(86 days)
The cassette COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6) contain an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of alkaline phosphatase in serum and plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
The cassette COBAS INTEGRA a-Amylase EPS Pancreatic (AMY-P / AMYUP) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of pancreatic or-amylase in serum, plasma, and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas).
The cassette COBAS INTEGRA C-reactive Protein (Latex), (CRPLX) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human C-reactive protein in serum and plasma. Measurements of C-reactive protein aids in evaluation of the amount of injury to tissue.
The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer, which is also known as the COBAS INTEGRA 700. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents. Through this submission, it is the intention of Roche to gain clearance for three additional COBAS Reagent Cassettes. These are the COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6), the COBAS INTEGRA a-Amylase EPS Pancreatic (AMY-P / AMYUP), and the COBAS INTEGRA C-Reactive Protein (Latex), (CRPLX).
The provided text is a 510(k) Summary for Roche COBAS® INTEGRA Reagent Cassettes, detailing the characteristics and performance of three new reagent cassettes (Alkaline Phosphatase IFCC liquid, α-Amylase EPS Pancreatic, and C-Reactive Protein (Latex)) compared to their legally marketed predicate devices.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The documents do not explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet in the same way modern AI/ML device submissions would. Instead, the "Performance Characteristics" section for each proposed device is presented alongside the performance of its predicate device, implying that equivalence in these characteristics is the underlying acceptance criterion for substantial equivalence.
Since specific acceptance criteria are not called out, I will present the reported performance characteristics for the new devices. The implicit acceptance criterion is "comparable performance to the predicate device."
| Performance Characteristic | COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 & ALPL6) (Proposed) | COBAS INTEGRA α-Amylase EPS Pancreatic (AMY-P / AMYUP) (Proposed) | COBAS INTEGRA C-Reactive Protein (Latex) (CRPLX) (Proposed) | Implicit Acceptance Criteria (Comparable to Predicate) |
|---|---|---|---|---|
| Intended Use | Quantitative determination of catalytic activity of alkaline phosphatase in serum and plasma | Quantitative determination of catalytic activity of pancreatic α-amylase in serum, plasma, and urine | Quantitative immunological determination of human C-reactive protein in serum and plasma | Must align with predicate device's intended use |
| Methodology | Enzymatic colorimetric using 4-Nitrophenylphosphate (IFCC) | Enzymatic colorimetric using substrate 4,6-ethylidene-p-nitrophenyl-α-D-malto-heptaoside | Particle enhanced immunoturbidimetric | Must be similar to or provide equivalent results to predicate device's methodology |
| Sample Type | Serum and Plasma | Serum, plasma, and urine | Serum and Plasma | Must be identical to predicate |
| Calibrator | Roche Calibrator (human) (K942706) | Roche Calibrator (human) (K942706) | CRP T Standard (K951595) | Must be compatible and provide comparable calibration to predicate |
| Controls | Roche Control Serum N and P (human) (K972214) | Roche Control Serum N and P (human) (K972214) | CRP T Control (K954992), CRP T N Control (Exempt) | Must be compatible and provide comparable control performance to predicate |
| Reagents | AMP in vial B (liquid); 4-Nitrophenylphosphate in vial C (liquid) | -enzyme, two monoclonal antibodies (mouse) in vial A (liquid); -substrate in vial C (liquid) | R1 BSA and immunoglobulins (mouse), vials A & B; R2 Latex particles coated with anti-CRP (mouse), vial C (liquid) | Must be chemically and functionally similar to predicate's reagents |
| Assay Range | 0-1500 U/L | Serum/Plasma and Urine: 0 - 1500 U/L | 0 - 160 mg/L | Similar or improved range compared to predicate |
| Sensitivity | 3.7 x 10^-4 ΔA/min per U/L of ALP | Serum/Plasma and Urine: 2.8 x 10^-4 ΔA/min per U/L of pancreatic α-amylase | 0.25 mg/L | Similar or improved sensitivity compared to predicate |
| Precision (Within-run %CV) | Level 1: 2.3; Level 2: 0.55 | Serum Level 1: 1.2; Serum Level 2: 0.91; Urine Level 1: 1.094; Urine Level 2: 0.8796 | Level 1: 1.8; Level 2: 1.5 | |
