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510(k) Data Aggregation
(29 days)
BIO-RAD LABORATORIES, INC., CLINICAL SYSTEMS DIVIS
The Bio-Rad VARIANT™ II TURBO HbA Ic Kit - 2.0 is intended for the quantitative determination of hemoglobin Alc in human whole blood using ion-exchange high performance liquid chromatography (HPLC) on the VARIANT II TURBO Hemoglobin Testing System. Measurement of hemoglobin Alc is effective in monitoring long term glycemic control in individuals with diabetes mellitus. The Bio-Rad VARIANT II TURBO HbAlc Kit - 2.0 is intended for professional Use.
The VARIANT II TURBO Hemoglobin Testing System is the next generation HPLC system with higher volume capability when compared to the VARIANT II testing system. The VARIANT II TURBO Hemoglobin Testing System provides an integrated method for sample preparation, separation, and determination of specific hemoglobin in whole blood. It is a fully automated, high-throughput system. It consists of 2 modules: the VARIANT II TURBO Sampling Station (VSS) and the VARIANT II TURBO Chromatographic Station (VCS). A personal computer (PC) is used to control the VARIANT II TURBO 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™.
The provided text describes a Special 510(k) Summary for a Device Modification related to the Bio-Rad VARIANT™ II TURBO HbA1c Kit - 2.0. This type of submission is for modifications to a legally marketed device that do not significantly alter its performance specifications, intended use, or operating principles.
Crucially, the document explicitly states:
- "When compared to the predicate device, there are no changes to the performance specifications, intended or indications for use, or operating principles."
- "Performance Claims: No change, claims transferred from predicate device."
Therefore, this specific submission does not present new acceptance criteria or a new study to prove device performance, as the performance claims are directly transferred from the predicate device (K122472). The modifications described are primarily software and firmware updates, customer-requested features, and defect fixes.
The document focuses on demonstrating that these changes do not affect product safety, effectiveness, and substantial equivalency claims to the predicate device. This is achieved through a risk management process, review of modifications, and design verification/validation tests.
Based on the provided text, I cannot extract the specific acceptance criteria and a study proving those criteria were met for this modified device because the submission relies on the established performance of its predicate.
However, I can describe what the document does provide in relation to an implicit "acceptance" or validation of the modifications:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not provide a table of new acceptance criteria for performance, nor new reported device performance data, because the performance claims are stated to be unchanged from the predicate device.
Instead, the "acceptance criteria" for the modifications themselves relate to successful verification and validation (V&V) testing.
| Acceptance Criteria (for modifications) | Reported Device Performance (for modifications) |
|---|---|
| "Determined whether risk mitigations, hazard controls, and residual risks were as safe and effective as the predicate device." | "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." | |
| "The modified product [is] safe, effective, and comparable to the predicate device." | |
| "Modified product [is] safe, effective, and comparable to the predicate device." (Derived from risk management report conclusion) | (See above) |
| No changes to performance specifications, intended use, indications for use, or operating principles (criteria implicitly met for substantial equivalence) | "When compared to the predicate device, there are no changes to the performance specifications, intended or indications for use, or operating principles." |
2. Sample Size Used for the Test Set and Data Provenance
The document details "design verification/validation tests" and a risk management process, but does not specify sample sizes for these tests. It also does not explicitly mention the country of origin or whether the data was retrospective or prospective, as the focus is on the software and firmware changes and their impact on safety and effectiveness, rather than a clinical performance study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document states: "For each identified risk, a Failure Mode and Effects Analysis (FMEA) was conducted. This was performed in a systematic manner by a trained risk assessment team until consensus was reached that an adequate analysis had been performed."
- Number of Experts: Not explicitly stated, but implies a "team" (more than one).
- Qualifications of Experts: Described as a "trained risk assessment team." No further specific qualifications (e.g., radiologist with X years of experience) are provided, which is typical for device engineering and risk management teams.
