Search Results

CRYOcheck Chromogenic Factor VIII is for clinical laboratory use in the quantitative determination of factor VIII activity in 3.2 % citrated human plasma. It is intended to be used in identifying factor VIII deficiency and as an aid in the management of hemophilia A in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor VIII is used for determination of FVIII activity and contains the following four components, packaged in glass vials and provided frozen to preserve the integrity of the components:

• Reagent 1: Bovine FX and a fibrin polymerization inhibitor, with activators and stabilizer.
• Reagent 2: Human FIIa, bovine FIXa, calcium chloride and phospholipids.
• Reagent 3: FXa substrate containing EDTA and a thrombin inhibitor.
• Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

In the first stage of the chromogenic assay, test plasma (containing an unknown amount of functional FVIII) is added to a reaction mixture comprised of calcium, phospholipids, human purified thrombin and FIXa, and bovine FX (Reagent 1 and Reagent 2). This mixture swiftly activates FVIII to FVIIIa, which works in concert with FIXa to activate FX. When the reaction is stopped, FXa production is assumed to be proportional to the amount of functional FVIII present in the sample. The second stage of the assay is to measure FXa through cleavage of a FXa-specific peptide nitroanilide substrate (FXa Substrate). P-nitroaniline is produced, giving a color that can be measured spectrophotometrically by absorbance at 405 nm.

Based on the provided FDA 510(k) Clearance Letter, the device in question is the CRYOcheck Chromogenic Factor VIII. This document details the clearance of a modified version of an existing device, emphasizing the differences from the previous version regarding interference claims and recovery of Factor VIII replacement therapies.

Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for each performance claim in a quantified manner (e.g., "Interference must be less than X%"). Instead, it reports the limits of non-interference found in their studies, implying these served as the de facto acceptance criteria. For the Factor VIII replacement therapy recovery, the acceptance criterion appears to be "accurate evaluation" across a range of concentrations, with specific over/under recovery noted.

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

• Interference Studies: Plasma samples were "spiked with possible interferents," and "10 replicates were tested alongside 10 replicates of the corresponding blank matrix control." The total number of individual patient samples from which this plasma was derived is not specified, nor is the country of origin. The study design implies a prospective spiking experiment in a laboratory setting.
• Recovery of Factor VIII Replacement Therapy: "Congenital FVIII deficient plasma was spiked with 14 FVIII replacement therapies at seven concentrations." The number of individual patient plasma units or lots of deficient plasma used is not specified. The study design implies a prospective spiking experiment in a laboratory setting.

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

N/A. This is an in vitro diagnostic device for quantitative determination of factor VIII activity, not an AI/imaging device requiring expert human readers for ground truth generation. The ground truth for these studies is established by the known concentrations of spiked interferents or FVIII replacement therapies, and the intrinsic properties of the FVIII deficient plasma.

4. Adjudication Method for the Test Set

N/A. As this is a quantitative in vitro diagnostic device, an adjudication method in the context of human expert review of imaging or clinical data is not applicable. The results are measured spectrophotometrically.

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

No, an MRMC study was not done. This type of study is relevant for AI imaging devices where human readers interpret medical images with and without AI assistance. This document describes an in vitro diagnostic device.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, this entire submission describes the standalone performance of the CRYOcheck Chromogenic Factor VIII assay. The device itself performs the quantitative determination of FVIII activity, entirely without a "human-in-the-loop" once the sample is loaded and the assay run according to protocol.

7. The Type of Ground Truth Used

• Interference Studies: The ground truth was the known concentration of the spiked interferent (e.g., Hemoglobin, Intralipid, Bilirubin, etc.) added to plasma samples, and the corresponding blank matrix control.
• Recovery of Factor VIII Replacement Therapy: The ground truth was the known concentration of the spiked FVIII replacement therapy added to congenital FVIII deficient plasma at various concentrations.

8. The Sample Size for the Training Set

N/A. This document describes an in vitro diagnostic assay based on chromogenic principles, not an AI/ML algorithm that requires a "training set" in the computational sense. The device's components (reagents, diluent buffer) and their interaction define the assay, which is then validated through performance studies.

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

N/A. See point 8. The "ground truth" for developing and optimizing such a chromogenic assay would stem from extensive biochemical research, characterization of reagents, and titrations against known standards, which is inherent in the development of any diagnostic assay, but not referred to as a "training set" or "ground truth establishment" in the AI/ML context.

Ask a specific question about this device

HemosIL Chromogenic Factor IX is an automated assay for the photometric, quantitative determination of factor IX activity in 3.2% citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series in the laboratory setting by a healthcare professional. HemosIL Chromogenic Factor IX is indicated for use on patients when identifying factor IX deficiency or measuring factor IX activity from patients on replacement therapy. For adult population only. For prescription use only.

