The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnomal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

Device Description

The Optilite IgM Kit comprises the following reagents: Antiserum: Goat anti IgM supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine. Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 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 a 510(k) submission for the Optilite IgM Kit, which is a quantitative in vitro measurement system for IgM in human serum, lithium heparin, or EDTA plasma. The submission is a modification to an existing device (K082129). The core of the submission revolves around demonstrating that the modified device maintains performance comparable to the previously cleared device, rather than proving initial efficacy or diagnostic accuracy.

Based on the provided text, here's an analysis of the acceptance criteria and study proving the device meets them:

Key Takeaway: This 510(k) submission is for a modification to an existing device (change of antibody source and buffer). Therefore, the "acceptance criteria" and "study" are primarily focused on demonstrating that this modification does not negatively impact the performance compared to the original, already cleared device. There is no new clinical effectiveness study to establish diagnostic accuracy against a disease state from scratch.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally framed as "no change in performance compared to the device cleared in K082129" or meeting specific pre-defined quantitative thresholds (e.g., allowable CV, limits of agreement).

Acceptance Criteria Category	Specific Acceptance Criteria (implicit/explicit)	Reported Device Performance and Conclusion
Precision/Reproducibility	No significant change in repeatability, within-laboratory, between-instrument, and between-lot precision compared to the predicate (K082129). (Implicit, demonstrated through comparison of observed CVs and SDs to historical or expected performance, as guided by CLSI EP5-A3). For example, meeting specific CV targets for different levels.	Repeatability and Within Laboratory: • Level 1: Total CV 4.9% • Level 5: Total CV 7.0%. Between Instrument: • Level 1: CV 5.2% • Level 5: CV 6.9%. Between Lot: • Level 1: CV 0.7% • Level 5: CV 1.5%. Conclusion: "The above results do not indicate any change in performance compared to the device cleared in K082129. The precision claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended."
Linearity/Assay Reportable Range	No significant change in linearity compared to the predicate (K082129). Demonstrated by strong correlation coefficient (r value) of the linear regression. (Implicit, based on historical performance).	Linear Regression Equation: y = 1.029 x – 0.1752 g/L r value: 0.998. Conclusion: "These results are comparable to those currently presented in the product insert and therefore do not indicate any change in performance compared to the device cleared in K082129. The linearity claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended."
Kit Stability (Accelerated)	Stability claim of 12 months (365 days) at 4°C verified with a maximum allowable difference of ±15% (per EP25-A).	Achieved Stability (equivalent at 4°C): • IR: 507 days • Low Control: 531 days • High Control: 878 days • Samples 1-3: 561 days. Decision: All "Pass." Conclusion: Verified stability claim. (Real-time study ongoing for further support).
Detection Limit (LoQ, LoD, LoB)	LoQ validated by all samples reporting within an allowable CV of 8%. No significant change in LoD or LoB from the predicate (0.01 g/L and 0.007 g/L respectively). (Implicit, based on historical performance as per EP17-A2).	LoQ: All tested samples were within the acceptance criteria of allowable CV of 8%. LoD: No change in performance observed after antisera change. LoB: No change in performance observed after antisera change. Conclusion: "The results generated do not indicate any change in performance compared to the device cleared in K082129. The LoB, LoD and LoQ claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended."
Method Comparison with Predicate Device	Agreement between the modified and predicate device, evidenced by low bias, tight limits of agreement, high correlation coefficient, and appropriate Passing Bablok regression results to demonstrate equivalence.	Bland Altman Mean Bias: -2.13% 95% Limits of Agreement: -9.63% to 5.36% Passing Bablok: y= 0.9775x + 0.009 (Slope 95% CI: 0.971 to 0.983; Intercept 95% CI: 0.001 to 0.016) Correlation coefficient: 0.999. Conclusion: "The above results do not indicate any change in performance compared to the device cleared in K082129. The comparison claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended."
Expected Values/Reference Range	Transferred reference interval accepted if ≤2 samples fall outside the limits of the reference interval.	Of 20 samples, 18 gave results within the reference interval (0.35 – 2.42 g/L). Two samples were slightly below the lower boundary (0.305 g/L and 0.319 g/L). Conclusion: "The results of this study therefore meet the acceptance criteria and indicate that the reference interval can be transferred from the originally cleared device."

