The Colormate III™ is to be used as an aid to the physician in monitoring the status of newborn babies for the development of hyperbilirubinemia. Following the physician's examination within the first hours after birth, newborn babies are initially measured and periodically monitored by the Colormate III™ for incremental changes in the yellow content of the skin color as compared to the baseline Colormate III™ measurements. Babies with Colormate III™ test results indicative of hyperbilirubinemia are to be re-evaluated by the attending physician for appropriate patient management.

Device Description

Colormate III™ (Colormate III or CM III) is a computer assisted noninvasive transcutaneous bilirubinometer which, through colorimetric technology, illuminates the skin of newborn babies and measures the yellow content of the skin color. The incremental changes of these color readings measured over time are compared to the newborn's baseline readings. These data are then automatically processed to provide a numerical index of estimated bilirubin count in mg/dl that has been shown to correlate with total serum bilirubin within a clinically useful range. The Colormate III, like other colorimeters, generates a set of tristimulus color coordinates for each measurement. It then performs a series of algorithms to produce final measurement results.

AI/ML Overview

The provided document describes the Colormate III™, a transcutaneous bilirubinometer, and a clinical study conducted to demonstrate its performance. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet. Instead, it presents performance metrics against visual assessment as a comparator, focusing on correlation, bias, and sensitivity. We can infer the performance goals from the reported results.

Metric (Inferred Acceptance Criteria)	Reported Device Performance (Colormate III™)	Comparator (Visual Assessment)
Correlation with Serum Bilirubin Concentration (r)	r = 0.90 (p < 0.01)	r = 0.67
Bias (between Colormate III and serum bilirubin)	Did not exceed 1.6 mg/dl in range 4.0-17.0 mg/dl; Less than 1 mg/dl from 7 to 17 mg/dl	N/A (Visual assessment inherently more subjective)
Correlation unaffected by race	Caucasian r = 0.91, Black r = 0.88, Hispanic r = 0.89, Oriental r = 0.91	N/A
Sensitivity for identifying bilirubin levels > 12.0 mg/dl	89% (statistically significantly better than visual assessment, p < 0.05)	61%
Reproducibility (Coefficients of Variation for tristimulus color coordinates)	Below 3%	N/A

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

Total Study Population: 1317 newborns
Test Set for Performance Comparison (Colormate III vs. Visual Assessment vs. Serum Bilirubin): 171 premature and full-term newborns who had concurrent Colormate III measurements, clinical visual estimates, and blood serum tests. These 171 newborns yielded 360 concurrent measurements.
Data Provenance: The document does not explicitly state the country of origin. However, the FDA 510(k) submission context implies the study was conducted to support marketing in the U.S. The study was a prospective clinical trial.

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

Number of Experts: The document mentions "the physician" and "clinicians" in the context of visual assessment, implying multiple physicians were involved in the visual estimates. However, it does not specify the exact number of physicians or their qualifications (e.g., years of experience, specialty).
Qualifications: Not specified. It can be inferred they were attending physicians or clinicians experienced in neonatal care.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for reconciling discrepancies between multiple visual assessments by clinicians. The study compares the Colormate III to "the clinicians' visual assessment," suggesting either a single visual assessment per case or an implicit consensus, but no formal adjudication process is detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improve with AI vs. Without AI Assistance

Type of Study: This was a comparative effectiveness study comparing the Colormate III (an AI-assisted device in its processing of colorimetric data) against human visual assessment without AI assistance and against the gold standard of serum bilirubin.
Effect Size of Human Readers Improve with AI vs. Without AI Assistance:
- The study does not evaluate "human readers improve with AI vs. without AI assistance" in the typical MRMC sense where human readers interpret images with and without AI output.
- Instead, it directly compares the device's algorithmic output ("Colormate III") against human visual assessment.
- The "effect size" is presented by comparing the correlation coefficient with serum bilirubin:
  - Colormate III: r = 0.90
  - Clinicians' visual assessment: r = 0.67
- And by sensitivity for detecting hyperbilirubinemia (>12.0 mg/dl):
  - Colormate III: 89%
  - Clinicians' visual assessment: 61%
- The Colormate III shows significantly higher accuracy and sensitivity than visual assessment.

