Search Results

The ADVIA Centaur® anti-CCP IgG (aCCP) assay is for in vitro diagnostic use in the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum or plasma (K2-EDTA and lithium heparin) using the ADVIA Centaur XP system. Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criteria diagnostic process, encompassing both clinical and laboratory-based assessments.

Quality Control:
The ADVIA Centaur® Anti-CCP IgG (aCCP) quality control material is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur aCCP assay using the ADVIA Centaur systems.

Master Curve Material (MCM):
The ADVIA Centaur® Anti-CCP IgG (aCCP) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur aCCP assay.

The ADVIA Centaur aCCP assay is a fully automated, two-step immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-human lgG as the Lite Reagent. The Solid Phase consists of biotinylated CCP coupled to streptavidin which is then coated onto magnetic latex microparticles.

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

Device Name: ADVIA Centaur® Anti-CCP IgG (aCCP) Assay

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate, quantitative table derived from a pre-defined standard (like a predicate device's performance). Instead, it compares the performance of the new device (ADVIA Centaur aCCP assay) to a predicate device (ARCHITECT Anti-CCP Assay) for several characteristics and implies that similar performance constitutes meeting the criteria for substantial equivalence. I will reconstruct a table showing the implied acceptance criteria (based on the predicate's performance or general expectations for such an assay) and the reported performance.

2. Sample Sizes and Data Provenance:

• Test Set (Clinical Performance):
  • Method Comparison Study: 253 samples (143 confirmed positive for RA, and 110 samples where other auto-antibodies may be present). Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but it is a clinical study.
  • Clinical Sensitivity and Specificity Study: 767 patient samples.
    • 307 confirmed-positive RA subjects.
    • 460 non-RA subjects with potentially cross-reacting conditions (22 subgroups).
    • Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective).
• Training Set: Not explicitly mentioned for this type of in vitro diagnostic assay. Immunoassays are generally calibrated and validated, not "trained" in the machine learning sense. The "training" in this context would likely refer to the development and optimization of the assay reagents and parameters.

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

• For RA Confirmation: "307 confirmed-positive RA subjects that were classified according to the American College of Rheumatology criteria." This implies expert clinical diagnosis based on established criteria, but the specific number and qualifications of individuals making these diagnoses are not provided.
• For Non-RA Subjects: "22 subgroups of non-RA subjects (n=460) with potentially cross-reacting conditions." This also implies clinical diagnosis by experts, but details are not provided.
• For Autoantibody Presence (Method Comparison): "110 samples where other auto-antibodies may be present." This suggests expert determination of autoantibody status, but details are not given.

4. Adjudication Method for the Test Set:

Not applicable or explicitly stated as this is an immunoassay, not an imaging device requiring expert adjudication of reader interpretations. The ground truth for clinical sensitivity and specificity is based on clinical diagnosis (American College of Rheumatology criteria for RA).

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging devices or AI tools that assist human readers in interpretation. The ADVIA Centaur anti-CCP IgG assay is a standalone diagnostic laboratory test.

6. Standalone Performance:

Yes, standalone performance was done. The entire document describes the standalone performance of the ADVIA Centaur aCCP assay in various analytical and clinical studies (linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, interference, precision, specimen collection comparison, clinical concordance with a predicate, and clinical sensitivity/specificity against clinical diagnosis). The results presented are solely the performance of the algorithm/assay without human intervention in the result determination.

7. Type of Ground Truth Used:

• Analytical Performance: Based on reference materials, spiked samples with known concentrations, or established analytical methods.
• Clinical Performance (Sensitivity/Specificity):
  • RA Diagnosis: American College of Rheumatology criteria (clinical diagnosis) for RA.
  • Non-RA Status: Clinical diagnosis of various conditions (22 subgroups).
• Method Comparison: The predicate device (ARCHITECT Anti-CCP Assay) results were used as a reference point for agreement.

8. Sample Size for the Training Set:

Not applicable in the machine learning sense. For an immunoassay, "training" is typically assay development, which involves optimizing reagents and parameters. The document doesn't specify sample sizes used during the development phase.

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

Not applicable. For an immunoassay, ground truth during development would involve well-characterized samples (e.g., confirmed positive/negative for CCP antibodies, known concentrations) to optimize the assay's performance characteristics. Specific details on this are not provided in the summary.

Ask a specific question about this device

QUANTA Flash CCP3 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-CCP3 antibodies in human serum. The presence of anti-CCP3 antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of rheumatoid arthritis.

QUANTA Flash CCP3 Calibrators are intended for use with the QUANTA Flash CCP3 chemiluminescent immunoassay for the determination of IgG anti-CCP3 antibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.

QUANTA Flash CCP3 Controls are intended for use with the QUANTA Flash CCP3 chemiluminescent immunoassay for quality control in the determination of IgG anti-CCP3 antibodies in human serum.

