(70 days)
The Optilite IgA CSF Kit is intended for the quantitative in vitro measurement of IgA in cerebrospinal fluid (CSF) using the Optilite analyser.
The Optilite IgA CSF Kit comprises the following reagents: Latex Reagent, Calibrator and Controls, and Reaction Buffer.
The provided text describes the performance characteristics of the Optilite IgA CSF Kit. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision (Total CV%) | Not explicitly stated, but generally <10% for clinical assays | Level 1 (2.24 mg/L): 4.0% |
| Level 2 (3.53 mg/L): 5.6% | ||
| Level 3 (4.59 mg/L): 4.4% | ||
| Level 4 (28.90 mg/L): 2.9% | ||
| Linearity/Assay Reportable Range | Deviation from linearity <10% | Confirmed over the range of 1.0-44.8 mg/L with deviation from linearity <10% |
| Traceability | Traceable to international reference material | Traceable to ERM-DA470k/IFCC |
| Kit Stability (Shelf life) | Sufficient for practical use | Up to 18 months |
| Open-Vial Stability | Sufficient for practical use | Up to 3 months (at 2-8°C) |
| On-Board Stability | Sufficient for practical use | Up to 30 days (on Optilite Analyser) |
| Limit of Quantitation (LoQ) | Defined as the bottom of the measuring range | 0.91 mg/L |
| Analytical Specificity (Interference) | No significant interference from common substances | No significant interference observed with hemoglobin (2.5g/L), bilirubin (100mg/L), acetaminophen (1324μmol/L), or acetylsalicylic acid (3.63mmol/L) |
| Method Comparison (Correlation) | High correlation with a predicate device (e.g., correlation coefficient > 0.95, slope near 1, intercept near 0) | Correlation coefficient 0.984; Passing Bablok: y = 1.05x - 0.02 (Slope 95% Cl: 1.03 to 1.07, Intercept 95% Cl: -0.07 to 0.05) |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility: 4 different samples were used. The number of runs (two per day for 5 days) and analysts (two) suggest multiple measurements for each sample. Data provenance is not explicitly stated but is implicitly from an internal laboratory study (prospective).
- Linearity: One serially diluted sample was used. Data provenance is implicitly from an internal laboratory study (prospective).
- Analytical Specificity: A CSF sample close to the medical decision point and an elevated CSF sample were tested. Data provenance is implicitly from an internal laboratory study (prospective).
- Method Comparison: 130 CSF samples (including 40 samples with analyte levels within the reference interval) were used. Data provenance is not explicitly stated, but it's likely from a collection of clinical samples. It is retrospective in nature as these are "samples" analyzed, not patients prospectively enrolled.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker. The "ground truth" for the test set is established by the reference methods or the true concentration of the analyte, not by expert interpretation in the same way an imaging or pathology device would involve human experts.
- For precision, the ground truth is the true concentration of IgA in the sample, measured repeatedly to assess variation.
- For linearity, the ground truth is the expected concentration based on the serial dilution.
- For traceability, the ground truth is the value assigned by the international reference material (ERM-DA470k/IFCC).
- For method comparison, the ground truth is the measurement obtained from the alternative commercially available assay (predicate device).
Therefore, the concept of "number of experts used" or their "qualifications" for establishing ground truth is not directly applicable in the context of this type of quantitative IVD performance study.
4. Adjudication Method for the Test Set
Not applicable. As a quantitative IVD, the results are numerical values, and adjudication by experts is not a standard practice for assessing performance metrics like precision, linearity, or method correlation.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) to assess the impact of AI assistance on human performance. The Optilite IgA CSF Kit is a standalone automated quantitative assay, not an AI-assisted interpretation tool.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the performance studies described are intrinsically standalone performance evaluations of the Optilite IgA CSF Kit (the "algorithm/device only" in this context) without human-in-the-loop performance. The device provides a quantitative measurement directly.
7. The Type of Ground Truth Used
- Precision and Linearity: The ground truth is based on the known or reference concentrations of the samples used in the study.