Factor IX activity in a patient's plasma is determined using a chromogenic method, in which human factor IX is activated by human factor XIa, and, when formed, factor IXa activates human factor X in the presence of human factor VIII, calcium and phospholipid. The amount of factor Xa generated is proportionate to the factor IX activity and is determined from the hydrolysis of a chromogenic factor Xa substrate. Results are determined by comparing a chromogenic signal to a calibration curve.

Here's a breakdown of the acceptance criteria and the studies that demonstrate the device's performance, based on the provided FDA 510(k) summary for the HemosIL Chromogenic Factor IX:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a separate table. However, it presents performance characteristics that implicitly serve as success metrics for the device's substantial equivalence. I've extrapolated these based on the study findings.

Ask a specific question about this device

In-vitro diagnostic automated assay for the quantitative determination of the von Willebrand antigen (VWF:Ag) in human plasma collected from venous blood samples in 3.2% sodium citrated tubes on the SYSMEX® CS-2500 analyzer.

As an aid used in the evaluation of patients aged 4 weeks and older with suspected or confirmed von Willebrand factor disorders and intended for prescription use.

Results of this test should always be interpreted in conjunction with the patient's medical history, clinical presentation and other laboratory findings.

The vWF Ag is an immunoturbidimetric assay for the quantitative, WHO-standardized determination of von Willebrand factor (VWF) antigen concentration.

The vWF Aq kit consist of a Latex Reagent (4 x 2 mL) which is a suspension of small polystyrene particles (latex) coated with rabbit anti-human VWF antibodies. The Reagent Diluent (4 x 4 mL) is provided within the kit which is a solution containing glycine. The Reagent Diluent is intended for dilution of the Latex Reagent. The vWF Ag kit is completed by the Buffer (4 x 5 mL) which is a glycine buffer. All components contain sodium azide (

Here's an analysis of the acceptance criteria and study details for the vWF Ag device, based on the provided text:

Acceptance Criteria and Device Performance

The document doesn't explicitly state "acceptance criteria" as a single, consolidated table with pass/fail values. Instead, it details performance characteristics established through various studies. I will present the reported device performance for several key metrics:

Study Details

2. Sample Sizes and Data Provenance

• Measuring Interval (LoQ): Five independent low-analyte plasma pools.
• Measuring Interval (Linearity): Not explicitly stated, but "a dilution series was prepared using a high plasma sample pool and a low plasma sample pool to equal 12 different dilutions."
• Specificity (Interference): "Individual native samples with and without interferent" for paired-difference experiments. "Single native plasmas" for Rheumatoid factors. The number of samples per interferent testing is not specified.
• Reference Interval:
  • Blood group O: n = 147
  • Blood group non-O: n = 159
  • Blood group independent: n = 306
  • Data Provenance: Three clinical study sites in the United States. The study involved apparently healthy subjects.
• Pediatric Population Measurements:
  • Blood group O: n = 21
  • Blood group non-O: n = 26
  • Total pediatric (independent of ABO blood group): n = 47
  • Data Provenance: "healthy pediatric subjects".
• Precision/Reproducibility:
  • External Reproducibility (Multicenter): Three (3) external sites in the USA (Sites 1, 2, and 3). Test samples included three plasma pools and three control materials. Each site used 5 days, 2 runs/day, 3 replicates/run (3x5x2x3).
  • Internal Precision (Single Site, Germany - Reagent Variability): One (1) site in Germany. 20 days, 2 runs/day, 2 replicates/run (20x2x2) with 3 different reagent lots.
  • Internal Precision (Single Site, Germany - Calibrator Variability): One (1) site in Germany. 20 days, 2 runs/day, 2 replicates/run (20x2x2) with 3 different calibrator lots.
  • Internal Precision (Single Site, Germany - Instrument Variability): One (1) site in Germany. 5 days, 2 runs/day, 4 replicates/run (5x2x4) on 3 SYSMEX® CS-2500 analyzers.
  • Data Provenance: Mixed (USA and Germany), all prospective measurements for the study.
• Method Comparison:
  • Site 1 (Germany): N = 107
  • Site 2 (United States): N = 115
  • Site 3 (United States): N = 117
  • Overall (Combined Sites): N = 339
  • Data Provenance: One external site in Germany (Site 1) and two external sites in the United States (Site 2 and Site 3). The samples tested "ensured the intended use population was tested". This implies a mix of patient samples. Retrospective or prospective nature is not explicitly stated but generally for method comparison, collected clinical samples are used.

3. Number of Experts and Qualifications (for Ground Truth)

The document describes in-vitro diagnostic assay performance, which typically relies on laboratory measurements rather than expert human interpretation of images or clinical findings where "ground truth" and "experts" as in radiology studies would be directly relevant.