The QUANTA Flash CCP3 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash CCP3 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.

Synthetic cyclic citrullinated peptide is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspended using resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. Serum samples are diluted by the BIO-FLASH with system rinse in a small disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(II)coproporphyrin in sodium hydroxide solution) and Trigger 2 (ureahydrogen peroxide in sodium chloride solution) are added to the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-CCP3 antibodies bound to the corresponding beads.

For quantitation, the QUANTA Flash CCP3 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash CCP3 Calibrators. Based on the results obtained with the two Calibrators included in the Calibrator Set (sold separately), an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU) from the instrument signal (RLU) obtained for each sample.

The QUANTA Flash CCP3 kit contains the following materials:

One (1) QUANTA Flash CCP3 Reagent Cartridge One (1) vial of Resuspension buffer One (1) Transfer pipette

The QUANTA Flash CCP3 reagent cartridge contains the following reagents for 100 determinations:

• a. CCP3 coated paramagnetic beads, lyophilized.
• b. Assay buffer - colored pink, containing Tris-buffered saline, Tween 20, protein stabilizers and preservatives.
• C. Tracer IgG - Isoluminol labeled anti-human IgG antibodies in buffer, containing protein stabilizers and preservative.

The QUANTA Flash CCP3 Calibrators kit contains two vials of Calibrator 1 and two vials of Calibrator 2:

QUANTA Flash CCP3 Calibrators:

• QUANTA Flash CCP3 Calibrator 1: Two (2) barcode labeled tubes containing 0.7 mL prediluted, ready to use reagent. Calibrators contain human antibodies to CCP3 in stabilizer and preservative.

• QUANTA Flash CCP3 Calibrator 2: Two (2) barcode labeled tubes containing 0.7 mL prediluted, ready to use reagent. Calibrators contain human antibodies to CCP3 in stabilizer and preservative.
  The QUANTA Flash CCP3 Controls kit contains two vials of Negative Control and two vials of Positive Control:

QUANTA Flash CCP3 Controls:

• QUANTA Flash CCP3 Negative Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to CCP3 in stabilizer and preservative.
• QUANTA Flash CCP3 Positive Control: Two (2) barcode labeled tubes containing 0.5 mL, ready to use reagent. Controls contain human antibodies to CCP3 in stabilizer and preservative.

The provided text describes the QUANTA Flash® CCP3 chemiluminescent immunoassay and its associated calibrators and controls. The study focuses on establishing the substantial equivalence of the new device to a predicate device (QUANTA Lite® CCP3 IgG ELISA) and demonstrating its analytical and clinical performance characteristics.

Here's an analysis of the acceptance criteria and study as requested:

1. Table of Acceptance Criteria and Reported Device Performance

The document details numerous acceptance criteria for various analytical and clinical performance characteristics. Below is a summary of some key areas:

Ask a specific question about this device

The IMMULITE 2000 Anti-CCP IgG assay is an in vitro diagnostic immunoassay for the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA or lithium heparin) on the IMMULITE 2000 system. Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criteria diagnostic process, encompassing both clinical and laboratory-based assessments.

The IMMULITE 2000 Anti-CCP IgG Calibration Verification Material (CVM) is for in vitro diagnostic use, as a control for calibration verification of the IMMULITE 2000 Anti-CCP IgG assay on the IMMULITE 2000 system.

The IMMULITE 2000 Anti-CCP IgG assay consists of the following components:

• Anti-CCP IgG bead pack coated with cyclic citrullinated peptide . (CCP) antigen
• Anti-CCP IgG reagent wedge containing bovine calf intestine . conjugated to a monoclonal murine anti-human IgG antibody
• Anti-CCP IgG adjustors, low and high, containing lyophilized . human serum with IgG reactive to CCP
• Anti-CCP IgG controls, negative and positive, containing human . serum
• . Autoantibody sample diluent containing protein/buffer matrix

The IMMULITE Anti-CCP IgG Calibration Verification Material consists of one set of four vials, containing low, intermediate and high levels of lyophilized human serum with IgG reactive to cyclic citrullinated peptide (CCP), in buffer with preservative, plus an anti-CCP-free sample.

The IMMULITE® 2000 Anti-CCP IgG Assay is an in vitro diagnostic immunoassay for the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP). It is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information.

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

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state acceptance criteria in a single, consolidated table. However, performance characteristics are reported, which implicitly define what the manufacturer considers acceptable for their device to perform as intended and to demonstrate substantial equivalence to the predicate device. Based on the performance characteristics presented, the following can be inferred as the "acceptance criteria" through the demonstrated results.

Ask a specific question about this device

The BioPlex® 2200 Anti-CCP kit is a multiplex flow immunoassay intended for the semiquantitative detection of IgG antibodies to Cyclic Citrullinated Peptide (CCP) in human serum or plasma (EDTA and sodium heparin). Detection of CCP antibodies is used as an aid in the diagnosis of rheumatoid arthritis and should be used in conjunction with other clinical findings and laboratory results.