- Traceability: The ground truth is the value assigned by the international reference material (ERM-DA470k/IFCC).
- Method Comparison: The ground truth for comparative purposes is the result obtained from an alternative commercially available assay (predicate device).
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI. This device is an in vitro diagnostic kit based on immunoturbidimetry, which is a chemical/biological reaction and measurement system, not a machine learning model that requires a training set. The term "training set" is not applicable here.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
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January 23, 2019
The Binding Site Group, Ltd. Natasha Verhaak Regulatory Affairs Officer 8 Calthorpe Road Birmingham, West Midlands, B15 1QT, UK
Re: K183151
Trade/Device Name: Optilite IgA CSF Kit Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, and E immunological test system Regulatory Class: Class II Product Code: CFN Dated: November 6, 2018 Received: November 14, 2018
Dear Natasha Verhaak:
We have reviewed vour 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 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
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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.
510(k) Number (if known) K183151
Device Name Optilite IgA CSF Kit
Indications for Use (Describe)
The Optilite IgA CSF Kit is intended for the quantitative in viro measurement of I.A. in cerebrospinal fluid (CSF) using the Optilite analyser.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Optilite IgA CSF Kit 510(k) Submission Summary
Natasha Verhaak Regulatory Affairs Officer The Binding Site Group Ltd. 8 Calthorpe Road Edgbaston Birmingham, West Midlands, B15 1QT, UK Telephone: +44 (0)121 456 9500 Email: natasha.verhaak@bindingsite.com or regulatory.submissions@bindingsite.com
A. 510(k) Number:
B. Purpose for Submission:
New device
C. Measurand:
lgA
D. Type of Test: Quantitative immunoturbidimetry
E. Applicant:
The Binding Site
F. Proprietary and Established Names: Optilite® IgA CSF Kit
G. Regulatory Information:
-
- Regulation section: 21 CFR 866.5510, Immunoglobulins A, G, M, D, and E immunological test system
-
- Classification: Class II
-
- Product code: CFN - method, nephelometric, immunoglobulins (G, A, M)
-
- Panel: Immunology (82)
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H. Intended use:
1. Intended use(s):
The Optilite IgA CSF Kit is intended for the quantitative in vitro measurement of IgA in cerebrospinal fluid (CSF) using the Optilite analyser.
2. Indication(s) for use:
Same as Intended use.
3. Special conditions for use statement(s):
Prescription use only
4. Special instrument requirements:
The Binding Site Optilite turbidimetric analyser (K110035)
I. Device Description:
The Optilite IgA CSF Kit comprises the following reagents:
Latex Reagent: Supplied in stabilised liquid form. Preservatives: 0.025% sodium azide, 0.1% E-amino-n-caproic acid (EACA) and 0.01% benzamidine, 0.05% ProClin.
Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Containing 0.099% sodium azide, 0.1% EACA and 0.01% benzamidine as preservatives. The concentration given on the quality control certificate has been obtained by comparison with the DA470k international reference material.
Reaction Buffer: Containing 0.099% sodium azide as a preservative.
J. Substantial equivalence information:
-
- Predicate device name(s) and 510(k) number(s): Beckman Coulter Low Concentration Immunoglobulin A (IGALC) reagent and Cerebrospinal Fluid Protein Calibrator (CSF CAL) (K993549)
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| Similarities | ||
|---|---|---|
| Item | Test device | Predicate |
| Intended use | In vitro quantification of IgA inCSF. | In vitro quantification of IgA inCSF (also serum). |
| Analyte | IgA | Same |
| Traceability | DA470k | Same |
| Reagent type | Latex enhanced | Same |
| Reference interval | < 2.0mg/L | Same |
| Assay type | Quantitative | Same |
| Specimen type | CSF | CSF (also serum) |
| Differences | ||
| Item | Test device | Predicate |
| Calibrator | Stabilised human serum | Human urine |
| Open vial stability | 3 months | 30 days |
| Antibody | Sheep anti-Human IgAantibody | Goat antihuman IgA |
| Method | Turbidimetric | Nephelometric |
| Measuring range | 0.91 – 20 mg/L (1+0)1.65 – 40 mg/L (1+1) | Initial: 2 – 70 mg/LExtended: 0.25 – 420 mg/L |
| Instrument | Binding Site Optilite | Beckman Coulter IMMAGE |
2. Comparison with predicate:
K. Standards and Guidance documents referenced:
CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline
CLSI EP7-A2 Interference Testing in Clinical Chemistry, Approved Guideline - Second Edition
CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach
CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition
L. Test Principle:
The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument.