4. Adjudication Method for the Test Set
The FMEA process involved a "trained risk assessment team until consensus was reached," suggesting a form of group adjudication, but no specific method like "2+1" or "3+1" is detailed. It implies a collaborative decision-making process to reach agreement on risk identification and mitigation.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study is typically used for diagnostic devices that involve human interpretation of results, where the AI might assist or replace that interpretation. This device is an automated in vitro diagnostic system for measuring HbA1c, and its modifications are software/firmware related, not involving human interpretation of clinical images or data in a way that would necessitate an MRMC study.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was Done
The device itself is an automated system. The "design verification/validation tests" would have evaluated the performance of the modified software and firmware in a standalone manner, integrated into the instrument, to ensure it met its functional and safety requirements. However, the document doesn't provide details on the specific "standalone" tests conducted beyond stating they "met established acceptance criteria" for the modifications.
7. The Type of Ground Truth Used
For the modifications, the "ground truth" was established based on:
- Identified potential risks and hazards (from reviewing modifications, design inputs, existing risk tables, customer complaints, and IEC 62304:2009 requirements).
- Predicate device claims and performance established during its initial clearance (K122472), against which the modified device's safety, effectiveness, and substantial equivalency were assessed.
For the predicate device's original performance claims (which are transferred), the ground truth for HbA1c measurement is based on:
- Certification by the NGSP as traceable to the Diabetes Control and Complications Trial (DCCT) Reference method.
- Certification by the IFCC as traceable to the IFCC Reference Measurement Procedure.
8. The Sample Size for the Training Set
Not applicable. This submission is for modifications to an existing in vitro diagnostic device, not a new algorithm that requires a "training set" in the context of machine learning. The software and firmware updates "include customer requested features, whereas both software and firmware include specific defect fixes," implying development rather than a machine learning training process.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no mention of a machine learning "training set" in this context.
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(28 days)
BIO-RAD LABORATORIES, INC., CLINICAL SYSTEMS DIVIS
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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(73 days)
BIO-RAD LABORATORIES, INC., CLINICAL SYSTEMS DIVIS
The Bio-Rad VARIANT™ II TURBO HbA1c Kit - 2.0 is intended for the quantitative determination of hemoglobin A1c in human whole blood using ion-exchange high performance liquid chromatography (HPLC) on the VARIANT™ II TURBO Hemoglobin Testing System. Measurement of hemoglobin A1c is effective in monitoring long term glycemic control in individuals with diabetes mellitus. The Bio-Rad VARIANT™ II TURBO HbA1c Kit-2.0 is intended for Professional Use Only.
The VARIANT II TURBO Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO HbA12 Kit - 2.0 is based on chromatographic separation of Hemoglobin A10 on a cation exchange cartridge. The VARIANT II TURBO HbA1c Kit - 2.0 contains an analytical cartridge, 5 prefilters, Elution Buffer A and B, Calibrator Level 1, Calibrator Level 2, Whole Blood Primer, sample vials and a CD-ROM with test parameters.
The VARIANT II TURBO Hemoglobin Testing System provides an integrated method for sample preparation, separation and the quantitative determination of HbAle in EDTA human whole blood. The VARIANT II TURBO Hemoglobin Testing System is a fully automated, high-throughput hemoglobin analyzer. It consists of two modules - the VARIANT II Chromatographic Station (VCS) and the VARIANT II Sampling Station (VSS). There have been hardware updates due to obsolescence of parts and firmware updates to support the replacement hardware components.
A personal computer is used to control the VARIANT II TURBO Hemoglobin Testing System using updated Clinical Data Management (CDM) software version 5.1.1.
Here's an analysis of the provided 510(k) summary, structured to answer your questions about acceptance criteria and the supporting study:
Some of the requested information, such as the specific country of origin for the data, the exact qualifications of experts, and the adjudication method for the test set, are not explicitly detailed in the provided 510(k) summary. This is typical for such regulatory documents, which focus on summarizing key performance data rather than granular study design details.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the "Method Comparison" study were based on a relative bias not exceeding +/- 10% at the decision points of 6% and 9% HbA1c.
| Criteria | Acceptance Criteria (Bias) | Reported Device Performance (Predicted Bias by regression) | Upper 95% confidence limit | Lower 95% confidence limit |
|---|---|---|---|---|
| Decision point: 6.0 %HbA1c | Between -10% and +10% relative bias | 0.2% | 0.5% | -0.1% |
| Decision point: 9.0 %HbA1c | Between -10% and +10% relative bias | -0.1% | 0.1% | -0.3% |
The "Analytical Specificity" study aimed to show no significant interference from common hemoglobin variants at specified concentrations.
