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CRYOcheck Hex LA is for clinical laboratory use as a qualitative test kit intended to aid in the detection of lupus anticoagulants (LA) in 3.2% citrated human plasma by the application of hexagonal phase phospholipids. CRYOcheck Hex LA should be used as an integrated test for lupus anticoagulant detection. For in vitro diagnostic use. The performance of this device has not been established in neonate and pediatric patient populations.

CRYOcheck Hex LA is comprised of three reagents supplied in a frozen format as follows:

LA Start: Pooled normal plasma with buffer and a heparin neutralizer.

LA Correct: Pooled normal plasma with buffer, a heparin neutralizer, and inverted hexagonal phase phospholipid.

LA APTT: Silica-based lupus sensitive APTT reagent with stabilizer.

1. Acceptance Criteria and Device Performance:

2. Sample Sizes and Data Provenance:

• Precision Study:
  • 3 control plasmas and 5 plasmas with varying LA positivity.
  • Tested in duplicate, twice a day for 20 days per lot of reagent (3 lots used).
• Reproducibility Study:
  • 3 control plasmas and 5 plasmas with varying LA positivity.
  • Each sample tested in triplicate, twice a day for 5 days for each of the 3 lots of reagent.
• Normal Range and Assay Cut-off Study:
  • Normal samples: 137 on Analyzer A, 126 on Analyzer B.
  • Each sample tested using 3 lots of CRYOcheck Hex LA.
• Shelf Life Stability Study:
  • 3 lots of CRYOcheck Hex LA.
  • 10 replicates of 3 controls tested at time = 0 and regular intervals up to 37 months.
  • One additional plasma sample close to the cut-off for one lot.
• In-Use Stability Study:
  • 3 lots of CRYOcheck Hex LA.
  • 5 replicates of 3 control plasmas and 4 test plasmas with varying levels of LA.
  • Tested at 0, 2, 4, 6, 7, 8, and 9 hours.
• Interference Studies:
  • Patient plasma samples spiked with possible interferents.
  • 20 replicates of spiked samples tested alongside 20 replicates of corresponding blank matrix control.
  • Single lot of CRYOcheck Hex LA used.
• Method Comparison Studies (Test Set):
  • Total samples: 446
    • 124 known (previously characterized) LA positive samples.
    • 75 normal (presumed LA negative) samples from individuals with other medical conditions including autoimmune disorders.
    • 220 LA target screening population samples.
  • Data Provenance: The document does not explicitly state the country of origin for the patient samples. The study involved one internal site and three external sites, suggesting a multi-center study. It is a retrospective study since samples were "known (previously characterized) LA positive" or "presumed LA negative."
• Sample Integrity Study:
  • 64 samples.

3. Number of Experts and Qualifications for Ground Truth:

• This device is an in vitro diagnostic (IVD) test, not an AI/imaging device requiring expert interpretation for ground truth.
• The ground truth for the method comparison study was established by comparing the CRYOcheck Hex LA results against a legally marketed predicate device, Staclot® LA (K923731).
• The determination of "known (previously characterized)" LA positive samples and "presumed LA negative" samples would implicitly rely on established clinical or laboratory diagnostic procedures, which are performed by qualified laboratory personnel, not typically "experts" in the sense of a radiology reader study.

4. Adjudication Method for the Test Set:

• Not applicable as this is a comparison study against a predicate device's results, not a human reader study needing adjudication. The "ground truth" for the test set was the result obtained from the predicate device (Staclot® LA).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

• No, an MRMC comparative effectiveness study was not done. This is an IVD device measuring a biomarker, not an imaging AI device assisting human readers. Therefore, the concept of "effect size" of how human readers improve with AI vs. without AI assistance is not relevant here.

6. Standalone Performance:

• Yes, the performance data presented (Precision, Reproducibility, Normal Range, Stability, Interferences) are essentially standalone (algorithm-only) performance characteristics of the CRYOcheck Hex LA device in a laboratory setting.
• The method comparison study also evaluated the device's performance independently against a predicate, effectively demonstrating its standalone performance in identifying LA status.

7. Type of Ground Truth Used:

• For the method comparison study (test set), the ground truth was comparison to a legally marketed predicate device (Staclot® LA).
• For the known LA positive/negative samples, the ground truth was "previously characterized" LA status, likely established through a combination of clinical diagnosis and existing laboratory methods.

8. Sample Size for the Training Set:

• This document describes a 510(k) submission for an in vitro diagnostic (IVD) device, not an AI/machine learning device that typically involves a "training set" in the same computational sense.
• The development and optimization of such an IVD assay would involve internal development samples and studies, but these are not referred to as "training sets" in the context of this regulatory filing. The provided information focuses on analytical and clinical performance validation.

9. How the Ground Truth for the Training Set Was Established:

• Not applicable due to the nature of the device as explained in point 8. The device's "training" or development would involve laboratory optimization and calibration using reference materials and characterized samples, but not "ground truth" in the AI sense for a dedicated "training set."

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The Sysmex® Automated Blood Coagulation Analyzer CS-2500 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of:

• . Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
• . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• . Fibrinogen (Fbg) with Dade® Thrombin Reagent
• . Coagulation Factor V with Dade® Innovin®
• . Coagulation Factor VII with Dade® Innovin®
• . Coagulation Factor VIII with Dade® Actin® FSL
• . Coagulation Factor IX with Dade® Actin® FSL
• . Lupus Anticoagulant with LA1 Screening / LA2 Confirmation Reagent
• . Factor V Leiden with Factor V Leiden Assay
• . Protein C with Protein C Reagent
• . Antithrombin (AT) with INNOVANCE® Antithrombin
• Protein C with Berichrom® Protein C
• D-dimer with INNOVANCE® D-Dimer
  The performance of this device has not been established in neonate and pediatric patient populations.

Intended Use for Factor V Leiden Assay:
The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.

Intended Use for Coagulation Factor VIII Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for Coagulation Factor IX Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for LA1 Screening / LA2 Confirmation Reagents:
LA1 Screening Reagent / LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.

The Sysmex® CS-2500 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent / LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table. The instrument is capable of measuring in Normal mode and Micro-sample mode. Options and accessories include a waste tank and a 2D barcode reader.

The provided document describes the 510(k) premarket notification for the Sysmex® Automated Blood Coagulation Analyzer CS-2500. This is a medical device, and the "study that proves the device meets the acceptance criteria" refers to the performance data submitted to demonstrate substantial equivalence to a predicate device.

It's important to note that this document is for an In Vitro Diagnostic (IVD) device, not an AI/ML algorithm for image interpretation. Therefore, many of the typical acceptance criteria and study designs associated with AI/ML (like multi-reader multi-case studies, expert adjudication for ground truth of imaging, or effect size of AI assistance for human readers) do not directly apply in the same way. Instead, the study focuses on analytical performance characteristics compared to a predicate device.

