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Found 5 results
510(k) Data Aggregation
| 1) Glycosylated hemoglobin assay, 21 CFR 864.7470 (LCP)
2) Hemoglobin A2 assay, 21 CFR 864.7400
| K063643 | 21 CFR 864.7400
The Bio-Rad VARIANT™ II Hemoglobin A Ic Program is intended for the percent determination of hemoglobin A Ic in human whole blood using ion-exchange high-performance liquid chromatography (HPLC). The Bio-Rad VARIANT II Hemoglobin Alc Program is intended for Professional Use Only. For in vitro diagnostic use. Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
The VARIANT™ II ß-thalassemia Short Program is intended for the separation and area percent determinations of hemoglobins A2 and F, and as an aid in the identification of abnormal hemoglobins in whole blood using ion-exchange high-performance liquid chromatography (HPLC). The Bio-Rad VARIANT II ß-thalassemia Short Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use. Measurement of the percent hemoglobin A2 and F are effective in screening of ß-thalassemia (i.e., hereditary hemolytic anemias characterized by decreased synthesis or more types of abnormal hemoglobin polypeptide chains).
The VARIANT II Hemoglobin Testing System is a fully automated, highthroughput hemoglobin analyzer. The VARIANT II Hemoglobin Testing System provides an integrated method for sample preparation, separation and determination of the relative percent of specific hemoglobin in whole blood. It consists of two modules - the VARIANT II Chromatographic Station (VCS) and the VARIANT II Sampling Station (VSS). In addition, a personal computer is used to control the VARIANT System using Clinical Data Management (CDM) Software.
A personal computer (PC) is used to control the VARIANT II Hemoglobin Testing System using Clinical Data Management (CDM™) software. The CDM software supports import of sample information from and export of patient results to a Laboratory Information System (LIS). Control results are displayed on Levy-Jennings Charts and are exportable to Unity Real Time™.
This K130860 submission is a Special 510(k) for a device modification, meaning the changes are to existing predicate devices (VARIANT II Hemoglobin A1c Program and VARIANT II ß-thalassemia Short Program) and aim to demonstrate substantial equivalence without impacting the core performance specifications, intended use, or operating principles. The modifications primarily involve software and firmware updates, along with a PC Board replacement.
Therefore, the study focuses on verification and validation (V&V) testing to ensure the modified device remains safe, effective, and substantially equivalent to its predicate. It does not present new performance data against specific acceptance criteria for diagnostic accuracy as would be expected for a novel device or a device with significant performance changes. Instead, it asserts that the changes do not affect the previously established performance claims.
Here's an analysis based on the provided text, focusing on how the device meets acceptance criteria related to its modifications:
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a device modification submission where the performance specifications are stated to be unchanged from the predicate, the acceptance criteria are implicitly that the modified device's performance is at least as good as the predicate device and that the modifications do not introduce new risks or degrade existing performance. The "performance" reported is the outcome of the verification/validation and risk management processes.
| Acceptance Criteria (Implicit for Device Modification) | Reported Device Performance (as stated in the submission) |
|---|---|
| No change to performance specifications | "When compared to the predicate device, there are no changes to the performance specifications, intended or indications for use, or operating principles." |
| "No change or impact, claims transferred from predicate device." (for both programs) | |
| No adverse impact on product safety and effectiveness | "Risk Analysis and Verification/Validation testing results demonstrate that the changes do not affect product safety, effectiveness, and substantial equivalency claims." |
| "Design verification/validation tests met established acceptance criteria." | |
| "deemed the modified product safe, effective, and comparable to the predicate device." | |
| Modifications developed under design controls | "In addition, these changes were designed, developed and implemented under established design control and GMP processes..." |
| Compliance with risk management for modifications | "In accordance with ISO 14971, and internal risk management processes and procedures a defined risk analysis was used to identify, mitigate, or eliminate potential risks associated with the device modifications." |
| "The risk evaluation for the device software and firmware modifications included the following tasks..." |
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify a numerical sample size for a "test set" in the traditional sense of a clinical or analytical performance study. Given the nature of a Special 510(k) for software/firmware/hardware changes, the "test set" would refer to the data and scenarios used during verification and validation (V&V) testing.
- Sample Size: Not explicitly stated as a number of patient samples. The V&V efforts would likely involve testing various functionalities, defect fixes using specific test cases, and potentially a range of instrument data (already available or specifically generated for V&V).
- Data Provenance: Not explicitly stated. For "defect corrections," the data likely originated from "customer feedback" and scenarios that caused the identified defects. For general V&V, it would involve internal testing data. It's implied to be retrospective, as it addresses "customer feedback" and "defects" from prior versions, but specific details are absent.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable or not provided for this submission. The ground truth in this context is typically related to diagnostic accuracy, which is not being re-evaluated because performance claims are "transferred from predicate device."
For defect fixes, the "ground truth" would be whether the defect is successfully resolved and the intended functionality works as designed. This is assessed by engineering and quality assurance teams during V&V. The document mentions "a trained risk assessment team" for FMEA, but not "experts" establishing a diagnostic ground truth for a test set.
