(58 days)
CODA is an integrated immunoassay analyzer intended for the automation of microplate based assays for in vitro diagnostic use. The system is open, such that a variety of microplate-based enzyme immunoassays (EIA's) can be programmed and run on the instrument. The sample and reagent pipettes, incubator, washer, reader and robotics are housed in the compact benchtop unit. CODA Operation and Data Management software operates in the Windows 95 environment utilizing icon-based commands for operator ease of use.
The Bio-Rad Coda Automated EIA Analyzer (Coda) is a compact, integrated immunoassay system designed for the automation of microplate based (8 wells by 12 strips) chemistries. The sampler, plate-shaker, incubator, washer, reader and robotics are housed in a single compact Main Unit. An external computer handles the operation and data management using software contained on a CD-ROM which operates in the Windows 95 environment.
Enzyme immunoassay (EIA) typically involves the addition of a defined volume of sample to a series of plastic microtitre wells which have been pre-coated with antigen or antibody. The wells are sometimes washed to remove unbound ligand before addition of enzyme conjugate to each well. After incubation, substrate is added followed by a second incubation. The enzyme reaction is "stopped" and the colored reactant product is measured by absorbance at a defined wavelength. The absorbance values of the unknowns are compared to absorbance of calibrators to determine the concentration of the ligand in the sample. The Coda provides an integrated, automated approach to carrying out the above steps all under control of the computer and associated software. All the steps may be programmed into a complete protocol or individual steps may be performed in a manual mode. The Coda is therefore virtually usable with any assay kit using microtite plates. Output from the spectrophotometer is measured by the computer. Calculation, curve-fitting, result interpretation and other aspects of data management and analysis are automatically performed by the software algorithms.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Bio-Rad Coda™ Automated EIA Analyzer:
Please note: The provided document is a 510(k) summary, which often focuses on demonstrating substantial equivalence to a predicate device rather than comprehensive clinical trial results for a novel device. As such, some of the information requested (especially regarding multi-reader multi-case studies, expert adjudication, and detailed ground truth for training) may not be fully addressed, as these types of studies might not be explicitly required or detailed in a 510(k) for this type of instrument.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implied/Not Explicitly Stated) | Reported Device Performance |
|---|---|---|
| Precision | ||
| Within-Run %CV (Low Control) | (Likely compared to predicate or internal standards for acceptable variability) | 8.6% |
| Within-Run %CV (Mid-Range Control) | (Likely compared to predicate or internal standards for acceptable variability) | 7.1% |
| Within-Run %CV (High Control) | (Likely compared to predicate or internal standards for acceptable variability) | Consistently > 25 ulU/mL |
| Within-Run %CV (Anemia Control) | (Likely compared to predicate or internal standards for acceptable variability) | 9.5% |
| Total Precision %CV (Low Control) | (Likely compared to predicate or internal standards for acceptable variability) | 9.6% |
| Total Precision %CV (Mid-Range Control) | (Likely compared to predicate or internal standards for acceptable variability) | 7.7% |
| Total Precision %CV (High Control) | (Likely compared to predicate or internal standards for acceptable variability) | Consistently > 25 ulU/mL |
| Total Precision %CV (Anemia Control) | (Likely compared to predicate or internal standards for acceptable variability) | 14.0% |
| Sensitivity (Measuring Range) | (Likely compared to predicate for comparable analytical detection) | 0.034 ulU/mL (lowest TSH distinguishable from zero standard at 95% CI) |
| Accuracy (Correlation) | High correlation required (e.g., r > 0.95 or 0.97) to demonstrate substantial equivalence to predicate device. | r = 0.995 (compared to Bio-Rad Radias Immunoassay System) |
| Carry-over | (Not specified, but tested) | Not explicitly quantified in this summary |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for each performance metric. Instead, the performance is presented to demonstrate that the device is "substantially equivalent" to predicate devices, implying that its performance is comparable and acceptable within the context of similar devices.
2. Sample Size Used for the Test Set and Data Provenance:
- Precision Studies: Twenty samples each of low, mid-range, and high control, plus a Bio-Rad anemia control (AN) were analyzed. This means at least 4 x 20 = 80 measurements were taken for precision.
- Correlation Study (Accuracy): 111 samples were used.
- Data Provenance: Not specified, but generally, studies for 510(k) submissions in the US are conducted in a controlled lab environment. It is unclear if the samples were retrospective or prospective, or their country of origin.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This information is not provided in the document. For an automated immunoassay analyzer, the "ground truth" for test samples is typically established by reference methods or validated laboratory measurements, not by human experts in the same way it would be for an image-based diagnostic AI.
4. Adjudication Method for the Test Set:
- Not applicable/Not provided. The testing involved comparing instrument readings to established values or to a predicate device, not adjudication of expert interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size:
- No, a MRMC study was not done. This type of study is typically performed for AI-powered diagnostic aids where human interpretation is a key component. The Coda is an automated immunoassay analyzer, not an AI for human-in-the-loop diagnostic interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, the studies described are standalone performance studies. The device (Coda™ Automated EIA Analyzer) itself is an automated system. The precision, sensitivity, and accuracy studies evaluate the instrument's performance autonomously. There is no "human-in-the-loop" component for its direct operation or result interpretation at the point of measurement; the human's role is to program assays and manage data.
7. The Type of Ground Truth Used:
- For Precision: Control samples (low, mid-range, high, and anemia control) with established target values.
- For Sensitivity: Zero standard (to determine the lowest distinguishable level).
- For Accuracy (Correlation): Measurements obtained from the predicate device, the Bio-Rad Radias Immunoassay System, for the same 111 samples. The predicate device's results served as the reference for comparison.
8. The Sample Size for the Training Set:
- Not applicable/Not provided. The Bio-Rad Coda™ Automated EIA Analyzer is an immunoassay instrument and does not appear to be an AI/machine learning device that requires a "training set" in the conventional sense for algorithm development. Its software manages the instrument's operations, calculations, and data interpretation based on predefined algorithms for curve-fitting and result interpretation, not on learned patterns from a training dataset.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable/Not provided. As explained in #8, there isn't a "training set" in the AI/ML context for this type of device. The ground truth for its operational parameters and calculation algorithms would be based on fundamental scientific principles of enzyme immunoassays, photometric measurements, and validated statistical methods for curve fitting, rather than a dataset trained by external ground truth.
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
John W. Nelson JUL 30 1997 .• Manager, Regulatory Affairs • Bio-Rad Laboratories 4000 Alfred Nobel Drive Hercules, California 94547-1803
K972024 Re : Coda™ Automated EIA Analyzer Requlatory Class: I Product Code: JJI May 30, 1997 Dated: Received: June 2, 1997
Dear Mr. Nelson:
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 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. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (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 requlation 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 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 requlation (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 Gutman
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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K yiday
JUL 300 1997
APPENDIX B
SUMMARY OF SAFETY AND EFFECTIVENESS
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Image /page/3/Picture/0 description: The image shows the logo for Bio-Rad. The text "BIO-RAD" is written in white, bold, sans-serif font. The plus sign in the middle of the text is slightly larger than the other letters. The text is set against a black, rounded rectangle.
Bio-Rad Laboratories
Diagnostics Group 4000 Alfred Nobel Dr. Hercules, CA 94547-1803 Telephone: 510 724-7000 Fax: 510 741-5824
SUMMARY OF SAFETY AND EFFECTIVENESS
| Submitter: | Bio-Rad Laboratories, Inc.Clinical Systems Division4000 Alfred Nobel DriveHercules, California 94547Phone 1-510-741-6015FAX 1-510-741-5824 |
|---|---|
| Contact Person: | John W. NelsonManager, Regulatory Affairs |
| Date Prepared: | May 30, 1997 |
| Product Trade Name: | Bio-Rad Coda™ Automated EIA Analyzer |
| Common Name: | Coda |
| Classification Name: | Enzyme Analyzer, for Clinical Use, 75JJI |
| Predicate Devices | 1. Radius™ Immunoassay System,Bio-Rad Laboratories, K930898. |
| 2. ACS 180 Automated ChemiluminescenceSystem, Ciba Corning, K902336. | |
| 3. Abbott IMX2 Analyzer, AbbottLaboratories, K931970. |
To establish substantial equivalence to an existing device, and thus establish the safety and effectiveness of the Bio-Rad Coda Automated EIA Analyzer, the Bio-Rad Coda Automated EIA Analyzer has been compared to the Bio-Rad Radias Immunoassay System K930898. A review of the intended use of each system shows them to be essentially the same in that they are capable of measuring a number of analytes based on the Enzyme Immunoassay (EIA) principle. The intended use of the Bio-Rad Coda Automated EIA Analyzer is stated as: CODA is an integrated immunoassay analyzer intended for the automation of microplate based assays for in vitro diagnostic use. The system is open, such that a variety of microplate-based enzyme immunoassays (EIA's) can be programmed and run on the instrument. The sample and reagent pipettes, incubator, washer, reader and robotics are housed in the compact benchtop unit. CODA Operation and Data Management software operates in the Windows 95 environment utilizing icon-based commands for operator ease of use. The intended use of the Bio-Rad Radias Immunoassay System is stated as: Radias is a fully automated immunoassay system utilizing ELISA based assays for in vitro diagnostic use.
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The Bio-Rad Coda Automated EIA Analyzer (Coda) is a compact, integrated immunoassay system designed for the automation of microplate based (8 wells by 12 strips) chemistries. The sampler, plate-shaker, incubator, washer, reader and robotics are housed in a single compact Main Unit. An external computer handles the operation and data management using software contained on a CD-ROM which operates in the Windows 95 environment.
Enzyme immunoassay (EIA) typically involves the addition of a defined volume of sample to a series of plastic microtitre wells which have been pre-coated with antigen or antibody. The wells are sometimes washed to remove unbound ligand before addition of enzyme conjugate to each well. After incubation, substrate is added followed by a second incubation. The enzyme reaction is "stopped" and the colored reactant product is measured by absorbance at a defined wavelength. The absorbance values of the unknowns are compared to absorbance of calibrators to determine the concentration of the ligand in the sample. The Coda provides an integrated, automated approach to carrying out the above steps all under control of the computer and associated software. All the steps may be programmed into a complete protocol or individual steps may be performed in a manual mode. The Coda is therefore virtually usable with any assay kit using microtite plates. Output from the spectrophotometer is measured by the computer. Calculation, curve-fitting, result interpretation and other aspects of data management and analysis are automatically performed by the software algorithms.
Bio-Rad Radias Immunoassay System (Radias) is a fully automated immunoassay system designed for high-capacity which, like the Coda, is based on ElA. All assay operations, including pipetting, diluting and incubating samples and reagents are performed by the Radius. Based on a "worklist" the Radius determines the quantities and types of reagents and microwell "strips" that will be needed for the run. The Radias can do multiple assays on the same sample. All reagents required by the Radius are supplied by Bio-Rad Laboratories in Radias compatible "troughs". Calculation, curve-fitting, result interpretation and other aspects of data management and analysis are automatically performed by the software algorithms.
The performance of the Bio-Rad Coda Automated EIA Analyzer was evaluated for precision, sensitivity, carry over, and accuracy. The precision studies were done according to NCCLS Evaluation protocol, Vol. 12, No 4, EP5-T2, Appendix C, pp 31-39. Twenty samples each of low, mid-range and high control plus a Bio-Rad anemia control (AN) were analyzed. The Within-Run % CV for the low control was 8.6 and for the mid-range control 7.1. The high control was consistently creater that 25 ulU/mL. The %CV for the anemia control was 9.5. Total precision for the low control was 9.6% and for the mid-range control 7.7% . Again the high control was consistently greater than 25 ulU/mL. The total precision for the anemia control was 14.0%. The measuring range (sensitivity) determined that the lowest level of TSH that could be distinguished from the zero standard is 0.034 ulU/mL at the 95% confidence limit on the Coda.
The correlation study, to determine accuracy, of Bio-Rad Coda Automated EIA Analyzer compared to the Bio-Rad Radias Immunoassay System followed NCCLS Document EP9-T. For 111 samples, the correlation coefficient, "r", was 0.995.
When comparing the Bio-Rad Coda Automated EIA Analyzer to the predicate, it can be concluded from the correlation study and similarities of the general characteristics of the two systems (Appendix C), that the Bio-Rad Coda Automated EIA Analyzer and the Bio-Rad Radias Immunoassay System are substantially equivalent. Based on the establishment of substantial equivalence, the safety and effectiveness of the Bio-Rad Coda Automated ElA Analyzer is confirmed.
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Statement of Intended Use
Page 1 of 1
510(k) Number (If Known)
Bio-Rad Coda™ Automated EIA Analyzer. Device Name:
CODA is an integrated immunoassay analyzer intended for the ndications for Use: automation of microplate based assays for in vitro diagnostic use. The system is open, such that a variety of microplate-based enzyme immunoassays (EIA's) can be programmed and run on the instrument. The sample and reagent pipettes, incubator, washer, reader and robotics are housed in the compact benchtop unit. CODA Operation and Data Management software operates in the Windows 95 environment utilizing icon-based commands for operator ease of use.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDHR, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR Over-The-Counter Use _
(Division Sign-Off)
Division of Clinical Laboratory Dexices
510(k) Number K972024
Laboratory Dexices
§ 862.2500 Enzyme analyzer for clinical use.
(a)
Identification. An enzyme analyzer for clinical use is a device intended to measure enzymes in plasma or serum by nonkinetic or kinetic measurement of enzyme-catalyzed reactions. This device is used in conjunction with certain materials to measure a variety of enzymes as an aid in the diagnosis and treatment of certain enzyme-related disorders.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.