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

Yes, a standalone performance assessment was done. The "Colormate III" performance metrics (correlation r=0.90, bias, sensitivity=89%) represent the algorithm's performance when measuring skin color and processing it to provide a numerical index of estimated bilirubin. The device's output is then used by a physician, but the reported performance metrics focus on the device's ability to correlate with blood serum levels.

7. Type of Ground Truth Used

The primary ground truth used for evaluating the Colormate III and visual assessment was total serum bilirubin concentration (BRC), measured via blood tests.
The document also describes how "a cutoff of 12.0 mg/dl of bilirubin" was used as an "acceptable level of clinical concern" for calculating sensitivity.

8. Sample Size for the Training Set

The document states: "Prior to undertaking a pivotal clinical trial to evaluate the Colormate III's performance, two phases of studies were conducted to validate the clinical approach and test criteria and determine calibration algorithms for subsequent validation."
This indicates that a training/calibration phase was performed before the pivotal clinical trial, but the sample size for these training/calibration studies is not explicitly provided.

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

The document implies that the ground truth for the training/calibration phase was also established using serum bilirubin blood tests in conjunction with Colormate III measurements. It states these studies were used to "determine calibration algorithms," which would necessitate comparing device readings to a reference standard (serum bilirubin) to build or refine its internal models. However, detailed methodology for training ground truth establishment is not provided.

Summary

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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three heads, representing the department's focus on health, human services, and science. The eagle is surrounded by a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" printed around it.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 2 4 1997

Thomas M. Tsakeris President Devices & Diagnostics Consulting Group 16809 Briardale Road Rockville, Maryland 20855

Re : K964590 Colormate™ Regulatory Class: II Product Code: MQM Dated: May 23, 1997 Received: May 23, 1997

Dear Mr. Tsakeris:

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, good manufacturing practice, labeling, and prohibitions aqainst 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. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical General regulation (21 CFR Part 820) and that, Devices: through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in requlatory 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 Requlations.

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Page 2

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 Aitman

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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APPENDIX F

(510 (K)) Summary

JUL 2 4 1997

510 (k) SUMMARY Colormate III™ November 14, 1996

K964590

This summary is provided in accordance with the Safe Medical Inis Bammary ID 1990 (SMDA), ai U.S.C. §360c(i)(3) and FDA's Devices Act of instally, 21 C.F.R. 807.92.

Submitter of 510(k) 1.0

Chromatics Color Sciences International, Inc. 5 East 80th Street New York, New York 10021-0109

Ms. Darby S. Macfarlane, CEO Attention:

212-717-6544 Telephone: 212-717-6675 Facsimile:

2.0 Name of Device

Trade/Proprietary Name 2.1

Colormate III™

Common/Usual Name 2.2

Transcutaneous Bilirubinometer (Colorimeter)

2.3 Classification Name

ੈ

Bilirubin (total and unbound) in the neonate test system (21 CFR 862.1113) ﺴﻤﺎ .

Reason for Submitting the 510(k) 3.0

This 510(k) is being submitted to notify FDA of Chromatics Color Sciences International's (CCSI) desire to commercially distribute for the first time the Colormate III.

4.0 Device Description

Colormate III™ (Colormate III or CM III) is a computer The assisted noninvasive transcutaneous bilirubinometer which, through colorimetric technology, illuminates the skin of newborn babies and measures the yellow content of the skin color. The incremental changes of these color readings measured over time are compared to the newborn's baseline readings. These data are then automatically processed to provide a numerical index of estimated bilirubin count in mg/dl that has been shown to correlate with total serum bilirubin within a clinically useful

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The Colormate III, like other colorimeters, generates a ranqe. set of tristimulus color coordinates for each measurement. It then performs a series of algorithms to produce final measurement results.