Here's an interpretation based on the provided document:

Acceptance Criteria and Device Performance

The acceptance criteria for this type of IVD device are typically established based on:

1. Method Comparison: Showing agreement with a legally marketed predicate device. This is evaluated using statistical methods like Passing-Bablok regression and Bland-Altman plots. Acceptance criteria would involve a high correlation coefficient (r), and a slope close to 1 and intercept close to 0, indicating strong agreement.
2. Reproducibility (Precision): Demonstrating the consistency of results when the test is repeated under varying conditions (within-run, between-run, between-day, and total variability). Acceptance criteria are typically expressed as a maximum allowable coefficient of variation (%CV).
3. Detection Capability (Limit of Quantitation): Proving the lowest concentration of an analyte that can be reliably measured. Acceptance criteria are usually based on a predefined maximum total error.
4. Linearity & Measuring Range: Confirming that the device produces results proportional to the concentration of the analyte across its claimed analytical measuring range. Acceptance criteria mean the measured linear range must encompass the claimed clinically reportable range.
5. Reference Interval: Establishing the range of test results expected in a healthy population. Acceptance criteria would be the successful determination of these intervals or confirmation of existing ones.
6. Clinical Performance (e.g., Cut-off Study): For specific assays, validating clinical performance characteristics like diagnostic accuracy against a gold standard (e.g., genotype for Factor V Leiden). Acceptance criteria would typically involve achieving high positive and negative percentage agreement.

1. Table of Acceptance Criteria and the Reported Device Performance

The document does not explicitly list the "acceptance criteria" numerical targets. Instead, it states that "Results from each application met the predetermined acceptance criteria." and later, "All reagents met the predetermined acceptance criteria." This implies that Siemens had internal, pre-defined thresholds for these performance metrics, which were successfully met.

Based on the performance data presented, here is a summary table, inferring the intent behind the reported results as meeting acceptance:

2. Sample sizes used for the test set and the data provenance

• Method Comparison:
  • Sample Size (for each application): Varied by site and application, ranging from N=8 to N=173 for individual sites.
    • Factor V Leiden: Total N = 494 (Combined Sites)
    • Coagulation Factor VIII: Total N = 408 (Combined Sites)
    • Coagulation Factor IX: Total N = 459 (Combined Sites)
    • Lupus Anticoagulant (LA1, LA2, Ratio): Total N = 347-402 (Combined Sites)
  • Data Provenance: Conducted at four external sites; 3 in the United States and one in Germany. Samples were patient samples. Retrospective (implied by "patient samples collected," likely frozen/stored retrospectively as this is an analyzer validation, not a live clinical trial for patient outcomes).
• Reproducibility Studies:
  • Sample Size: Not explicitly stated as a number of distinct patient samples. The study design followed CLSI EP05-A2, which involves repetitive testing of control materials or pooled patient samples over multiple days/runs. "Twenty-day precision studies" were performed.
  • Data Provenance: One external site in Germany and two external sites in the United States.
• Detection Capability, Linearity & Measuring Range:
  • Sample Size: Not explicitly stated as a number of distinct patient samples. These studies typically use diluted samples or spiked samples to cover the analytical range.
  • Data Provenance: Not specified, but likely conducted at the same or similar labs as the other analytical performance studies.
• Reference Interval:
  • Sample Size: Between N=187 and N=193 samples per application.
  • Data Provenance: Three clinical study sites in the United States. Study population did not include neonate and pediatric patient populations.
• Factor V Leiden Cut-off Study:
  • Sample Size: N = 381 patients (combined from US and OUS sites), with N=127 patients from the US.
  • Data Provenance: Three different clinical sites (one site in the US and two sites in Germany). Samples were citrated plasma from patients submitted for thrombophilia screening, collected and then frozen.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable in the context of this IVD device. Ground truth for clinical assays is typically established by:

• Comparison to a legally marketed predicate device: As seen in the method comparison.
• Defined analytical standards: For precision, linearity, and detection limits.
• Clinical gold standard: For the Factor V Leiden cut-off study, genetic testing (Factor V Leiden PCR method) served as the "reference," which is an objective laboratory test, not expert interpretation.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable for an IVD device analytical performance study. Adjudication is relevant for subjective assessments, particularly in imaging or clinical endpoints. This study measures quantitative values from blood samples.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an IVD device (blood coagulation analyzer), not an AI imaging algorithm. There are no "human readers" interpreting images assisted by AI in this context.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in a way. The device (Sysmex® CS-2500) functions as a standalone instrument to measure coagulation parameters. The performance studies (method comparison, reproducibility, detection capability, linearity, reference interval) evaluate the device's output without direct human "interpretation" of raw signals for diagnosis, but rather human use of the device and its generated numerical reports. The "algorithm" here refers to the instrument's internal measurement and calculation procedures rather than a predictive AI model.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" or reference for this device's performance evaluation was primarily:

• Predicate Device: For method comparison (Sysmex® CA-1500). The predicate itself is a legally marketed device with established performance.
• Analytical Standards/Reference Materials: For studies like reproducibility, detection capability, and linearity.
• External Laboratory Test (PCR): For the Factor V Leiden study, the "Reference (Factor V Leiden PCR method)" served as the objective ground truth for the genetic variant.

8. The sample size for the training set

Not applicable. This document is for the validation of an IVD medical device (a physical instrument and associated reagents), not a machine learning model that requires a "training set" in the conventional sense. The "training" of such a device refers to its design, calibration, and internal programming by the manufacturer, which is distinct from data-driven machine learning.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the context of an AI/ML model. The "ground truth" (or design specifications and analytical performance ranges) for such a device is established through comprehensive engineering, chemical, and biological research and development, following recognized industry standards (e.g., CLSI guidelines).

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The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of:

• . Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
• . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• . Fibrinogen (Fbg) with Dade® Thrombin Reagent
• . Coagulation Factor V with Dade® Innovin®
• . Coagulation Factor VII with Dade® Innovin®
• . Coagulation Factor VIII with Dade® Actin® FSL
• . Coagulation Factor IX with Dade® Actin® FSL
• . Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent
• . Factor V Leiden with Factor V Leiden Assay
• . Protein C with Protein C Reagent
• . Antithrombin (AT) with INNOVANCE® Antithrombin
• Protein C with Berichrom® Protein C
• D-dimer with INNOVANCE® D-Dimer

The performance of this device has not been established in neonate and pediatric patient populations.

Intended Use for Factor V Leiden Assay:

The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.

Intended Use for Coagulation Factor VIII Deficient Plasma:

In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for Coagulation Factor IX Deficient Plasma:

In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for LA1 Screening and LA2 Confirmation Reagents:

LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.

The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent and LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table.