4. Adjudication Method for the Test Set
Not applicable/not provided. No "adjudication method" for interpreting results from a test set is mentioned because the submission directly states that performance specifications and claims are unchanged and transferred from the predicate. The "ground truth" for V&V testing of software/firmware changes is based on successful execution of tests and resolution of identified bugs, not on expert consensus interpretation of diagnostic output.
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 device is an automated in vitro diagnostic (HPLC system) for measuring specific hemoglobin levels, not an AI-assisted diagnostic imaging or interpretation tool that involves human readers. Therefore, an MRMC study is not relevant to this submission.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was Done
The device itself (VARIANT II Hemoglobin Testing System with CDM Software) operates as a standalone automated system for measurement. The changes are to its software/firmware. The V&V testing would assess the functionality of this automated system in its modified state. So, the testing effectively evaluates the "standalone" performance of the modified system, but it's not a new standalone study; it's a re-validation of the existing standalone system after modifications. The performance claims are asserted to be the same as the predicate (which was a standalone device).
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
For the original predicate devices, the ground truth for establishing performance (e.g., accuracy of HbA1c or HbA2/F measurements) would have been based on comparison to reference methods or clinical outcomes.
For this specific submission (device modification):
- For defect corrections: The "ground truth" is the successful elimination of the defect and the proper functioning of the software features (e.g., CDM not crashing, calibrator reassignment working). This is validated through internal software testing.
- For performance: The submission directly states "No change or impact, claims transferred from predicate device." This means the ground truth for performance measures (precision, accuracy, linearity, etc.) was established during the original predicate device's clearance and is implicitly inherited rather than re-established in detail for this modification. The V&V here confirmed that the modifications did not degrade the ability to achieve those previously established performance characteristics.
8. The Sample Size for the Training Set
Not applicable/not provided. This device is not described as involving a machine learning algorithm that requires a "training set." The software and firmware updates are for controlling the HPLC system and managing data, not for learning from data in the way an AI algorithm would.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As no training set for a machine learning algorithm is involved, this question is not relevant to the submission.
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Code LCP]
HbA2: Hemoglobin A2 Quantitation
[21CFR 864.7400/Prod.
Total Ghb run on the Variant ™ II Hemoglobin Testing System with CDM 4.0 Regulation Number: 21 CFR 864.7400
This software submission covers three assays with three different intended uses:
Hemoglobin A1c:
The VARIANT II Hemoglobin A1c Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).
The VARIANT II Hemoglobin Alc Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.
Beta-thalassemia:
The VARIANT II Beta thalassemia Short Program is intended for the separation and area percent determinations of hemoglobin A2 and F, and as an aid in the identification of abnormal hemoglobins in human whole blood using ionexchange high-performance liquid chromatography (HPLC).
The VARIANT II Beta-thalassemia Short Program is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.
Total GHb:
The VARIANT II Total GHb Program is intended for the separation and area percent determination of total glycated hemoglobin (GHb) in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).
The VARIANT II Total GHb Program with is intended for use only with the Bio-Rad VARIANT II Hemoglobin Testing System. For in vitro diagnostic use.
Indications for Use:
This software submission covers three assays and has two different Indications for Use:
HbA1c & GHb: Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
HbA2 and HbF: Measurement of the percent hemoglobin A2 and F are effective in screening of β-thalassemia (i.e. hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains).
The VARIANT II Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II Hemoglobin A1c and Beta-thalassemia Short Program are based on chromatographic separation of hemoglobins on a cation exchange cartridge. The Total GHb Program is based on principles of boronate affinity high pressure liquid chromatography to separate glycated hemoglobin from non-glycated hemoglobin.
The new feature in this submission is the upgrade in CDM software. The current software (3.5) requires Windows NT and Object Store N.T. These products are nearing the end of their lifecycle. CDM 4.0 software is needed to transfer the CDM software to Microsoft XP Operating System and Object Store version 4.0.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Bio-Rad VARIANTT II Hemoglobin Testing System with CDM 4.0.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria in this submission are implicit, established by demonstrating substantial equivalence to predicate devices (CDM 3.5 versions of the programs). The key performance metrics evaluated are accuracy (method correlation) and precision.
