The Synovasure Alpha Defensin Lateral Flow Test Kit is a qualitative visually read immunochromatographic assay for the detection of human host response proteins, Alpha Defensins 1-3, in the synovial fluid of adults with a total joint replacement who are being evaluated for revision surgery. The Synovasure Alpha Defensin Lateral Flow Test Kit results are intended to be used in conjunction with other clinical and diagnostic findings as an aid in the diagnosis of periprosthetic joint infection (PJ). The Synovasure Alpha Defensin Lateral Flow Test Kit is not intended to identify the etiology or severity of a PJI.

The Synovasure Alpha Defensin Control Kit is used in the Synovasure Alpha Defensin Lateral Flow Test Kit as assayed quality control samples to monitor performance and reliability of the Synovasure Alpha Defensin Lateral Flow Test Kit.

Device Description

The Synovasure Alpha Defensin (AD) Lateral Flow (LF) Test Kit is an immunoassay for the detection of alpha defensin levels in the synovial fluid of patients with a potential PJI. Antibodies specific to alpha defensin bind host alpha defensin in the synovial fluid, become immobilized on the lateral flow test strip, and are detected as a colored line due to the use of a colloidal gold reporter.

AI/ML Overview

This document describes the Synovasure Alpha Defensin Lateral Flow Test Kit and its performance.

The device is a qualitative, visually-read immunochromatographic assay for detecting human host response proteins, Alpha Defensins 1-3, in synovial fluid of adults with total joint replacement being evaluated for revision surgery. It is intended to aid in the diagnosis of periprosthetic joint infection (PJI) when used with other clinical and diagnostic findings. It does not identify the etiology or severity of PJI.

Here's an analysis of the provided information regarding acceptance criteria and the study proving the device meets them:

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

The provided document does not explicitly state acceptance criteria in a quantitative table format for the device's performance. Instead, it references a "Method comparison study to demonstrate equivalent performance between proposed device with modified cassette geometry and existing version of the Alpha Defensin Lateral Flow Test Device was performed." This implies that the acceptance criterion was "equivalent performance" to the predicate device. However, specific metrics (e.g., sensitivity, specificity, accuracy) and their target values are not provided within this summary.

Therefore, a table cannot be fully constructed from the provided text. To illustrate, if specific targets were present:

Performance Metric	Acceptance Criteria	Reported Device Performance
Not specified	Not specified	Not specified
Sensitivity	[e.g., >= 85%]	Not explicitly stated
Specificity	[e.g., >= 90%]	Not explicitly stated
Accuracy	[e.g., >= 88%]	Not explicitly stated

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

The document mentions a "Method comparison study," but it does not specify the sample size for this study. It also does not provide information on the data provenance (e.g., country of origin, retrospective or prospective nature of the data).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document does not provide information on the number of experts used to establish ground truth or their qualifications. Given that the device detects "human host response proteins" and aids in "diagnosis of periprosthetic joint infection (PJI) ... in conjunction with other clinical and diagnostic findings," the ground truth likely involves clinical diagnosis of PJI, which would typically be established by medical professionals. However, specifics are missing.

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

The document does not provide information on any adjudication method used for establishing the ground truth or evaluating the device's performance in the method comparison study.

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

This device is described as a "qualitative visually read immunochromatographic assay" (a lateral flow test kit) and not an AI-assisted diagnostic tool for image analysis. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study evaluating human readers' improvement with AI assistance would not be applicable to this type of device, and no such study is mentioned.

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

This is a visually read test kit, implying a human-in-the-loop component for reading the test result. Therefore, a "standalone algorithm only" performance study would not be applicable in the same way it would be for an AI-driven image analysis algorithm. The "method comparison study" likely evaluates the performance of the device itself (including human interpretation) against a reference method or the predicate device.

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

The document states the device results "are intended to be used in conjunction with other clinical and diagnostic findings as an aid in the diagnosis of periprosthetic joint infection (PJI)." This strongly suggests that the ground truth for PJI diagnosis was established based on clinical diagnosis, which typically involves an expert consensus of various clinical, laboratory, and imaging findings, and potentially surgical/pathological confirmation. However, the specific components of the ground truth (e.g., specific clinical criteria, culture results, pathology reports) are not detailed.

8. The sample size for the training set

The document describes a "method comparison study" between the proposed device and an existing version. It does not mention a separate "training set" as would be typical for machine learning models. This is likely because the device is a conventional in-vitro diagnostic test, not an AI/ML-based device.

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

As there is no mention of a "training set" for an AI/ML model, this question is not applicable to the information provided. The "ground truth" for the performance evaluation set is implicitly clinical diagnosis of PJI, as discussed in point 7.

Summary

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August 11, 2021

CD Diagnostics Inc Pragnya Bakka Regulatory Affairs Specialist 650 Naamans Road Suite 100 Claymont, Delaware 19703

Re: K212204

Trade/Device Name: Synovasure Alpha Defensin Lateral Flow Test Kit (1 Kit), Synovasure Alpha Defensin Lateral Flow Test Kit (5 Test), Synovasure Alpha Defensin Lateral Flow Test Kit (10 Test), Synovasure Alpha Defensin Flow Test Kit (30 Test), Synovasure Alpha Defensin Control Kit Regulation Number: 21 CFR 866.3230 Regulation Name: Device To Detect And Measure Non-Microbial Analytes To Aid In The Detection And Identification Of Localized Human Infections Regulatory Class: Class II Product Code: QGN Dated: July 14, 2021 Received: July 15, 2021

Dear Pragnya Bakka:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of

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Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Maria Ines Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) DEN180032

Device Name

Synovasure Alpha Defensin Lateral Flow Test Kit

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

In accordance with 21 CFR §807.92 and the Safe Medical Devices Act of 1990, the following information is provided for the Synovasure Alpha Defensin Lateral Flow Test Kit 510(k) premarket notification. The submission was prepared in accordance with the FDA guidance document, 'Format for Traditional and Abbreviated 510(k)s', issued on August 12, 2005.

