(282 days)
The Roche Acetaminophen assay is an in vitro test for the quantitative determination of toxic levels of acetaminophen in serum and plasma on Roche COBAS Integra, Roche/ Hitachi and cobas c system analyzers.
The Roche Diagnostics Acetaminophen assays under consideration in this submission are the same assays as were cleared on the COBAS Integra in K991598, Hitachi 917 in K013757 and cobas c501 in K060373 for the quantitative determination of toxic levels of Acetaminophen in human serum and plasma on automated clinical chemistry analyzers. The same reagents are used on all three systems. Acetaminophen is hydrolyzed by an arylacylamidase to yield p-aminophenol and acetate. Subsequently, the p-aminophenol is converted to an indophenol in the presence of o-cresol and a periodate catalyst. The production of indophenol is followed colorimetrically. The change in absorbance is directly proportional to the quantitative drug concentration in the sample.
The acceptance criteria for the Roche Acetaminophen assay are based on demonstrating substantial equivalence to previously cleared predicate devices: Roche COBAS Integra Acetaminophen assay (K991598), Roche/Hitachi Acetaminophen assay (K013757), and cobas c501 Acetaminophen assay (K060373). The study performed by Roche Diagnostics focused on validating the performance of the new Roche Acetaminophen assays on the cobas 8000 Modular Analyzer Series, specifically on the cobas c501 and Hitachi 917 platforms, and confirming similar performance on the COBAS Integra platform.
The study did not explicitly state "acceptance criteria" in terms of numerical thresholds for performance metrics. Instead, it demonstrated equivalence by comparing the analytical characteristics of the new assays with those of the predicate devices. The key performance aspects compared include:
1. Table of Acceptance Criteria (Implied) and Reported Device Performance:
| Feature | Implied Acceptance Criteria (Equivalent to Predicate) | Reported Device Performance (Roche Acetaminophen assay) |
|---|---|---|
| Indications for Use | Quantitative determination of toxic levels of acetaminophen in serum and plasma. | Same as predicate (stated as "Same" in tables). |
| Technology | Enzymatic-end point assay. | Same as predicate (stated as "Same" in tables). |
| Sample types | Serum and plasma. | Same as predicate (stated as "Same" in tables). |
| Calibrators | COBAS Integra calibrators. | Same as predicate (stated as "Same" in tables). |
| Reagents | R1: Sodium periodate 3.75 mmol/L, R2: Arylacylamidase (microbial) ≥7000U/L; o-cresol 3.75 mmol/L (order varies on Integra). | Same as predicate (stated as "Same" in tables). |
| Analytical Sensitivity (LoB) | cobas c501/Hitachi 917: 1.2 µg/ml; COBAS Integra: 0.7 µg/ml (LDL). | cobas c501/Hitachi 917/COBAS Integra: 1.2 µg/ml. |
| Analytical Sensitivity (LoD) | Not explicitly stated for predicate in this K. | cobas c501/Hitachi 917/COBAS Integra: 2.4 µg/ml. |
| Analytical Sensitivity (LoQ) | Not explicitly stated for predicate in this K. | cobas c501/Hitachi 917/COBAS Integra: 15 µg/ml. |
| Measuring range | cobas c501: 1.2-500 µg/ml; Hitachi 917: 1.2-600 µg/ml; COBAS Integra: 0.7-300 µg/ml. | cobas c501/Hitachi 917: 15-500 µg/ml; COBAS Integra: 15-300 µg/ml. |
| Interferences (Bilirubin) | Bilirubin interference at Acetaminophen level of 50 µg/ml. | Bilirubin interference at Acetaminophen level of 15, 30 and 50 µg/ml. |
Important Note on Measuring Range and Sensitivity: While the new device's LoB is 1.2 µg/ml for all platforms, the "Measuring range" starts at 15 µg/ml. This is a key difference from the predicate devices which had measuring ranges starting at their respective LDLs (1.2 µg/ml or 0.7 µg/ml). The LoQ (Limit of Quantitation) of 15 µg/ml seems to define the lower end of the measuring range for the new device. Additionally, the new assays performed more extensive bilirubin interference testing (at 15, 30, and 50 µg/ml) compared to the predicates (only at 50 µg/ml).
2. Sample size used for the test set and the data provenance:
- The document does not explicitly state the sample sizes used for the analytical performance studies (e.g., for LoB, LoD, LoQ, measuring range, specificity, or interference testing).
