(28 days)
TBI Flex® reagent cartridge: The TBI method for the Dimension® clinical chemistry system is an in vitro diagnostic test intended to quantitatively measure total bilirubin in human serum and plasma. Measurements of total bilirubin are used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gallbladder disease.
DBI Flex® reagent cartridge: The DBI method for the Dimension® clinical chemistry system is an in vitro diagnostic test intended to quantitatively measure direct bilirubin in human serum and plasma. Measurements of direct bilirubin are used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder disease.
TBI/DBI Calibrator: The Dimension® Bilirubin Calibrator is an in vitro diagnostic product intended to be used to calibrate the Direct Bilirubin (DBI) and Total Bilirubin (TBI) methods for the Dimension® clinical chemistry system. This product was designed to meet the needs of users to assure accurate results over the assay range of these methods.
Total Bilirubin and Direct Bilirubin Flex® reagent cartridge. There are no changes in the device operating principle or reagents which comprise the total and direct Flex® reagent cartridges with this revision.
A. TBI Flex® reagent cartridge: Diazotized sulfanilic acid is formed by combining sodium nitrite and sulfanilic acid at low pH. Bilirubin (unconjugated) in the sample is solubilized by dilution in a mixture of caffeine/benzoate/acetate/EDTA. Upon addition of the diazotized sulfanilic acid, the solubilized bilirubin including conjugated bilirubins (mono and diglucoronides) and the delta form (billiprotein-bilirubin covalently bound to albumin) is converted to diazo-bilirubin, a red chromophore representing the total bilirubin which absorbs at 540 nm and is measured using a bichromatic (540, 700 nm) endpoint technique. A sample blank correction is used.
B. DBI Flex® reagent cartridge: Diazotized sulfanilic acid is formed by combining sodium nitrite and sulfanilic acid at low pH. The sample is diluted in 0.5M HC1. A blank reading is taken to eliminate interference from non-bilirubin pigments. Upon addition of the diazotized sulfanilic acid, the conjugated bilirubin is converted to diazobilirubin, a red chromophore which absorbs at 540 nm and is measured using a bichromatic (540, 700 nm) endpoint technique.
Total bilirubin and Direct bilirubin calibrator. Purified water will be used as the low level calibrator instead of a low concentration of ditauro-bilirubin. This change was made to prevent lot to lot shifts in quality control recovery at the low end of the assay.
The provided 510(k) summary (K060628) details the acceptance criteria and the study that proves the device meets these criteria for the TBI Flex® reagent cartridge, DBI Flex® reagent cartridge, and the associated TBI/DBI Calibrator.
1. Table of Acceptance Criteria and Reported Device Performance:
The document refers to Design Input Requirements (DIRs) and states that "All goals were achieved." However, the exact quantitative acceptance criteria are not explicitly detailed in the main body but are referenced as being in "Appendix D." Without Appendix D, a precise table of acceptance criteria versus reported performance cannot be generated. Based on the provided text, the qualitative acceptance criteria for "Performance studies" are:
| Acceptance Criteria Category | Reported Device Performance |
|---|---|
| Method Comparison | Achieved (Study performed) |
| Open-Well Stability | Achieved (Study performed) |
| Interference | Achieved (Study performed) |
| Recovery | Achieved (Study performed) |
| Analytical Sensitivity | Achieved (Study performed) |
| Precision | Achieved (Study performed) |
| Reference Range | Achieved (Study performed) |
| Shelf Life Stability | Achieved (Study performed) |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set:
- Method Comparison: "more than 100 frozen serum samples"
- Analytical Sensitivity: "20 replicate batches"
- For other tests (Open-Well Stability, Interference, Recovery, Precision, Reference Range, Shelf Life Stability), specific sample sizes for the test set are not explicitly stated within the provided text, beyond the general statement that "Performance studies were conducted internally versus the DIR goals described above. All goals were achieved."