Here's a breakdown of the acceptance criteria and study information for the Sysmex® Automated Blood Coagulation Analyzer CS-5100, based on the provided text:

Important Note: The provided document is a 510(k) summary for a medical device. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving absolute safety and effectiveness from scratch. Therefore, the "acceptance criteria" discussed are primarily related to showing that the new device performs comparably to the predicate for specific applications, and "ground truth" is often established by comparing to the predicate device's results.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values in the format of a table as it pertains to specific numerical thresholds for accuracy, sensitivity, or specificity. Instead, the acceptance criteria for most studies (Method Comparison, Reproducibility, Detection Capability, Linearity) are generally described as "met the predetermined acceptance criteria." However, for the Factor V Leiden Cut-off Study, specific performance metrics (Sensitivity and Specificity) are provided and imply acceptance criteria. For the Method Comparison, the implicit acceptance criterion is that the results demonstrate equivalence to the predicate device, as confirmed by Passing-Bablok regression and Bland-Altman plots.

Here's an attempt to extract and summarize:

2. Sample Size and Data Provenance for Test Set

• Method Comparison:
  • Sample Sizes:
    • Factor V Leiden: N = 495 (combined from 4 sites)
    • Coagulation Factor VIII: N = 432 (combined from 4 sites)
    • Coagulation Factor IX: N = 475 (combined from 4 sites)
    • LA 1 Screening Reagent: N = 369 (combined from 3 sites, 1 site had N=4)
    • LA 2 Confirmation Reagent: N = 353 (combined from 3 sites, 1 site had N=17)
    • LA Ratio: N = 306 (combined from 3 sites, 1 site had N=4)
  • Data Provenance: 4 external sites, 3 in the United States and 1 in Germany. Retrospective or prospective is not explicitly stated for individual samples, but the comparison uses "patient samples" and "were measured on both the predicate device... as well as the new device."
• Reproducibility Studies:
  • Sample Sizes: Not explicitly stated as number of patient samples, but testing used 2 runs per day, 2 replicates per run, over 20 days. These studies typically use control materials at various levels rather than a large set of unique patient samples for performance assessment.
  • Data Provenance: 1 external site in Germany, 2 external sites in the United States.
• Detection Capability Studies:
  • Sample Sizes: Not specified beyond stating "calibrated assays."
  • Data Provenance: Not specified beyond referring to the method.
• Linearity & Measuring Range:
  • Sample Sizes: Not specified beyond stating "calibrated assays."
  • Data Provenance: Not specified beyond referring to the method.
• Reference Interval Studies:
  • Sample Sizes:
    • Factor V Leiden: N = 193
    • Coagulation Factor VIII: N = 190
    • Coagulation Factor IX: N = 188
    • LA 1 Screening Reagent (fresh): N = 185
    • LA 1 Screening Reagent (frozen): N = 191
    • LA 2 Confirmation Reagent (fresh): N = 185
    • LA 2 Confirmation Reagent (frozen): N = 191
    • LA1/LA2 Ratio (fresh): N = 184
    • LA1/LA2 Ratio (frozen): N = 191
  • Data Provenance: 3 clinical study sites in the United States.
• Factor V Leiden Cut-off Study:
  • Sample Size: N = 381 (of which N = 127 from the US)
  • Data Provenance: Citrated plasma samples from patients submitted for thrombophilia screening were collected by three different clinical sites (one site in the US and two sites in Germany). The samples were frozen.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of "experts" in the traditional sense of clinicians or radiologists establishing ground truth. For coagulation analyzers, the "ground truth" is typically established by comparing the new device's measurements to a reference method or a predicate device's measurements that are already accepted as accurate and reliable.

• In the Method Comparison study, the predicate device (Sysmex® CA-1500) serves as the reference for comparison, meaning its results are the "ground truth" against which the new device's results are measured for equivalence.
• In the Factor V Leiden Cut-off Study, the "ground truth" for confirming the presence of the Factor V Leiden variant was established by the Factor V Leiden genotype (PCR method). The number of experts involved in performing or interpreting these PCR tests is not specified, but they would typically be laboratory professionals trained in molecular diagnostics.

4. Adjudication Method for the Test Set

No explicit adjudication method (like "2+1" or "3+1") is described, as the studies are primarily quantitative comparisons against established methods or predicate device results, rather than subjective interpretations requiring adjudication by multiple readers.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC study was done. This type of study (comparing human reader performance with and without AI assistance) is typically relevant for interpretative diagnostic devices, such as imaging systems, where human experts make diagnoses. The Sysmex® CS-5100 is an automated blood coagulation analyzer that provides quantitative measurements, not interpretations, so an MRMC study is not applicable here.

6. Standalone Performance Study (Algorithm Only)

Yes, standalone performance studies were done. All the studies described (Method Comparison, Reproducibility, Detection Capability, Linearity, Reference Interval, Factor V Leiden Cut-off Study) assess the performance of the Sysmex® CS-5100 device itself, functioning independently, without human-in-the-loop interpretation or intervention in the measurement process. The device outputs quantitative results, and these studies evaluate the accuracy, precision, and clinical relevance of those outputs.

7. Type of Ground Truth Used

• Method Comparison: Comparison against the results obtained from the predicate device (Sysmex® CA-1500), which is itself a legally marketed device with established performance.
• Factor V Leiden Cut-off Study: Factor V Leiden genotype (PCR method). This is a definitive molecular pathology test.
• Detection Capability, Linearity, Reference Interval studies: These generally establish the device's inherent analytical characteristics against internal standards or established statistical methodologies (CLSI guidelines), rather than using an external "ground truth" from experts or a pathology panel in the same way an interpretative diagnostic device might.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning. The Sysmex® CS-5100 is a an automated laboratory instrument for performing coagulation tests, not a software algorithm that undergoes a training phase with a distinct dataset. The performance data presented are for validation/testing of the device's operational capabilities across predefined assays using various samples.

9. How Ground Truth for the Training Set Was Established

Since a "training set" in the machine learning sense is not applicable or explicitly mentioned for this device, a method for establishing its ground truth is also not provided. The development and calibration of such instruments typically involve rigorous analytical methods and the use of certified reference materials and control samples, rather than a "ground truth" established from a large dataset for algorithm training.

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HemosIL Silica Clotting Time is intended for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems by the use of screening (SCT Screen) and confirmatory (SCT Confirm) reagents sensitized to phospholipid dependent antibodies. For in vitro diagnostic use.

The HemoIL SCT assay, consisting of SCT Screen and SCT Confirm, is intended to simplify and standardize the detection of Lupus Anticoagulants (LA) in clinical evaluations. SCT Screen is poor in phospholipid making it sensitive to LA. The additional amount of phospholipid in SCT Confirm neutralizes LA to give shorter clotting times. Silica Clotting Time in the presence of calcium, directly activates the intrinsic pathway of coagulation. SCT Screen and SCT Confirm are therefore unaffected by factor VII deficiencies or inhibitors.

This document is not structured as a typical study report, but rather as a 510(k) summary for a Special 510(k) submission. A Special 510(k) is used when a modification is made to a legally marketed device, and the modification does not affect the device's indications for use or its fundamental scientific technology. In this case, the modification is to the device's labeling (specifically, clarifying heparin interference information) based on updated guidance (CLSI Guideline H60-A).

