(52 days)
Determination of serum and plasma bilirubin is useful in the screening of liver function disorders or in the diagnosis of jaundice.
When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH3, direct bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the direct bilirubin concentration in the sample can be obtained by measuring the adsorbances before and after the vanadate oxidation.
This document is a 510(k) Summary of Safety and Effectiveness for the Wako Direct Bilirubin V assay. It highlights that the device is based on a chemical oxidation method and can determine direct bilirubin concentration in serum and plasma samples. The primary goal of the submission is to add plasma as an approved sample type to an already existing and approved device (Wako's previous Direct Bilirubin assay, 510(k) #970986).
1. Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state specific performance acceptance criteria in numerical terms (e.g., sensitivity, specificity, accuracy thresholds). Instead, the crucial acceptance criterion for this 510(k) submission is "substantial equivalency" to the previously marketed device (Wako's Direct Bilirubin assay, 510(k) #970986).
The reported device performance is:
- "shows good correlation with conventional methods"
- "practically no interference by coexistent serum and plasma substances"
- "convenient ready-to-use liquid type reagent"
Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criterion | Reported Device Performance |
|---|---|
| Substantial Equivalency to Predicate Device | Confirmed by FDA's 510(k) clearance letter (K053132) |
| Good correlation with conventional methods | Stated in the 510(k) summary |
| Minimal interference from coexistent substances | Stated in the 510(k) summary |
| Ease of Use | Described as "convenient ready-to-use liquid type reagent" |
2. Sample Size Used for the Test Set and Data Provenance
The document does not provide details on the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It only states that the submission adds the use of plasma as a sample to the previously cleared device. Therefore, any testing related to substantial equivalence for plasma samples would have been conducted, but the specific details are not included in this summary.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This submission describes an in vitro diagnostic (IVD) assay for measuring bilirubin, not an imaging device or one requiring expert interpretation of results for ground truth establishment. Therefore, the concept of "experts used to establish ground truth" as it applies to, for example, radiologists interpreting images, is not applicable here. The "ground truth" for chemical assays typically relies on established reference methods, calibrated standards, and a comparison to a predicate device.
4. Adjudication Method for the Test Set
Given that this is an IVD assay and not an imaging or interpretative device, an "adjudication method" in the sense of multiple experts resolving discrepancies is not applicable. Assay results are quantitative measurements, and accuracy is typically assessed against reference methods or the performance of a predicate device.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not applicable for this type of in vitro diagnostic assay. MRMC studies are typically used to evaluate the diagnostic performance of human readers, often with and without AI assistance, in interpreting medical images or other complex data. This device is an automated chemical assay.
6. Standalone Performance Study
The information provided within this summary does not explicitly describe a separate "standalone" study in the way it might be for an AI algorithm. However, the 510(k) submission itself implicitly represents a standalone performance evaluation by comparing its performance to predicate devices (the previous Wako Direct Bilirubin assay) and conventional methods. The core of a 510(k) relies on demonstrating that the new device is "substantially equivalent" in performance to a legally marketed predicate device. This inherently means its performance was evaluated independently to make that claim.
7. Type of Ground Truth Used
The ground truth for chemical assays like this is typically established through:
- Comparison to established, validated reference methods: The summary mentions "good correlation with conventional methods," indicating such comparisons were likely part of the underlying studies.
- Calibrated standards: Assays are typically validated against precisely known concentrations of the analyte (bilirubin in this case).
- Performance of the predicate device: The primary ground truth for this specific submission is the performance of the legally marketed predicate device (Wako's previous Direct Bilirubin assay, 510(k) #970986), against which "substantial equivalency" is claimed.
8. Sample Size for the Training Set
The concept of a "training set" with a specified sample size is primarily relevant to machine learning or AI algorithms. This device is a chemical reagent-based assay. Therefore, a "training set" in the machine learning sense is not applicable. The development of such assays involves extensive R&D, formulation optimization, and analytical validation.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the context of AI is not applicable for this chemical assay. The validation of the assay's chemical principles and performance would have involved laboratory studies using known bilirubin concentrations, spiked samples, and clinical samples analyzed by reference methods and the predicate device to ensure accuracy, precision, and linearity.
{0}------------------------------------------------
Wako Chemicals USA, Inc. 1600 Bellwood Road, Richmond, VA 23237 U.S.
DEC 3 0 2005
K053/32
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 123 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 Direct 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, direct bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the direct 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 Direct Bilirubin V assay is demonstrated by its substantial equivalency to our previous Direct Billrubin assay (510(K) # 970986). The previously marketed device (510k# 970986) 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) # 970986.
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 Mvrothecium varrucaria MT-1. Agric. Biol. Chem. 45: 2383-2384. (1981).
(5) Tokuda K. and Tanimoto K. New method of measuring serum billrubin 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).
Lori Creasy
November 7, 2005 Regulatory Affairs Specialist Wako Diagnostics 1600 Bellwood Road Richmond, VA 23237
{1}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/1/Picture/2 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized eagle with three overlapping wings, representing the department's commitment to health, human services, and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the eagle.
DEC 3 0 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Lori Creasy Regulatory Affairs Specialist Wako Chemicals, USA Inc. 1600 Bellwood Road Richmond VA, 23237
Re: K053132
Trade/Device Name: Wako Direct Bilirubin V Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: LFM 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).
{2}------------------------------------------------
Page 2 -
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
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
{3}------------------------------------------------
| 510(k) Number (if known): | ||
|---|---|---|
| --------------------------- | -- | -- |
Device Name: Wako Direct Bilirubin V
Indications For Use:
Determination of serum and plasma bilirubin is useful in the screening of liver function disorders or in the diagnosis of jaundice.
Prescription Use
AND/OR
Over-The-Counter Use
(Part 21 CFR 801 Subpart D)
(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)
CAC
Division Sign Off
Office of Diagnostic Device
Evaluation and Safety
10(k) K05 3132
Page 1 of
§ 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.