KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay

K161951 · Kronus, Inc. · PNI · Jul 22, 2016 · Immunology

Device Facts

• Record ID: K161951
• Device Name: KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay
• Applicant: Kronus, Inc.
• Product Code: PNI · Immunology
• Decision Date: Jul 22, 2016
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.5665
• Device Class: Class 2

Indications for Use

The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay is for the semi-quantitative determination of autoantibodies to Aquaporin-4 in human serum. The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay may be useful as an aid in the diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD). The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay is not to be used in conjunction with other clinical, laboratory, and radiological (e.g. MRI) findings.

Device Story

The KRONUS AQP4Ab ELISA is an in vitro diagnostic assay for detecting autoantibodies to Aquaporin-4 in human serum. The device utilizes an enzyme-linked immunosorbent assay (ELISA) format. It is intended for use in clinical laboratory settings by trained laboratory professionals. The assay provides semi-quantitative results that assist clinicians in the diagnosis of NMO and NMOSD. Results are interpreted by healthcare providers in conjunction with other clinical, laboratory, and radiological findings to support patient management and diagnostic decision-making.

Clinical Evidence

Bench testing only. Real-time closed-kit stability studies conducted to validate the extension of shelf-life from 4.5 months to 9 months at 4°C.

Technological Characteristics

Manual ELISA assay; storage at 4°C; shelf-life 9 months. Fundamental scientific technology remains unchanged from predicate.

Indications for Use

Indicated for semi-quantitative determination of AQP4 autoantibodies in human serum to aid in the diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD).

Regulatory Classification

Identification

An Aquaporin-4 autoantibody immunological test system is a device that consists of reagents used to measure by immunochemical techniques autoantibodies in human serum samples that react with Aquaporin-4 (AQP4Ab). The measurements aid in the diagnosis of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) in conjunction with other clinical, laboratory, and radiological (e.g., magnetic resonance imaging) findings.

Special Controls

An Aquaporin-4 autoantibody immunological test system must comply with the following special controls: 1) Premarket notification submissions must include the following information: i) A detailed device description including: A) A detailed description of all components including all required ancillary reagents in the test. B) If applicable, a detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals. C) If applicable, detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. D) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the specified testing procedures. E) Detailed specifications for sample collection, processing, and storage. F) A detailed description of methodology and assay procedure. G) A description of how the assay cut-off (the medical decision point between positive and negative) was established and validated as well as supporting data. H) Detailed specification of the criteria for test results interpretation and reporting. ii) Detailed information demonstrating the performance characteristics of the device, including: A) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-site, and total precision for multiple nonconsecutive days, as applicable. A well characterized panel of patient samples or pools from the indicated population that covers the device measuring range must be used. B) Device linearity data generated from samples covering the device measuring range, if applicable. C) Information on traceability to a reference material and description of value assignment of calibrators and controls, if applicable. D) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation, if applicable. E) Device analytical specificity data, including interference by endogenous and exogenous substances, as well as cross-reactivity with samples derived from patients with other autoimmune diseases or conditions. F) Device instrument carryover data, when applicable. G) Device stability data, including real-time stability under various storage times and temperatures. H) Specimen stability data, including stability under various storage times, temperatures, freeze-thaw, and transport conditions, where appropriate. I) Method comparison data generated by comparison of the results obtained with the device to those obtained with a legally marketed predicate device with similar indications of use. A well-characterized panel of patient samples from the indicated population covering the device measuring range must be used. J) Specimen matrix comparison data, if more than one specimen type or anticoagulant can be tested with the device. Samples used for comparison must be from well-characterized patient samples covering the device measuring range. K) Clinical performance must be established by comparing data generated by testing samples from the indicated population and the differential diagnosis or non-target disease groups with the device to the clinical diagnostic standard. (1) The diagnosis of NMO and NMOSD must be based on clinical findings, laboratory tests (e.g., serological tests), and radiological tests (e.g., Magnetic Resonance Imaging). (2) The differential diagnosis or non-target disease group must include the applicable diseases or conditions, including but not be limited to the following: multiple sclerosis, stroke, lyme disease, shingles, syphilis, human immunodeficiency virus, hepatitis B, tuberculosis, Sjörgen's Syndrome, systemic lupus erythematous, systemic vasculitis, sarcoidosis, Graves' disease, Hashimoto's disease. Type I diabetes, rheumatoid arthritis, Addison's disease, and Myasthenia Gravis. (3) Diagnosis of diseases or conditions for the differential or nontarget disease groups must be based on established diagnostic criteria and clinical evaluation. (4) For all samples, the diagnostic clinical criteria and the demographic information must be collected and provided. (5) The clinical validation results must demonstrate clinical sensitivity and clinical specificity for the test values based on the presence or absence of NMO and NMOSD. (6) The data must be summarized in tabular format comparing the interpretation of results to the disease status. L) Expected/ reference values generated by testing an adequate number of samples from apparently healthy normal individuals. iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. 2) The device's 21 CFR 809.10(b) compliant labeling must include warnings relevant to the device including: i) A warning statement that reads "The device is for use by laboratory professionals in a clinical laboratory setting." ii) A warning statement that reads "The device is not to be used as a standalone device but as an adjunct to other clinical information. A diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD) should not be made on a single test result. The clinical symptoms, results from physical examination, laboratory tests (e.g., serological tests), and radiological tests (e.g. Magnetic Resonance Imaging), when appropriate, should always be taken into account when considering the diagnosis of NMO and NMOSD." 3) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol and performance studies performed in accordance with special control (1)(ii) and a summary of the results.

