(345 days)
For the in-vitro qualitative screening IgG, M autoantibodies against B2-glycoprotein 1 (B2GP1) present in A, This kit may be used in conjunction with human serum. assays and clinical information to aid the anticardiolipin anerouralis of thrombosis in at risk patients having, for example, antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) .
Bindazyme® Anti-B2 GP1 Screen EIA Test Kit
This is an FDA Premarket Notification (510(k)) K991804 for a diagnostic test kit, not a device that would typically have the kind of performance criteria and study structure you're asking about (e.g., AI algorithms, MRMC studies, specific effect sizes for human reader improvement).
The document describes the Bindazyme® Anti-B2 GP1 Screen EIA Test Kit, an in-vitro diagnostic device for the qualitative screening of IgG and IgM autoantibodies against B2-glycoprotein 1 (B2GP1) in human serum. This type of device's "performance" is typically evaluated through clinical sensitivity, specificity, accuracy, precision, and agreement with predicate devices or reference methods.
Therefore, many of the specific questions you've asked, such as "effect size of how much human readers improve with AI vs without AI assistance," "adjudication method," and "number of experts used to establish the ground truth for the test set," are not applicable to this type of medical device submission.
However, I can extract the relevant information that is present or infer what would typically be part of such a submission for an in vitro diagnostic kit.
Here's an attempt to answer based on the provided document and typical expectations for an IVD kit:
1. A table of acceptance criteria and the reported device performance
The provided document does not explicitly list acceptance criteria or detailed reported device performance in this summary letter. For EIA kits, typical acceptance criteria and performance metrics would include:
| Acceptance Criteria (Typical for EIA Kit) | Reported Device Performance (Not explicitly in this document, but inferred) |
|---|---|
| Clinical Sensitivity: Ability to correctly identify positive samples. | (Would be provided in a separate performance study section of the 510(k), comparing results to a gold standard or predicate device. Typically reported as a percentage.) |
| Clinical Specificity: Ability to correctly identify negative samples. | (Would be provided in a separate performance study section of the 510(k). Typically reported as a percentage.) |
| Accuracy/Agreement: Overall agreement with a reference method or predicate device. | (Typically reported as overall percent agreement, positive percent agreement, and negative percent agreement.) |
| Precision/Reproducibility: Consistency of results when tested multiple times. | (Would include within-run, between-run, and between-day precision, often expressed as %CV.) |
| Linearity/Assay Range: The range over which the assay gives accurate results. | (Not directly applicable for a 'screening' qualitative kit, but quantitative versions would have this.) |
| Interference: Lack of significant impact from common interfering substances. | (Would be tested with various endogenous and exogenous substances; results would confirm no significant interference within specified limits.) |
| Cross-reactivity: No significant reactivity with related or potentially interfering antibodies/substances. | (Specific antibodies or substances would be tested to ensure no false positives.) |
| Shelf-life stability: Device maintains performance over its stated shelf-life. | (Real-time or accelerated stability studies would support the expiration date.) |
| Substantial Equivalence: Demonstrated equivalence to a legally marketed predicate device. | This is the primary acceptance criterion for 510(k) approval. The FDA letter confirms that the device is substantially equivalent to legally marketed predicate devices. |
2. Sample size used for the test set and the data provenance
The provided document does not specify the sample size for the test set or the data provenance. For an IVD kit, performance studies would typically involve:
- Sample Size: Varies but would be sufficient to achieve statistically significant results, often hundreds of samples (e.g., 200-500 or more) including both positive and negative cases from various patient populations.
- Data Provenance: Could be prospective (newly collected samples) or retrospective (archived samples), and would typically specify the disease prevalence represented, as well as characteristics of the patient population (e.g., patients suspected of APS/SLE, healthy controls, other autoimmune conditions). Country of origin is usually not explicitly stated in the summary, but data would be from clinical sites.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This question is not applicable in the context of an in vitro diagnostic test kit that measures a biomarker (antibodies). Ground truth for such a device is typically established by:
- Reference Methods: Comparison against an established "gold standard" laboratory method (e.g., another FDA-cleared or well-validated EIA kit, IFA, Western Blot, or a quantitative immunoassay).
