BINDING SITE BINDAZYME ANTI-GBM EIA DIAGNOSTIC TEST KIT by THE BINDING SITE, LTD.

For the in-vitro measurement of specific IgG autoantibodies against the glomerular basement membrane (GBM) specifically the C-terminal end of type IV collagen, present in human serum. It is intended as an aid in the diagnosis of Goodpast's syndrome, in conjunction with other clinical findings.

Device Description

BINDAZYME Anti-GBM EIA Diagnostic Test Kit

AI/ML Overview

This document is a 510(k) clearance letter from the FDA for an in vitro diagnostic test kit, specifically the "Binding Site BINDAZYME® Anti-GBM Enzyme Immunoassay Diagnostic Test Kit."

It's important to understand that a 510(k) clearance for an in vitro diagnostic (IVD) device is fundamentally different from the regulatory process for AI-powered medical image analysis devices. The information requested in your prompt (e.g., sample size for test set, number of experts, adjudication methods, MRMC studies, standalone performance, training set details) is typically associated with the comprehensive clinical validation studies required for AI devices, especially those that provide diagnostic insights from medical images.

For an IVD like the one described in this document, the "performance" typically refers to analytical performance (sensitivity, specificity, precision, accuracy relative to a reference method) and clinical performance (how well the test results correlate with the presence or absence of the disease in a patient population, and its utility in diagnosis). The document provided is not a study report; it's an FDA clearance letter affirming substantial equivalence to a predicate device. Therefore, it does not contain the detailed study information you are asking for regarding acceptance criteria, sample sizes, expert involvement, or AI-specific validation methods.

However, I can infer and state what would typically be expected for such a device and what some of the closest information might be, based on the nature of a 510(k) submission for an IVD.

Absence of Specific Information:

The provided document (FDA 510(k) clearance letter) does not contain the detailed study information required to answer most of your questions about acceptance criteria and study design as it pertains to AI/ML devices. This document is a regulatory approval letter based on a separate submission, not the submission itself or a study report.

Inferences Based on IVD Nature and 510(k) Process (General Expectation, Not from Document):

For an in-vitro diagnostic (IVD) device, the "acceptance criteria" and "study" would typically refer to analytical and clinical performance studies, which are evaluated against a predicate device or accepted standards for diagnosing a specific condition.

Based on the provided document and general understanding of IVD 510(k) clearances, here's what can be stated or inferred:

Table of Acceptance Criteria and Reported Device Performance:
- Acceptance Criteria: Not specified in the provided document. For an IVD like this, acceptance criteria would typically relate to analytical performance (e.g., sensitivity, specificity, precision, linearity, range) and clinical performance (e.g., agreement with a gold standard or predicate device in patient populations).
- Reported Device Performance: Not explicitly detailed in the provided document. The FDA's letter states that "we have determined the device is substantially equivalent... to legally marketed predicate devices." This implies that the device's performance, as demonstrated in its 510(k) submission, was deemed comparable to that of a predicate device already on the market. Specific metrics (e.g., sensitivity, specificity, accuracy values) are not present in this clearance letter.
Sample Size Used for the Test Set and Data Provenance:
- Not specified in the provided document. For an IVD, the test set would typically involve patient samples (sera in this case) from individuals with and without the condition of interest. The size and characteristics of this sample set would have been part of the 510(k) submission.
- Data Provenance: Not specified in the provided document. Typically, clinical studies for IVDs involve samples collected from various clinical sites. Whether these were prospective or retrospective samples is not mentioned.
Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
- Not applicable in the typical sense for this IVD. The "ground truth" for an IVD like the Anti-GBM EIA would be established through a combination of:
  - Clinical diagnosis: Based on patient symptoms, imaging, biopsy, and other laboratory tests.
  - Reference method(s): Comparison to other established laboratory tests or panels for GBM autoantibodies.
  - Pathological confirmation: In some cases, kidney biopsy findings would be definitive "ground truth."
- Therefore, it's not about "experts establishing ground truth for a test set" in the context of image interpretation, but rather clinical and pathological confirmation of disease status.
Adjudication Method for the Test Set:
- Not applicable as typically understood for AI evaluation. Adjudication (e.g., 2+1, 3+1) is common in reader studies for AI devices. For an IVD, the "ground truth" is established via clinical diagnosis and/or reference laboratory methods, not by multiple expert readers interpreting the test output for ground truth.
If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No, this is highly unlikely for an IVD kit. MRMC studies are primarily designed for evaluating the performance of imaging devices or AI algorithms that assist human readers in interpreting medical images. This device is a laboratory assay.
If a Standalone Performance was done:
- Yes, in spirit, for an IVD. An IVD kit's performance is inherently "standalone" in that it provides a quantitative or qualitative result based directly on the patient sample. Its performance (e.g., sensitivity, specificity, positive predictive value, negative predictive value) would have been evaluated relative to the true disease status or a reference method. It operates without human interpretation of complex outputs in the way an AI image analysis algorithm does.
The Type of Ground Truth Used:
- Likely a combination of clinical diagnosis, other established laboratory methods, and possibly pathology (e.g., kidney biopsy results) for the presence or absence of Goodpasture's syndrome. The device measures IgG autoantibodies against GBM, which is a specific marker for the disease. Ground truth would confirm the actual pathological or clinical state of the patient.
The Sample Size for the Training Set:
- Not specified in the provided document. For an IVD, internal development and validation would involve numerous samples, but it's not referred to as a "training set" in the same way as for AI algorithms. It's more about assay optimization and internal validation samples.
How the Ground Truth for the Training Set Was Established:
- Not specified in the provided document. For an IVD's internal development and optimization, ground truth would be established similarly to the test set: through well-characterized patient samples with known clinical and/or pathological diagnoses, or through spiked samples for analytical validation.

Summary:

The provided document is an FDA 510(k) clearance letter for an in vitro diagnostic test kit, not a detailed study report for an AI-powered device. Therefore, it does not contain the specific information about acceptance criteria, sample sizes, expert involvement, and AI-specific validation methods that your questions are structured around. The "study" for this device would have focused on analytical and clinical performance to demonstrate substantial equivalence to a predicate device, which is a different paradigm from AI device validation.

Summary

{0}------------------------------------------------

Image /page/0/Picture/2 description: The image shows a black and white logo. The logo consists of a stylized eagle with its wings spread, facing to the right. To the left of the eagle is text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES" in a circular arrangement. The text is in all caps and is smaller than the eagle symbol.

FEB 2 3 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

The Binding Site, Limited C/O Mr. Jay H. Geller East Tower, Suite 600 2425 West Olympic Boulevard Santa Monica, California 90404

Re: K984619

Trade Name: Binding Site BINDAZYME® Anti-GBM Enzyme Immunoassay Diagnostic Test Kit

Regulatory Class: II Product Code: MVJ Dated: December 23, 1998 Received: December 29, 1998

Dear Mr. Geller:

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.

{1}------------------------------------------------

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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman.

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

{2}------------------------------------------------

Page__________________________________________________________________________________________________________________________________________________________________________

10(k) Number (if known):	K984419
Device Name:	BINDAZYME

Anti-GBM EIA Diagnostic Test Kit## Indications For Use:

INDICATIONS FOR USE STATEMENT

Anti-GBM EIA Diagnostic Test Kit Device Name:

For the in-vitro measurement of specific IgG Indications for Use: autoantibodies against the glomerular basement membrane (GBM) specifically the C-terminal end of type IV collagen, present in It is intended as an aid in the diagnosis of human serum. in conjunction with other clinical syndrome, Goodpasture's findings.

Voter E. Maples

(Division Sign Off) Division of Jimear Laboratury Leve & 984619 510(k) NumiDer _______________________________________________________________________________________________________________________________________________________________

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use b (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.5660 Multiple autoantibodies immunological test system.

(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).