Here's the table:
| Device | Program | Performance Metric | Acceptance Criteria (Implicit - based on predicate performance) | Reported Device Performance (CDM 4.0 vs. CDM 3.5 Predicate) |
|---|---|---|---|---|
| VARIANT™ II Hemoglobin Testing System | Hemoglobin A1c Program | Accuracy (Method Correlation) | ||
| Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 (indicating good correlation with predicate) | r² = 0.9978 | ||
| Slope = 1.0119 | ||||
| Intercept = 0.0002 | ||||
| Precision (Within-run %CV) | Normal & Diabetic samples show comparable precision to predicate | Normal Sample: 1.1% (CDM 4.0) vs. 1.5% (CDM 3.5) | ||
| Diabetic Sample: 1.2% (CDM 4.0) vs. 0.7% (CDM 3.5) | ||||
| Precision (Total Precision %CV) | Normal & Diabetic samples show comparable precision to predicate | Normal Sample: 2.6% (CDM 4.0) vs. 2.1% (CDM 3.5) | ||
| Diabetic Sample: 2.7% (CDM 4.0) vs. 1.7% (CDM 3.5) | ||||
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (HbA2) | Accuracy (Method Correlation) | ||
| Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9924 | ||
| Slope = 1.0070 | ||||
| Intercept = -0.0034 | ||||
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (HbF) | Accuracy (Method Correlation) | ||
| Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9991 | ||
| Slope = 0.9806 | ||||
| Intercept = 0.0192 | ||||
| VARIANT™ II Hemoglobin Testing System | Beta thalassemia Short Program (Precision) | Precision (Within-run %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for HbA2 and HbF for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. |
| Precision (Total Precision %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for HbA2 and HbF for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. | ||
| VARIANT™ II Hemoglobin Testing System | Total GHb Program | Accuracy (Method Correlation) | ||
| Least Squares Regression | r² close to 1, slope close to 1, intercept close to 0 | r² = 0.9991 | ||
| Slope = 1.0054 | ||||
| Intercept = 0.042 | ||||
| Precision (Within-run %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. | ||
| Precision (Total Precision %CV) | (Data format unclear in provided text for direct comparison of specific %CV values for CDM 4.0 vs. 3.5, but overall statement is "equivalent") | Stated as "equivalent" between CDM 4.0 and CDM 3.5, though specific numbers are hard to extract due to formatting issues in the provided text. |
2. Sample Size Used for the Test Set and Data Provenance
- Hemoglobin A1c Program (Accuracy): 40 EDTA whole blood samples.
- Beta thalassemia Short Program (Accuracy): 40 EDTA whole blood samples.
- Total GHb Program (Accuracy): 40 EDTA whole blood samples.
- Precision Studies (all programs): Although specific sample numbers are sometimes noted as
n=40orn=80for the combined precision data, it's important to note these refer to the number of individual measurements or patient samples, not necessarily distinct patients. The studies involved analyzing "duplicate aliquots of normal HbA1c and diabetic HbA1c patient samples and controls" over several days. - Data Provenance: The document states "EDTA whole blood samples" and "patient samples and controls." It does not specify the country of origin or if the data was retrospective or prospective. Given the context of method correlation and precision, it's likely these were carefully selected samples to cover the analytical range, and are prospective in nature for the purpose of the study.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This submission is for an in vitro diagnostic device (IVD) that measures specific biomarkers (HbA1c, HbA2, HbF, GHb) using analytical techniques (HPLC). The "ground truth" for such devices is typically established through a reference method or a highly accurate existing method.
In this case, the device's performance is compared against its predicate device (the older CDM 3.5 version of the same program). The predicate device itself would have been validated against a reference method.
- No external human experts were explicitly used to establish "ground truth" for the test set in this particular comparative study. The ground truth is the measurement obtained from the predicate device (CDM 3.5).
- The standardization for HbA1c and GHb is stated as "Traceable to the Diabetes Control and Complications Trial (DCCT) reference method and IFCC. Certified via the National Glycohemoglobin Standardization Program (NGSP) for HbA1c." This indicates that the values obtained by both the new and predicate devices are ultimately traceable to established clinical reference standards, which is how the "ground truth" of the concentration values is ensured.
4. Adjudication Method for the Test Set
Not applicable. This is not a study involving human interpretation of images or data that would require adjudication. It's a quantitative measurement device, and the comparison is statistical (regression and precision).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No. This is an in vitro diagnostic device for quantitative measurement, not an AI or imaging device requiring human reader interpretation or MRMC studies.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance evaluations of the device (system including software) in terms of its analytical accuracy and precision. There is no human-in-the-loop aspect being evaluated here, as the device is designed for automated measurement.
7. The Type of Ground Truth Used
The "ground truth" for the performance evaluation in this 510(k) submission is the measurements obtained from the predicate device (the Bio-Rad VARIANT II Hemoglobin Testing System running CDM 3.5). The new device (CDM 4.0) is compared directly to the predicate to demonstrate substantial equivalence, meaning it performs similarly.
Underlying this, the initial "ground truth" for quantitative values for HbA1c is linked to reference methods (DCCT and IFCC) and certification (NGSP). For HbA2 and HbF, the ground truth is also tied to established quantitative analysis using HPLC.
8. The Sample Size for the Training Set
The document does not describe a "training set" in the context of machine learning or AI. This device is an analytical instrument with associated software. The software (CDM 4.0) is an upgrade to manage the data and system on a new operating system, not a machine learning algorithm that is "trained."
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" in the machine learning sense for this device. The software update primarily concerns operating system compatibility and database management, not the underlying analytical algorithm itself.
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Code LCP] and
HbA 2 : Hemoglobin A 2 Quantitation
[21CFR 864.7400 / Prod.
The D-10TM Hemoglobin A1c Program is intended for the percent determination of hemoglobin Alc in human whole blood using ion-exchange high performance liquid chromatography (HPLC). The D-10 Hemoglobin A1c Program is intended for use only with the Bio-Rad D-10 Hemoglobin Testing System. For In Vitro Diagnostic Use.