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M. Performance Characteristics (if/when applicable):
1. Analytical performance:
Precision/Reproducibility: a.
The precision study was based on CLSI EP5-A2 Evaluation of Precision Performance of Clinical Quantitative Measurement Methods. The study was performed over 5 working days, with 2 runs per day. Two users assessed 4 different samples, using 2 reagent lots each on 3 analysers.
Results:
| Precision Summary | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Mean(mg/L) | Within run | Between run | Between day | Total | |||||
| SD | CV % | SD | CV % | SD | CV % | SD | CV % | ||
| Level 1 | 2.24 | 0.03 | 1.3 | 0.04 | 1.9 | 0.07 | 3.3 | 0.09 | 4.0 |
| Level 2 | 3.53 | 0.09 | 2.5 | 0.08 | 2.3 | 0.16 | 4.4 | 0.20 | 5.6 |
| Level 3 | 4.59 | 0.04 | 0.8 | 0.05 | 1.1 | 0.20 | 4.2 | 0.20 | 4.4 |
| Level 4 | 28.90 | 0.48 | 1.7 | 0.56 | 1.9 | 0.40 | 1.4 | 0.84 | 2.9 |
b. Linearity/assay reportable range:
A linearity study was performed following CLSI Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (EP6-A). The linearity of this assay has been confirmed using a serially diluted sample over the range of 1.0-44.8mg/L with deviation from linearity <10%.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
i) Traceability:
The calibration of the assay is traceable to ERM-DA470k/IFCC.
ii) Kit Stability:
Real-time stability - The Optilite IgA CSF Reagent, Calibrator and Controls have a shelf life of up to 18 months.
Open-vial stability - The Optilite IgA CSF Reagent, Calibrator and Controls can be stored, opened at 2-8°C for up to 3 months.
On-board stability - The Optilite IgA CSF Reagent can be stored on-board the Optilite Analyser for up to 30 days.
- d. Detection limit.
The limit of quantitation (LoQ) for this assay is defined as the bottom of the measuring range, 0.91mg/L. The LoQ validation study was based on CLSI EP17-A2 Evaluation of the Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline -2nd Edition.
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e. Analytical specificity:
A study was performed following CLSI EP7-A2: Interference Testing in Clinical Chemistry, Approved Guideline. A CSF sample close to the medical decision point and an elevated CSF sample were tested. No significant assay interference effects were observed in CSF when tested with haemoglobin (2.5g/L), bilirubin (100mg/L), acetaminophen (1324μmol/L) or acetylsalicylic acid (3.63mmol/L).
f. Assay cut-off:
Not determined
2. Comparison studies:
a. Method comparison with predicate device:
A comparison study was performed by analysing 130 CSF samples (including 40 samples with analyte levels within the reference interval) using the Optilite IgA CSF Kit and an alternative commercially available assay. Passing Bablok regression analysis generated the following results:
| Passing Bablok | Slope 95% Cl | Intercept 95% Cl |
|---|---|---|
| y= 1.05x -0.02 | 1.03 to 1.07 | -0.07 to 0.05 |
Correlation coefficient 0.984
b. Matrix comparison:
None
3. Clinical studies:
a. Clinical Sensitivity: None determined
b. Clinical specificity: None determined
c. Other clinical supportive data (when a. and b. are not applicable): Not applicable
-
- Clinical cut-off:
None determined
- Clinical cut-off:
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5. Expected values/Reference range:
The reference range of <2.0 mg/L was transferred from literature in common with the predicate device.
N. Proposed Labelling:
The labelling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).