The BioPlex® 2200 Anti-CCP kit is intended for use with the Bio-Rad BioPlex® 2200 System.

The BioPlex® 2200 Anti-CCP kit uses multiplex flow immunoassay, a methodology that permits simultaneous detection and identification of antibodies in a single tube. "CCP IgG" is an acronym for the detection of IgG antibodies to Cyclic Citrullinated Peptide.

One (1) population of fluorescent beads is coated with antigens associated with cyclic citrullinated peptide (CCP). The BioPlex® 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel and incubates the mixture. After a wash cycle to remove unbound antibody, anti-human IgG conjugated to phycoerythrin is added and the mixture is incubated at 37°C. Excess conjugate is removed in another wash cycle and the washed beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the assay and control beads is determined by the fluorescence embedded in the surface of the bead and the amount of immobilized antibody is determined by the fluorescence of the anti-IgG reporter conjugate. Raw data are calculated in relative fluorescence intensity (RFI).

Three additional dyed beads, Internal Standard Bead (ISB), Serum Verification Bead (SVB) and Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction and the absence of significant non-specific binding. Refer to the BioPlex® 2200 System Operation Manual for more information.

The instrument is calibrated using a set of six (6) distinct calibrator vials, supplied separately by Bio-Rad Laboratories.

Here's an analysis of the provided text regarding the BioPlex® 2200 Anti-CCP Kit, focusing on the acceptance criteria and the study conducted to prove it meets them.

Based on the provided document, this 510(k) is a Special 510(k) for a device modification, not an initial clearance for a new device. The modification is very specific: changing the frequency of Reagent Pack Quality Control (QC) testing from "once per pack and per day" to "once per day or per new reagent pack lot." Therefore, the "study" described is primarily focused on demonstrating that this change in QC frequency does not negatively impact the device's performance or safety.

Acceptance Criteria and Reported Device Performance

While specific performance metrics (e.g., sensitivity, specificity, precision, accuracy) are not explicitly provided or re-evaluated in this modification document, the conclusion of "substantial equivalence" regarding the performance of the modified QC test frequency implies that the critical performance characteristics of the assay itself (as established by the original K093954 clearance) are maintained. The risk analysis (FMEA) would have justified that the reduced QC frequency does not introduce unacceptable errors. |

Study Details Pertaining to this Special 510(k)

The document describes a Risk Analysis rather than a traditional clinical or analytical performance study with patient samples. The "study" here is a design control activity and risk management exercise to justify the change in QC frequency.

1. Sample size used for the test set and the data provenance: Not applicable in the context of this specific Special 510(k) submission. No clinical or analytical test set with biological samples is described for this modification. The "test set" in this context refers to the parameters and outcomes evaluated in the FMEA.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The "ground truth" for the FMEA would be the expected performance characteristics of the device and the potential failure modes in a manufacturing/quality control context, as understood by Bio-Rad's internal experts (e.g., quality engineers, design engineers, regulatory affairs, manufacturing personnel). These qualifications are not specified in the public summary.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable. This refers to consensus among experts, which isn't described for the FMEA process in this summary. The FMEA process itself is a systematic analysis.

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: Not applicable. This device is an in vitro diagnostic (IVD) kit, not an AI-assisted diagnostic imaging or interpretation tool.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. This is an IVD kit used with an instrument, not a standalone algorithm.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.): For this specific modification, the "ground truth" is implied to be the established safety and effectiveness of the predicate device (BioPlex® 2200 Anti-CCP Kit, K093954) and the expected control afforded by the QC procedure. The FMEA evaluates potential deviations from this "ground truth" (i.e., failure modes) and their impact.

7. The sample size for the training set: Not applicable. This is not an AI/ML device, and no "training set" is mentioned for this modification.

8. How the ground truth for the training set was established: Not applicable.

Summary of the "Study" (Design Control Activities) for this Modification

The "study" conducted for this Special 510(k) primarily comprised:

• Failure Mode and Effect Analysis (FMEA): This systematically identified potential risks and impacts associated with the change in QC frequency.
  • Purpose: To "facilitate, capture, and quantify potential impacts of false positive or negative patient results."
  • Metric: Risk Priority Number (RPN) – a quantitative measure combining severity, occurrence, and detection of potential risks.
  • Outcome: Specific mitigations were recommended if the RPN exceeded a chosen threshold.
• Risk Management Report: Concluded that the modified QC procedure "fulfills the requirements of the specifications of the design control process." This implies that the FMEA demonstrated that the proposed change does not introduce unacceptable risks or compromise the device's performance.