Therefore, the primary "study" proving the device meets acceptance criteria in this context is the demonstration that the changes are only to the labeling and do not impact the assay's performance compared to the predicate device. This type of submission relies heavily on the predicate's prior clearance and the assertion that the core device technology and performance remain unchanged.

Given this, I will describe the "acceptance criteria" and "device performance" in terms of substantiating that the change in labeling does not alter the device's substantial equivalence to its predicate.

Here's the breakdown of information, addressing your points where applicable based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance
The document describes a Special 510(k) submission. This type of submission is based on the premise that there are no actual changes to the device's performance, but rather to its labeling or minor design aspects.
Therefore, no new "test set" data from patient samples is typically required or provided for a Special 510(k) for a labeling change. The claim of substantial equivalence rests on the device being unchanged and performing as cleared under its predicate (K050221). The "study" here is the comparison demonstrating no change to the device itself.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
Not applicable. No new clinical or analytical performance study requiring a ground truth determination from experts on a new test set was conducted for this Special 510(k) submission. The changes are to informational labeling based on a published guideline (CLSI H60-A).

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable, as no new test set requiring expert adjudication was utilized for this type of submission.

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 in vitro diagnostic (IVD) reagent for a laboratory test (detection of Lupus Anticoagulants), not an imaging device or an AI-powered diagnostic system designed for human reader assistance.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This is an IVD reagent, not an algorithm. Its performance is measured directly by clinical laboratory methods.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
Not applicable to this Special 510(k) based on a labeling change. The original predicate device (K050221) would have established its performance against appropriate reference methods or clinical outcomes during its initial clearance process. For this submission, the "ground truth" is that the device itself has not changed and therefore its previously established performance holds. The update to the labeling regarding heparin interference aligns with an industry-accepted guideline (CLSI Guideline H60-A).

8. The sample size for the training set
Not applicable. No training set was used for this Special 510(k) submission.

9. How the ground truth for the training set was established
Not applicable. No training set was used for this Special 510(k) submission.

In summary of the "study":

The "study" in this Special 510(k) is a comparison study that demonstrates the "modified device" is identical in all functional aspects to the "predicate device," with the only changes being to the instructional labeling regarding heparin interference. The acceptance criterion is that no functional or performance changes were introduced, and therefore the device remains substantially equivalent to the previously cleared predicate (K050221). The proof is in the documentation confirming no changes to formulation, operating principle, indications for use, stability, specimen requirements, software, or test parameters.

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HEMOCLOT Quanti VL is an in vitro diagnostic test for the quantitative determination of Factor V Leiden (FVL) activity in human citrated plasma, using automated or manual methods, by its resistance to the action of Activated Protein C ( APC).

Patients with the Factor V-L (mutalion R506Q), are exposed to an increased thrombotic risk.

Biophen V-L CAL (undiluted), at defined Factor V-Leiden (FV-L) concentrations, for the callibration of Factor V-Leiden aclivity on human plasma, using the Hemoclot Quanti V-L kit.

Factor V-L Cafibrator, pre diluted (1:20) human plasmas. at defined Factor V-Leiden (FV-L) concentrations, for the calibration of Factor V-L activity on human plasma using Hemoclot Quanti V-L Kit.

Biophen Act PC-r Control Plasma contains human plasma, presenting an Activated Protein C Resistance (APC-R) is used as quality control plasma for the testing of Activated Protein C resistance (APC-R) on human plasma using Hemoclot Quarti V-L Kit.

(Updated) BIOPHEN Normal Control Plasma is a set of 12 vials of normal citrated human plasma for the quality control of some coagulation factors. The following table shows parameters, which are measured using assays from HYPHEN BioMed or from other manufacturers, and according to the package inserts:

DVVtest, DVVconfirm are registered trademarks from American Diagnostica, Inc.

The BIOPHEN Normal Control Plasma is tested for the absence of Lupus Anticoagulant and can be used as a negative control for this investigation. This control plasma is also tested for the absence of Activated Protein C resistance (Act PC-7). When the APTT is performed with or without Activated Protein C (APC) the ratio obtained (APTT + APC/APTT) is ≥2.00.

• 1. HEMOCLOT Quanti V-L is an in vitro diagnostic test kit containing 3 vials of each of the following 2 lyophilized reagents:
     R1: Reagent 1: Clotting mixture containing human Fibrinogen, human prothrombin, Protein S at a constant concentration, optimized for the assay, and human Activated Protein C, lyophilized. It also contains a heparin neutralizing substance. Each vial is to be reconstituted with exactly 2 ml of distilled water.

R2: Reagent 2: Purified Human Factor Xa, containing rabbit brain phospholipds (cephalin), lyophilized. Each vial is to be reconstituted with exactly 1 ml of distilled water.

Calibrators and controls to be used with the test kit are supplied separately. The following calibrators and control are included in this submission:

• 2. Factor V-L Calibrator is a calibrator kit containing 3 vials each of 1.0 ml prediluted human plasma (1:20), freeze dried, at 4 different concentrations of FV-L, to cover the assay range, from 10% to 100%. Each vial is restored with 1.0 ml Owren Koller type buffer.
• 3. BIOPHEN V-L CAL (Undiluted) is a calibrator kit containing 3 vials each of 0.5 ml undiluted human plasma, freeze dried, at 3 different concentrations of FV-L, to cover the assay range, from about 10% to 100%. Each vial is restored with 0.5 ml distilled water.
• BIOPHEN Act PC-r Control Plasma is a controls kit containing 12 vials of 0.5 ml human 4. plasma, presenting an Activated Protein C Resistance (APC-R), citrated and Iyophilized. Each vial is to be reconstituted with exactly 0.5 ml of distilled water.
• BIOPHEN Normal Control Plasma manufactured by Hyphen-Biomed, is also used with the test kit and is currently marketed in the US under 510(k) # K043451, It is a controls kit containing 12 vials of 1.0 ml of normal citrated human plasma, lyophilized. Each vial is to be reconstituted with exactly 1.0 ml of distilled water.

Here's an analysis of the provided text regarding the acceptance criteria and study for the HEMOCLOT Quanti V-L device:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in terms of numerical thresholds for sensitivity, specificity, or agreement. Instead, it demonstrates consistency with a predicate device and molecular biology results. The performance is presented as direct agreement percentages.

2. Sample Size Used for the Test Set and Data Provenance

• Comparison with Predicate Device (COATEST APCr):
  • Sample Size: 189 total samples (108 Normal, 70 Abnormal, 10 inconclusive/borderline based on detailed table analysis: 108 Normal + 1 Abnormal + 2 Inconclusive=111 from Predicate Normal; 7 Abnormal + 70 Abnormal + 1 Inconclusive = 78 from Predicate Abnormal). However, the "Sample Size" row explicitly states 189 for the overall comparison.
  • Data Provenance: "combined from 4 studies (2 in US, 2 in Europe)." This indicates a retrospective or prospective collection across multiple sites. The specific nature (retrospective/prospective) is not explicitly stated, but clinical studies often involve a mix.
• Comparison with Molecular Biology:
  • Sample Size: 21 total samples (15 Normal, 6 Abnormal).
  • Data Provenance: Not explicitly stated, but implied to be part of the overall validation studies.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the use of "experts" for establishing ground truth in the traditional sense of clinical readings.