• For the "Reference Interval" and "Pediatric Population" studies: These likely involved general medical professionals or phlebotomists for sample collection, and laboratory technicians for running the assays. The "ground truth" here is the biological sample itself and the reference standard used (WHO standard for calibration traceability). No "experts" in the sense of adjudicating findings (e.g., radiologists) were explicitly mentioned.

4. Adjudication Method (for Test Set)

Not applicable. This is an in-vitro diagnostic assay, not a device requiring human interpretation of results requiring adjudication for a test set. The performance is assessed based on quantitative measurements against predefined analytical performance metrics and comparison to a predicate device.

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

No. This is an in-vitro diagnostic device (an assay), not an imaging or diagnostic AI system that aids human readers. The document details a method comparison study between the proposed device and a predicate device, which is a different type of comparative effectiveness.

6. Standalone Performance (i.e., algorithm only without human-in-the-loop performance)

Yes, the studies reported are for the standalone performance of the vWF Ag assay on the SYSMEX® CS-2500 analyzer. This is an automated assay, meaning it operates without human-in-the-loop performance for result generation. Interpretations of historical context or other lab findings are mentioned as necessary in conjunction with the test results, but the test itself is standalone.

7. Type of Ground Truth Used

• Measuring Interval, Specificity, Precision/Reproducibility: The "ground truth" for these analytical performance studies is based on:
  • Known concentrations in prepared samples (e.g., dilutions from plasma pools, spiked samples with interferents).
  • Reference materials (e.g., control materials, calibrators).
  • WHO Standard (reagents traceable to WHO 6th International Standard Factor VIII / Von Willebrand Factor (07/316)).
• Reference Interval & Pediatric Population: The "ground truth" is derived from empirically measuring VWF:Ag levels in a defined population of "apparently healthy subjects" using the device itself.
• Method Comparison: The "ground truth" for comparison is the performance of the legally marketed predicate device (STA® - Liatest® VWF:Ag on the STA R Max® analyzer).

8. Sample Size for the Training Set

Not applicable. This document describes the performance of a VWF Ag assay, which is an immunoturbidimetric test, not an AI/ML algorithm that requires a training set in the conventional sense. The "training" for such a system would involve optimizing the assay's chemical reagents and instrument parameters, which is part of the development process but not disclosed as a distinct "training set" of data.

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

Not applicable, as there's no explicitly defined "training set" for an AI/ML algorithm. The assay's analytical performance and calibration are established using reference materials and pooled samples with known or established values, as described in point 7.

Ask a specific question about this device

CRYOcheck Chromogenic Factor IX is for clinical laboratory use in the quantitative determination of factor IX activity in 3.2% citrated human plasma. It is intended to be used in identifying factor IX deficiency and as an aid in the management of hemophilia B in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor IX is used for determination of FIX activity and contains the following four components, packaged in vials, and provided frozen to preserve the integrity of the components:
Reagent 1: Human FVIII, human FX, bovine FV and a fibrin polymerization inhibitor.
Reagent 2: Human FXIa, human FII, calcium chloride and phospholipids
Reagent 3: FXa Substrate containing EDTA and a thrombin inhibitor.
Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

The provided text describes the performance of the CRYOcheck Chromogenic Factor IX device. Here's a breakdown of the acceptance criteria and the study that proves the device meets these criteria, based on the information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with pass/fail thresholds for each performance characteristic. Instead, it presents study results and concludes that the device performed effectively and demonstrates substantial equivalence. However, we can infer some criteria from the performance data presented.

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

• Multi-Reagent Lot Precision: 6 samples (1 normal reference control, 2 abnormal reference controls, 3 patient plasma samples).
• Multi-Reagent Lot Site to Site Reproducibility: 6 samples (1 normal reference control, 2 abnormal reference controls, 3 patient plasma samples).
• Linearity/Assay Reportable Range: 14 sample dilutions.
• Reference Interval: 128 normal, ostensibly healthy individuals.
• Shelf-Life Stability: Not specified, but likely involved multiple reference controls and patient plasma samples at each time point.
• In-Use Stability: Not specified, but involved multiple reference controls and patient plasma samples.
• Detection Limit (LoB): 4 blank plasma samples from individuals with severe congenital hemophilia B.
• Detection Limit (LoD): 4 plasma samples with low FIX activity from congenital hemophilia B donors.
• Detection Limit (LoQ): 4 plasma samples with low FIX activity from congenital hemophilia B donors.
• Interferences: Not specified, but likely involved spiked plasma samples.
• Recovery of FIX Replacements: Congenital FIX deficient plasma spiked with 7 FIX replacement therapies at 7 concentrations.
• Method Comparison Studies: 368 human plasma samples. These samples were from normal ostensibly healthy individuals, patients with von Willebrand disease, patients with congenital and acquired hemophilia A and B, and patients on recombinant factor IX treatments.
• Sample Integrity: 65 plasma samples.