The conclusion of these activities was that "the performance of the modified QC test frequency is substantially equivalent to the current cleared kit." This statement is the direct evidence that the acceptance criterion (maintaining safety and effectiveness despite the QC change) was met.

Ask a specific question about this device

The Axis-Shield Anti-CCP test is a semi-quantitative/qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate). Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA), and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments. For in vitro diagnostic use.

The Axis-Shield Anti-CCP device contains the following components: a microtitre plate with 8 x 12-well breakapart strips coated with purified synthetic cyclic citrullinated peptide, in a resealable foil pack with desiccant; ready to use calibrators (diluent with or without IqG antibodies against CCP2); positive and negative assay controls (human plasma with or without IgG antibodies against CCP); ready-to-use reference control; goat anti-human IgG horseradish peroxidase conjugate: TMB substrate; sample diluent (5x) wash buffer (10x); ready-to-use stop solution.

Here's an analysis of the provided text, extracting the requested information about acceptance criteria and the supporting study:

The provided text describes a 510(k) submission for the Axis-Shield Anti-CCP device, claiming substantial equivalence to the DIASTAT™ Anti-CCP Assay. The primary study presented is a method comparison and concordance analysis between the two devices.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific numeric thresholds (e.g., "concordance must be >95%"). Instead, it presents the achieved performance and implies that this level of performance was considered "substantially equivalent" to the predicate.

• Axis-Shield anti-CCP AUC: 0.910 (95% CI: 0.881 to 0.940)
• DIASTAT™ anti-CCP AUC: 0.903 (95% CI: 0.871 to 0.934) (using suggested cut-off of 5.0 U/mL) |

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

• Sample Size for Test Set: 514 samples.
• Data Provenance: Not explicitly stated (e.g., country of origin, demographics of participants). The document only mentions using "human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate)." It's a clinical performance study comparing two assays, implying human samples. The study appears to be retrospective as it involves running existing banked samples on both devices for comparison.

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

The ground truth in this study is based on the results of the predicate device (DIASTAT™ Anti-CCP Assay). This is a comparison study, not a study aiming to establish the accuracy against a gold standard for Rheumatoid Arthritis diagnosis directly. Therefore, there were no human experts establishing a separate ground truth for the test set beyond the predicate device's results.

4. Adjudication Method for the Test Set

The concept of an adjudication method (like 2+1 or 3+1) is typically relevant when establishing a ground truth based on multiple expert opinions. Since the ground truth for comparison was the predicate device's results, no expert adjudication method was used for the test set. The devices were likely run independently and their results compared.

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

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (ELISA assay), not an imaging-based AI system that requires human interpretation. Therefore, there is no "human readers improve with AI vs. without AI assistance" effect size to report.

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

• Yes, the study primarily demonstrates the standalone performance of the Axis-Shield Anti-CCP device by comparing its output (antibody levels) directly to the predicate device's output. ELISA assays are inherently standalone tests; human involvement is in performing the lab procedure, not in interpreting the raw results in a way that would classify it as "human-in-the-loop" for the algorithm itself.

7. The Type of Ground Truth Used

The "ground truth" for the comparison study was the results obtained from the legally marketed predicate device (DIASTAT™ Anti-CCP Assay). While the intended use notes the test is an "aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information," the study itself does not directly use a definitive RA diagnosis (e.g., pathology, long-term outcomes, or consensus clinical diagnosis) as its ground truth for evaluation. Instead, it assumes the predicate's results are acceptable and compares the new device's results to them.

8. The Sample Size for the Training Set

The document does not provide information on a training set for the Axis-Shield Anti-CCP device. ELISA assays are typically developed through biochemical optimization and validation, not through machine learning training on a 'training set' in the conventional AI sense. The "clinical performance" study described is a validation or test set study for the finished device.

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

As there is no mention of a training set in the context of an algorithm requiring ground truth, this information is not applicable and not provided in the document.

Ask a specific question about this device

The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

The CCPoint® test is a colloidal gold based lateral flow immunoassay. Reactive cyclic citrullinated peptides are immobilised as a discrete line on a porous membrane located in the test zone.

The detection reagent, consisting of colloidal gold particles conjugated to anti-human IgG, is deposited within the device onto the conjugate pad.

In the assay procedure, a sample of serum or plasma is added to the sample port. A blood cell separation membrane transfers the sample fluid onto the porous membrane. After a short incubation running buffer is added to the buffer port. This buffer mobilizes the colloidal gold particles from the conjugate pad. The gold particles and the sample move by capillary force across the membrane.

If the sample contains anti-CCP antibodies they will bind to the peptide-antigens and a red line will appear in the test zone (marked T). If the sample does not contain any anti-CCP antibodies no line will appear. With any sample a red control line should appear in the control zone (marked C). The control ensures that the coated colloidal gold is still active.