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information: (i) A detailed device description including: (A) A detailed description of all components including all required ancillary reagents in the test; (B) If applicable, a detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals; (C) If applicable, detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software; (D) A detailed description of appropriate internal and external quality controls that are recommended or provided. The description must identify those control elements that are incorporated into the specified testing procedures; (E) Detailed specifications for sample collection, processing, and storage; (F) A detailed description of methodology and assay procedure; (G) A description of how the assay cutoff (the medical decision point between positive and negative) was established and validated as well as supporting data; and (H) Detailed specification of the criteria for test results interpretation and reporting. (ii) Detailed information demonstrating the performance characteristics of the device, including: (A) Device precision/reproducibility data generated from within-run, between-run, between-day, between-lot, between-site, and total precision for multiple nonconsecutive days, as applicable. A well characterized panel of patient samples or pools from the indicated population that covers the device measuring range must be used. (B) Device linearity data generated from samples covering the device measuring range, if applicable. (C) Information on traceability to a reference material and description of value assignment of calibrators and controls, if applicable. (D) Device analytical sensitivity data, including limit of blank, limit of detection, and limit of quantitation, if applicable. (E) Device analytical specificity data, including interference by endogenous and exogenous substances, as well as cross-reactivity with samples derived from patients with other autoimmune diseases or conditions. (F) Device instrument carryover data, when applicable. (G) Device stability data, including real-time stability under various storage times and temperatures. (H) Specimen stability data, including stability under various storage times, temperatures, freeze-thaw, and transport conditions, where appropriate. (I) Method comparison data generated by comparison of the results obtained with the device to those obtained with a legally marketed predicate device with similar indications of use. A well-characterized panel of patient samples from the indicated population covering the device measuring range must be used. (J) Specimen matrix comparison data, if more than one specimen type or anticoagulant can be tested with the device. Samples used for comparison must be from well-characterized patient samples covering the device measuring range. (K) Clinical performance must be established by comparing data generated by testing samples from the indicated population and the differential diagnosis or non-target disease groups with the device to the clinical diagnostic standard. ( *1* ) The diagnosis of NMO and NMOSD must be based on clinical findings, laboratory tests (*e.g.,* serological tests), and radiological tests (*e.g.,* magnetic resonance imaging).( *2* ) The differential diagnosis or non-target disease group must include the applicable diseases or conditions, including but not be limited to the following: Multiple sclerosis, stroke, Lyme disease, shingles, syphilis, human immunodeficiency virus, hepatitis B, tuberculosis, Srgen's syndrome, systemic lupus erythematous, systemic vasculitis, sarcoidosis, Graves' disease, Hashimoto's disease, Type I diabetes, rheumatoid arthritis, Addison's disease, and myasthenia gravis.( *3* ) Diagnosis of diseases or conditions for the differential or non-target disease groups must be based on established diagnostic criteria and clinical evaluation.( *4* ) For all samples, the diagnostic clinical criteria and the demographic information must be collected and provided.( *5* ) The clinical validation results must demonstrate clinical sensitivity and clinical specificity for the test values based on the presence or absence of NMO and NMOSD.( *6* ) The data must be summarized in tabular format comparing the interpretation of results to the disease status.(L) Expected/reference values generated by testing an adequate number of samples from apparently healthy normal individuals. (iii) Identification of risk mitigation elements used by the device, including description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing. (2) The device's 21 CFR 809.10(b) compliant labeling must include warnings relevant to the device including: (i) A warning statement that reads “The device is for use by laboratory professionals in a clinical laboratory setting”; and (ii) A warning statement that reads “The device is not to be used as a stand-alone device but as an adjunct to other clinical information. A diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD) should not be made on a single test result. The clinical symptoms, results from physical examination, laboratory tests ( *e.g.,* serological tests), and radiological tests (*e.g.* Magnetic Resonance Imaging), when appropriate, should always be taken into account when considering the diagnosis of NMO and NMOSD.”(3) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol and performance studies performed in accordance with paragraph (b)(1)(ii) of this section and a summary of the results.

Submission Summary (Full Text)

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SPECIAL 510(k): Device Modification OIR Decision Summary

To: THE FILE

RE: K161951

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II, Class III or Class I devices requiring 510(k). The following items are present and acceptable:

1. The name and 510(k) number of the SUBMITTER'S previously cleared device. The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay was cleared under DEN150030.
2. Submitter's statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials (labeling changes are permitted as long as they do not affect the intended use).
3. A description of the device MODIFICATION(S), including clearly labeled diagrams, engineering drawings, photographs, user's and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

This change was for :

a) whole-kit stability (shelf-life) extension from 4.5 months to 9 months.

4. Comparison Information (similarities and differences) to applicant's legally marketed predicate device including, labeling, intended use, physical characteristics, and performance studies (real-time closed-kit stability) is shown in the table below.

| Summary of Similarities and Differences: | | |
| --- | --- | --- |
| Characteristic | Predicate Device: The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay | Modified Device: The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay |
| Intended Use | For the semi-quantitative determination of autoantibodies to Aquaporin-4 in human serum. The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay may be useful as an aid in the diagnosis of Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorders (NMOSD). The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay is not to be used alone and is to be used in conjunction with other clinical, laboratory, and radiological (e.g. MRI) findings. | Same |

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| Summary of Similarities and Differences: | | |
| --- | --- | --- |
| Characteristic | Predicate Device: The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay | Modified Device: The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay |
| Assay Type | Manual ELISA | Same |
| Shelf-life Stability | 4.5 months at 4°C | 9.0 months at 4°C |

5. A Design Control Activities Summary which includes:

a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis.
b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter's description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared (or their preamendment) device.