• For the comparison with the predicate device, the "ground truth" for the test set was the classification (Normal/Abnormal) provided by the COATEST APCr kit. This is a laboratory diagnostic assay, not an expert human interpretation.
• For the comparison with Molecular Biology, the "ground truth" was the molecular biology result itself (indicating presence or absence of the R506Q mutation). This is an objective genetic test, not subject to expert interpretation.

4. Adjudication Method for the Test Set

Not applicable. As the ground truth was established by another diagnostic assay (COATEST APCr) or molecular biology, there was no human adjudication process involved. The results were compared against these established methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No. This study is for an in vitro diagnostic (IVD) assay, which measures an analytical marker in human plasma. It does not involve human readers interpreting images or data, so an MRMC study comparing human readers with and without AI assistance is not relevant or applicable here.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, this entire study represents the standalone performance of the HEMOCLOT Quanti V-L device. It evaluates the device's ability to classify samples as Normal, Abnormal, or Inconclusive based on its own measurements, compared against a predicate device and a molecular biology reference. There is no human interpretation involved in the direct result generation of the HEMOCLOT Quanti V-L assay itself.

7. The Type of Ground Truth Used

• Comparison with Predicate Device: The ground truth was the result obtained from the COATEST APC Resistance V (K963111) predicate device.
• Comparison with Molecular Biology: The ground truth was the molecular biology result for the Factor V Leiden (mutation R506Q). This is pathology/genetic testing data, considered a highly objective measure for the presence of the mutation.

8. The Sample Size for the Training Set

The document doesn't explicitly mention a separate "training set" for the HEMOCLOT Quanti V-L assay in the context of machine learning or AI. For IVD kits like this, the "training" typically refers to the optimization and validation performed by the manufacturer during product development, using various samples to establish assay parameters, linearity, sensitivity, specificity, and reproducibility. The performance data presented here is the validation or "test" set used to demonstrate substantial equivalence.

9. How the Ground Truth for the Training Set Was Established

As there's no mention of a traditional machine learning "training set" with separate ground truth establishment, this question is not fully applicable in the context of this document. For IVD development, the "ground truth" for calibrators, controls, and method development would have been established through highly characterized reference materials, potentially confirmed by molecular methods or established clinical diagnoses of FVL status.

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Wortham Laboratories Stasis 1 Coagulation Control (Normal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and Fibrinogen assays. It will yield PT, APTT, and Fibrinogen values in the normal range.
Wortham Laboratories Stasis 2 Coagulation Control (Abnormal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). It will yield PT, and APTT values in the moderate abnormal range.
Wortham Laboratories Stasis 3 Coagulation Control (Abnormal) is intended for use as a quality control to monitor the performance of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT). It will yield PT, and APTT values in the strongly abnormal range.
Wortham Laboratories Serathan-B PT reagent is an in-vitro diagnostic reagent intended in a clinical laboratory for the quantitative determination of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway. Serathan-B is a moderately sensitive thromboplastin reagent.
Wortham Laboratories Serathan-A PT reagent is an in-vitro diagnostic reagent intended in a clinical laboratory for the quantitative determination of Prothrombin Time (PT) testing for the detection of coagulation abnormalities in the extrinsic pathway. Serathan-A is a highly sensitive thromboplastin reagent.
Wortham Laboratories Intrin-EA APTT is an in-vitro diagnostic reagent used in the clinical laboratory for the quantitative determination of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway. Intrin-EA reagent is sensitive to mild coagulopathies.
Wortham Laboratories Intrin-SI is an in-vitro diagnostic reagent used in the clinical laboratory for the quantitative determination of Activated Partial Thromboplastin Time (APTT) testing for the detection of coagulation abnormalities in the intrinsic pathway. Intrin-SI reagent is sensitive to heparin and lupus anticoagulant plasmas.
Wortham Laboratories Fibrinogen Control Low, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.
Wortham Laboratories Fibrinogen Control Normal, a quantitative control plasma, is intended for use in the quality control of fibrinogen assays.
Wortham Laboratories Thrombin Reagent is intended for thrombin to convert fibrinogen in the quantitative determination of fibrinogen in plasma samples.
Wortham Laboratories Fibrinogen Assay Set, containing a complete set of Normal Fibrinogen Control (200-400 mg/dl), Thrombin Reagent (100 IU/ml), and Fibrinogen Buffer, is intend for use in the quantitative determination of fibrinogen in plasma samples.
Wortham Laboratories Heparin Control Level 1, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.
Wortham Laboratories Heparin Control Level 2, is intended as a quality control of the Activated Partial Thromboplastin Time (APTT) during heparin monitoring.
Wortham Laboratories Calcium Chloride Solution 0.02 M (CaCl2) is intended for quantitative use with ellagic acid (Intrin-EA) or silicon particulate activators (Intrin-SI) in performing the activated partial thromboplastin time (APTT) on citrated plasma.
Wortham Laboratories Fibrinogen Buffer is designed as a diluent for fibrinogen studies.

Wortham Laboratories Stasis 1 Coagulation Control (Normal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Stasis 2 Coagulation Control (Abnormal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBSAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Stasis 3 Coagulation Control (Abnormal) is a liquid stable citrated plasma obtained from healthy donors. Stabilizers and buffers have been added to the plasma. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found to be non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Serathan-B PT Reagent is a liquid stable extract of rabbit thromboplastin containing calcium, stabilizer and buffer. Serathan-B is an in-vitro diagnostic reagent intended for use for the performance of Prothrombin Time (PT) testing and quantitative PT-based factor assays for Factors II, V. VII and X.
Wortham Laboratories Scrathan-A PT Reagent is a liquid stable extract of rabbit thromboplastin containing calcium, stabilizer and buffer. Serathan-A is an in-vitro diagnostic reagent intended for use for the performance of Prothrombin Time (PT) testing and quantitative PT-based factor assays for Factors II, V. VII and X.
Wortham Laboratories Intrin-EA APTT reagent is intended for use in determining activated partial thromboplastin time (APTT) and coagulation factor assays that are based on a modified APTT. The capacity of blood to form a fibrin clot by way of the intrinsic hemostatic pathway requires coagulation factors XII, XI, IX, VIII, platelet lipids and calcium. The assay is performed by the addition of a suspension of rabbit cephalin with the surface activator ellagic acid.
Wortham Laboratories Intrin-SI APTT Reagent is a liquid stable extract of rabbit brain thromboplastin, containing stabilizers and buffers. Intrin-SI is an in-vitro diagnostic reagent intended for use for the performance of a citrated Partial Thromboplastin Time (APTT) testing and quantitative PTT-based factor assays for Factors XII, XI, IX and VIII.
Wortham Laboratories Fibrinogen Low Control is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Fibrinogen Normal Control is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Thrombin Reagent is a liquid stable preparation of activated bovine proteins (Factor IIa).
Wortham Laboratories Fibrinogen Assay Set contains a liquid stable preparation of citrated plasma obtained from healthy donors, which contains stabilizers, buffers, and a bovine reagent and buffer solution which are also provided in the set. Each unit of source material used in the preparation of the control has been tested by an EDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Heparin Control Level 1 is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains sodium heparin, stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodies to HIV and HCV.
Wortham Laboratories Heparin Control Level 2 is a liquid stable preparation of citrated plasma obtained from healthy donors, which contains sodium heparin, stabilizers and buffers. Each unit of source material used in the preparation of the control has been tested by an FDA approved method and found non-reactive for HBsAg and negative for antibodics to HIV and HCV.
Wortham Laboratories Calcium Chloride Solution 0.02 M (CaCl2) is intended for quantitative use with ellagic acid (Intrin-EA) or silicon particulate activators (Intrin-SI) in performing the activated partial thromboplastin time (APTT) on citrated plasma.
Fibrinogen Buffer : 1.3% TAPSO Buffer. 0.9% sodium chloride, 0.1% sodium azide and stabilizers; pH 7.35 ± 0.05.