Here's a breakdown of the acceptance criteria and the study details for the CCPoint® kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission primarily focuses on demonstrating substantial equivalence to a predicate device (Immunoscan RA anti-CCP test kit) and providing clinical performance metrics. Explicit "acceptance criteria" for the CCPoint® beyond achieving substantial equivalence and acceptable clinical performance are not explicitly stated as numerical targets in the same way one might see for a completely novel device claim. However, the reported performance serves as the basis for the FDA's substantial equivalence determination.

Implied Acceptance Criteria / Performance Benchmarks (derived from the predicate comparison and clinical performance):

2. Sample Size and Data Provenance (Test Set)

• Sample Size for Predicate Comparison (Table 1a): 1062 frozen retrospective sera.
  • 606 from RA patients
  • 456 apparently healthy blood donors
• Sample Size for Predicate Comparison (Table 1b, subset): 399 samples (extracted from Table 1a, specifically those in the range of 15-1600 U/mL with the ELISA).
• Sample Size for Clinical Sensitivity/Specificity (Table 2 & Specificity Tables): 1815 frozen retrospective sera with clinical characterization.
  • 596 patients with clinically defined RA
  • 456 Blood donors
  • 187 non-RA arthritis
  • 43 Psoriatic arthritis
  • ... (various other disease/control groups listed in the document, totaling 1815)
• Data Provenance: "frozen retrospective sera". The country of origin is not explicitly stated in the provided text.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. It mentions "Patients with clinically defined RA" and "frozen retrospective sera with clinical characterisation," suggesting that clinical diagnoses and medical records were used to categorize samples. However, there's no detail on who made or confirmed these diagnoses, nor any adjudication process by experts specifically for the study.

4. Adjudication Method (Test Set)

No adjudication method (e.g., 2+1, 3+1) is mentioned or described for establishing the ground truth of the test set. The clinical characterization appears to be based on pre-existing diagnoses in the retrospective sera.

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

No MRMC comparative effectiveness study was done. The device is a visually read rapid diagnostic test, and the performance study described is an agreement study against a predicate device and a clinical sensitivity/specificity study against clinical diagnoses. It does not evaluate human readers' improvement with or without AI assistance.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone performance study was done. The CCPoint® is a visually read, qualitative rapid lateral flow test. The performance data presented (percent agreements, sensitivity, specificity) reflects the output of the device itself (the presence or absence of a red line) when interpreted visually according to its intended use instructions by trained laboratory professionals. There is no separate "algorithm" being assessed independent of the visual interpretation of the test result; the visual interpretation is the algorithm's output.

7. Type of Ground Truth Used

• For Predicate Comparison (Tables 1a, 1b): The ground truth was established by the results of the predicate device, Immunoscan RA anti-CCP ELISA.
• For Clinical Sensitivity and Specificity (Table 2 and subsequent specificity tables): The ground truth was "clinical characterization" or "clinically defined RA" for the RA patient group, and diagnostic categories (e.g., "Blood donors," "non-RA arthritis," "Systemic collagen disease") for the control and disease groups. This indicates clinical diagnoses/outcomes information as the ground truth.

8. Sample Size for the Training Set

The document does not mention a separate "training set" or "validation set" in the context of machine learning. This is a diagnostic device comparison and clinical performance study, not an AI/machine learning model development. Therefore, there's no reported sample size for a training set in that sense. The samples used for the performance evaluation are considered a test set.

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

As there is no mention of a traditional "training set" for an AI/ML model, this question is not applicable. The device's mechanism is a biochemical immunoassay, not a learning algorithm that requires a training phase.

Ask a specific question about this device

The BioPlex™ 2200 Anti-CCP Kit is a multiplex flow immunoassay intended for the semi-quantitative detection of IgG antibodies to Cyclic Citrullinated Peptide (CCP) in human serum and EDTA or heparinized plasma. Detection of CCP antibodies may be used as an aid in the diagnosis of rheumatoid arthritis and should be used in conjunction with other clinical information.

The BioPlex 2200 Anti-CCP kit is intended for use with the Bio-Rad BioPlex 2200 system.

The BioPlex™ 2200 Anti-CCP Calibrator Set is intended for the calibration of the BioPlex 2200 Anti-CCP Reagent Pack.

The BioPlex™ 2200 Anti-CCP Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 instrument and BioPlex 2200 Anti-CCP Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 Anti-CCP Control Set has not been established with any other Anti-CCP assay.

The BioPlex™ 2200 Anti-CCP IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. "CCP IgG" is an acronym for the detection of IgG antibodies to Cyclic Citrullinated Peptide.