Indications for Use & Intended Use 5.0

Indications For Use 5.1

The Colormate III is to be used as an aid to the physician in monitoring the status of newborn babies for the development of hyperbilirubinemia. Following the physician's examination within the first hours after birth, newborn babies are initially measured and periodically monitored by the Colormate III for incremental changes in the yellow content of the skin color as compared to the baseline Colormate III measurements. Babies with Colormate III test results indicative of hyperbilirubinemia to be re-evaluated by the attending physician for are appropriate patient management.

Intended Use 5.2

computer assisted non-invasive Colormate III is a The transcutaneous bilirubinometer which, through colorimetric technology, illuminates the skin of newborn babies and measures the yellow content of the skin color. The incremental changes of these color readings measured over time are compared to the newborn's baseline Colormate III readings. These data are then automatically processed to provide a numerical index of predicted bilirubin count in mg/dl that has been shown to correlate with total serum pilirubin concentration within a clinically useful range.

Substantial Equivalence 6.0

The Colormate III is "substantially equivalent" (as defined in 21 U.S.C. § 360c(i)) in principle, performance, and safety and effectiveness to at least two legally marketed predicate devices. The first predicate device, the Unistat Bilirubinometer manufactured by Leica, Inc. (K922770), is a bilirubinometer which operates by measuring the absorption of visible light through a sample of unreacted serum. The several wavelengths determines the level absorption at ot bilirubin present in the sample. The second device, the Ingram Icterometer, commercially distributed preenactment (marketed since 1950's) by Cascade Health Care Products, Salem, Oregon, is a noninvasive aid used as a color reference by the physician during his/her visual assessment of the newborn's skin for jaundice or yellowing. The yellow color of the subcutaneous tissue is matched to a corresponding "yellow hue" stripe for a reference score.

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The Colormate III and predicate devices can be used as aids in monitoring the development of hyperbilirubinemia in the newborn.

the Colormate III has comparable technological Further, characteristics to those of the predicate devices. The underlying principles of the Colormate III and the predicate devices are the same in that the Colormate III and the predicate devices base their measurements on the unique absorbance characteristics of bilirubin in the visible spectrum. That is, the level of bilirubin (whether intravascular or extravascular) is easily detected by its characteristic absorption of visible Bilirubin strongly absorbs light in the wavelenqths light. between approximately 400 to 540 nm. These correspond to the blue and violet portions of the visible spectrum. qreen, Therefore, an increase in bilirubin is seen as a direct absorption of these colors in transmitted or reflected light or as a relative increase in the complementary color of yellow. This latter effect is seen in the yellowing (jaundice) of the infant's skin during hyperbilirubinemia.

The Colormate III, like the predicate Unistat Bilirubinometer, directly measures the bilirubin concentration via its absorption of visible light. The Colormate III measures the interstitial subcutaneous concentration and the Unistat measures the intravascular concentration.

The Colormate III and the noninvasive predicate device, as well as the visual assessment by the physician, operate on the principle that increasing levels of serum bilirubin during hyperbilirubinemia results in corresponding increases in the level of interstitial biligubin. The painted stripes of precisely graded yellow hues in the Ingram Icterometer provide the physician with a visual aid to gauge the depth of jaundice in the newborns and estimate the serum bilirubin levels. The Colormate III expands on this concept. The Colormate III replaces the human eye with a colorimeter having more accuracy and precision and provides the physician with a numerical index of estimated serum bilirubin in mg/dl.

7.0 Performance Data

The performance testing provided demonstrates that the Colormate III is statistically significantly more accurate and precise than visual assessment alone and can aid the physician in monitoring hyperbilirubinemia in the newborn. Further, these data demonstrate that the Colormate III interstitial readings highly correlated (r = 0.90, p<0.01) are with serum or intravascular bilirubin readings within a clinically useful range.

A series of reproducibility studies were conducted using the Measurements were made using (A) a standard Colormate III.

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calibration tile, (B) adult subjects and (C) newborn babies with varying degrees of jaundice. The coefficients of variation (CV) for the tristimulus color coordinates calculated by the Colormate III and used in its numerical index are below 3%.