Sponsor:	CD Diagnostics Inc.650 Naamans Road, Suite100, Claymont, DE,19703.(302-367-7770)
Contact Person:	Pragnya BakkaRegulatory Affairs SpecialistTelephone: (973-307-8038)Fax: (302-367-7771)
Date:	14-July-2021
Subject Device:	Trade Name: Synovasure Alpha Defensin Lateral FlowTest Kit, Synovasure Alpha Defensin Lateral Flow TestKit (5 Test), Synovasure Alpha Defensin Lateral FlowTest Kit (10 Test), Synovasure Alpha Defensin LateralFlow Test Kit (30 Test), Synovasure Alpha DefensinControl Kit
	Classification Name:• QGN- Lateral Flow ImmunochromatographyAssay For Host Infection Biomarkers (21 CFR866.3230)

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Predicate Device(s):

Synovasure Alpha CD DEN180032 Defensin Lateral Flow Diagnostics Test Kit, Synovasure Inc. Alpha Defensin Lateral Flow Test Kit (5 Test). Synovasure Alpha Defensin Lateral Flow Test Kit (10 Test), Synovasure Alpha Defensin Lateral Flow Test Kit (30 Test), Synovasure Alpha

Defensin Control Kit

The Synovasure Alpha Defensin Lateral Flow Test Kit is a qualitative visually read immunochromatographic assay for the detection of human host response proteins, Alpha Defensins 1-3, in the synovial fluid of adults with a total joint replacement who are being evaluated for revision surgery. The Synovasure Alpha Defensin Lateral Flow Test Kit results are intended to be used in conjunction with other clinical and diagnostic findings as an aid in the diagnosis of periprosthetic joint infection (PJI). The Synovasure Alpha Defensin Lateral Flow Test Kit is not intended to identify the etiology or severity of a PJI.

Device Description:

Intended Use and Indications for Use:

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Summary of Technological Characteristics:

The rationale for substantial equivalence is based on consideration of the following characteristics:

Intended Use: Same as the predicate device •
Indications for Use: Same as the predicate device .
. Materials: Same as the predicate device

Design Features: Similar to predicate device with . minor modifications

Sterilization: Not applicable .

Summary of Performance Data (Nonclinical and/or Clinical)

Non-Clinical Tests: ●

Method comparison study to demonstrate o equivalent performance between proposed device with modified cassette geometry and existing version of the Alpha Defensin Lateral Flow Test Device was performed.
Clinical Tests: ●

o NA

Substantial Equivalence Conclusion

The information provided within this submission demonstrates that the Synovasure Aplha Defensin Lateral Flow Test Kit is substantially equivalent to the predicate device

Regulation Number and Section

§ 866.3230 Device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections.

(a)
Identification. A device to detect and measure non-microbial analytes to aid in the detection and identification of localized human infections is identified as an in vitro diagnostic device intended for the detection and qualitative measurement, quantitative measurement, or both of one or more non-microbial analytes in human clinical specimens to aid in the assessment, identification, or both of a localized microbial infection when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of human specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) An intended use with a detailed description of what the device detects and measures, the type of results provided to the user, the sample type, whether the measure is qualitative and/or quantitative, the clinical indications for the test use, and the specific population(s) for which the device is intended.
(ii) A detailed description of the performance characteristics of the device for all intended specimen types from the analytical and clinical studies (as applicable) required under paragraphs (b)(3)(ii) and (iii) of this section.
(iii) A detailed explanation of the interpretation of results, including acceptance criteria for evaluating the validity of individual runs (
e.g., assessment of internal and/or external quality controls, as applicable).(iv) The following limiting statements:
(A) A statement that a negative test result does not preclude the possibility of infection;
(B) A statement that the test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) A statement that consistent device performance is dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) A statement that details any limitations associated with the samples, as appropriate (
e.g., collected on the day of admission to the intensive care unit).(3) Design verification and validation must include the following:
(i) A detailed device description, including as appropriate, all device parts; control elements incorporated into the test procedure; instrument requirements; reagents required but not provided; and the principle of device operation and test methodology, including all preanalytical methods for the processing of specimens and the methodology from obtaining a sample to the result; design of primer/probe sequences; rationale for target analyte selection; and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies including analytical sensitivity (Limit of Detection, Limit of Quantitation, and Limit of Blank), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross-contamination, specimen stability, within-lab precision, reproducibility, and linearity, as applicable.
(iii) Detailed documentation and results either from a clinical study, that includes prospective (sequentially collected) samples for each intended specimen type that are representative of the intended use populations and, when determined to be acceptable by FDA, additional characterized clinical samples; or, when determined to be acceptable by FDA, an equivalent sample set. The clinical study must compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (
e.g., the predefined statistical analysis plan), clinical study report, testing results, and results of all statistical analyses.(iv) An evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and sex distribution) similar to the intended use population of the device.(v) Documentation of an appropriate end user device training program that will be offered as part of efforts to mitigate the risks of false results, failure to operate the device correctly, and failure to interpret test results correctly.
(vi) An appropriate risk mitigation strategy to ensure that the device does not prevent any other device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(vii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.