WAKO TOTAL BILIRUBIN V, MODELS 410-22701, 998-23291, 416-22801, 990-23191 by WAKO CHEMICALS, USA, INC.

Wako Total Bilirubin V is based on a chemical oxidation method, utilizing vanadate as an oxidating agent, shows good correlation with conventional methods, practically no interference by coexistent serum and plasma substances, and is convenient ready-to-use liquid type reagent. When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH3, total bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the total bilirubin concentration in the sample can be obtained by measuring the adsorbances before and after the vanadate oxidation.

AI/ML Overview

This submission is for a reagent, the Wako Total Bilirubin V assay, and thus the acceptance criteria and study design are related to the analytical performance of the assay rather than a diagnostic device that requires expert consensus or advanced imaging.

Here's an analysis of the provided text in relation to your request:

Acceptance Criteria and Device Performance

The provided text does not explicitly state specific numerical acceptance criteria for the Wako Total Bilirubin V assay. Instead, it relies on demonstrating "substantial equivalency" to a previously marketed device (510(K) # 970985).

The reported device performance, in terms of meeting implicit acceptance criteria, is based on the following:

Substantial Equivalency: The key claim is that "The safety and effectiveness of the Wako Total Bilirubin V assay is demonstrated by its substantial equivalency to our previous Total Bilirubin assay (510(K) # 970985)."
Correlation with Conventional Methods: The device "[Wako Total Bilirubin V] shows good correlation with conventional methods."
Interference by Coexistent Serum and Plasma Substances: It demonstrates "practically no interference by coexistent serum and plasma substances."
Convenience and Stability: It is also "convenient ready-to-use liquid type reagent."

Table of Acceptance Criteria and Reported Device Performance (Inferred):

Acceptance Criteria Category (Inferred)	Specific Criteria (Inferred/Implicit)	Reported Device Performance
Accuracy/Comparability	Substantial equivalency to predicate device (510(K) # 970985) for serum samples; good correlation with conventional methods.	Meets: Demonstrated substantial equivalency to predicate device. Shows good correlation with conventional methods (diazo coupling, bilirubin oxidase enzymatic).
Interference	Minimal interference from coexistent serum and plasma substances.	Meets: "practically no interference by coexistent serum and plasma substances."
Stability/Usability	"Convenient ready-to-use liquid type reagent." (This is more a design feature than a performance criterion, but contributes to overall assessment.)	Meets: Described as "convenient ready-to-use liquid type reagent." This implies stability and ease of use, addressing a disadvantage of older methods (unsatisfactory stability of reagents after preparation).
New Sample Type Performance	Performance for plasma samples is equivalent to its established performance for serum samples and to the predicate device for serum.	Meets: The submission "adds the use of plasma as a sample" with "no changes to performance claims already established in 510(k) # 970985" for serum, implying equivalent performance for plasma.

Study Details

Given the nature of the submission (510(k) for an in vitro diagnostic reagent, primarily adding a sample type), the study described is an analytical validation comparing the new device to a predicate and conventional methods. It is not a clinical study involving human readers or extensive ground truth establishment in the way a diagnostic imaging device would be studied.

Sample Size used for the test set and the data provenance:
- Sample Size: Not explicitly stated in the provided text.
- Data Provenance: Not explicitly stated, but typical for such submissions would be laboratory-based analytical studies using human serum and plasma samples. It does not specify country of origin or whether it's retrospective or prospective, but these are generally prospective analytical studies for IVD reagents.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in the sense of expert human interpretation of images/data. The "ground truth" (or reference values) would be established by the "conventional methods" mentioned (diazo coupling, bilirubin oxidase enzymatic method) which are laboratory-based chemical analyses, often performed by trained medical technologists or clinical chemists. No specific number or qualifications of individual "experts" are provided as this is a chemical assay validation.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is an analytical performance study of a chemical reagent, not a diagnostic interpretation study requiring adjudication of expert opinions.
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. This is not an AI-assisted diagnostic device, nor is it a study involving human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is inherently a "standalone" device in the sense that it is a chemical reagent that performs its function without a human-in-the-loop interpretative step once the sample is added. However, the term "standalone" usually refers to AI algorithms. In the context of IVDs, this refers to the assay's analytical performance on its own. The description implies such a standalone analytical validation was performed.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" for bilirubin measurement is established through reference laboratory methods, specifically the "conventional methods" like the diazo coupling method and the bilirubin oxidase enzymatic method, which are well-established chemical assays for bilirubin quantification.
The sample size for the training set:
- Not applicable. This is a chemical reagent, not a machine learning algorithm that requires a "training set."
How the ground truth for the training set was established:
- Not applicable. (See #7).

Summary

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DEC 30 2005

Wako Chemicals USA. Inc. 1600 Bellwood Road, Richmond, VA 23237 U.S.A

510(K) Summary of Safety and Effectiveness

Serum and plasma measurement is widely used as a screening test for liver functions. The methods most widely used for determination of serum bilirubin are the diazo coupling method 1.2.3 and the bilirubin oxidase enzymatic method . However, these methods have disadvantages such as interference by coexistent serum substances unsatisfactory stability of reagents after preparation. Wako Total Bilirubin V is based on a chemical oxidation method, utilizing vanadate as an oxidating agent, shows good correlation with conventional methods, practically no interference by coexistent serum and plasma substances, and is convenient ready-to-use liquid type reagent®.

When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH3, total bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the total bilirubin concentration in the sample can be obtained by measuring the adsorbances before and after the vanadate oxidation.

The safety and effectiveness of the Wako Total Bilirubin V assay is demonstrated by its substantial equivalency to our previous Total Bilirubin assay (510(K) # 970985). The previously marketed device (510k# 970985) was marketed for serum samples and this submission adds the use of plasma as a sample. There are no changes to performance claims already established in 510(k) # 970985.

References:

(1) Malloy H. T., Evelyn K. L. The determination of bilirubin with the photoelectric colorimetry. J. Biol. Chem., 199: 481-490, (1937).

(2) Jendrassik L., Cleghorn R. A. Photometrische bilirubinbestimmung. Biochem. Z., 289: 1-14, (1937).

(3) Michaelsson M. Bilirubin determination in serum and urine. Scand. J. Clin. Lab. Invest., 12 (Suppl 56): 1-80. (1937).

(4) Murao S., Tanaka N. A new enzyme "bilirubin oxidase" produced by Myrothecium varrucaria MT-1. Agric. Biol. Chem. 45: 2383-2384, (1981).

(5) Tokuda K. and Tanimoto K. New method of measuring serum bilirubin using vanadic acid. Jpn. J. Clin. Chem., 22 (2), 116-122 (1993).

(6) Carl A.Burtis, Edward R. Ashwood, TIETZ TEXTBOOK of Clinical Chemistry, second edition, P1468 (SAUNDERS).

loe Creasy

Lori Creasy November 7, 2005 Regulatory Affairs Specialist Wako Diagnostics 1600 Bellwood Road Richmond, VA 23237

Telephone (804) 271-7677 Facsimile (804) 271-7791 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/1/Picture/12 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus, a symbol often associated with medicine and healthcare, with three lines forming a stylized shape. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the caduceus symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 3 0 2005

Ms. Lori Creasy Regulatory Affairs Specialist Wako Chemicals, USA Inc. 1600 Bellwood Road Richmond VA, 23237

Re: K053131

Trade/Device Name: Wako Total Bilirubin Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: JFM Dated: November 7, 2005 Received: November 9, 2005

Dear Ms. Creasy:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto G. A.

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE:

510(k) Number (if known):

Device Name: Wako Total Bilirubin V

Indications For Use:

Indication of serum and plasma bilirubin is useful in the screening of liver function disorders or in the diagnosis of jaundice.

Prescription Use
(Part 21 CFR 801 Subpart D)
✓

Over-The-Counter Use AND/OR (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

SIU(k).

Office of In Vi. . Diagnostic Device Evaluation and Safety 113333

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Regulation Number and Section

§ 862.1110 Bilirubin (total or direct) test system.

(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.