| Interference Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Hemoglobin variants (HbS, HbC, HbD, HbE) | No significant interference (implicitly, results within pre-defined clinical limits or not exceeding a certain difference from non-variant samples). The predicate had issues with specific variants showing > ±10% difference. | No significant interference was observed at the following concentrations: HbS ≤67%, HbC ≤72%, HbD ≤55%, and HbE ≤41%. |
| Interference from HbA2 | No interference from β-thalassemia trait HbA2 concentrations up to 10% of total hemoglobin. | β-thalassemia trait, as indicated by increased HbA2 concentrations up to 10%, does not interfere with the assay. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Method Comparison): 100 EDTA whole blood human samples and 16 samples prepared by mixing EDTA whole blood samples with either purified HbAo or purified HbA1c. Total: 116 samples.
- Sample Size (Analytical Specificity): Not explicitly stated as a number of individual samples, but described as "Two fresh, EDTA non-variant human blood sample pools at 6.5% and 8.0-9.0% HbA1c" and "Fresh, EDTA human homozygous blood samples for each of the 4 hemoglobin variants (e.g. E, D, S, and C)." Series of test sample pools prepared by dilution.
- Data Provenance: The data used for method comparison and analytical specificity were "EDTA whole blood human samples" and "fresh, EDTA human homozygous blood samples." The country of origin is not specified but is implicitly from a clinical laboratory setting. The studies appear to be prospective or concurrent as they involved preparing and running samples specifically for the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the summary. The ground truth for the method comparison study was established by the predicate device's software version 4.03. For the analytical specificity, the "true" HbA1c values for the variant samples were likely determined by a reference method or assumed based on the preparation of the samples (e.g., dilution of homozygous variant samples).
4. Adjudication Method for the Test Set
This information is not provided in the summary. For a quantitative assay like HbA1c, adjudication typically involves comparing the device's results against a gold standard or a highly accurate reference method. In the method comparison, the predicate device's results served as the reference for the modified software.
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
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not applicable here. This document describes a medical device, the Bio-Rad VARIANT™ II TURBO HbA1c Kit - 2.0, which is an automated in vitro diagnostic (IVD) assay to measure HbA1c. It is not an AI-based diagnostic tool that assists human readers/interpreters.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device itself is a standalone automated system for quantitative determination of HbA1c. The evaluation performed (method comparison and analytical specificity) effectively represents its standalone performance because it directly measures HbA1c levels without human interpretation of complex images or signals requiring AI assistance. The study compares the performance of the updated software/system to a previous version, which is a standalone comparison.
7. The Type of Ground Truth Used
- Method Comparison: The ground truth for the method comparison study was established by the predicate device's software version 4.03 (meaning the measurements obtained from the same system running the older software). This is a "comparative ground truth" when assessing software changes.
- Analytical Specificity: For variant interference, the ground truth was effectively implicit in the preparation of the samples (known variant concentrations, and expected HbA1c values in the pools). The goal was to show that the presence of these variants does not interfere with the HbA1c measurement, meaning the device's reading should remain accurate despite the variant's presence.
8. The Sample Size for the Training Set
This information is not provided in the summary. This device is an in vitro diagnostic (IVD) kit using high-performance liquid chromatography (HPLC) and associated software. While software might undergo internal development and validation (which could involve "training" in a broad sense, especially for algorithms identifying peaks), the concept of a "training set" as it applies to machine learning or AI models is not directly relevant or typically disclosed for this type of IVD device in a 510(k) summary. The summary focuses on comparing the new software's performance against the old, representing an update to an established analytical method.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the context of AI/ML is not directly applicable. If one considers the development of the analytical method and software, the ground truth for establishing parameters would have been derived from extensive analytical chemistry principles and experiments, likely involving reference methods and characterized samples to ensure accurate chromatographic separation and calculation of HbA1c. This foundational work would be part of the product's overall development, not explicitly detailed as a "training set" in this 510(k) summary.
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(30 days)
BIO-RAD LABORATORIES INC., CLINICAL SYSTEMS DIVISI
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended as a qualitative screen for the presence of hemoglobins F, A, S, D, C, and E in eluates of neonatal blood collected on filter paper by high-performance liquid chromatography (HPLC).