2. Sample Sizes Used for the Test Set and Data Provenance

Precision Studies (Repeatability and Within Laboratory):
- Sample Size: 5 different samples. For each level, N=80 for Repeatability/Within Lab Summary (20 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, but typically internal lab data (e.g., from the manufacturer's R&D or QC labs).
Precision Studies (Between Instrument):
- Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, typically internal lab data.
Precision Studies (Between Lot):
- Sample Size: 5 different samples. For each level, N=24 (6 working days * 2 runs/day * 2 reps/run).
- Data Provenance: Not explicitly stated, typically internal lab data.
Linearity Study:
- Sample Size: Dilution series from a high pool (8.44 g/L) and a low pool (0.17 g/L). Each diluted sample tested in 3 replicates.
- Data Provenance: Not explicitly stated, typically internal lab data.
Kit Stability (Accelerated):
- Sample Size: 6 replicates of controls, internal reference, and samples.
- Data Provenance: Not explicitly stated, typically internal lab data.
Detection Limit (LoQ) Study:
- Sample Size: Four samples.
- Data Provenance: Not explicitly stated, typically internal lab data.
Method Comparison with Predicate Device:
- Sample Size: 120 serum samples and 60 plasma samples (total 180 samples).
- Data Provenance: Not explicitly stated, but typically clinical samples or commercial samples purchased for the study. Given the medical context, these would be human samples. The study was conducted as per pre-submission meeting Q171503, implying a prospective design for this specific comparative testing.
Expected Values/Reference Range:
- Sample Size: 20 samples from apparently healthy US donors.
- Data Provenance: Prospective collection of samples from US donors.

Overall Data Provenance: The document explicitly mentions "20 samples from apparently healthy US donors" for the reference range study. For other analytical performance studies (precision, linearity, stability, detection limit), the provenance is not specified, but these are typically conducted in-house by the manufacturer (retrospective analysis vs. new data collection is not detailed, but likely new data generation for the modified kit).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This device is an in vitro diagnostic (IVD) for quantitative measurement of IgM. The "ground truth" for IVDs of this nature is established by the reference measurement procedure or the assigned/target values of calibrators and controls used in the analytical performance studies, not by clinical expert consensus in the way a diagnostic imaging AI might establish ground truth from radiologists.

For Analytical Studies (Precision, Linearity, LoD/LoQ, Stability): The ground truth for these samples are their known or reference concentrations, which are determined by highly accurate laboratory methods or traceable standards (e.g., ERM-DA470k/IFCC for IgM). No clinical experts are involved in establishing this type of ground truth.
For Method Comparison: The "ground truth" in this context is the result obtained from the predicate device (the unmodified K082129 kit), as the goal is to show agreement between the modified and unmodified kit.
For Reference Range Study: The "ground truth" is the established reference interval for IgM in a healthy population. The study assessed whether the modified kit's results for healthy individuals fell within this known range.

Therefore, the concept of "experts establishing ground truth" as it applies to reader studies for imaging devices does not directly apply here.

4. Adjudication Method for the Test Set

Given that this is an IVD kit for quantitative measurement and not an imaging device requiring human interpretation, there is no mention of an adjudication method among multiple human readers. The analytical performance is evaluated against quantitative measurements, established standards, or the performance of the predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. MRMC studies are specific to diagnostic performance, typically for imaging devices where multiple readers interpret cases with and without AI assistance. This submission is for an IVD kit that provides a quantitative measurement, not an interpretative diagnosis requiring human readers in the loop. The "comparison" done was a method comparison between the modified kit and the predicate kit.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, in essence. The "device" here is the Optilite IgM Kit used on the Optilite analyser. Its performance is evaluated analytically (precision, linearity, limits, stability) and comparatively against its predicate. This is a standalone performance assessment of the kit, which automatically provides quantitative results. There is no human interpretative step that the kit is assisting or replacing within its intended use.