The Bio-Rad D-10™ Dual Program system is intended for the percent determination of hemoglobins A1c, A2 and F, and for the detection of abnormal hemoglobins in human whole blood using ion-exchange high performance liquid chromatography (HPLC). The Bio-Rad D-10™ Dual Program is intended for Professional Use Only. For in vitro diagnostic use.
Measurement of the percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus, and measurement of the percent HbA2 and HbF are effective in screening of ß—thalassemias (i.e., hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains). Detection of hemoglobin variants such as hemoglobins S, C, D and E by HPLC is effective in presumptive identification of these variants.
The Bio-Rad Hemoglobin Testing System is a fully automated analyzer consisting of a single module that rovides an integrated method for sample preparation, and determination of specific hemoglobins in whole blood. The Bio-Rad Hemoglobin Testing System provides an integrated method for the separation and determination of the relative percent of specific hemoglobins (e.g. A2, F and A1c in whole blood). The separation is based on the principles of high performance liquid chromatography. The system can accommodate 1 to 10 samples per run using a single rack currently.
The new feature in this submission is the optional D-10 Rack Loader which will be available for use with the D-10 Hemoglobin Testing System. The D-10 Rack Loader accommodates 5 racks and automatically transports each rack into and out of the D-10 System. The D-10 Rack Loader offers continuous loading, allowing the operator to insert or remove racks during a run.
The Bio-Rad D-10 Hemoglobin Testing System with the D-10 Rack Loader demonstrates substantial equivalence to its predicate devices (D-10 Hemoglobin A1c Program and D-10 Dual Program without the Rack Loader) through method correlation and precision studies.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the demonstration of substantial equivalence to the predicate devices. The study aims to show that the new device, with the rack loader, performs as similarly as possible to the predicate devices. The reported device performance is presented as correlation and precision data against these predicate devices.
D-10 Hemoglobin A1c Program (3-minute run):
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9950, Slope = 0.9415, Intercept = 0.2714 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbA1c:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9956, Slope = 0.9827, Intercept = 0.1208 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbA2:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9975, Slope = 0.9902, Intercept = 0.2476 |
| Precision | Similar %CVs to Predicate | See detailed table below |
D-10 Dual Program (6.5-minute run) - HbF:
| Metric | Acceptance Criteria (Implied: Similar to Predicate) | Reported Device Performance (New Device vs. Predicate) |
|---|---|---|
| Accuracy | High Correlation to Predicate (r² close to 1, slope close to 1, intercept close to 0) | r² = 0.9956, Slope = 1.0188, Intercept = -0.3863 |
| Precision | Similar %CVs to Predicate | See detailed table below |
Detailed Precision Tables (New Device with Rack Loader vs. Predicate without Rack Loader):
D-10 HbA1c Program (3 minute):
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Normal Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 5.6 | 5.9 |
| Within run (%CV) | 0.6 | 0.8 |
| Total Precision (%CV) | 1.5 | 1.8 |
| Diabetic Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 11.0 | 13.1 |
| Within run (%CV) | 0.6 | 0.3 |
| Total Precision (%CV) | 1.4 | 0.9 |
D-10 Dual Program (6.5 minutes) HbA1c:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Normal Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 5.5 | 5.9 |
| Within run (%CV) | 0.7 | 0.8 |
| Total Precision (%CV) | 1.5 | 1.8 |
| Diabetic Sample | ||
| n= | 400 | 80 |
| Mean (%HbA1c) | 10.6 | 13.1 |
| Within run (%CV) | 0.4 | 0.3 |
| Total Precision (%CV) | 1.2 | 0.9 |
D-10 Dual Program (6.5 minutes) HbA2:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Low Sample | ||
| n= | 400 | 80 |
| Mean (%HbA2) | 2.9 | 2.2 |
| Within run (%CV) | 1.8 | 4.5 |
| Total Precision (%CV) | 3.6 | 5.3 |
| High Sample | ||
| n= | 400 | 80 |
| Mean (%HbA2) | 4.9 | 5.4 |
| Within run (%CV) | 1.2 | 1.7 |
| Total Precision (%CV) | 3.6 | 3.1 |
D-10 Dual Program (6.5 minutes) HbF:
| New Device (with Rack Loader) | Predicate (without Rack Loader) | |
|---|---|---|
| Low Sample | ||
| n= | 400 | 80 |
| Mean (%HbF) | 1.4 | 2.1 |
| Within run (%CV) | 2.1 | 1.7 |
| Total Precision (%CV) | 2.9 | 3.3 |
| High Sample | ||
| n= | 400 | 80 |
| Mean (%HbF) | 6.6 | 8.7 |
| Within run (%CV) | 0.8 | 1.4 |
| Total Precision (%CV) | 1.8 | 2.0 |
2. Sample sizes used for the test set and the data provenance:
-
Accuracy (Method Correlation) Test Sets:
- D-10 HbA1c Program: 40 EDTA whole blood samples.