Data Provenance: The document does not explicitly state the country of origin for the patient or donor samples. The studies involve both internal and external sites for reproducibility and method comparison. The mention of "congenital hemophilia B donors" and "patients with von Willebrand disease, and congenital and acquired hemophilia A and B" suggests the use of patient samples, implying a clinical or diagnostic context. The studies are retrospective in nature as they involve testing existing plasma samples.

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

For the studies described, the "ground truth" for Factor IX activity is established by:

• Reference controls: These are quality control materials with known or assigned values for FIX activity.
• Patient plasma samples: Their FIX activity is determined either by the device itself (for precision and reproducibility) or by a "comparator method" or "validated laboratory developed chromogenic factor IX assay" (for method comparison and LoQ studies).
• Spiked samples: For linearity, interference, and recovery studies, known amounts of FIX or interfering substances are added to samples to create a controlled "ground truth."
• Congenital FIX deficient plasma: For LoB, LoD, and recovery studies, plasma from individuals with a known severe deficiency serves as a baseline.

The document does not mention specific "experts" in the context of radiologists or similar roles establishing ground truth through consensus. Instead, the ground truth is based on:

• Established assay methods: The comparator method and the validated laboratory developed chromogenic factor IX assay are implicitly considered accurate for determining FIX activity. The qualifications of the personnel running these assays are not individually listed but are assumed to be trained laboratory professionals.
• Reference materials: Reference controls have assigned values.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (like 2+1 or 3+1) is typically relevant for studies where human expert interpretation is compared, e.g., in medical image analysis. In this context of an in vitro diagnostic device for quantitative determination in plasma, such an adjudication method is not described or applicable. The "ground truth" is based on the results of the reference methods, reference materials, and defined sample preparations.

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 type of study is not relevant for an in vitro diagnostic device like the CRYOcheck Chromogenic Factor IX, which directly measures a biomarker rather than assisting human readers in interpreting complex data like medical images. The device itself is the "reader" providing a quantitative result.

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

Yes, the studies presented are all standalone (algorithm only) performance assessments for the CRYOcheck Chromogenic Factor IX device. The device itself performs the quantitative determination of factor IX activity. The results are generated by the instrument (IL ACL TOP Series or TOP 50 Series Instruments) based on the reagents and the plasma sample, without human interpretative input in the output. Human operators are involved in running the tests, but not in interpreting the quantitative output in a way that typical human-in-the-loop AI studies would assess.

7. The Type of Ground Truth Used

The ground truth used in these studies includes:

• Assigned values of reference controls: For precision and reproducibility.
• Results from a "comparator device" or "validated laboratory developed chromogenic factor IX assay": For method comparison and limit of quantitation. These are considered gold standards for FIX activity measurement.
• Known concentrations in spiked samples: For linearity, interference, and recovery studies.
• Known characteristics of congenital FIX deficient plasma: For detection limits and recovery studies.
• Plasma samples from "normal, ostensibly healthy individuals": For establishing reference intervals.

This primarily falls under the category of established assay methods and reference materials.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. The CRYOcheck Chromogenic Factor IX is an in vitro diagnostic assay, not an AI/ML algorithm that requires training data. Its performance is based on chemical and enzymatic reactions, and its parameters are established through conventional analytical validation studies like those described.

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

As there is no "training set" in the AI/ML sense for this device, this question is not applicable. The device's operational parameters and performance are intrinsically defined by its design, chemical components, and the analytical validation tests presented.

Ask a specific question about this device

Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

The VWF:Ag kit is a latex particle enhanced immunoturbidimetric assay to quantify VWF:Ag in plasma. When a plasma containing VWF:Ag is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of VWF:Ag in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

The provided text describes a Special 510(k) submission for the HemosIL von Willebrand Factor Antigen assay. This submission focuses on a modification to the reagent's open vial stability claim, reducing it from 3 months to 14 days, rather than introducing a new AI/ML device or significant performance changes. Therefore, many of the requested categories related to AI/ML device performance, ground truth, and expert evaluation are not directly applicable.

Here's an analysis based on the provided text, focusing on the relevant sections for acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size: Not specified in the provided text. The text only mentions "testing."
• Data Provenance: Not specified in the provided text.
• Retrospective or Prospective: Not specified.

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. This submission concerns a chemical reagent's stability, not an AI/ML device requiring expert ground truth for interpretation. The "ground truth" here is the chemical performance of the reagent over time.

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

Not applicable. Adjudication methods are relevant for subjective interpretations, typically in diagnostic imaging or similar fields. This study assesses objective chemical stability.