The provided text describes 12 distinct devices from Wortham Laboratories, each with its own acceptance criteria and study findings. Due to the volume, I will provide a detailed breakdown for the first device, Stasis 1 Coagulation Control (Normal), and then summarize the general approach for the others as they follow a similar pattern.

Device: Wortham Laboratories Stasis 1 Coagulation Control (Normal)

1. Acceptance Criteria and Reported Device Performance:

The acceptance criteria for Wortham Laboratories Stasis 1 Coagulation Control (Normal) are implicitly established by demonstrating comparable or superior performance to the predicate device, Pacific Hemostasis Coagulation Control Level I. The reported device performance is presented in terms of Coefficient of Variation (CV%) for precision.

Note: The acceptance criteria are "performance equal to or better than the predicate" for most quantitative metrics, and "same" for qualitative metrics like intended use and assay factors. The tables above directly compare the new device's performance to the predicate's stated performance, indicating the new device met or exceeded the predicate's precision values.

2. Sample size used for the test set and the data provenance:

The document mentions "Mechanical assays of Stasis 1 to the predicate normal plasma control" and "Mechanical measurements of the APTT in both Stasis 1 and Pacific Hemostasis Level 1 Control," along with "The processing of the Fibrinogen levels in both study graphs."

• Sample size: Not explicitly stated as a number of individual samples or runs for the test set. The data is presented as statistical measures (standard deviation, CV%) which are derived from a series of measurements, implying repeated testing.
• Data provenance: Not explicitly stated. The context suggests that the testing was performed by Wortham Laboratories, likely internally. It does not provide information about the country of origin of the data or if it was retrospective or prospective. The source material for the control is "liquid stable citrated plasma obtained from healthy donors," but this refers to the control product itself, not the clinical data.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not provided. The "ground truth" for this device appears to be the quantitative measurements obtained from the predicate device (Pacific Hemostasis Coagulation Control Level I) and the established ranges for PT, APTT, and Fibrinogen in normal plasma. The comparison is against established quantitative performance metrics of a legally marketed predicate, not against expert consensus on a clinical outcome.

4. Adjudication method for the test set:

Not applicable. This is a comparison of quantitative laboratory performance metrics of a new control product against an existing predicate control. There is no human adjudication of diagnostic outcomes involved.

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 a medical device for in-vitro diagnostic quality control, not an AI-assisted diagnostic tool interpreted by human readers.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Not applicable. This device is a quality control product, not an algorithm. Its performance is measured directly by laboratory instruments (e.g., fibrometer).

7. The type of ground truth used:

The ground truth or reference standard for comparison is the performance characteristics of a legally marketed predicate device (Pacific Hemostasis Coagulation Control Level I). The "Expected Range" values are based on "Mechanical Mean ± 2SD," implying statistically derived ranges from repeated measurements, rather than pathology, expert consensus on images, or true outcomes data for individual patients.

8. The sample size for the training set:

Not applicable. This device is a quality control product, not an AI/ML algorithm that requires a training set.

9. How the ground truth for the training set was established:

Not applicable, as there is no training set for this type of device.

Summary for other devices (Stasis 2, Stasis 3, Serathan-B PT Reagent, Serathan-A PT Reagent, Intrin-EA APTT Reagent, Intrin-SI APTT Reagent, Fibrinogen Control Plasma (Low), Fibrinogen Control Plasma (Normal), Thrombin Reagent, Fibrinogen Assay Set, Heparin Control Plasma Level 1, Heparin Control Plasma Level 2, Calcium Chloride Solution 0.02 M, Fibrinogen Buffer):

All other devices described in the document (Stasis 2, Stasis 3, Serathan-B, Serathan-A, Intrin-EA, Intrin-SI, Fibrinogen Controls, Thrombin Reagent, Fibrinogen Assay Set, Heparin Controls, Calcium Chloride Solution, Fibrinogen Buffer) follow a very similar pattern to Stasis 1 Coagulation Control.

• Acceptance Criteria and Reported Device Performance: This is consistently established by comparing the new device's performance metrics (primarily Coefficient of Variation (CV%) and standard deviation (SD) for precision, and expected ranges) directly against a specific predicate device's reported performance. The new device consistently demonstrates comparable or improved precision compared to its respective predicate.
• Sample Size for Test Set, Data Provenance, Number of Experts, Adjudication Method, MRMC Studies, Standalone Performance, Ground Truth Type, Training Set Size, and Training Set Ground Truth:
  • Sample Size: Not explicitly stated as the number of individual tests or samples; reported as statistical measures (SD, CV%) derived from repeated measurements.
  • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Implied internal testing by Wortham Laboratories.
  • Experts/Adjudication/MRMC/Standalone: Not applicable to these types of in-vitro diagnostic quality control and reagent products, as they are evaluated based on quantitative laboratory performance against chemical/biological standards or predicate product performance, not human diagnostic interpretation.
  • Ground Truth Type: For all these devices, the ground truth for evaluation is the established performance characteristics of the legally marketed predicate device, as well as the expected physiological/clinical ranges for the assays they control or participate in (e.g., normal/abnormal PT/APTT/Fibrinogen values).
  • Training Set: Not applicable, as these are not AI/ML algorithms.

The overall conclusion for all devices is a claim of "substantial equivalence" to their respective predicates based on comparable intended use, technological characteristics, and performance data consistently showing competitive or superior precision and expected ranges.

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cryocheck Clot APCR is a clotting assay intended to screen for resistance to activated protein C in citrated human plasma from individuals with the factor V Leiden mutation.

cryocheck Clot APCR consists of:

• 5 x 2.0 mL Activator Reagent (APC-AR) .
• 5 x 4.0 mL Russell's Viper Venom Reagent (APC-RV)

Here's a breakdown of the acceptance criteria and study information for the cryocheck™ Clot APCR™ device, based on the provided 510(k) summary:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity, specificity, or correlation. Instead, it frames the acceptance criteria implicitly as "comparable precision," "identical results when challenged with interfering substances and factor deficiencies," and "identical sensitivity and specificity" when compared to the predicate device. The primary performance metric reported is a correlation coefficient.