- D-10 Dual Program (HbA1c): 40 EDTA whole blood samples.
- D-10 Dual Program (HbA2): 39 EDTA whole blood samples.
- D-10 Dual Program (HbF): 39 EDTA whole blood samples.
- Data Provenance: The document does not specify the country of origin of the data. It implies the samples are human anticoagulated whole blood (EDTA) and patient samples (normal and diabetic, low and high concentration for HbA2 and HbF). The study appears to be an internal validation study and implicitly prospective for the "new device" performance, as it compares it concurrently to the "predicate device" performance using the same samples where appropriate for method correlation.
-
Precision Test Sets:
- For the new device (with D-10 Rack Loader), for each analyte (HbA1c, HbA2, HbF) and concentration level (Normal/Diabetic or Low/High), n=400 (two samples run on each of five racks, twice a day over 20 working days, with duplicate aliquots analyzed per run).
- For the predicate device (without D-10 Rack Loader), for each analyte and concentration level, n=80 (two samples run on one rack, twice a day over 20 working days, with duplicate aliquots analyzed per run).
- Data Provenance: Similar to accuracy, the country of origin is not specified. The samples are described as "EDTA whole blood patient samples." The protocol appears to be prospective for establishing precision for both the new and predicate systems under the specific test conditions. The document notes that "precision samples are different, since they were run at different time periods," indicating separate precision studies for the new and predicate configurations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in-vitro diagnostic (IVD) test for quantitative measurement of hemoglobin components. The "ground truth" for method correlation and precision studies is typically established by comparing the new device's measurements against a recognized reference method or a legally marketed predicate device (as in this case).
- The document does not mention the use of human experts (e.g., radiologists) to establish ground truth. The ground truth for this type of device is the quantitative value determined by the existing, validated methods (the predicate devices).
4. Adjudication method for the test set:
- Not applicable. This is a quantitative IVD device. "Adjudication" typically refers to resolving discrepancies between human readers or between an algorithm and human readers, often in image-based diagnostics. Here, the comparison is between two analytical methods (new device vs. predicate device).
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 not a diagnostic imaging device involving human readers or AI assistance in interpretation. It is a fully automated analytical instrument.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the entire study pertains to the standalone performance of the Bio-Rad D-10 Hemoglobin Testing System with the D-10 Rack Loader. The device itself is an automated analyzer, meaning its performance is "algorithm only" in the sense that the measurement process is automated, without human intervention in the result generation beyond sample loading and instrument operation. The comparison is against the standalone performance of predicate automated analyzers.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for evaluating the new device's performance is the measurements obtained from the existing, legally marketed predicate devices (Bio-Rad D-10 Hemoglobin A1c Program and D-10 Dual Program without the D-10 Rack Loader).
- For HbA1c, the predicate device (and by extension the new device) is traceable to the Diabetes Control and Complications Trial (DCCT) reference method and IFCC, and certified by the National Glycohemoglobin Standardization Program (NGSP). This constitutes a high-order reference for HbA1c.
- For HbA2 and HbF, the document states, "The Joint Committee on Traceability in Laboratory Medicine has not identified a higher order reference method or reference material for the quantitation of HbA2 and HbF," implying the predicate device's established performance serves as the practical ground truth for comparison.
8. The sample size for the training set:
- This document describes performance studies (accuracy and precision) for a new version of an existing device (adding a rack loader). It does not explicitly mention a "training set" in the context of machine learning model development. For IVD devices, validation typically involves performance studies on clinical samples, rather than a separate "training" and "test" set as seen in AI/ML. The samples used for method correlation and precision testing serve as the validation data for the device's performance.
9. How the ground truth for the training set was established:
- Not applicable, as a distinct "training set" for an AI/ML model is not described in the context of this IVD device submission. The device's underlying principles (ion-exchange high performance liquid chromatography) are well-established analytical methods, not derived from machine learning. The comparison is made against the established performance of predicate devices.
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(8 days)
Code LCP] and
HbA₂: Hemoglobin A₂ Quantitation
[21CFR 864.7400 / Prod.
The Bio-Rad D-10™ Dual Program system is intended for the percent determination of hemoglobins A1c, A2, and F and for the detection of abnormal hemoglobins in human whole blood using ion-exchange high performance liquid chromatography (HPLC). Measurement of the percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus, and measurement of the percent HbA2 and HbF is effective in long-term monitoring of ß—thalassemias (i.e., hereditary hemolytic anemias characterized by decreased synthesis of one or more types of abnormal hemoglobin polypeptide chains). Detection of hemoglobin thalassemia variants such as hemoglobins S, C, D and E by HPLC is effective in presumptive identification of these variants. The Bio-Rad D-10TM Dual Program is intended for Professional Use Only. For in vitro diagnostics use.