One (1) population of fluorescent beads is coated with antigens associated with cyclic citrullinated peptide (CCP). Three populations of fluorescent beads function as assay controls (see below). The BioPlex™ 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel and incubates the mixture at 37°C. After a wash cycle to remove unbound antibody, anti-human IgG conjugated to phycoerythrin is added and the mixture is incubated at 37°C. Excess conjugate is removed in another wash cycle and the washed beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the assay and control beads is determined by the fluorescence embedded in the surface of the bead and the amount of immobilized antibody is determined by the fluorescence of the anti-IgG reporter conjugate. Raw data are calculated in relative fluorescence intensity (RFI).

Three additional dyed beads, Internal Standard Bead (ISB), Serum Verification Bead (SVB) and Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction and the absence of significant non-specific binding. Refer to the BioPlex™ 2200 System Operation Manual for more information.

The instrument is calibrated using a set of six distinct calibrator vials, supplied separately by Bio-Rad Laboratories. The six vials representing six different analyte concentrations are used for calibration. The cut-off value and assignment of the calibrators are determined by performing concordance and Receiver Operator Characteristic (ROC) analysis using Axis-Shield DIAStat Anti-CCP predicate results as the reference. The result for anti-CCP is expressed as arbitrary units (U/mL). Results of 3 U/mL as positive.

The BioPlex 2200 Anti-CCP Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 Anti-CCP Reagent Pack in the clinical laboratory. The Control Set includes a negative and a positive control. The BioPlex Anti-CCP Positive Control is manufactured to give positive results, with values above the cut-off for the analyte. The BioPlex Anti-CCP Negative Control is manufactured to give negative results, with values below the cut-off for the analyte. The recommended frequency for performing quality control is once every 24-hour testing period. Performing quality control is also necessary after each new assay calibration and certain service procedures.

Here's a summary of the acceptance criteria and study details for the BioPlex™ 2200 Anti-CCP Kit, based on the provided 510(k) summary report:

Acceptance Criteria and Device Performance

Study Details

1. Sample Sizes and Data Provenance (Test Set):

   • Precision/Reproducibility:
     • CLSI EP5-A2: 3 panels (serum, EDTA plasma, heparinized plasma), each with 10 samples plus 2 controls. Each panel member was assayed 80 times (2 times in 2 separate daily runs over 20 days).
     • CLSI EP15-A2: 3 panels (serum, EDTA plasma, heparinized plasma), each with 10 samples plus 2 controls. Each panel member was tested in quadruplicate over 5 days (20 replicates).
   • Linearity: 3 high anti-CCP IgG positive patient samples (ranging 241-270 U/mL) and their dilutions, assayed in replicates of four. For onboard dilution, 3 high positive samples for each dilution (1:4, 1:10, 1:100), assayed in replicates of ten.
   • Limit of Detection: Low positive, high negative, and blank samples in replicates of fifty (50).
   • Interfering Substances: Specific substances at various concentrations (e.g., Hemoglobin ≤ 500 mg/dL). Number of samples not explicitly stated for this specific test, but design follows CLSI EP7-A2.
   • Cross-Reactivity: 163 ANA samples and 72 other samples containing potential cross-reactants.
   • Assay Cut-off Determination: 1394 patient samples (177 normal, 504 RF-tested/positive, 82 older, 287 RA, 344 non-RA).
   • Method Comparison: 997 specimens (300 healthy blood donors, 496 diagnosed RA patients, 201 other rheumatic disease patients). 822 samples within the detection range were evaluated.
   • Matrix Comparison: 41 matched sets of serum and plasma (EDTA and heparin) from the same donor, spiked with high positive anti-CCP IgG serum, evaluated in replicates of two.
   • Clinical Sensitivity and Specificity: Same 997 specimens as Method Comparison.
   • Expected Values/Reference Range: 300 apparently healthy donors.
   • Prevalence: 300 apparently healthy blood donors and 300 clinical samples submitted for RF/anti-CCP testing.

   Data Provenance:

   • The 997 specimens for Method Comparison and Clinical Sensitivity/Specificity were purchased from commercial suppliers and were frozen serum.
   • Adjudication for RA diagnosis in these patients was by physician's diagnosis or ICD-9 code 714.0.
   • The CLSI EP15-A2 Reproducibility Study was performed at "one clinical trial site."
   • The report does not specify the country of origin for the data; it implies a single clinical site for some studies. The phrase "purchased from commercial suppliers" for patient specimens suggests retrospective data.

2. Number of Experts and Qualifications (Ground Truth for Test Set):

   • The report does not explicitly state the number of experts or their specific qualifications for establishing the ground truth beyond:
     • For RA patients: "Patients previously diagnosed with RA were selected by either physicians' diagnosis or an ICD-9 code 714.0." This implies a physician's diagnosis as the primary ground truth for RA status.
     • For the assay cut-off, the BioPlex 2200 results were compared against the Axis-Shield DIASTAT anti-CCP predicate assay as the reference for confirming positive or negative status.
   • This is not a traditional "expert consensus" in the sense of multiple radiologists reviewing images, but rather relies on a predicate device and existing clinical diagnoses.