2. Sample Size and Data Provenance

• Sample Size for Test Set: 207 clinical samples.
• Data Provenance: The document states that clinical tests were performed "at Precision BioLogic and a US university hospital-based clinical coagulation laboratory." This indicates the data is prospective clinical data collected from human subjects (patients). The clinical samples were from "the target population for the assay."

3. Number of Experts and Their Qualifications for Ground Truth

The document does not specify the number of experts used to establish ground truth or their qualifications. The comparison is made against a predicate device, implies that the predicate device's results are considered the reference standard, rather than independently established expert ground truth.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method for the test set. The comparison appears to be a direct one-to-one comparison of results between the new device and the predicate device for each sample.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. The study focuses on comparing the new device's performance to a predicate device, not on assessing human reader performance with or without AI assistance.

6. Standalone (Algorithm Only) Performance Study

Yes, the study is a standalone performance study. The device itself is an in vitro diagnostic (IVD) assay that provides a result (clotting time ratio). The "performance" being evaluated is the accuracy and reliability of this assay in classifying samples compared to the predicate device. There is no human-in-the-loop component described for the operation of this specific device or its interpretation in the context of the study.

7. Type of Ground Truth Used

The "ground truth" for the test set was essentially the results obtained from the predicate device (GradiLeiden V). The study compared the cryocheck Clot APCR's performance to the GradiLeiden V results across the 207 clinical samples.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" or its size. Since this is an in vitro diagnostic assay rather than an AI/machine learning algorithm, the concept of a distinct training set in the typical machine learning sense does not apply. The development of the assay would involve R&D and validation, but not a "training set" in the computational context.

9. How Ground Truth for Training Set Was Established

As noted above, the concept of a training set as it applies to AI/ML is not relevant here. The "ground truth" for the development and validation of such an assay would typically be established through robust laboratory methods, perhaps using known Factor V Leiden positive and negative samples, and comparison to established clinical diagnostic methods, but specific details of this process for assay development are not provided in the 510(k) summary.

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The STA® - Cephascreen® kits provide reagents for the determination of the activated partial thromboplastin time (APTT) in citrated plasma on the STA® line of analyzers suitable to these reagents.

The STA®-Cephascreen kits provide reagents for the determination of the activated partial thromboplastin time (APTT) according to Langdell R.D. et al. (1) and Larrieu M. J., Weilland C. (2) by analyzers of the STA® line suitable to these reagents.
STA®-Cephascreen ®: reagent containing cephalin (platelet substitute), prepared from rabbit cerebral tissues (2) and a polyphenolic activator (patent pending) in a buffered medium.
The STA®-Cephascreen ® is available in two different kit sizes:

• STA®-Cephascreen®©(REF00308) containing 12x4 mL vials ready for . use reagent
• STA®-Cephascreen®쓰(REF 00310) containing 12x10 mL vials of ready . for use reagent
  The STA®-Cephascreen® reagents are provided in liquid form, ready for use after stabilization and mixing when a vial is opened.

Here's an analysis of the provided text regarding the STA®-Cephascreen Kit, focusing on acceptance criteria and the supporting study:

The document describes a 510(k) summary for the STA®-Cephascreen Kit, which is a reagent for determining activated partial thromboplastin time (APTT). The primary purpose of this submission is to demonstrate substantial equivalence to a predicate device, the STA®-C.K.Prest® kit.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for the STA®-Cephascreen Kit in the traditional sense of numerical thresholds for sensitivity, specificity, or accuracy compared to a gold standard. Instead, the study aimed to demonstrate substantial equivalence to the predicate device.

The reported performance is based on the correlation between the new device and the predicate device.

2. Sample Size Used for the Test Set and Data Provenance:

• Sample Size: 125 plasma samples.
  • 40 plasmas from presumed normal individuals
  • 20 plasmas from patients receiving unfractionated heparin (UFH) therapy
  • 20 plasmas from patients receiving low molecular weight heparin (LMWH) therapy
  • 15 plasmas from patients receiving oral anticoagulant (AVK) therapy
  • 10 LA positive plasma samples
  • 10 plasmas from patients with factor VIII deficiency (F. VIII Def.)
  • 10 plasmas from patients with factor IX deficiency (F. IX Def.)
• Data Provenance: Not explicitly stated regarding country of origin. The manufacturer is French (Diagnostica Stago, France), but the distributor is in the US (Diagnostica Stago, Inc., Parsippany, NJ). The plasma types suggest clinical samples, but whether they were collected retrospectively or prospectively, or from what geographic region, is not specified. It's common for such studies to use retrospectively collected samples from a clinical lab specializing in coagulation.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications:

This type of study does not involve "experts" establishing a ground truth in the sense of image interpretation or diagnostic classification. Instead, the "ground truth" for the test set is established by the measurement value provided by the predicate device (STA®-C.K.Prest® kit). The study compares the new device's readings to those of the predicate. Therefore, information about the number and qualifications of experts is not applicable here.

4. Adjudication Method for the Test Set:

Not applicable. There is no adjudication method described as this is a comparative analytical performance study, not a diagnostic accuracy study relying on human interpretation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No, an MRMC comparative effectiveness study was not done. This is an in-vitro diagnostic (IVD) device for laboratory testing, not an AI-powered diagnostic tool for human readers. Therefore, the concept of "human readers improving with AI vs. without AI assistance" does not apply.

6. Standalone Performance Study:

Yes, a standalone performance study was done implicitly. The STA®-Cephascreen Kit was used "exactly as described by their respective package inserts" to determine APTT values. The study then compared these standalone results to those obtained from the predicate device. The correlation data (r, a, b values) represent the analytical performance of the new device when used independently and compared to an established method.

7. Type of Ground Truth Used:

The "ground truth" for this study is the measurements obtained from the legally marketed predicate device, STA®-C.K.Prest® kit. The goal was to show that the new device produces results comparable to the predicate when measuring the same plasma samples. This is a common approach for demonstrating substantial equivalence for new IVD devices that perform the same function as existing ones.

8. Sample Size for the Training Set:

The document does not mention a "training set." This type of comparative analytical performance study for an IVD device does not typically involve machine learning or AI models requiring a training set in the conventional sense. The device is a reagent kit, not an algorithm that learns from data.

9. How Ground Truth for the Training Set Was Established:

Not applicable, as no training set is mentioned or implied for this type of IVD device study.

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HemosIL SynthASil is a high quality synthetic phospholipid reagent for the in vitro determination of Activated Partial Thromboplastin Time (APTT) in human citrated plasma on IL Coagulation and ELECTRA Systems.