- Clinical Diagnosis: Clinical diagnosis of a condition (e.g., Antiphospholipid Syndrome (APS) or Systemic Lupus Erythematosus (SLE)) as determined by a physician (e.g., rheumatologist) using established diagnostic criteria, often supported by other laboratory tests and clinical findings.
4. Adjudication method for the test set
This is not applicable in the traditional sense for an IVD kit's performance study regarding ground truth. If comparison against a predicate device led to discordant results, those discordant samples might undergo further testing with a tie-breaker method or a more definitive reference method.
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
Not applicable. MRMC studies and "human readers improve with AI" are concepts relevant to AI-powered image analysis or diagnostic support systems, not a chemical-based in vitro immunoassay test kit. This device is read objectively (e.g., spectrophotometrically) and does not involve human interpretation of complex images or data that AI would assist with.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a manual or semi-automated immunoassay kit; there is no embedded algorithm in the sense of AI. The "algorithm" is the biochemical reaction and the reading of optical density according to the manufacturer's instructions. Its performance is inherent in the kit's design and reagents.
7. The type of ground truth used
For an in-vitro diagnostic test like the Bindazyme® Anti-B2 GP1 Screen EIA Test Kit, the ground truth would most likely be based on:
- Clinical Diagnosis: Diagnosis of Antiphospholipid Syndrome (APS) or Systemic Lupus Erythematosus (SLE) according to established clinical criteria (e.g., revised Sapporo criteria for APS, ACR/SLICC criteria for SLE), often supported by other laboratory findings and clinical presentation.
- Reference Method: Results from a previously cleared or well-established laboratory method for detecting anti-B2GP1 antibodies or associated conditions.
- Expert Consensus (indirectly): The diagnostic criteria themselves are often products of expert consensus; however, direct "expert consensus" on this specific kit's results is not how ground truth is typically established for biomarker assays.
8. The sample size for the training set
The document does not specify a training set size. For IVD kits, "training set" is usually not discussed in the context of machine learning. Instead, it would refer to:
- Assay Development and Optimization: Samples used during the development phase to fine-tune reagent concentrations, incubation times, cut-off values, etc. This is an iterative process and not typically reported with a fixed "sample size" like a clinical validation study.
- Cut-off Determination: A separate set of well-characterized samples (e.g., healthy controls and known positives) would be used to establish the assay's cut-off value using statistical methods (e.g., ROC analysis, percentile calculation).
9. How the ground truth for the training set was established
Similar to point 8, the concept of a "training set" with ground truth in the AI sense is not applicable. For the development and optimization samples, ground truth would be established through:
- Well-characterized samples: Use of samples from patients with confirmed diagnosis of APS/SLE (based on clinical criteria and other serological markers) and samples from healthy individuals or those with other autoimmune diseases where anti-B2GP1 is expected to be absent.
- Comparison to existing methods: Performance against established laboratory methods during the development process.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three abstract human figures or flowing lines, arranged in a way that suggests movement or connection.
MAY - 5 2000
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
The Binding Site c/o Mr. Jay H. Geller West Tower, Suite 4000 2425 West Olympic Boulevard Santa Monica, California 90404
Re: K991804
Trade Name: Bindazyme® Anti-B2 GP1 Screen EIA Test Kit Regulatory Class: II Product Code: MSV Dated: March 31, 2000 Received: April 4, 2000
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.
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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" (21CFR 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
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| Page | of------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
|---|---|
510(k) Number (if known): 1991809
Device Name:_
Indications For Use:
INDICATIONS FOR USE STATEMENT
Bindazyme® Anti-B2 GP1 Screen EIA Test Kit Device Name:
For the in-vitro qualitative screening IgG, Indications for Use: M autoantibodies against B2-glycoprotein 1 (B2GP1) present in A, This kit may be used in conjunction with human serum. assays and clinical information to aid the anticardiolipin anerouralis of thrombosis in at risk patients having, for example, antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE) .
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Titu E. Mäderi
(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
(Optional Format 1-2-96)
§ 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).