3. Adjudication Method (Test Set):

   • For RA diagnosis (ground truth): "Physicians' diagnosis or an ICD-9 code 714.0" serves as the primary adjudication for RA status for the clinical samples.
   • For assay cut-off determination: "All samples were confirmed positive or negative by the Axis-Shield DIASTAT anti-CCP predicate assay." This indicates the predicate device acted as the gold standard for concordance.
   • No "2+1" or "3+1" expert adjudication method is mentioned.

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

   • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described. This report focuses on the standalone performance of the in vitro diagnostic device (IVD) compared to a predicate IVD, rather than comparing human readers with and without AI assistance. The device is an automated assay, not an AI-based image analysis tool for human readers.

5. Standalone Performance:

   • Yes, the entire study focuses on the standalone performance of the BioPlex™ 2200 Anti-CCP Kit relative to its intended use and a predicate device. The performance characteristics (precision, linearity, LoD, specificity, method comparison, clinical sensitivity/specificity) are all measures of the algorithm/device itself, without human interpretation as part of the primary diagnostic step.

6. Type of Ground Truth Used:

   • Predicate Device Results: For assay cut-off determination and method comparison, the Axis-Shield DIASTAT Anti-CCP predicate immunoassay was used as the reference/ground truth.
   • Clinical Diagnosis: For clinical sensitivity and specificity, the ground truth for "diagnosed RA patients" relied on physicians' diagnosis or ICD-9 code 714.0.
   • Apparent Health Status: For healthy donor groups, "apparently healthy blood donors" formed the negative ground truth.

7. Sample Size for Training Set:

   • The report does not explicitly mention a "training set" in the context of machine learning. This is a traditional IVD device, not an AI/ML-based diagnostic.
   • The calibrators are fundamental to the assay's function and can be considered analogous to a training component. The BioPlex 2200 Anti-CCP Calibrator Set consists of six distinct calibrator vials. The cut-off value and assignment of the calibrators are determined by performing concordance and Receiver Operator Characteristic (ROC) analysis using Axis-Shield DIAStat Anti-CCP predicate results as the reference (as stated in section 2).

8. How Ground Truth for Training Set Was Established:

   • As this is not an AI/ML device with a distinct "training set" in that sense, the concept of ground truth for a training set does not directly apply.
   • For the calibrators, which define the assay's measurement scale and interpretation: "The BioPlex 2200 Anti-CCP Calibrators are assigned relative units from predicate Axis-Shield DIASTAT Anti-CCP Calibrators." BioPlex 2200 Anti-CCP Calibrators are prepared by blending defibrinated and delipidated human plasma units with known anti-CCP IgG activity in a processed human serum matrix. This means the ground truth for calibrator assignment is derived from measurements established by the predicate device and characterized human disease state plasma.

Ask a specific question about this device

The TheraTest EL-anti-CCP/2™ test is intended for use in clinical laboratories as an in vitro diagnostic test for the detection and measurement of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum by enzyme-linked immunosorbent assay (ELISA). It is intended to aid in the diagnosis of Rheumatoid arthritis (RA) in conjunction with other clinical findings and laboratory tests.

Not Found

Based on the provided text, the following information can be extracted regarding the acceptance criteria and the study that proves the device meets them:

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

The provided text is a 510(k) clearance letter from the FDA. It does not contain a table of specific acceptance criteria or detailed reported device performance. The letter states that the FDA "reviewed your Section 510(k) premarket notification... and have determined the device is substantially equivalent... to legally marketed predicate devices." This implies that the device met the performance standards demonstrated by the predicate device(s) in the 510(k) submission, but those specific criteria and performance values are not present in this document.

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

This information is not available in the provided text. The FDA letter is a conclusion of the review, not the detailed submission 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)

This information is not available in the provided text. The device is a "Rheumatoid factor immunological test system," implying its output is a direct measurement, and ground truth would likely be established through clinical diagnosis of Rheumatoid Arthritis, but the specifics are not detailed here.

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

This information is not available in the provided text.

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

The device described is an "ELISA" (enzyme-linked immunosorbent assay) for detecting autoantibodies. This is a laboratory test, not an AI-based imaging or diagnostic tool that would typically involve "human readers" or MRMC studies in the context of improving human performance. Therefore, an MRMC study with human readers and AI assistance is not applicable to this type of device.

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

This refers to the device's performance as a standalone test. The "TheraTest EL-anti-CCP/2TM" is an in vitro diagnostic test, meaning its performance is inherently standalone in the sense that it provides a result (detection and measurement of autoantibodies) without direct human intervention in the assay itself. The indication for use states it is "intended to aid in the diagnosis of Rheumatoid arthritis (RA) in conjunction with other clinical findings and laboratory tests," acknowledging that a physician still interprets the result within a broader clinical picture. The specific performance metrics (e.g., sensitivity, specificity, accuracy) of this standalone test are not provided in the letter, but would have been part of the 510(k) submission.