The product is used for the evaluation of the intrinsic coagulation pathway, APTT substitution test and the monitoring of heparin therapy.

HemosIL SynthASil is a high quality synthetic phospholipid reagent for the in vitro determination of Activated Partial Thromboplastin Time (APTT) in human citrated plasma on IL Coagulation and ELECTRA Systems.

The product is used for the evaluation of the intrinsic coagulation pathway, APTT substitution test and the monitoring of heparin therapy.

This document describes the performance data for the HemosIL SynthASil device after optimization of its APTT parameter settings on the ACL Futura and ACL Advance systems. The stated purpose of this submission is to demonstrate substantial equivalence to the predicate device (K953981 HemosIL SynthASil) and to the HemosIL SynthASil reagent run on the ACL TOP system (K033414).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document implicitly uses the performance of the predicate device (K953981 HemosIL SynthASil) and the HemosIL SynthASil on the ACL TOP (K033414) as the acceptance criteria for achieving "improved correlation" and "substantial equivalence." While explicit numerical acceptance criteria are not presented in a table format, the performance data provided aims to demonstrate this correlation.

2. Sample Size Used for the Test Set and Data Provenance

• Precision Test Set: The sample size for the precision study is not explicitly stated as a number of individual samples. It mentions "three levels of control plasma" and "assessed over multiple runs." This implies multiple measurements were taken for each of these three control levels.
• Method Comparison Test Set: For each of the four SynthASil lots, n=93 or n=92 citrated plasma samples were used.
• Data Provenance: The document does not specify the country of origin for the data. The study appears to be prospective in nature, performed to optimize and validate the device settings for regulatory submission. The samples are referred to as "human citrated plasma."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of in-vitro diagnostic device (reagent for APTT determination) does not typically involve human expert interpretation for establishing ground truth in the same way an imaging AI device would. The "ground truth" for the method comparison is the measurement obtained from the predicate device or the ACL TOP system, which are themselves validated instruments. Therefore, there were no human experts establishing ground truth in this context.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is an objective measurement study comparing an optimized device's performance to established methods, not subjective human interpretation requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC study was done. This study concerns the performance of an in-vitro diagnostic reagent and instrument settings, not a device that involves human interpretation of results requiring a comparison of human reader performance with and without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, this is effectively a standalone performance study. The document describes the performance of the HemosIL SynthASil reagent and its optimized settings on the ACL Futura and ACL Advance instruments. The results reported (precision, slope, intercept, r) are direct measurements from the device system without requiring human-in-the-loop analysis. The "algorithm" here refers to the optimized parameter settings and the reagent's performance characteristics.

7. Type of Ground Truth Used

• The ground truth used for the method comparison study was the measurements obtained from a legally marketed predicate device (K953981 HemosIL SynthASil) or an equivalent, legally marketed device (HemosIL SynthASil on the ACL TOP system - K033414). This is a form of "reference standard" or "comparative standard" established by existing, validated medical devices.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI models. Instead, it refers to the "optimization" of APTT parameter settings. While this optimization process would have involved testing and refining these settings on various samples, the specific sample size, type, and method used for this optimization are not detailed in this summary. It's implied that the "optimization" process served a similar purpose to training, but no specific dataset is identified as a training set.

9. How the Ground Truth for the Training Set Was Established

Since there is no explicitly defined "training set" in the context of an AI/ML model, the concept of establishing ground truth for it is not directly applicable here. The "optimization" likely involved iterative adjustments of the parameter settings and testing them against known reference values or comparative measurements (similar to the method comparison's ground truth, but likely a larger or different set of samples used during development) to achieve the desired performance, particularly for correlation with the ACL TOP and predicate devices.

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HemosIL Silica Clotting Time is intended for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems by the use of screening (SCT Screen) and confirmatory (SCT Confirm) reagents sensitized to phospholipid dependent antibodies. For in vitro diagnostic use.

HemosIL Silica Clotting Time is intended for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems by the use of screening (SCT Screen) and confirmatory (SCT Confirm) reagents sensitized to phospholipid dependent antibodies.

Here's a summary of the acceptance criteria and study details for the HemosIL Silica Clotting Time device, based on the provided text:

Acceptance Criteria and Device Performance

Note: The document explicitly states that the device "is substantially equivalent to the commercially available predicate devices (HemosIL LAC Screen and HemosIL LAC Confirm) in performance and intended use." This implies that the acceptance criteria were based on demonstrating comparable performance to these predicate devices rather than pre-defined absolute thresholds, for the correlation and clinical performance metrics. For precision, the reported %CVs fall within generally acceptable ranges for diagnostic assays.

Study Details

1. Sample size used for the test set and the data provenance:

   • Method Comparison Study: 210 citrated plasma samples (120 normals/90 abnormals)
   • Clinical Study: 206 citrated plasma samples (121 normals/85 abnormals)
   • Data Provenance: "in-house study" and "clinical study." The document does not specify the country of origin, but given the manufacturer (Lexington, MA, USA) and the 510(k) submission to the FDA, it is highly probable the studies were conducted within the US or followed US regulatory guidelines. The studies appear to be retrospective as they involved analyzing collected plasma samples.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. The ground truth appears to be based on the results from the predicate devices (HemosIL LAC Screen and HemosIL LAC Confirm) for comparison. The classification of samples as "normals" and "abnormals" for Lupus Anticoagulants would have been based on established clinical diagnostic criteria, likely involving expert interpretation of multiple tests, but this detail is not provided.

3. Adjudication method for the test set:

   • The document does not describe a specific adjudication method. As the primary comparison is against predicate devices, the "ground truth" for the test set is established by the results of those predicate devices.

4. 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. This device is an in-vitro diagnostic (IVD) assay, not an AI-assisted imaging or diagnostic tool that requires human reader interpretation. Therefore, an MRMC study is not applicable.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes. The reported performance metrics (slope, intercept, r, sensitivity, specificity, precision) are for the HemosIL Silica Clotting Time device running on an IL Coagulation System, indicating a standalone (algorithm/device only) performance evaluation. There is no mention of human-in-the-loop performance.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

   • The ground truth for the test sets (both method comparison and clinical) appears to be established by the results obtained from the predicate devices (HemosIL LAC Screen and HemosIL LAC Confirm). Additionally, for the clinical study, it's mentioned that "All known Lupus Anticoagulant samples (n=48) tested as part of this study gave SCT normalized ratios > 1.24," suggesting that a subset of the abnormal samples had a pre-established clinical diagnosis of Lupus Anticoagulant, likely based on a combination of tests and expert consensus.

7. The sample size for the training set:

   • The document does not specify a separate "training set" in the context of machine learning. This is an IVD device, and the development process would involve formulation, optimization, and characterization rather than AI model training. The "in-house study" and "clinical study" are performance validation studies.

8. How the ground truth for the training set was established:

   • Not applicable as there is no mention of a separate training set in the context of an AI/ML model for this IVD device. The development of such a device focuses on reagent formulation and instrument calibration, typically using well-characterized samples and reference methods.

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