7. The Type of Ground Truth Used

For Analytical Performance (Precision, Linearity, LoD/LoQ, Stability):
- Traceability: ERM-DA470k/IFCC (a certified reference material for immunoglobulins). This is a highly robust form of ground truth based on international standards.
- Known Concentrations: Samples and controls with established or assigned target values.
For Method Comparison:
- Predicate Device Results: The results from the previously cleared Optilite IgM Kit (K082129) served as the reference for comparison to demonstrate equivalence.
For Reference Range Study:
- Established Reference Interval: The pre-determined reference range (0.35 – 2.42 g/L) for IgM in a healthy population served as the ground truth against which results from healthy donors were compared.

There is no pathology confirmation or outcomes data mentioned, as these are typically used for assessing clinical accuracy or impact on patient management, which is beyond the scope of this 510(k) for a modified quantitative IVD.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm. This submission is for an immunoturbidimetric test kit, not an AI-powered diagnostic system. The "training" of such a system would refer to the development and optimization of the reagent formulation and methods, which involves extensive R&D and internal testing, often with many samples. However, the document provided focuses on the validation testing required for regulatory submission.

The section M. Performance Characteristics details the validation experiments for the modified kit. These are the test sets to prove performance, not training sets.

9. How the Ground Truth for the Training Set Was Established

As noted above, there is no "training set" in the AI/ML sense described. For the development of the original device and its subsequent modifications, the "ground truth" would be established through:

Reference materials: Calibrating the assay against international reference standards (e.g., ERM-DA470k/IFCC).
Internal validation: Testing against well-characterized in-house samples and controls with known concentrations.
Method optimization: Iteratively adjusting reagent concentrations and reaction parameters to achieve desired analytical performance (sensitivity, specificity, precision, linearity) based on these known samples and reference materials.

The provided document focuses on the verification and validation studies for a pre-defined modified product, demonstrating its performance against regulatory requirements, rather than the developmental phase of the original or modified kit's creation.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in a stacked format.

July 15, 2019

The Binding Site Group Ltd. Natasha Verhaak Regulatory Affairs Officer 8 Calthorpe Road Edgbaston, B15 1QT Gb

Re: K191635

Trade/Device Name: Optilite IgM 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: June 13, 2019 Received: June 19, 2019

Dear Natasha Verhaak:

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 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

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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 mediation-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,

Douglas Jeffery, Ph.D. Branch Chief Immunology and Flow Cytometry Branch Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.

510(k) Number (if known) K191635

Device Name Optilite IgM Kit

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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information unless it displays a currently valid OMB number."

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Optilite IgM Kit Special 510(k) Submission Summary

Submitter Details

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

Date Prepared: 4th July 2019

A. 510(k) Number:

K191635

B. Purpose for Submission:

Modification to an existing device

C. Measurand: lgM
D. Type of Test: Quantitative immunoturbidimetry

E. Applicant:

The Binding Site

F. Proprietary and Established Names:

Optilite IgM 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)

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H. Intended use:

1. Intended use(s):

The Optilite IgM Kit is intended for the quantitative in vitro measurement of IgM in human serum, lithium heparin or EDTA plasma using the Binding Site Optilite analyser. Measurement of IgM aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test results are to be used in conjunction with other clinical and laboratory findings.

The intended use is the same as the cleared kit and has not been changed.

3. Indication(s) for use:

Same as Intended use.

1. Special conditions for use statement(s):
  Prescription use only

3. Special instrument requirements:

The Binding Site Optilite analyser

l. Device Description:

The Optilite IgM Kit comprises the following reagents:

Antiserum: Goat anti IgM supplied in stabilised liquid form. Preservatives: 0.099% sodium azide, 0.1% E-amino-n-caproic acid (EACA), 0.5% BSA and 0.01% benzamidine.