| (Second Set) Level 1: 2.0; Level 2: 2.4 | %CV values should be within acceptable clinical laboratory limits and comparable to predicate | |||
| Precision (Total %CV) | Level 1: 2.7; Level 2: 1.3 | Serum Level 1: 1.7; Serum Level 2: 1.6; Urine Level 1: 1.2; Urine Level 2: 1.1 | Level 1: 2.9; Level 2: 2.7 | |
| (Second Set) Level 1: 2.5; Level 2: 2.4 | %CV values should be within acceptable clinical laboratory limits and comparable to predicate | |||
| Accuracy (Corr. Coeff. (r)) | 0.999 | Serum: 0.999; Urine: 0.999 | 0.993 | Correlation coefficient should be high (close to 1), indicating strong agreement with predicate or reference method |
| Accuracy (Linear Regression) | 1.00x + 0.15 U/L | Serum: 1.03x + 0.3 U/L; Urine: 1.00x + 1.4 U/L | 1.07x - 6.2 mg/L | Slope should be close to 1 and y-intercept close to 0, indicating minimal bias relative to predicate or reference method |
2. Sample Size Used for the Test Set and Data Provenance
The "test set" in this context refers to the clinical samples used to evaluate the performance characteristics (precision and accuracy) of the new reagent cassettes.
-
COBAS INTEGRA Alkaline Phosphatase IFCC liquid (ALPL2 and ALPL6):
- Accuracy Sample Size (n): 252
- Data Provenance: Not specified, but generally for in vitro diagnostic (IVD) devices, these studies use patient samples collected in a clinical laboratory setting. The origin (country) and retrospective/prospective nature are not detailed in this summary.
-
COBAS INTEGRA α-Amylase EPS Pancreatic (AMY-P / AMYUP):
- Accuracy Sample Size (n):
- Serum: 246
- Urine: 106
- Data Provenance: Not specified, same general assumptions as above.
- Accuracy Sample Size (n):
-
COBAS INTEGRA C-Reactive Protein (Latex) (CRPLX):
- Accuracy Sample Size (n): 244
- Data Provenance: Not specified, same general assumptions as above.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For IVD devices like these, "ground truth" for method comparisons is typically established by running the same samples on a legally marketed predicate device or a highly accurate reference method. It does not involve human expert consensus in the way image-based diagnostics might.
4. Adjudication Method for the Test Set
This is not applicable and therefore not provided. Adjudication methods like 2+1 or 3+1 are used in studies where human readers interpret data, and their disagreements need to be resolved. For quantitative chemical assays, the measurement itself is the "reader," and comparison is made to another assay.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance
This is not applicable as the device is an in-vitro diagnostic reagent cassette for automated analyzers, not an AI or imaging device involving human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the performance data presented (assay range, sensitivity, precision, accuracy) represent the standalone performance of the reagent cassettes on the COBAS INTEGRA Analyzer. There is no human-in-the-loop component being evaluated for the measurement itself, only for the instrument's operation and result interpretation by laboratory personnel.
7. The Type of Ground Truth Used
For these types of in vitro diagnostic assays, the "ground truth" for the accuracy studies is implicitly established by comparing the results from the new device to those obtained from the legally marketed predicate device (or a recognized reference method). The correlation coefficients and linear regression data are direct comparisons to the predicate. For example, the accuracy section "Corr. Coefficient (r)" and "Linear regression" are direct comparisons between the proposed device and the cleared predicate device.
8. The Sample Size for the Training Set
This information is not provided and is likely not applicable in the same way it would be for an AI/ML device. For chemical reagents, "training" typically refers to the R&D and optimization phase to develop the reagent formulation and instrument application. It's not a discrete "training set" of patient data used to optimize an algorithm parameters that are then locked.
9. How the Ground Truth for the Training Set was Established
Similar to point 8, this is not provided and likely not applicable in the context of an AI/ML device. The "ground truth" during reagent development would involve analytical methods to confirm the chemical properties and performance of the reagents.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.