- The document does not specify the data provenance (e.g., country of origin, retrospective or prospective).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not applicable to this type of submission. This is a 510(k) for an in vitro diagnostic (IVD) assay based on chemical/enzymatic reactions. The "ground truth" for an IVD assay's analytical performance (e.g., concentration of acetaminophen) is established through reference methods, certified reference materials, and robust analytical chemistry techniques, not through expert consensus on images or clinical outcomes.
4. Adjudication method for the test set:
- This information is not applicable as it pertains to expert reviews of data, which is not how analytical performance of IVD assays is typically established.
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:
- No, an MRMC comparative effectiveness study was not done. This is an IVD device, not an AI-powered diagnostic system that assists human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance described is the standalone performance of the analytical assay (the "algorithm" here is the chemical reaction and measurement system). There is no "human-in-the-loop" performance being evaluated in the context of this device's function.
7. The type of ground truth used:
- The "ground truth" for the analytical performance of this assay would be established using reference methods (e.g., gas chromatography-mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC) for acetaminophen quantification) and certified reference materials with known concentrations of acetaminophen. The document doesn't explicitly detail the reference methods used but implies the use of quantitative standards for calibration and evaluation.
8. The sample size for the training set:
- This information is not explicitly stated as it's an analytical assay and not a machine learning algorithm that typically requires a distinct "training set." The development of such assays involves extensive R&D, method optimization, and analytical validation which uses various samples and experiments, but these are not typically referred to as a "training set" in the context of AI/ML.
9. How the ground truth for the training set was established:
- As above, the concept of a "training set" with established ground truth in the AI/ML sense is not applicable here. The analytical accuracy and precision are established through internal validation studies using known concentrations of analytes and comparison to reference methods, not through human-adjudicated ground truth.
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510(k) Summary: Roche cobas 8000 Modular Analyzer Series (Revised 12-20-2011)
| Introduction | The information in this 510(k) Summary is being submitted in accordancewith the requirements of 21 CFR 807.92. |
|---|---|
| Submittername, address,contact | Roche Diagnostics9115 Hague RdIndianapolis IN 46250Contact person: Angelo PereiraPhone: 317-521-3544Fax: 317-521-2324Email : angelo.pereira@roche.comDate prepared: December 20, 2011 |
| Device Name | Proprietary name: Roche Acetaminophen assayCommon names: Enzymatic assay for the determination of acetaminophenClassification names: Acetaminophen test system (21 CFR 862.3030).Product code LDP |
| PredicateDevice | We claim substantial equivalence to the following predicate devices: RocheCOBAS Integra Acetaminophen assay (K991598), the Roche/HitachiAcetaminophen assay (K013757) and the cobas c501 Acetaminophen assay(K060373). |
| Intended use /Indications foruse | The Roche Acetaminophen assay is an in vitro test for the quantitativedetermination of toxic levels of acetaminophen in serum and plasma onRoche COBAS Integra, Roche/ Hitachi and cobas c system analyzers. |
| DeviceDescription | The Roche Diagnostics Acetaminophen assays under consideration in thissubmission are the same assays as were cleared on the COBAS Integra inK991598, Hitachi 917 in K013757 and cobas c501 in K060373 for thequantitative determination of toxic levels of Acetaminophen in human serumand plasma on automated clinical chemistry analyzers. The same reagents areused on all three systems.Acetaminophen is hydrolyzed by an arylacylamidase to yield p-aminophenol |
DEC 2 3 2011
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and acetate. Subsequently, the p-aminophenol is converted to an indophenol in the presence of o-cresol and a periodate catalyst. The production of indophenol is followed colorimetrically. The change in absorbance is directly proportional to the quantitative drug concentration in the sample.