The Bio-Rad VARIANT™nbs Sickle Cell Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
The Bio-Rad VARIANT™nbs Sickle Cell Program is for use only with the Bio-Rad VARIANT™nbs Newborn Screening System.
The presence of hemoglobin S (HbS) in a patient blood sample is indicative of sickle cell disease or sickle cell trait. Diagnosis of sickle cell disease prior to the age of four months allows for the administration of a prophylactic treatment with penicillin. Prophylactic treatment with penicillin has shown to decrease morbidity and mortality.
The VARIANTnbs Newborn Screening System uses the principles of high-performance liquid chromatography (HPLC). The VARIANTnbs Sickle Cell Program is based on the chromatographic separation of hemoglobins F, A, S, D, C, and E on a cation exchange cartridge.
The new feature in this submission is the upgrade of the Genetic Data Management (GDM) software. The current software (GDM 2.01) requires Microsoft Windows NT. This product is nearing the end of its lifecycle. GDM 3.0 software is needed to transfer the GDM software to the Microsoft Windows XP Operating System.
Acceptance Criteria and Study Details for Bio-Rad VARIANT™nbs Sickle Cell Program with GDM 3.0
This document outlines the acceptance criteria and the study conducted to demonstrate that the Bio-Rad VARIANT™nbs Sickle Cell Program run on the VARIANT™nbs Newborn Screening System using Genetic Data Management (GDM) 3.0 Software meets these criteria.
1. Table of Acceptance Criteria and Reported Device Performance
The primary acceptance criteria for the new GDM 3.0 software update was to maintain 100% agreement with the predicate device (GDM 2.01) in identifying the presence of specific hemoglobins.
| Acceptance Criteria | Reported Device Performance (GDM 3.0 vs. GDM 2.01) |
|---|---|
| 100% agreement for Hemoglobin | 100% agreement |
| Type FA | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAS | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAC | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type FAD | 100% agreement |
| 100% agreement for Hemoglobin | 100% agreement |
| Type H | Not explicitly listed as "H" in the provided table, but |
| 100% agreement for all other | the overall "Total" agreement is 100%. |
| specific hemoglobin types | |
| (implied by overall "Total") |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The provided document does not explicitly state the total number of patient samples used in the correlation study. It lists categories of hemoglobin types (FA, FAS, FAC, FAD, and an unspecified "H" type) and indicates 100% agreement for each. While a total count of samples is not given, the implicit message is that all samples tested within these categories showed agreement.
- Data Provenance: The study was conducted "at an external site". The country of origin is not specified but is presumably the United States, given the FDA submission. The study compared results from the predicate device and the new device ran on the same samples on the same day, suggesting it was a prospective comparison of the new software's performance on existing samples, rather than entirely retrospective data analysis.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document describes a "method correlation study" where samples run on the predicate device (GDM 2.01) were repeated on the GDM 3.0 platform. The "ground truth" in this context is established by the results obtained from the predicate device (GDM 2.01). There is no mention of external human experts establishing a separate ground truth for this correlation study, as the comparison is specifically between the two software versions and their agreement.
4. Adjudication Method for the Test Set
No explicit adjudication method is described. The study directly compares the results of the two software versions. Since the goal was to demonstrate 100% agreement, any discrepancy would inherently require investigation. However, with 100% agreement reported, no further adjudication process for conflicting results was needed or mentioned.
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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic system for qualitative screening of hemoglobins using HPLC and software for data management, not an AI-assisted diagnostic imaging or interpretation tool for human readers. The change is an upgrade to the operating system and features of the data management software.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The study described is a standalone performance comparison between the GDM 3.0 software and the predicate GDM 2.01 software. It assesses the algorithm's (software's) ability to produce the same qualitative results as the older version when processing the same samples. While human operators are involved in running the HPLC system, the software's output is the focus of the comparison, making it a standalone assessment of the software's correlation with its predecessor.
7. The Type of Ground Truth Used
The ground truth used for this study was the results generated by the predicate device (VARIANT™nbs Sickle Cell Program with GDM 2.01). The objective was to demonstrate that the new GDM 3.0 software produced identical qualitative results to the previously cleared and established predicate device.