Prior to undertaking a pivotal clinical trial to evaluate the Colormate III's performance, two phases of studies were corducted to validate the clinical approach and test criteria and determine calibration algorithms for subsequent validation.

A clinical study was conducted to compare (1) the performance of the Colormate III using colorimetric measurement technology to estimate serum bilirubin concentration (BRC) from the yellow content of the color of the skin and (2) the ability of the physician to visually assess the same yellow color of the skin and make a clinical estimate of the BRC. Neonates enrolled in the study underwent the usual course of physical examination (including a visual assessment of the yellowness of the skin for bilirubinemia), monitoring and care. Colormate III skin color measurements, employing a number of anatomical sites on an infant, were made concurrently with serum bilirubin blood tests and physicians' visual estimates.

trial involved a sequence of 1317 newborns. The The study included a mix of the following races: 487 (37%) Caucasians, 298 (23%) Blacks, 427 (32%) Hispanics, 82<(6%) Orientals and 20 (2%) others. One Thousand Thirty-seven (1037) babies were did not develop hyperbilirubinemia) normal -(i.e., and. therefore, did not underqo blood serum tests. One Hundred Nine (109) babies did not have initial measurements made within acceptable time frames. The remaining 171 premature and full term newborns with 360 concurrent. Colormate III measurements, clinical visual estimates and blood serum tests demonstrated that the Colormate III was better correlated (p<0.05) with serum bilirubin concentration (r = .90) than was the clinicians' visual assessment (r = 67).

The estimation of bias between the Colormate III test and comparative serum did not exceed 1.6 mg/dl in the clinically useful range of 4.0 to 17.0 mg/dl (less than 1 mg/dl from 7 to 17 mg/dl). In addition, the correlation of Colormate III with serum readings was relatively unaffected by race (Caucasian r = .91, Black r = .88, Hispanic r = .89, Oriental r = .91).

Additionally, the relative sensitivities of the visual measurement and the Colormate III results to serum values were computed and compared using a contingency table approach to data presentation and a cutoff of 12.0 mq/dl of bilirubin as an acceptable level of clinical concern. The clinicians' visual assessment agreed above the cutoff of 12.0 with serum only 61% of the time while the Colormate III agreement (sensitivity of the Colormate III) was over 89% in the same patients. The sensitivity of the Colormate III™ was statistically

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siqnificantly better than that for the visual assessment, in Sighried.cry booosi erum values above and below the accepted level of clinical concern of 12.0 mg/dl, p<.05. Further, exactly the same conclusions were reached when higher or lower levels were examined (e.g., 8.0 or 14.0). Sensitivity revers - were - Chamillour (sated significantly higher sensitivity for the Colormate III than that for the visual assessment.

In conclusion, the Colormate III performance was superior to visual examination in estimating the true level of serum bilirubin, in addition to an excellent corrrelation to serum bilirubin throughout a clinically useful range.

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Colormate III™ Device Name:

Indications For Use:

The Colormate III™ is to be used as an aid to the physician in The Corormate III is of newborn babies for the development of monitoring the Statub of Mowing the physician's examination hyperollirubinema. within the and periodically monitored by the Colormate III" for measured and perfoundains perlow content of the skin color as Herementar change eline Colormate III™ measurements. Babies Colormate III™ test results indicative of with with - Coromate - The to be re-evaluated by the attending physician for appropriate patient management.

Intended Use:

is a computer assisted non-invasive Colormate III™ The transcutaneous bilirubinometer which, through colorimetric eranoodogy, illuminates the skin of newborn babies and measures the yellow content of the skin color. The incremental changes ene forem color readings measured over time are compared to the of cheborn's baseline Colormate III™ readings. These data are then newborn bally processed to provide a numerical index of predicted bilirubin count in mg/dl that has been shown to products with total serum bilirubin concentration within a clinically useful range.

A rationale for clinical utility is provided on the following page .

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use:	✓ OR Over-The-Counter:
(Per 21 CFR 801.109)	(Optional Format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number	K964590
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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.