(153 days)
HbA1C Enzymatic Assay is intended for the in vitro quantitative determination of stable HbA1c (glycated hemoglobin A1c; A1c) in human whole blood samples. Measurement of hemoglobin A1C is a valuable indicator for long-term diabetic control.
The Diazyme's HbA1C assay kit is a clinical test kit, intended for quantitative determination of HbA1C to monitor long-term glucose control in individuals with diabetes mellitus. The Diazyme's HbA1C assay kit is comprised of a Reagent 1, Reagent 2, Lysis Buffer, THb Reagent, and calibrators. Measurement of hemoglobin A1C is determined enzymaticly by subjecting lyseted samples to extensive protease digestion. This process releases amino acids including glycated valines from the hemoglobin octa peptide. Fructosyl valine oxidase (FVO) then serves as a substrate for fructosyl valine oxidase (FVO) which releases N-terminal valines and produces hydrogen peroxide. The hydrogen peroxide is measured using a peroxidase catalyzed reaction. Total hemoglobin is determined separately by conversion of all hemoglobin derivatives of the samples into hematin using an alkaline method. HbA1C concentration is expressed as a concentration ratio of glycated hemoglobin to total hemoglobin.
The provided text describes the Diazyme HbA1C Enzymatic Assay. Here's an analysis of its acceptance criteria and the study proving it meets those criteria:
1. Table of Acceptance Criteria and the Reported Device Performance:
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | CV% to be low/acceptable | Intra-Assay Precision: |
| 5.3% Alc: CV%= 3.5% | ||
| 12% Alc: CV%= 1.6% | ||
| Inter-Assay Precision: | ||
| 5.3% Alc: CV%= 5.0% | ||
| 12% Alc: CV%= 7.2% | ||
| Correlation with Predicate Device | High correlation coefficient (close to 1) | Correlation coefficient of 0.92 with Tosoh's Automated HPLC Analyzer. |
| Interference | Minimal or no significant interference from common substances at specified concentrations | No significant interference observed from: |
| Triglyceride (2000 mg/dl) | ||
| Bilirubin (10 mg/dl) | ||
| Ascorbic Acid (4 mg/dl) | ||
| Uric Acid (5 mg/dl) | ||
| Glucose (2400 mg/dl) | ||
| Accuracy / Equivalence | "Excellent accuracy" and "substantially similar" to the predicate device, with "no significant deviation" in results from clinical patient samples. | The precision, correlation, and interference studies are presented as evidence for excellent accuracy and substantial equivalence. The document explicitly states: "There is no significant deviation between the results obtained by Diazyme's and [predicate device] actively testing clinical patient samples." |
| Safety and Effectiveness | To be safe and effective for its intended use | Concluded to be safe and effective based on the presented studies. |
Study that Proves the Device Meets Acceptance Criteria:
The study presented to prove the device meets the acceptance criteria is a comparison study against a legally marketed predicate device (Tosoh Medics, Inc. Automated HPLC Analyzer: HbA1c Variant Analysis Mode, K011434), along with internal performance evaluations for precision and interference.
- Comparison Study: Diazyme's HbA1C Enzymatic Assay showed a correlation coefficient of 0.92 with the predicate device. This high correlation is presented as evidence of substantial equivalence.
- Precision (Reproducibility) Study: Both Intra-Assay and Inter-Assay precision were evaluated at two HbA1c levels (5.3% and 12%). The CV% values are reported as shown in the table above.
- Interference Study: The assay was tested for interference from common substances (Triglyceride, Bilirubin, Ascorbic Acid, Uric Acid, Glucose) at clinically relevant concentrations. No significant interference was found.
2. Sample size used for the test set and the data provenance:
- Sample Size for Test Set: The document mentions "actively testing clinical patient samples" for the comparison study, but does not specify the exact number of samples used for the correlation study or the precision/interference studies.
- Data Provenance: Not explicitly stated, but the mention of "clinical patient samples" implies retrospective or prospective clinical samples. The country of origin is not provided.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. For an HbA1C assay, the "ground truth" for the comparison study would typically be the results generated by the predicate device and for internal studies, carefully prepared reference materials or controls. The document does not describe an expert panel establishing ground truth in the way it might for an imaging AI device.
4. Adjudication method for the test set:
Not applicable in the context of an HbA1C enzymatic assay. Adjudication methods like 2+1 or 3+1 are typically used for subjective clinical assessments where multiple experts independently rate cases, and discrepancies are resolved. For a quantitative assay like this, the "ground truth" is established by the reference method (predicate device) and analytical measurements.
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:
Not applicable. This is an in vitro diagnostic device for quantitative determination of HbA1C, not an AI-assisted diagnostic imaging or classification tool that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the device is inherently a standalone (algorithm/assay only) system. Its performance is evaluated purely on its analytical capabilities (precision, accuracy, correlation to a reference method, interference). It does not involve human interpretation in its primary function.
7. The type of ground truth used:
- For the comparison study, the results from the predicate device (Tosoh Medics, Inc. Automated HPLC Analyzer: HbA1c Variant Analysis Mode) served as the ground truth/reference method.
- For precision studies, presumably calibrated control materials with known HbA1C concentrations were used.
- For interference studies, spiked control materials with known concentrations of interfering substances were used.
8. The sample size for the training set:
Not applicable. This is a traditional in vitro diagnostic (IVD) assay based on enzymatic reactions, not a machine learning or AI algorithm that requires a "training set" in the computational sense. The development of the assay would involve various R&D experiments, but not a formally defined "training set" like for AI models.
9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" in the AI/machine learning sense. The ground truth for developing and validating the assay relies on established biochemical principles, analytical chemistry techniques, and comparison to recognized reference methods.
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).