- Data Provenance:
- Method Comparison: "frozen serum samples obtained from clinical laboratories." The country of origin is not specified, but the submission is to the US FDA, implying U.S. or internationally acceptable clinical laboratory samples.
- The studies are described as "conducted internally," suggesting they were done by Dade Behring Inc. There's no indication of prospective or retrospective studies, but given the nature of the tests (e.g., method comparison against a commercial control lot, testing for interference, stability), they would generally be prospective experiments conducted to validate the modified device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
This device is an in vitro diagnostic chemistry system for measuring bilirubin. The "ground truth" for such devices is typically established through a combination of:
- Reference Methods: Comparison to established, highly accurate reference methods or clinical laboratory standards.
- Predicate Device Performance: Comparison to the legally marketed predicate device (as done here).
- Known Concentrations: Use of samples with known concentrations of the analyte (e.g., for recovery, analytical sensitivity, and calibrator validation).
The concept of "experts establishing ground truth" in the context of radiologists or similar interpretive medical professionals is not applicable here. The "experts" involved would be the qualified laboratory personnel conducting the studies and verifying the results against established laboratory standards and the predicate device. Their specific number and qualifications (e.g., "radiologist with 10 years of experience") are not detailed in the document, as it falls under standard laboratory practices and personnel qualifications for an IVD manufacturer.
4. Adjudication Method for the Test Set:
Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical trials involving subjective interpretations (like imaging) where multiple readers assess cases and a consensus or tie-breaking mechanism is needed. This is not applicable to an in vitro diagnostic device for quantitative measurement like a bilirubin assay, where the "ground truth" is determined by objective analytical measurements, comparison to reference materials, or predicate device performance.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study:
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not conducted for this device. MRMC studies are specific to diagnostic devices where human readers interpret outputs (e.g., medical images) and AI assistance might improve their performance. This device is an automated, quantitative chemical assay and does not involve human readers interpreting "cases" in the clinical sense that an MRMC study would measure.
6. Standalone Performance Study:
Yes, a standalone performance study was implicitly done. The "Performance studies" described under "Design Testing and Evaluation" (Method Comparison, Open-Well Stability, Interference, Recovery, Analytical Sensitivity, Precision, Reference Range, Shelf Life Stability) are all evaluating the algorithm/device's performance independently against predefined analytical goals and the predicate device. These studies assess the device's accuracy, precision, linearity, and stability in a standalone manner. The comparison to the predicate device serves as the primary benchmark for demonstrating substantial equivalence.
7. The Type of Ground Truth Used:
The ground truth used for performance evaluation can be inferred from the study types:
- Predicate Device Performance: The primary ground truth is the performance of the legally marketed predicate devices (Dade Behring TBIL Flex® reagent cartridge (K861700), Dade Behring DBIL Flex® reagent cartridge (K862359), and Dade Behring TBIL/DBIL Calibrator (K861700)). The studies aimed to demonstrate that the revised device is "substantially equivalent in principle and performance" to these predicates.
- Known Concentrations/Reference Materials: For tests like Recovery, Analytical Sensitivity, and calibrator production (e.g., using purified water for the low level), samples with known or traceable concentrations of bilirubin or reference materials are used to establish ground truth for quantitative accuracy.
- Clinical Laboratory Samples: For Method Comparison, "frozen serum samples obtained from clinical laboratories" are tested against a "commercial control lot" (presumably using a well-established method, possibly the predicate itself).
8. Sample Size for the Training Set:
The document describes this as a revision to an existing product, and the studies mentioned are for verification and validation (V&V) of the revised device, not for the training of an AI algorithm. There is no mention of an AI component or machine learning model that would require a "training set." This is an in vitro diagnostic reagent and calibrator kit for a chemical analysis system.
9. How the Ground Truth for the Training Set Was Established:
As there is no mention of an AI component requiring a training set, this question is not applicable in the context of the provided 510(k) summary. The "ground truth" establishment described in this submission pertains to the analytical performance validation of the chemical assays and calibrators.
§ 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.