The IL Synthesis™ is a family of fully automatic, microprocessor controlled, blood gas, electrolytes, glucose, hematocrit and co-oximeter analyzers that was cleared for market by K963800. A new measured co-oximeter parameter is being added on the IL Synthesis™ for the semiquantitative determination of total bilirubin in whole blood from neonates. Elevated bilirubin levels in the blood of newborns is used to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

Device Description

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the IL Synthesis™ Bilirubin parameter, as presented in the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific numerical thresholds for slope, intercept, or correlation coefficient. Instead, it describes what the results "showed" and concludes that they are "statistically similar" to the predicate device. For precision, specific acceptance criteria (e.g., maximum allowable SD) are not provided, only the observed SD values.

Acceptance Criterion (Implicit)	Reported Device Performance
Comparative Performance (vs. Predicate Device)	Linear Regression Analysis:
Substantially equivalent performance to predicate device.	Slope: 0.925
(Implicit: Results are statistically similar)	Intercept: 1.097
	Correlation Coefficient (R): 0.969
	Conclusion: "indicating that the results are statistically similar."
Precision	Within-run Precision (5 replicates per instrument, per level):
Acceptable precision for clinical use (implicit).	Level 1 Bilirubin (mg/dL):
(Implicit: SDs are within expected ranges for the measurement)	Instrument 1: Mean 1.1, SD 0.95
	Instrument 2: Mean 0.6, SD 0.78
	Instrument 3: Mean 1.3, SD 0.38
	Level 2 Bilirubin (mg/dL):
	Instrument 1: Mean 2.3, SD 0.55
	Instrument 2: Mean 1.7, SD 0.49
	Instrument 3: Mean 3.7, SD 0.45

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

Sample Size: 309 whole blood samples.
Data Provenance: The document does not explicitly state the country of origin or whether the study was retrospective or prospective. It only mentions "In a comparative performance study" and "whole blood samples."

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) device measuring a biomarker (bilirubin). The "ground truth" for the comparative study was established by another analytical method (the predicate device, Sigma's Bilirubin, Total and Direct on a spectrophotometer), not by clinical experts making diagnoses based on the results.
Therefore, the concept of "experts establishing ground truth" as it would apply to image interpretation or clinical decision-making is not directly applicable here. The predicate device itself acts as the reference method.

4. Adjudication Method for the Test Set

Not applicable. The study compares the new device's measurements against a reference method (the predicate device) directly. There is no human interpretation or adjudication involved in establishing the "ground truth" values for the bilirubin levels.

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

No, an MRMC comparative effectiveness study was not done. This study focuses on the analytical performance of an IVD device measuring a biomarker, not on human interpretation of images or data.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, this study is inherently a standalone performance evaluation of the device. The IL Synthesis™ analyzes samples automatically, and the performance data presented (comparative and precision) reflects the device's output without human intervention in the measurement process itself.

7. The Type of Ground Truth Used

Comparative Ground Truth: The "ground truth" or reference for the comparative study was the measurement results from the predicate device: Sigma's Bilirubin, Total and Direct on a spectrophotometer. This is a form of reference method comparison or method comparison validation.
Precision Ground Truth: For the precision study, the ground truth is simply the intrinsic variability of the device measuring the same sample multiple times.

8. The Sample Size for the Training Set

The document describes a 510(k) submission for an already existing device (IL Synthesis™) with the addition of a new measured parameter (Bilirubin). It does not provide information about a "training set" in the context of machine learning. IVD device development typically involves analytical validation studies rather than machine learning training sets.
If we interpret "training set" as the data used to initially develop and optimize the bilirubin measurement method for the IL Synthesis™, that information is not provided in this summary. The 309 samples described are for performance validation against the predicate.

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

As noted above, the concept of a "training set" and its "ground truth" in the machine learning sense is not applicable or detailed in this 510(k) summary for an IVD device. The summary focuses on the validation of the new parameter's performance against a legally marketed predicate device.

Summary

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K980646

6 1998 MAY

Section 3-- 510(k) Summary IL Synthesis™- -- Addition of Bilirubin as a Measured Parameter (Summary of Safety and Effectiveness)

Submitted by:

Carol Marble Senior Regulatory Affairs Specialist Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02173 Phone: (781) 861-4467 (781) 861-4464 Fax:

Contact Person:

Carol Marble -- Phone: (781) 861-4467

Summary Prepared:

February 18, 1998

Name of the device:

Addition of Bilirubin as Measured Parameter for Use with IL Synthesis™ Neonate Whole Blood Samples

Classification name(s):

Bilirubin (total and unbound) in the neonate test system Class I 862.1113

Identification of predicate devices:

K832236 Sigma's Bilirubin, Total and Direct

Description of the device/intended use(s):

Statement of how the Technological Characteristics of the Device compare to the Predicate device:

Bilirubin as a measured parameter for use with neonate whole blood samples on the IL Synthesis™ is substantially equivalent in performance, intended use and safety and effectiveness to the predicate device: Sigma's Bilirubin, Total and Direct.

Summary of Performance Data:

In a comparative performance study, 309 whole blood samples ranging in bilirubin level from 0 to 20.0 mg/dL were tested using several IL Synthesis™ instruments and Sigma's Bilirubin, Total and Direct on a spectrophotometer. The results showed a slope of 0.925, an intercept of 1.097 and a correlation coefficient of 0.969 indicating that the results are statistically similar.

A precision study on two sample levels assessed on three different IL Synthesis™ instruments in runs of 5 replicates each gave the following results:

			Instrument 1		Instrument 2		Instrument 3
Parameter	Level	n	mean	SD	mean	SD	mean	SD
Bilirubin	1	5	1.1	0.95	0.6	0.78	1.3	0.38
(mg/dL)	2	5	2.3	0.55	1.7	0.49	3.7	0.45

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Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol, with three curved lines representing the bird's body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Carol Marble Senior Requlatory Affairs Specialist Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, Massachusetts 02173-3190

K980646 Re : IL Synthesis™ - Addition of Bilirubin as a Measured -Parameter for Neonate Whole Blood Samples Regulatory Class: I Product Code: MQM February 18, 1998 Dated: Received: February 19, 1998

Dear Ms. Marble:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, qood manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਰੇ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Requlation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or 16 2019 10 10:20 requlations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: IL Synthesis™ -- Addition of Bilirubin as Measured Parameter for Neonate Whole Blood Samples

Indications for Use:

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K980646

Prescription Use(Per 21 CFR 801.019)	OR Over-The-Counter Use
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Section 2 IL Synthesis™: Addition of Bilirubin Parameter 510(k) Page 1 of 1

Regulation Number and Section

§ 862.1113 Bilirubin (total and unbound) in the neonate test system.

(a)
Identification. A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).(b)
Classification. Class I.