The Optilite IgM CSF Kit is intended for the quantitative in vitro measurement of IgM in cerebrospinal fluid (CSF) samples using the Optilite analyser.

Device Description

The Optilite IgM 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.

AI/ML Overview

The provided text describes the 510(k) submission for the Optilite IgM CSF Kit, an in vitro diagnostic device, not an AI/ML-based device. Therefore, the questions related to AI/ML specific criteria, such as expert adjudication, MRMC studies, standalone algorithm performance, and training set details, are not applicable to this submission.

The acceptance criteria and device performance evaluation for this diagnostic kit are centered on analytical performance characteristics, which are standard for laboratory assays.

Here's a breakdown of the applicable information from the provided text:

1. Table of acceptance criteria and the reported device performance:

Performance Characteristic	Acceptance Criteria (from CLSI Guidelines and Internal Standards)	Reported Device Performance
Precision
Total Precision (%CV)	<10%	Level 1: 7.2%Level 2: 5.9%Level 3: 3.6%Level 4: 4.2%
Within-run Precision (%CV)	<5%	Level 1: 3.9%Level 2: 2.8%Level 3: 2.2%Level 4: 2.3%
Between-run Precision (%CV)	<8%	Level 1: 1.5%Level 2: 2.5%Level 3: 2.6%Level 4: 2.9%
Between-day Precision (%CV)	<8%	Level 1: 5.9%Level 2: 4.6%Level 3: 1.3%Level 4: 2.0%
Linearity/Assay Reportable Range	Deviation from linearity <10% over the measuring range	Confirmed over 0.07 - 4.55 mg/L with deviation from linearity <10%
Detection Limit (LoQ)	Not explicitly stated as a numerical criterion, but defined as the bottom of the measuring range.	0.11 mg/L (bottom of measuring range)
Analytical Specificity (Interference)	Mean results from spiked samples within 10% of control samples.	Not affected by Acetaminophen (1324µmol/L), Acetylsalicylic Acid (3.62mmol/L), Bilirubin (80mg/L), Haemoglobin (1g/L)
Method Comparison (Regression Analysis)	Not explicitly stated as a numerical criterion for slope/intercept, but implied to show substantial equivalence.	N=155 samples, Slope: 1.02, 95% CI: 1.00 to 1.04; Intercept: 0.07, 95% CI: 0.03 to 0.09; Pearson's r: 0.997

2. Sample size used for the test set and the data provenance:

Precision Study: 4 sample preparations tested (details on the specific number of aliquots or patient samples composing these preparations are not given). The study design involved 2 runs per day (each in duplicate) over 5 days using 3 analyzers.
Linearity Study: A serially diluted sample was used. Specific N is not provided.
Detection Limit (LoQ) Study: The study was based on CLSI EP17-A2. Specific N is not provided.
Analytical Specificity (Interference) Study: Samples at different IgM concentrations were spiked with interfering substances and tested. Specific N is not provided.
Method Comparison Study: A total of 239 samples were initially tested, including 219 native CSF samples and 20 patient samples spiked with purified IgM. 155 of these samples were within the measuring range and used for regression analysis.
Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the samples would be human CSF.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This is a quantitative immunodiagnostic assay, not an imaging device requiring expert interpretation for ground truth. The "ground truth" for this device's performance is established by reference methods, international standards (ERM-DA470k/IFCC), and the inherent accuracy and precision of the measurements themselves validated against established statistical methodologies (CLSI guidelines).

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

Not applicable, as this is a quantitative diagnostic assay, not a subjective interpretation task that requires adjudication.

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, as this is not an AI/ML-based device that assists human readers.

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

The device is an automated turbidimetric analyzer (Optilite) performing a quantitative assay. Its performance is inherently "standalone" in the sense that the instrument provides a numerical result without human interpretation being part of the result generation. The performance metrics presented (precision, linearity, detection limit, method comparison) are its standalone performance.

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

The ground truth or reference for this quantitative assay is:

Traceability: Established through calibration traceable to the ERM-DA470k/IFCC international reference material.
Method Comparison: Comparison against a legally marketed predicate device (Human IgM CSF Kit for use on SPAPLUS K120750) using patient samples. The predicate device itself serves as a reference point for substantial equivalence.
Statistical Methodologies: Adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines for evaluating precision, linearity, detection capability, and interference.

8. The sample size for the training set:

Not applicable, as this is not an AI/ML device that requires a "training set."

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

Not applicable, as this is not an AI/ML device.

Summary

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

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. Next to that is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

May 28, 2019

The Binding Site Group Ltd. Kanika Darbar Regulatory Affairs Officer The Binding Site Group Ltd. 8 Calthorpe Road Edgbaston Birmingham. West Midlands, B15 1QT, UK

Re: K190686

Trade/Device Name: Optilite IgM 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: March 8, 2019 Received: March 18, 2019

Dear Kanika Darbar:

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

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

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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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,

Doug Jeffery, Ph.D. Deputy Division Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K190686

Device Name Optilite IgM CSF Kit

Indications for Use (Describe)

The Optilite IgM CSF Kit is intended for the quantitative in vitro measurement of IgM in cerebrospinal fluid (CSF) samples 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Optilite IgM CSF Kit 510(k) Submission Summary

Kanika Darbar 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: kanika.darbar@bindingsite.com or regulatory.submissions@bindingsite.com Preparation Date: 28-May-2019

A. 510(k) Number:

K190686

B. Purpose for Submission:

New device

C. Measurand:

lgM

D. Type of Test: Quantitative immunoturbidimetry

E. Applicant:

The Binding Site

F. Proprietary and Established Names: Optilite® IgM CSF Kit

G. Regulatory Information:

1. Regulation section: 21 CFR 866.5510, Immunoglobulins A, G, M, D, and E immunological test system
1. Classification: Class II
1. Product code: CFN - method, nephelometric, immunoglobulins (G, A, M)
1. Panel: Immunology (82)