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

Not applicable. This is not an AI/ML device or a diagnostic interpretation study involving human readers.

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

Not applicable. This is not an AI/ML diagnostic algorithm. The study assesses the standalone performance of the reagent's stability.

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

The "ground truth" for this study is the measured performance characteristics of the HemosIL von Willebrand Factor Antigen reagent (e.g., accuracy, precision, linearity) after being opened and stored for various durations up to 14 days, compared to its performance when fresh or within its original 3-month stability claim. The study aims to demonstrate that the reagent's performance remains acceptable throughout the 14-day open-vial period.

8. The sample size for the training set

Not applicable. There is no "training set" as this is not an AI/ML model being developed. The study is a stability test.

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

Not applicable. Refer to point 8.

Summary of the Study:

The study described is an open vial stability study for the HemosIL von Willebrand Factor Antigen reagent. The purpose was to provide data to support a change in the labeled open vial stability claim from 3 months to 14 days.

• Study Design: The study was likely a prospective laboratory study where the reagent was opened, stored at 2-8°C, and then tested at various time points (e.g., day 0, day 7, day 14) to assess its performance.
• Methodology: The testing was performed in accordance with the established CLSI EP25-A guideline, which provides guidance for evaluating reagent stability. This guideline would specify how to conduct the study, what performance parameters to measure (e.g., accuracy, precision, linearity), and acceptance criteria.
• Acceptance Criteria for the Study: While not explicitly listed in quantitative terms, the acceptance criteria would dictate the permissible deviation in performance (e.g., % bias, % CV) of the open and stored reagent compared to a freshly opened reagent or a reference measurement, over the 14-day period. The text states "Testing verified all acceptance criteria were met," implying these criteria were predefined and successfully achieved.
• Conclusion: The study demonstrated that the reagent maintained its defined performance specifications for 14 days after opening when stored at 2-8°C, thus supporting the modified insert claim.

Ask a specific question about this device

Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

The VWF:Ag kit is a latex particle enhanced immunoturbidimetric assay to quantify VWF:Ag in plasma. When a plasma containing VWF:Ag is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of VWF:Ag in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

The provided document is a 510(k) Summary for the HemosIL von Willebrand Factor Antigen device. It describes a Special 510(k) submission rather than a traditional premarket notification that would typically include substantial new performance data. The core of this submission is a modification to a limitation/interference claim regarding Rheumatoid Factor (RF) rather than a broader study proving overall device performance against new acceptance criteria.

Therefore, the requested information, particularly regarding a comprehensive study with a test set, expert adjudication, MRMC studies, and standalone performance for an AI/algorithm-based device, is not present in this document. This submission pertains to an in-vitro diagnostic (IVD) assay that measures a biological marker, not an AI-powered diagnostic device.

However, I can extract the relevant information from the document regarding the acceptance criteria related to the modified claim and the "study" (which in this context refers to the basis for the change, here being a literature reference and internal design control activities rather than a new clinical trial).

Here's an attempt to answer based on the provided document, while clarifying what information is missing due to the nature of this particular 510(k) submission:

Acceptance Criteria and Device Performance for HemosIL von Willebrand Factor Antigen (K200033) - Modifed Rheumatoid Factor Interference Claim

This 510(k) submission is a Special 510(k), indicating a minor change to an already cleared device. The "acceptance criteria" and "study" are specifically focused on the modified claim regarding Rheumatoid Factor interference, rather than a broad re-evaluation of the device's overall performance. No new clinical study was conducted for this specific submission to prove general device performance. Instead, the modification is based on internal design control activities and a literature reference.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criterion for this specific modification is the non-interference within a certain concentration range of Rheumatoid Factor (RF). The "reported device performance" reflects a change in the claimed non-interference level.

Note on "Acceptance Criteria" for a Special 510(k): For this type of submission, the primary acceptance criterion is that the modified device remains substantially equivalent to the predicate device and that the change does not introduce new questions of safety or effectiveness. For the specific change (RF interference), the acceptance is based on the rationale provided (literature reference). No specific quantitative performance metric (e.g., accuracy, sensitivity, specificity) for the RF non-interference claim is explicitly stated, other than the new 50 IU/mL threshold being deemed acceptable.

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

• Test Set Sample Size: Not applicable. The document explicitly states: "Performance data are unnecessary since the current Rheumatoid Factor claim in the HemosIL von Willebrand Factor Antigen insert is being replaced with a limitation and a supporting literature reference." This indicates that a dedicated new test set for this specific change was not used for performance validation.
• Data Provenance: Not explicitly stated as new data was not generated. The basis for the change is a "supporting literature reference."

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

• Not applicable. There was no new test set requiring expert ground truth establishment for this specific change.