Calibrator and Controls: Pooled human serum, supplied in stabilised liquid form. Contain 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): Optilite IgM Kit (K082129)

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2. Comparison with predicate:

Similarities
Item	Modified device	Registered device
Intended Use	Quantitative in vitro measurement ofIgM	Same
Test Method	Turbidimetric	Same
Specimen Type	Serum, lithium heparin, EDTA plasma	Same
Assay type	Quantitative	Same
On-board Stability	30 days	Same
Calibration traceability	DA470k	Same
Measuring Range	1+90.1 – 3.8 g/L1+190.2 – 7.5 g/L1+3994 – 150 g/L	Same
Adult ReferenceInterval	0.35 – 2.42 g/L	Same
Instrument	Optilite	Same
Antigen excesscapacity	74.48 g/L	Same
Calibration method	Pooled human sera	Same
Controls	Pooled human sera	Same
Open vial stability	3 months	Same
Antibody processing	Affinity purification, specificityconfirmed by IEP	Same

Differences
Item	Modified device	Registered device
Source of detection antibody	Goat antibody	Sheep antibody
Antibody resting buffer	GBS and PBS (50:50)	GBS

K. Standards and Guidance documents referenced:

CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

CLSI EP5-A3 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition

CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents- 1® 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 studies were based on CLSI EP5-A3 Evaluation of Precision Performance of Clinical Quantitative Measurement Methods as was agreed in pre-submission meeting Q171503.

The repeatability and within laboratory study was performed over 20 working days, with 2 runs per day and 2 reps per run. 5 different samples were assessed using 1 reagent lot on 1 analyser.

Repeatability and Within Laboratory Summary
	N	Mean (g/L)	Within run		Between run		Between day		Total
			SD	CV %	SD	CV %	SD	CV %	SD	CV %
Level 1	80	0.217	0.003	1.3	0.002	1.1	0.010	4.6	0.011	4.9
Level 2	84	0.457	0.034	7.4	0.000	0.0	0.020	4.4	0.039	8.6
Level 3	80	1.823	0.011	0.6	0.013	0.7	0.032	1.8	0.037	2.0
Level 4	80	3.008	0.022	0.7	0.018	0.6	0.049	1.6	0.057	1.9
Level 5	80	10.415	0.325	3.1	0.586	5.6	0.299	2.9	0.734	7.0

Repeatability and Within Laboratory Results:

The between instrument precision study was performed over 6 working days with 2 runs per day and 2 reps per run. 5 different samples were assessed using 1 reagent lot on 3 different analysers.

Between Instrument Results:

	N	Mean(mg/L)	BetweenInstrument
			SD	CV %
Level 1	24	0.218	0.011	5.2
Level 2	24	0.456	0.027	5.9
Level 3	24	1.875	0.062	3.3
Level 4	24	3.145	0.112	3.5
Level 5	24	11.240	0.778	6.9

The between lot precision study was performed over 6 working days with 2 runs per day and 2 reps per run. 5 different samples were assessed using 2 reagent lots on 1 analyser.

Between Lot Results:

	N	Mean(mg/L)	Between Lot
			SD	CV %
Level 1	24	0.215	0.002	0.7
Level 2	24	0.457	0.009	1.9
Level 3	24	1.801	0.015	0.8
Level 4	24	2.985	0.019	0.6
Level 5	24	10.265	0.151	1.5

The above results do not indicate any change in performance compared to the device cleared in K082129. The precision claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

b. Linearity/assay reportable range:

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A linearity study was carried out as per the original submission (K082129) where a dilution series was produced from a high pool with a known concentration of 8.44 g/L and a low pool concentration of 0.17 g/L. Each diluted sample was tested in 3 replicates and a linear regression analysis was carried out. The linear regression equation was shown to be y= 1.029 x – 0.1752 g/L, with an r value of 0.998

These results are comparable to those currently presented in the product insert and therefore do not indicate any change in performance compared to the device cleared in K082129. The

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linearity claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

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:

Accelerated Stability

Accelerated stability studies were carried out to verify that the stability of the kit is unchanged in accordance with ISO 23640:2015. 6 replicates of controls, internal reference and samples were tested over a period equivalent to 13-months and analysed in line with EP25-A with a maximum allowable difference of ±15% in order to verify the stability claim of 12 months. Reagents were stored at 37℃ to accelerate the study by a factor of 10.