The Bio-Rad D-10™ Dual Program is a new device system that utilizes the principles of high performance liquid chromatography (HPLC), by which chromatographic separation of performance nquild chromatography (THLC), of willen exchange cartridge. The Bio-Rad D-10™ nemogrooms is a new program system that combines the determination of percent hemoglobin A = 1 = d for diabetes monitoring with percent hemoglobins A2 and F used for evaluation of (3 = thalassemia. The D-10™ Dual Program system consists of two different reagent programs with two intended uses. The D-10TM Dual Program reagent kit has a short program (3 minutes) for the determination of hemoglobin Are in which the components exactly the same as the D-10™ Hemoglobin Atc Program (K031043) reagents. The second program includes an extended program (6.5 minutes) that can be used for the determination of HbA2, HbF as well as HbA1c The components are exactly the same as the D-10™ Hemoglobin A12 Program (K031043) system and reagents with an additional HbA2/F/A1e Calibrator/Diluent Set and floppy diskette for the new program parameters.
Here's a breakdown of the acceptance criteria and study information for the Bio-Rad D-10™ Dual Program, based on the provided text:
Acceptance Criteria and Device Performance
The acceptance criteria for the Bio-Rad D-10™ Dual Program are not explicitly stated as distinct pass/fail thresholds in the document. Instead, the study aims to demonstrate substantial equivalence to existing predicate devices (VARIANT™ II Hemoglobin A1c Program and VARIANT™ II β-thalassemia Short Program). The performance of the D-10™ Dual Program is compared against these predicates across several metrics.
Table of Acceptance Criteria (Inferred by comparison to predicate) and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implied: Comparable to Predicate) | Bio-Rad D-10™ Dual Program Reported Performance (6.5 Minutes) |
|---|---|---|
| HbA1c Accuracy | r² ≥ ~0.98, Slope ~1, Intercept ~0 | r² = 0.9843, Slope = 0.9906, Intercept = 0.4310 |
| HbA2 Accuracy | r² ≥ ~0.98, Slope ~1, Intercept ~0 | r² = 0.9832, Slope = 1.0898, Intercept = -0.2407 |
| HbF Accuracy | r² ≥ ~0.99, Slope ~1, Intercept ~0 | r² = 0.9959, Slope = 0.9497, Intercept = -0.1785 |
| HbA1c Precision (Normal Sample) | Total Precision (%CV) comparable to predicate (~2.1%) | Total Precision (%CV) = 1.8% |
| HbA1c Precision (Diabetic Sample) | Total Precision (%CV) comparable to predicate (~1.7%) | Total Precision (%CV) = 0.9% |
| HbA2 Precision (Low Sample) | Total Precision (%CV) comparable to predicate (~2.0%) | Total Precision (%CV) = 5.3% |
| HbA2 Precision (High Sample) | Total Precision (%CV) comparable to predicate (~2.1%) | Total Precision (%CV) = 3.1% |
| HbF Precision (Low Sample) | Total Precision (%CV) comparable to predicate (~3.9%) | Total Precision (%CV) = 3.3% |
| HbF Precision (High Sample) | Total Precision (%CV) comparable to predicate (~1.4%) | Total Precision (%CV) = 2.0% |
| HbA1c Linearity | % Recovery for theoretical vs. observed HbA1c comparable to predicate (e.g., 97-100%) | % Recovery for HbA1c is "essentially the same" (example: 97.7-100%) |
| HbA2 Linearity | % Recovery for theoretical vs. observed HbA2 comparable to predicate (e.g., 91-100%) | % Recovery for HbA2 is "essentially the same" (example: 91.2-100%) |
| HbF Linearity | % Recovery for theoretical vs. observed HbF comparable to predicate (e.g., 89-110%) | % Recovery for HbF is "essentially the same" (example: 100-112.5%) |
| Interference (Labile Hb on HbA1c) | No significant interference up to predicate levels (4.8%) | No significant interference up to 3.5% |
| Interference (Labile Hb on HbF) | No significant interference up to predicate levels (Not Applicable) | No significant interference up to 2.6% |
| Interference (Bilirubin) | No interference up to 20 mg/dL | No interference up to 20 mg/dL |
| Interference (Lipids) | No interference up to ~4600-6000 mg/dL | No interference up to 5680 mg/dL |
| Interference (EDTA) | No interference up to 11x EDTA | No interference up to 11x EDTA |
Study Details for Demonstrating Equivalence:
The study described is a series of laboratory performance evaluations comparing the Bio-Rad D-10™ Dual Program (6.5 minute extended program) to its predicate devices.
2. Sample Size Used for the Test Set and Data Provenance:
- HbA1c Accuracy: 40 EDTA whole blood samples.
- HbA2 Accuracy: 40 EDTA whole blood samples.
- HbF Accuracy: 40 EDTA whole blood samples.
- HbA1c Precision: 80 measurements for each of two sample types (normal, diabetic) for both the D-10 Dual and VARIANT II HbA1c programs (total 320 measurements). Samples were EDTA whole blood patient samples.
- HbA2 Precision: 80 measurements for each of two sample types (low, high) for both the D-10 Dual and VARIANT II β-thalassemia Short programs (total 320 measurements). Samples were EDTA whole blood patient samples.
- HbF Precision: 80 measurements for each of two sample types (low, high) for both the D-10 Dual and VARIANT II β-thalassemia Short programs (total 320 measurements). Samples were EDTA whole blood patient samples.