4. Adjudication Method for the Test Set

• Not applicable. No new test set requiring adjudication was used.

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

• Not applicable. This device is an in-vitro diagnostic assay, not an AI-assisted diagnostic tool that would typically involve human readers.

6. Standalone Performance Study (Algorithm Only)

• Not applicable. This device is an in-vitro diagnostic assay. The concept of "standalone performance" typically applies to AI algorithms operating independently of human interpretation.

7. Type of Ground Truth Used

• For the modified RF interference claim: The "ground truth" for the new claim (non-interference up to 50 IU/mL) is based on a "supporting literature reference" combined with internal design control activities and possibly previous knowledge/studies that led to the revised understanding of RF interference. No new direct "ground truth" (e.g., from pathology, clinical outcomes, or expert consensus on new data) was established for this specific special 510(k).

8. Sample Size for the Training Set

• Not applicable. This is an IVD assay, not an AI/machine learning algorithm that requires a training set.

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

• Not applicable. No training set was used.

Summary of Key Takeaway from the Document:

This 510(k) submission (K200033) is a Special 510(k) for the HemosIL von Willebrand Factor Antigen. The purpose is to modify the product insert's "Limitations/Interfering substances" section concerning Rheumatoid Factor interference. The submission states that no new performance data was generated or deemed necessary for this change because it relies on existing knowledge and a literature reference. Therefore, the detailed requirements for a study proving device performance (especially for an AI/algorithm) are not met by this particular regulatory filing, as it pertains to a different type of device and a very specific, limited modification.

Ask a specific question about this device

CRYOcheck Chromogenic Factor VIII is for clinical laboratory use in the quantitative determination of factor VIII activity in 3.2% citrated human plasma. It is intended to be used in identifying factor VIII deficiency and as an aid in the management of hemophilia A in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor VIII is used for determination of FVIII activity and contains the following four components, packaged in glass vials and provided frozen to preserve the integrity of the components:
Reagent 1: Bovine FX and a fibrin polymerization inhibitor, with activators and stabilizers.
Reagent 2: Human FIIa, human FIXa, calcium chloride and phospholipids.
Reagent 3: FXa substrate containing EDTA and a thrombin inhibitor.
Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

The CRYOcheck Chromogenic Factor VIII device is intended for the quantitative determination of Factor VIII (FVIII) activity in human plasma to identify FVIII deficiency and aid in Hemophilia A management.

Here's an analysis based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the successful outcomes of various studies, aligning with CLSI guidelines and demonstrating performance comparable to the predicate device. Specific numerical acceptance criteria were not explicitly stated as pass/fail thresholds in the document, but the reported performance values are presented as the fulfillment of these criteria.

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

• Precision Study: One normal and two abnormal reference controls, and five patient plasma samples (representing very low, mid, normal, and high FVIII activity). Each sample was measured in duplicate, twice a day for 20 days (total 80 replicates per sample per lot) with 3 lots of the device. Data provenance is internal (as it's an internal study).
• Reproducibility Study: One normal and two abnormal reference controls, and three patient plasma samples (representing very low, normal, and high FVIII activity). Each sample was measured in triplicate, twice a day for 5 days at each of 3 sites with 3 lots of the device. Data provenance includes one internal and two external sites, but specific countries are not mentioned beyond "Canada" for the submitter. This appears to be prospective data collection for the study.
• Linearity/Assay Reportable Range Study: Fifteen sample dilutions created by combining high FVIII plasma (260%) with congenital FVIII deficient plasma (0%). Each level was tested in quadruplicate. Data provenance is internal (as it implies an internal study).
• Reference Interval Study: One hundred and twenty ostensibly healthy individuals $\geq$ 18 years. Data provenance is not specified beyond "citrated plasma samples collected from". This appears to be prospective data collection.
• Shelf-Life Stability Study: Six plasma samples representing low to normal FVIII activity levels. Three lots of the device were tested at various time points up to 37 months (13 months completed). Data provenance is internal.
• In-Use Stability Study: Six plasma samples representing low to normal FVIII activity levels. Three lots of the device were tested at various time points. Data provenance is internal.
• Detection Limit (LoB/LoD/LoQ) Studies:
  • LoB: Four blank plasma samples from individuals with severe congenital hemophilia A.
  • LoD: Four plasma samples with low FVIII activity from congenital hemophilia A donors.
  • LoQ: Aliquots of four plasma samples with low FVIII activity from congenital hemophilia A donors.
    All samples for LoB/LoD were measured in triplicate over five days using three lots of the device. For LoQ, samples were tested in triplicate on five different days at an external laboratory. Data provenance for LoB/LoD/LoQ samples is from individuals with hemophilia A.
• Interference Studies: Plasma samples spiked with possible interferents. Ten replicates of each spiked sample and 10 replicates of corresponding blank matrix control were tested. Data provenance is internal.
• Method Comparison Studies: Three hundred and eighteen human plasma samples from normal individuals, patients with congenital or acquired hemophilia A, and various types of von Willebrand disease. Samples were distributed across three sites. Data provenance spans "normal ostensibly healthy individuals and from patients". This appears to be prospective data collection.
• Sample Integrity Study: Forty-six plasma samples. Data provenance is not further specified. This appears to be prospective data collection at two external sites.