{4}------------------------------------------------

H. Intended use:

1. Intended use(s):

The Optilite IgM CSF Kit is intended for the quantitative in vitro measurement of IgM in cerebrospinal fluid (CSF) samples 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 IgM 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:

1. Predicate device name(s) and 510(k) number(s):

Human IgM CSF Kit for use on SPAPLUS K120750

{5}------------------------------------------------

2. Comparison with predicate:

Similarities
Item	Test device	Predicate
Assay type	Quantitative	Same
Specimen Type	CSF	Same
Antibody	Sheep anti-human-IgM	Same
Intended use	Quantitative in vitro measurement of IgM in cerebrospinal fluid	Same
Calibration	Traceable to DA470k	Same
On-boardstability	30 days	Same
ReferenceInterval	<1.3mg/L	same
Method	Turbidimetric	Same
	Differences
Item	Test device	Predicate
Measuring range	0.11 - 4.0mg/L (1+0 dilution)1.0 - 40mg/L (1+9 dilution)	0.3 – 7.0mg/L (1+0dilution)3.0 - 70.0mg/L (1+9dilution)
Calibrator	Liquid stabilised human serum	Lyophilised
Open VialStability	3 months	2 months
Instrument	Binding Site Optilite	Binding Site SPAPLUS

K. Standards and Guidance documents referenced:

CLSI EP17-A2 Evaluation of the Detection Capability for Clinical Laboratory Measurement Procedures; 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.

{6}------------------------------------------------

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

Precision/Reproducibility: a.
The studies were based on CLSI EP5-A2, where 4 sample preparations were tested in 2 runs per day (each of the 2 runs in duplicate) over 5 days using 3 analysers. Acceptance criteria were total precision (%CV<10%), within-run precision (%CV<5%), between-run precision (%CV<8%), and between-day precision (%CV<8%). A summary of the results is shown below. All results are in mg/L.

Results:

Precision Summary
	Mean(mg/L)	Within run		Between run		Between day		Total
		SD	CV %	SD	CV %	SD	CV %	SD	CV %
Level 1	0.20	0.01	3.9	0.00	1.5	0.01	5.9	0.01	7.2
Level 2	0.44	0.01	2.8	0.01	2.5	0.02	4.6	0.03	5.9
Level 3	1.20	0.03	2.2	0.03	2.6	0.02	1.3	0.04	3.6
Level 4	3.02	0.07	2.3	0.09	2.9	0.06	2.0	0.13	4.2

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 0.07 - 4.55 mq/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 IgM CSF Reagent, Calibrator and Controls have a shelf life of up to 19 months.

Open-vial stability - The Optilite IgM CSF Reagent, Calibrator and Controls can be stored, opened at 2-8°C for up to 3 months.

On-board stability - The Optilite IgM CSF Reagent can be stored on-board the Optilite Analyser for up to 30 days.

{7}------------------------------------------------

d. Detection limit.

The limit of quantitation (LoQ) for this assay is defined as the bottom of the measuring range, 0.11mg/L. The LoQ validation study was based on CLSI EP17-A2 Evaluation of the Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – 2m Edition.

e. Analytical specificity:
Interferences were assessed according to CLSI EP7-A2 by testing samples at different IgM concentrations. Each sample was spiked with interfering substances and tested. For noninterference to be claimed, the mean results from the spiked samples must be within 10% of the mean of the control samples. The data demonstrated that the assay was not affected by the following substances at the concentrations given below.

Results:

Interferent	Concentration	Interferent	Concentration
Acetaminophen	1324µmol/L	Bilirubin	80mg/L
Acetylsalicylic Acid	3.62mmol/L	Haemoglobin	1g/L

f. Assay cut-off:

Not determined

2. Comparison studies:

a. Method comparison with predicate device:
A total of 239 samples were initially tested in this study, and these consisted of 219 native CSF samples and an additional 20 patient samples which were spiked with purified IgM.

155 of these tested samples were within the measuring range and were included in the regression analysis. These results are presented below.

N	Sample Range	Passing Bablok	Slope95% CI	Intercept95% CI
155	0.251–39.35 mg/L	$y = 1.02x + 0.07$	1.00 to 1.04	0.03 to 0.09

Pearson's r
0.997

b. Matrix comparison:

None

{8}------------------------------------------------

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

4. Clinical cut-off:

None determined

5. Expected values/Reference range:

The reference range of <1.3 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.

Regulation Number and Section

§ 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).

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

CONTINUE ON A SEPARATE PAGE IF NEEDED.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW *

Optilite IgM CSF Kit 510(k) Submission Summary

A. 510(k) Number:

B. Purpose for Submission:

C. Measurand:

D. Type of Test: Quantitative immunoturbidimetry

E. Applicant:

F. Proprietary and Established Names: Optilite® IgM CSF Kit

G. Regulatory Information:

H. Intended use:

1. Intended use(s):

2. Indication(s) for use:

3. Special conditions for use statement(s):

4. Special instrument requirements:

I. Device Description:

J. Substantial equivalence information:

1. Predicate device name(s) and 510(k) number(s):

2. Comparison with predicate:

K. Standards and Guidance documents referenced:

L. Test Principle:

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

Results:

b. Linearity/assay reportable range:

ii) Kit Stability:

d. Detection limit.

Results:

2. Comparison studies:

3. Clinical studies:

4. Clinical cut-off:

5. Expected values/Reference range:

N. Proposed Labelling:

O. Conclusion:

§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW