CHIRON DIAGNOSTICS ACS:180 TROPONIN I ASSAY (CTNI) by CHIRON DIAGNOSTICS CORP.

For the quantitative determination of cardiac troponin I in serum or heparinized plasma and as an aid in the diagnosis of acute myocardial infarction using the Chiron Diagnostics ACS: 180® Automated Chemiluminescence Systems.

Device Description

Not Found

AI/ML Overview

The provided documents are an FDA 510(k) clearance letter for the Chiron Diagnostics ACS:180® Troponin I Assay. While they confirm the device's substantial equivalence and provide its intended use, they do not contain detailed information about acceptance criteria, specific study designs, or performance metrics beyond the general statement of substantial equivalence.

Therefore, I cannot fully answer your request based solely on the provided text. The FDA clearance letter typically refers to information submitted by the manufacturer in their 510(k) application, which would contain such details.

However, based on the context of a 510(k) submission for an in-vitro diagnostic (IVD) device like a Troponin I assay, I can infer the types of information that would likely be present in the full submission, and frame a partial answer accordingly:

Based on the provided FDA 510(k) clearance letter (K980528) for the Chiron Diagnostics ACS:180® Troponin I Assay, the following information can be inferred or is directly stated, but detailed specifics on acceptance criteria and study data are not present in these documents.

The letter confirms the device is substantially equivalent to legally marketed predicate devices and is intended for "quantitative determination of cardiac troponin I in serum or heparinized plasma and as an aid in the diagnosis of acute myocardial infarction using the Chiron Diagnostics ACS: 180® Automated Chemiluminescence Systems."

To fully address your request, one would need to review the complete 510(k) submission (e.g., the Special Controls Guidance Document for Cardiac Troponin devices, or the specific studies performed by Chiron Diagnostics).

Here's an outline of what would typically be found in a 510(k) submission for such a device, and why the provided documents don't offer the detailed answers:

1. A table of acceptance criteria and the reported device performance

Information in provided document: Not present.
Inferred: For an IVD like this, acceptance criteria would typically include:
- Analytical Sensitivity: Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ).
- Analytical Specificity: Interference studies (hemoglobin, triglycerides, bilirubin, common medications), cross-reactivity with other cardiac or skeletal muscle proteins.
- Precision/Reproducibility: Within-run (intra-assay) and between-run (inter-assay) precision (CV%) at various concentrations, often near the medical decision points.
- Linearity/Reportable Range: Demonstration that the assay accurately measures concentrations across its claimed range.
- Accuracy/Method Comparison: Comparison against a legally marketed predicate device or a reference method using patient samples, typically assessed by correlation (regression analysis) and bias (e.g., Bland-Altman plots). This would be key for demonstrating "substantial equivalence."
- Clinical Performance (aid in diagnosis of AMI): This would involve sensitivity and specificity for diagnosing AMI, usually against a clinical endpoint (e.g., WHO criteria for AMI, or consensus diagnosis by clinicians). This would involve establishing cutoff values.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Information in provided document: Not present.
Inferred: The 510(k) submission would detail:
- Sample Size: Typically hundreds to thousands of patient samples for method comparison and clinical performance studies. Smaller numbers for analytical performance (e.g., precision, linearity).
- Provenance: This would state whether samples were from specific hospitals, regions, or collected to meet specific demographic criteria. They would likely be retrospective, but could include prospective elements for clinical studies. The country of origin would be specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Information in provided document: Not present.
Inferred: For the "aid in the diagnosis of acute myocardial infarction" claim:
- Ground Truth for AMI: Typically established by a panel of independent cardiologists or emergency physicians, sometimes alongside a review of patient charts, ECGs, cardiac imaging, and serial cardiac marker results, based on established clinical guidelines (e.g., ESC/ACC/AHA/WHF Universal Definition of Myocardial Infarction). These experts would need to be board-certified with relevant clinical experience. The number would vary, but typically 2-3 independent clinicians would review each case.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Information in provided document: Not present.
Inferred: If multiple experts were used to establish clinical ground truth for AMI, an adjudication method would be employed. Common methods include:
- Consensus: All experts must agree.
- Majority Rule: E.g., 2 out of 3 agree.
- Adjudicator: If there's disagreement among initial reviewers, a senior expert (the "plus 1") reviews the case and makes the final determination.

5. 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

Information in provided document: Not present.
Inferred: This device is an in-vitro diagnostic assay (blood test), not an imaging AI diagnostic device for "human readers." Therefore, an MRMC study comparing human reader performance with and without AI assistance is not applicable to this type of device. The "AI" is the automated instrument (ACS:180) that performs the assay, not a cognitive aid for a human interpreter of an image.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Information in provided document: Yes, implicitly.
Answer: The performance metrics for an IVD assay (like sensitivity, specificity, accuracy, precision, etc.) are inherently "standalone" in the sense that they reflect the analytical and clinical performance of the assay system itself, irrespective of human interpretation in real-time. The result is quantitative (a number), and its diagnostic utility is then interpreted by a clinician.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Information in provided document: Not present explicitly in the clearance letter.
Inferred:
- Analytical Performance: Ground truth for concentration would be established by reference methods, gravimetric dilutions, or certified reference materials.
- Clinical Performance (for AMI diagnosis): The 'ground truth' for the diagnosis of Acute Myocardial Infarction would be established by a combination of:
  - Clinical judgment/Expert Consensus: As described in point 3, based on comprehensive patient data (symptoms, ECG changes, imaging, and potentially serial cardiac marker trends from a predicate device or reference method).
  - Outcomes Data: Patient follow-up to confirm definitive diagnosis or rule out AMI.

8. The sample size for the training set

Information in provided document: Not present.
Inferred: While "training set" is more common for machine learning, for an IVD assay, method development involves extensive testing and optimization. The sample size for validation studies (which are analogous to "test sets" for performance evaluation) is distinct from the samples used during initial research, development, and optimization. The 510(k) would focus on the validation study sample sizes.

9. How the ground truth for the training set was established

Information in provided document: Not present.
Inferred: For the development/optimization phase of an IVD, ground truth for calibrators and controls would be established by meticulous analytical chemistry techniques and comparison to established reference standards. For clinical performance optimization, similar methods to those in point 7 would be used, but in an iterative process to refine assay parameters and cutoffs.

Summary

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

William J. Pignato Director of Requlatory Affairs Chiron Diagnostics 63 North Street Medfield, Massachusetts 02052-1688

MAR - 3 1998

Re : K980528 Chiron Diagnostics ACS:180® Troponin I Assay Regulatory Class: II Product Code: MMI Dated: February 10, 1998 Received: February 11, 1998

Dear Mr. Pignato:

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 requirements, as set torth 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 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 regulations.

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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 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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Company Confidential

Page of of ___________________________________________________________________________________________________________________________________________________________________

510(k) Number (if known):

14980528

Device Name: Chiron Diagnostics ACS:180 Troponin I Assay

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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

(Division Sign-Off)
Division: of Clinical Laboratory Devices
510(k) Number: K980528

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.