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

For this in vitro diagnostic device, "ground truth" is typically established by reference methods or accepted clinical classifications rather than expert consensus on individual images or cases.

• For studies like Precision, Reproducibility, Linearity, Stability, and Detection Limits, the "ground truth" for the FVIII activity levels in controls and calibrators would be established by the manufacturer's internal characterization methods, traceable to international standards if applicable (though not explicitly stated as such for FVIII activity). The expertise would lie in clinical chemistry, hematology, and laboratory medicine for the development and validation of these reference materials and methods. No specific number or qualification of experts is mentioned for these.
• For the Reference Interval Study, the ground truth is derived from the statistical distribution of FVIII activity in a population of ostensibly healthy individuals. This doesn't involve individual expert ground-truthing but rather statistical analysis.
• For the Method Comparison Study, the ground truth for FVIII activity was established by a comparator device, Coatest SP FVIII (K042576), used at a central reference laboratory. The "experts" in this context are the trained laboratory personnel performing the reference method.
• For sample selection in studies involving "congenital hemophilia A donors" or "patients with congenital or acquired hemophilia A and various types of von Willebrand disease," the diagnosis (which forms part of the "ground truth" for classifying these samples) would have been made by medical professionals (e.g., hematologists) based on standard clinical and laboratory diagnostic criteria. No specific number or qualifications are given.

4. Adjudication Method for the Test Set

Adjudication methods like "2+1" or "3+1" are typically used for subjective diagnostic tasks, often involving image interpretation or clinical reviews. Since the CRYOcheck Chromogenic Factor VIII is a quantitative assay for FVIII activity, the "adjudication method" is the quantitative measurement itself, often with replicates and statistical analysis, as detailed in the study designs (e.g., "in duplicate," "in triplicate"). No expert adjudication in the traditional sense is described or expected for this type of device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are primarily for evaluating the impact of a new diagnostic tool on the diagnostic performance of human readers, typically with subjective assessments. This device is a quantitative in vitro diagnostic, not a tool for human reading in the conventional sense.

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

Yes, the device operates as a standalone algorithm (assay) measuring FVIII activity. The performance studies described (Precision, Reproducibility, Linearity, Reference Interval, Stability, Detection Limits, Interferences, Method Comparison, Sample Integrity) all represent the performance of the device itself, without human-in-the-loop diagnostic interpretation as part of its core function, other than trained laboratory personnel operating the instrument and interpreting numerical output.

7. The Type of Ground Truth Used

The ground truth used for these studies varies by the specific test:

• Reference materials and controls: For precision, linearity, and detection limit studies, the ground truth for FVIII activity levels is based on established values of these materials, likely traceable to international standards or well-characterized internal standards.
• Healthy population data: For the reference interval, the ground truth for "normal" FVIII activity is derived from a statistically representative healthy population.
• Comparator device: For the method comparison study, the ground truth was established by the predicate device, Coatest SP FVIII (K042576).
• Clinical diagnosis: For studies involving patient samples (e.g., hemophilia A, von Willebrand disease), the ground truth for their disease status would be based on clinical diagnosis by medical professionals.

8. The Sample Size for the Training Set

The document describes performance studies (validation tests) for the device. It does not provide information on a "training set" in the context of machine learning. This is because the device is a chemical assay, not an AI/ML-based diagnostic system that would require a training set to develop its model.

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

As no training set is mentioned or applicable for this type of chemical assay device, this question is not relevant based on the provided information.

Ask a specific question about this device

The CRYOcheck FVIII Inhibitor Kit is for clinical laboratory use in conjunction with a Factor VIII activity assay to enable the performance of a modified Nijmegen-Bethesda assay using 3.2% citrated human plasma. It enables the determination of a functional FVIII inhibitor titer to aid in the clinical management of congenital hemophilia A in individuals aged 2 years or older. For in vitro diagnostic use.