Accelerated Stability Results

Parameter	IR	Control		Sample
		Low	High	1	2	3
Accelerated stabilityachieved (days)	51.5	54	89.2	57	57	57
Equivalent at 4ºC (days)	507	531	878	561	561	561
Stability required at 4ºC(days)	365	365	365	365	365	365
Decision	Pass	Pass	Pass	Pass	Pass	Pass

Real Time Stability

To further support the results of the accelerated stability testing, a real time stability study is currently being carried out in accordance with EP25-A and as was agreed in pre-submission meeting Q171503.

On Board Stability

On-board stability studies were carried out as per the original submission and showed no difference in the cleared on-board stability claim

d. Detection limit.

The limit of quantitation (LoQ) for this assay is defined as the bottom of the measuring range, 0.1 g/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 in accordance with pre-submission meeting Q171503. Four samples were tested using two reagent lots. The LoQ claim was validated by all the samples reporting within the acceptance criteria of an allowable CV of 8%.

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The limit of detection (LoD) represents the lowest measurable analyte level that can be distinguished from zero, this was estimated as 0.01 g/L in the original submission and the limit of blank (LoB) was estimated to be 0.007g/L. Additional testing was carried out following the antisera change and no change in performance was observed.

The results generated do not indicate any change in performance compared to the device cleared in K082129. The LoB, LoD and LoQ claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

e. Analytical specificity:

As per original submission K082129

f. Assay cut-off:

Not determined

1. Comparison studies:

a. Method comparison with predicate device:

A comparison study was performed by analysing 120 serum samples and 60 plasma samples using the modified Optilite IgM Kit and the unmodified K082129 kit which is already commercially available. The study was carried out in accordance with pre-submission meeting Q171503. Bland Altman and Passing Bablok regression analysis generated the following results:

Bland Altman Mean Bias	95% Limits of Agreement
-2.13%	-9.63% to 5.36%
Passing Bablok	Slope 95% CI Intercept 95% CI
Passing Bablok	Slope 95% CI	Intercept 95% CI
$y= 0.9775x + 0.009$	0.971 to 0.983	0.001 to 0.016

Correlation coefficient
0.999
Predicate Sample Range (g/L)	Test Samples Range (g/L)
0.121 – 16.464	0.130 – 15.688

The above results do not indicate any change in performance compared to the device cleared in K082129. The comparison claims in the product insert therefore still accurately represent the performance of the modified kit and do not need to be amended.

b. Matrix comparison:

Serum and plasma matrices were included in the above method comparison study. As per the original submissionK082129, no difference between matrices were observed.

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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

1. Clinical cut-off:
  None determined

5. Expected values/Reference range:

Following the protocol agreed in Q171503, 20 samples from apparently healthy US donors were tested using the modified assay. The acceptance criteria for the transfer is ≤2 samples falling outside of the limits of the reference interval to be transferred.

Of the 20 samples tested, 18 gave results within the reference interval, ranging from 0.480 to 1.522 g/L. Two samples were close to the lower boundary of the reference interval (0.35g/L) with results of 0.305 and 0.319 g/L. The results of this study therefore meet the acceptance criteria and indicate that the reference interval can be transferred from the originally cleared device.

N. Proposed Labelling:

The labelling is sufficient, and it satisfies the requirements of 21 CFR Part 809.10.

The labelling is the same as the cleared kit and has not been changed.

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).