the total assay time is reduced from 135 minutes to 90 minutes. All incubation times are now performed at 37°C, and an alternative manual washing method was added.

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Public Health Service

Image /page/3/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with its wings spread, with three human figures in the negative space between the wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.

MAR 3 1 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Cecilia Matos-Rosa Regulatory Compliance INTRACEL Corporation 1330 Piccard Drive Rockville, MD 20850

Re : K990664 Trade Name: Bartels PRIMA System Clostridium difficile Toxin A Enzyme Immunoassay (EIA) Regulatory Class: I Product Code: LLH Dated: March 1, 1999 Received: March 1, 1999

Dear Ms. Matos-Rosa:

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 In addition, FDA may publish further regulatory action. 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

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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" Other general information on your (21 CFR 807.97). responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,

Steven Sutman

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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006003

510(k) Number (if known): K990664

Device Name: Bartels Clostridium difficile Toxin A EIA

Indications For Use:

Bartels Clostridium difficille Toxin A Enzyme Immunoassay (EIA) is intended for the qualitative detection of Clostridium difficille Toxin A in human fecal specimens as an aid in the diagnosis of Clostridium difficilleassociated disease.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K990664

Image /page/5/Picture/8 description: The image shows the words "Prescription Use" in bold font, followed by the text "(Per 21 CFR 801.109)" in a smaller font. There is a line under the words "Prescription Use" with a large X drawn over the line. The text is left-aligned and appears to be part of a form or document.

(Optional 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.