The FVIII Inhibitor Kit is used in the CDC modification of the Nijmegen-Bethesda assay and contains the following components:
Imidazole Buffered Pooled Normal Plasma (IB-PNP): Pooled normal plasma from a minimum of twenty donors with a factor VIII activity value of 95-113% and buffered with imidazole to a pH of 7.3 – 7.5.
Imidazole Buffered Bovine Serum Albumin (IB-BSA): A 4% BSA solution buffered with imidazole to a pH of 7.3-7.5.
Negative Factor VIII Inhibitor Control: Pooled normal plasma from a minimum of five donors buffered with HERES to a pH of 6.2-8.2
Positive Factor VIII Inhibitor Control: HEPES buffered (pH 6.2-8.2) immunodepleted FVIII deficient plasma to which anti-human FVIII antibodies have been added.

The document provided describes the performance characteristics and studies for the CRYOcheck FVIII Inhibitor Kit, rather than an AI/ML-driven medical device. Therefore, a direct mapping to all the requested criteria for AI/ML device acceptance (such as MRMC studies, number of experts for ground truth, adjudication methods, and training set details) is not possible.

However, I can extract and present the information relevant to the device's performance and the studies conducted to demonstrate its effectiveness, aligning with the spirit of the acceptance criteria for a diagnostic kit.

Device: CRYOcheck™ FVIII Inhibitor Kit

Intended Use: For clinical laboratory use in conjunction with a Factor VIII activity assay to enable the performance of a modified Nijmegen-Bethesda assay using 3.2% citrated human plasma. It enables the determination of a functional FVIII inhibitor titer to aid in the clinical management of congenital hemophilia A in individuals aged 2 years or older. For in vitro diagnostic use.

Acceptance Criteria and Reported Device Performance

Since this is an in-vitro diagnostic kit and not an AI/ML device, the "acceptance criteria" are related to standard analytical performance characteristics. The table below summarizes the key performance metrics and the reported results.

• Negative Plasma Sample: SD 0.1 BU/mL (29.0% CV)
• Low Plasma Sample: 8.2% CV
• Mid Plasma Sample: 8.3% CV
• High Plasma Sample: 8.4% CV |
  | Reproducibility (Multi-Reagent Lot Site to Site) | - Kit Negative Control: SD 0.1 BU/mL (422.7% CV) - Kit Positive Control: 16.0% CV - Negative Plasma Sample: SD 0.1 BU/mL (28.4% CV) - Low Plasma Sample: 10.6% CV - Mid Plasma Sample: 8.3% CV - High Plasma Sample: 13.2% CV
  (Pooled 3-Site Data) The results demonstrated a pooled reproducibility of ≤16% CV for the positive samples and 0.1 BU/mL SD for the negative plasma sample. |
  | Linearity/Assay Reportable Range | Linearity Range: 0.2 to 1402.9 BU/mL. |
  | Shelf-Life Stability | Supported a 12-month shelf-life stability claim when stored at

Ask a specific question about this device

For the quantitative determination of free protein S antigen in human plasma collected from venous blood samples in 3.2% sodium citrate tubes on the Sysmex® CS-5100 analyzer.

As an aid in the diagnosis of protein S deficiency in patients who are suspected of free protein S deficiency. The performance of this device has not been established in neonate and pediatric patient populations.

The INNOVANCE® Free PS Ag assay is an immunoturbidimetric assay. The reagent kit consists of two components. One component (Reagent) contains polystyrene particles coated with two different monoclonal antibodies both specific for free protein S. This latex reagent aggregates when mixed with samples containing free protein S. The degree of aggregation is directly proportional to the concentration of free protein S in the test sample and is detected turbidimetrically via the increase in turbidity.

The provided document describes the Siemens Healthcare Diagnostics Products GmbH's INNOVANCE Free PS Ag device (K181525) and its performance data in support of its substantial equivalence to a predicate device.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a single table of "acceptance criteria" against which all performance metrics are directly compared. Instead, it discusses various studies with implicit acceptance criteria (e.g., successful verification of LoQ, fulfillment of predetermined criteria for Passing-Bablok regression). I'll compile a table based on what can be inferred for key performance characteristics.

Ask a specific question about this device

IL Hemosil. von Willebrand Activity is an in vitro diagnostic automated immunolurbidometric assay for the quantitative determination of von Willebrand activity in human citrated plasma on IL Coagulation Systems.

Not Found

The provided document is a 510(k) premarket notification letter from the FDA regarding a medical device called "HemosIL von Willebrand Activity." This document is a regulatory approval letter and indications for use, not a study report or clinical trial summary. Therefore, it does not contain the detailed information necessary to answer the questions about acceptance criteria, device performance, study design, or ground truth establishment.

The document indicates that the device is an in vitro diagnostic automated immunoturbidometric assay for the quantitative determination of von Willebrand activity in human citrated plasma. However, it does not provide any specific performance metrics, acceptance criteria, or details of a study that proves the device meets such criteria.

To answer your questions, I would need access to the actual 510(k) submission document or a summary of the clinical performance data, which is not present in this regulatory letter.

Ask a specific question about this device