- Linearity (HbA1c, HbA2, HbF): Eight EDTA-based blood standards (n=2 for each standard) were used for comparison. The document also mentions a "first linearity study" using seven standards (n=2 for each).
- Specificity and Interference: Varies by substance.
- Carbamylated hemoglobin: Specimens spiked with sodium cyanate.
- Labile hemoglobin: Samples spiked with glucose.
- Bilirubin, Lipids, EDTA: Patient pools or individual blood samples obtained as EDTA-anticoagulated blood, with concentrated interfering substances added.
Data Provenance: The document does not explicitly state the country of origin. It indicates that samples were "human whole blood samples" or "human anticoagulated whole blood (EDTA)," and "patient bloods." The context of a 510(k) submission to the FDA for a device manufactured by Bio-Rad Laboratories (Hercules, California) suggests the studies would likely be conducted in the United States or under similar regulatory standards. The studies appear to be retrospective in the sense that they are conducted on collected samples to evaluate the device performance against established methods, rather than following patients prospectively.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:
Not applicable. This is an in vitro diagnostic device for quantitative chemical analysis, not an imaging device requiring expert interpretation for ground truth. Ground truth for chemical assays is typically established by reference methods or validated (predicate) assays, or by preparing samples with known concentrations. The predicate devices serve this role.
4. Adjudication Method for the Test Set:
Not applicable for this type of quantitative assay comparison. The comparison is statistical (regression, percentage recovery, CV) against reference methods or predicate devices.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, this is not an MRMC study. This device is an automated in vitro diagnostic (IVD) device for biochemical analysis, not an imaging device that would involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the performance data presented is for the Bio-Rad D-10™ Dual Program as a standalone device, reporting quantitative values of HbA1c, HbA2, and HbF. The comparison is directly between the new device and the predicate laboratory instruments.
7. The Type of Ground Truth Used:
For accuracy and precision, the "ground truth" for the D-10™ Dual Program is established through method correlation with predicate devices (VARIANT™ II Hemoglobin A1c Program and VARIANT™ II β-thalassemia Short Program). For linearity, "ground truth" refers to the theoretical concentrations of HbA1c, HbA2, and HbF in the prepared standards. For specificity/interference, ground truth involves known concentrations of interfering substances added to samples. The predicates themselves are established and cleared devices, implying their results are considered accurate and reliable. The HbA1c predicate is also traceable to the DCCT reference method and IFCC, and certified by NGSP.
8. The Sample Size for the Training Set:
The document describes performance studies for the new device as compared to predicate devices. It does not explicitly mention a "training set" in the context of machine learning, as this device relies on HPLC principles and established chemical analysis methods, not an AI/ML algorithm that would undergo specific training.
9. How the Ground Truth for the Training Set was Established:
As above, the concept of a "training set" and associated ground truth establishment is not directly applicable in the context of this traditional IVD device and its submission. The studies involve validation against predicate methods and known standards.
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| Classification Name: | Class II, JPD
21 CFR 864.7400
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Trade/Device Name: G7 Automated HPLC Analyzer: Beta-thalassemia Mode Regulation Number: 21 CFR § 864.7400
The G7 Automated HPLC Analyzer: Beta-thalassemia Mode is intended for IN VITRO DIAGNOSTIC USE ONLY for the separation and area percent determinations of hemoglobins A2 and F and as an aid in the detection and presumptive identification of abnormal hemoglobins in whole blood using ion-exchange high performance liquid chromatography (HPLC).
The G7 Automated HPLC Analyzer: Beta-thalassemia Mode reagents and software are intended only for use on the Tosoh G7 Automated HPLC Analyzer.
The G7 Automated HPLC Analyzer - Beta-thalassemia Mode is an automated High Performance Liquid Chromatography (HPLC) system that separates and reports HbF and HbA2 quantitative percentages in whole blood. A chromatographic tracing of the hemoglobin products found in the sample is also produced which allows for the comparison of an individual chromatogram with standard patterns of known composition. The operational portion of the G7 Beta-thalassemia Mode is composed of a sampling unit, liquid pump, degasser, detector, microprocessors, sample loader, floppy disk drive unit, operational panel and a printer all of which have already been cleared by the FDA (K011434). The reagents and software program specific to the Beta-thalassemia Mode consist of calibrators, elution buffers, column and software only.
The G7 Automated HPLC System - Beta-thalassemia Mode uses a cation exchange column and separates the hemoglobin in the blood into fractions. The separation is accomplished by eluting the hemoglobins from the column with a gradient of three elution buffers containing increasing salt concentrations. The resulting report is printed out on the on-board printer and can be stored on a floppy disk in the on-board floppy disk drive. The data can also be transmitted to a host computer through the RS232 port. The result report includes a sample ID, date, time, area percentages and retention time in minutes of each individual peak detected. Peaks that meet the retention time "windows" pre-set in the software are labeled as F, A0, A2, D+, S+, C+. All others are designated in order of appearance as PXX and are listed in order of appearance.