The following tables illustrate the similarities and differences between the current Acetaminophen assays and the predicate assays
| Feature | Cobas c501Acetaminophen | Cobas c501Acetaminophen(Predicate K060373) |
|---|---|---|
| Indications for Use | In Vitro test for thequantitative determinationof toxic levels ofacetaminophen in serumand plasma on Roche/Hitachi and cobas c systems | Same |
| Technology | Enzymatic- end point | Same |
| Sample types | Serum and plasma | Same |
| Calibrators | COBAS Integra calibrators | Same |
| Reagents | R1: Sodium periodote 3.75mmol/LR2: Arlyacylamidase(microbial)≥7000U/L: o-cresol 3.75 mmol/L | Same |
| Analytical Sensitivity | LoB 1.2 µg/mlLoD 2.4 µg/mlLoQ 15 µg/ml | Lower detection level(LDL) 1.2 µg/ml |
| Measuring range | 15-500 µg/ml | 1.2-500 µg/ml |
| Interferences | Bilirubin interference atAcetaminophen level of 15,30 and 50 µg/ml | Bilirubin interference atAcetaminophen level of50µg/ml |
Table A- cobas c501
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Table B- Hitachi 917
1
| Feature | Hitachi 917Acetaminophen | Hitachi 917Acetaminophen(Predicate K060373) |
|---|---|---|
| Indications for Use | The Roche Acetaminophenassay is for the quantitativedetermination of toxiclevels of acetaminophen inhuman serum or plasma onautomated clinicalchemistry analyzers | Same |
| Technology | Enzymatic- end point | Same |
| Sample types | Serum and plasma | Same |
| Calibrators | COBAS Integra calibrators | Same |
| Reagents | R1: Sodium periodote 3.75mmol/LR2: Arlyacylamidase(microbial)≥7000U/L; o-cresol 3.75 mmol/L | Same |
| Analytical Sensitivity | LoB 1.2 µg/mlLoD 2.4 µg/mlLoQ 15 µg/ml | Lower detection level(LDL) 1.2 µg/ml |
| Measuring range | 15-500 µg/ml | 1.2-600 µg/ml |
| Interferences | Bilirubin interference atAcetaminophen level of 15,30 and 50 µg/ml. | Bilirubin interference atAcetaminophen level of50µg/ml |
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| Feature | COBAS IntegraAcetaminophen | COBAS IntegraAcetaminophen(Predicate K991598) |
|---|---|---|
| Indications for Use | In Vitro test for thequantitative determinationof toxic levels ofacetaminophen in serum orheparinized plasma onCOBAS INTEGRA systems | Same |
| Technology | Enzymatic- end point | Same |
| Sample types | Serum and plasma | Same |
| Calibrators | COBAS Integra calibrators | Same |
| Reagents | R1: Arlyacylamidase(microbial)≥7000U/L; o-cresol 3.75 mmol/LR2: Sodium periodote 3.75mmol/L | Same |
| Analytical Sensitivity | LoB 1.2 µg/mlLoD 2.4 µg/mlLoQ 15.0 µg/ml | Lower detection level(LDL) 0.7 µg/ml |
| Measuring range | 15-300 µg/ml | 0.7-300 µg/ml |
| Interferences | Bilirubin interference atAcetaminophen level of 15,30 and 50 µg/ml. | Bilirubin interference atAcetaminophen level of50µg/ml |
Table C – COBAS Integra 800
Conclusion The Acetaminophen assays are substantially equivalence to the following predicate devices: Roche COBAS Integra Acetaminophen assay (K991598), the Roche/Hitachi Acetaminophen assay (K013757) and the cobas c501 Acetaminophen assay (K060373). This submission included additional information on interference caused by bilirubin in order to help improve the safe and effective use of the products.
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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized representation of a human figure, possibly symbolizing health and well-being.
10903 New Hampshire Avenue Silver Spring, MD 20993
Roche Diagnostics c/o Angelo Pereira 9115 Hague Road Indianapolis, IN 46250-0416
DEC 2 3 2011
Re: K110726
Trade Name: ROCHE ACETAMINOPHEN ASSAY Regulation Number: 21 CFR §862.3030 Regulation Name: Acetaminophen Test System Regulatory Class: Class II Product Codes: LDP Dated: December 7, 2011 Received: December 8, 2011
Dear Mr. Pereira:
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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...
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) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours.
$
Counney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices 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: Roche Acetaminophen Assay
Indications For Use:
The Roche Acetaminophen assay is an in vitro test for the quantitative determination of toxic levels of acetaminophen in serum and plasma on Roche COBAS Integra, Roche/ Hitachi and cobas c system analyzers.
Prescription Use XXX
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)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K110726
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§ 862.3030 Acetaminophen test system.
(a)
Identification. An acetaminophen test system is a device intended to measure acetaminophen, an analgestic and fever reducing drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of acetaminophen overdose.(b)
Classification. Class II.