8. The Sample Size for the Training Set
The provided summary does not mention a training set in the typical sense for machine learning or AI models. The GDM 3.0 is a software upgrade to an existing HPLC system, primarily focusing on operating system compatibility and usability enhancements, not a new algorithm requiring a training phase from scratch. Therefore, the concept of a "training set" for the algorithm itself is not directly applicable in this context. The development process would have involved internal testing and validation, but this information is not part of the public summary provided.
9. How the Ground Truth for the Training Set Was Established
As explained above, a dedicated "training set" for an AI algorithm is not applicable to this software upgrade. The "ground truth" for ensuring the functionality of the GDM 3.0 software during its development would have been established through rigorous software testing against known sample profiles and expected outputs, confirming its accuracy in processing the chromatographic data according to the established scientific principles of HPLC for hemoglobin separation. This typically involves using reference materials and clinically characterized samples.
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(91 days)
BIO-RAD LABORATORIES INC., CLINICAL SYSTEMS DIVISI
The Bio-Rad VARIANT™ II TURBO Link 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 TURBO Link Hemoglobin A1c Program is for use with the VARIANT II TURBO Link Hemoglobin Testing System interfaced with an automated sample transport system.
The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is for Professional Use Only.
Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
The VARIANT II TURBO Link Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO Link Hemoglobin A lc Program is based on chromatographic separation of Hemoglobin Alc on a cation exchange cartridge. The reagents in the VARIANT II TURBO Link Hemoglobin A 1c Program have the same formulation as the reagents in the VARIANT II TURBO Hemoglobin A1c Program.
Here's a breakdown of the acceptance criteria and study details for the Bio-Rad VARIANT™ II TURBO Link Hemoglobin A1c Program, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the comparison to the predicate device. The study aims to demonstrate substantial equivalence by showing similar performance.
| Performance Metric | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (VARIANT™ II TURBO Link) |
|---|---|---|
| Accuracy | Similar regression analysis to predicate | R² = 0.998, Slope = 0.983, Intercept = 0.225 |
| Precision | Equivalent within-run and total precision | Normal: Within run %CV = 0.62, Total %CV = 1.27 |
| Diabetic: Within run %CV = 0.47, Total %CV = 0.92 | ||
| Linearity | Similar linear range | 4.1 – 17.6 % HbA1c |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 180 EDTA whole blood patient samples for accuracy, and 80 normal and 80 diabetic patient samples for precision.
- Data Provenance: Not explicitly stated, but given the context of a 510(k) submission for a US market, it's highly probable the data was collected in the US. The document does not specify if the data was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. For HbA1c measurements, the "ground truth" is typically the reference method itself (HPLC in this case, specifically traced to DCCT and IFCC, and certified by NGSP), rather than expert consensus on individual samples. The study compares the new device's measurements to those of the predicate device (which is also traceable to these standards).
4. Adjudication Method for the Test Set
This information is not applicable as the ground truth is established by a quantitative analytical method (HPLC traceable to standards), not by human interpretation requiring adjudication.
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
This question is not applicable. This is a submission for an in vitro diagnostic device (analyzing blood samples) and not an imaging or AI-assisted diagnostic tool that would involve human "readers" or AI assistance in interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
This device operates as a standalone analytical instrument. The reported performance metrics (accuracy, precision, linearity) are reflective of its standalone performance without human input influencing the measurement itself, beyond standard laboratory procedures for sample handling and instrument operation. The "algorithm" here refers to the underlying HPLC and data processing, which operate automatically.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth for the device's performance is established by:
- Traceability to recognized reference methods: Diabetes Control and Complications Trial (DCCT) reference method and IFCC.
- Certification: via the National Glycohemoglobin Standardization Program (NGSP).
- Comparison to a legally marketed predicate device: The VARIANT II TURBO Hemoglobin A1c Program (K040872 and K063400), which itself would adhere to these traceability and certification standards.
Essentially, the ground truth is anchored by widely accepted analytical reference standards for HbA1c measurement.
8. The Sample Size for the Training Set
This information is not applicable/not provided. This is a regulatory submission for a diagnostic instrument, not a machine learning model that undergoes "training." The device's performance is validated through accuracy, precision, and linearity studies directly comparing it to a predicate and reference standards, rather than by training on a dataset.
9. How the Ground Truth for the Training Set Was Established
This question is not applicable for the same reasons as #8.
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(20 days)
BIO-RAD LABORATORIES INC., CLINICAL SYSTEMS DIVISI
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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