All automated processes in the G7 Beta-thalassemia Mode are controlled by internal microprocessors using software downloaded via the on-board floppy disk drive.
The Tosoh G7 Automated HPLC Analyzer: Beta-thalassemia Mode is intended for in vitro diagnostic use for the separation and area percent determinations of hemoglobins A2 and F, and as an aid in detecting and presumptively identifying abnormal hemoglobins in whole blood using ion-exchange high-performance liquid chromatography (HPLC).
Here’s a breakdown of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to predicate devices, where the device's performance (correlation, imprecision) should be comparable to or better than the predicate.
| Acceptance Criteria (Implied by Predicate) | Reported Device Performance (Tosoh G7 Beta-thalassemia Mode) |
|---|---|
| Quantitative HbA2 Performance | |
| Correlation with Helena Beta-Thal HbA2 Quik Column™ (Predicate) | Slope: 0.9318, Y-Intercept: -1.08, Correlation Coefficient: 0.9318 |
| HbA2 Imprecision (CV%) | 1.3 - 2.1% (intra-assay); 2.4 - 3.3% (between day) |
| HbA2 Upper Linearity Limit | Up to 12.8 % |
| Quantitative HbF Performance | |
| Correlation with Bio-Rad VARIANT BETA-THALASSEMIA SHORT PROGRAM (Predicate) | Slope: 0.778, Y-Intercept: 1.15, Correlation Coefficient: 0.9906 |
| HbF Imprecision (CV%) | 4.3 - 13.5% (intra-assay); 2.2 - 7.7% (between day) |
| HbF Upper Linearity (Reportable) | Up to 35.0 % |
| Qualitative Hemoglobin Identification Performance | |
| Agreement with Beckman Paragon® Hemoglobin Electrophoresis (Predicate) | 100% agreement between G7 Presumptive Result and Electrophoresis Result for the specific categories reported in the comparative analysis table (e.g. HbA/HbS*, HbA/HbC*). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Quantitative HbA2 Test Set:
- Sample Size: 75 patient specimens.
- Data Provenance: Not explicitly stated, but "Patient specimens were analyzed" suggests clinical samples. The type of study (retrospective/prospective) is not specified, but typically, these comparative studies are conducted prospectively or using archived clinical samples.
- Quantitative HbF Test Set:
- Sample Size: 57 patient specimens.
- Data Provenance: Not explicitly stated, but "Patient specimens were analyzed" suggests clinical samples. The type of study is not specified.
- Qualitative Hemoglobin Identification Test Set:
- Sample Size: 155 total comparisons (patient whole blood samples).
- Data Provenance: Whole blood from patients "suspected of having hemoglobinopathies" were tested. This suggests clinical samples with a range of conditions. The type of study is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the test set was not established by human experts in the traditional sense. Instead, it was established by predicate devices that are already commercially available and considered legally marketed for their respective intended uses.
- For quantitative HbA2, the predicate device was Helena Laboratories' Beta-Thal HbA2 Quik Column™.
- For quantitative HbF, the predicate device was Bio-Rad Laboratories VARIANT™ BETA-THALASSEMIA SHORT PROGRAM.
- For qualitative hemoglobin identification, the predicate device was Beckman Paragon® Hemoglobin Electrophoresis.
4. Adjudication Method for the Test Set
There was no human "adjudication method" in the context of resolving disagreements between multiple human readers. The comparison was directly between the Tosoh G7 device and the predicate laboratory devices. The "ground truth" for each sample was implicitly determined by the result from the predicate device (or in the case of qualitative identification, agreement with the predicate result).
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 MRMC comparative effectiveness study was done. This device is an automated in vitro diagnostic analyzer, not an AI-assisted diagnostic tool designed to improve human reader performance. The study focuses on the device's analytical performance compared to established laboratory methods.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance study was done. The G7 Automated HPLC Analyzer: Beta-thalassemia Mode operated as an algorithm-only device (i.e., automated instrument) to process samples and generate results, which were then compared against established predicate devices. There is no human interaction described as part of its performance in these studies, only in the interpretation of its results.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth for the performance studies was based on results obtained from legally marketed predicate laboratory devices. These predicate devices represent established and accepted methods for measuring HbA2, HbF, and identifying abnormal hemoglobins.
8. The Sample Size for the Training Set
The document does not provide information about a "training set" for the device's software or analytical methods. This is a traditional in vitro diagnostic device, not a machine learning or AI algorithm that typically goes through a distinct training phase with a labeled dataset. The instrument and its software, including elution protocols and peak "windows," are developed and validated by the manufacturer internally, but a dedicated "training set" in the AI sense is not usually disclosed or relevant for such devices in an FDA submission of this nature.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the context of, for example, a machine learning model is not applicable here. The ground truth for the development and internal validation of the instrument's operational parameters (e.g., software "windows" for hemoglobin components) would have been established through extensive analytical testing by the manufacturer, likely using characterized samples and reference methods. However, the details of this internal development and validation are not part of this 510(k) summary, which focuses on the comparative study for substantial equivalence.
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