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

The ground truth for this type of device would likely be the clinical diagnosis of Rheumatoid Arthritis (RA), established by rheumatologists based on a combination of patient symptoms, physical examination, imaging, and other laboratory tests (e.g., ACR/EULAR classification criteria for RA). The device itself measures specific autoantibodies, and its performance would be assessed against this clinical diagnosis. However, the exact methodology for establishing this ground truth is not detailed in the provided text.

8. The sample size for the training set

Given that this is an ELISA diagnostic kit, there isn't typically a "training set" in the machine learning sense. The device's performance is established through validation studies on clinical samples. The sample size used for these validation studies is not available in the provided text.

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

As noted in point 8, the concept of a "training set" in the machine learning context does not directly apply to this type of in vitro diagnostic device. For the clinical validation samples (which would be analogous to a test set in ML), the ground truth would be established by clinical diagnosis of Rheumatoid Arthritis, likely by rheumatologists using established diagnostic criteria. The specifics are not available in the provided text.

Ask a specific question about this device

The Immunoscan CCPlus® test kit is an enzyme-linked immunosorbent assay (ELISA) for qualitative and semi-quantitative determination of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. The analysis should be performed by trained laboratory professionals. "For in vitro diagnostic use".

The Immunoscan CCPlus® test kit is a modification of the Immunoscan RA anti-CCP Test kit, K052133. It is an enzyme-linked immunosorbent assay (ELISA) for qualitative and semi-quantitative determination of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. The analysis should be performed by trained laboratory professionals. "For in vitro diagnostic use".

The wells are coated with Cyclic Citrullinated Peptides. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.

The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase labelled antibodies to human IgG binds to the antibodies in the wells in this second incubation.

After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the colour intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units.

Here's a breakdown of the acceptance criteria and study information for the Immunoscan CCPlus® device, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The Immunoscan CCPlus® device is a modification of the Immunoscan RA anti-CCP Test kit and its performance is compared to this predicate device. The acceptance criteria are implicitly set by demonstrating substantial equivalence to the predicate device, implying that the modified device's performance characteristics should be similar to or better than the predicate's.

Study Information

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

   • Comparative Agreement Study (Immunoscan CCPlus® vs. Predicate):
     • Sample Size: 628 frozen retrospective sera.
     • Data Provenance: 368 samples from RA patients, 260 samples from apparently healthy blood donors. The country of origin is not specified but is likely Sweden, given the manufacturer's location. The data is retrospective.
   • Clinical Sensitivity and Specificity Study (Immunoscan CCPlus®):
     • Sample Size: 1180 frozen retrospective sera.
     • Data Provenance: The origin of these samples is not specified beyond being "frozen retrospective sera with clinical characterisation." The distribution includes 399 patients with clinically defined RA and various control and disease groups. Country of origin not specified; data is retrospective.

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

   • The document describes the use of "clinically defined RA" for the ground truth of RA patients and "apparently healthy blood donors" or "non-RA diseased patients" for controls.
   • It does not specify the number of experts, their qualifications, or the process by which "clinical characterisation" or "clinically defined RA" was established. This suggests that the ground truth was based on pre-existing clinical diagnoses rather than a panel of experts reviewing the cases specifically for this study.

3. Adjudication method for the test set:

   • No adjudication method (e.g., 2+1, 3+1) is mentioned or implied for establishing the ground truth of the clinical samples. The "clinically defined RA" and control groups appear to have pre-determined diagnoses.

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 (ELISA) assay that directly measures antibodies. It does not involve human readers interpreting images or data alongside an AI, so an MRMC study is not applicable. The device provides a quantitative or semi-quantitative result directly.

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

   • Yes, this is a standalone device in the sense that the test results are generated by the assay without real-time human interpretation affecting the output. The assay produces a direct quantitative or semi-quantitative result for anti-CCP antibodies. The results are then used by trained laboratory professionals in conjunction with other clinical findings.

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

   • The ground truth for the clinical sensitivity and specificity study was based on clinical characterization/diagnosis, specifically "clinically defined RA" for the RA group and various diagnosed control groups (e.g., SLE, IBD, blood donors, etc.) for the non-RA groups. This implies a combination of clinical symptoms, other laboratory findings, and possibly imaging, leading to a physician's diagnosis. It is not explicitly stated to be expert consensus, nor pathology or direct outcomes data, but rather an established clinic diagnosis.

7. The sample size for the training set:

   • The document does not specify a training set. This is typical for traditional in-vitro diagnostic assays, which are usually developed using analytical methods and then validated with clinical samples, rather than "trained" in the machine learning sense. The information provided pertains solely to the validation/test sets.

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

   • Since no training set is mentioned for an algorithm, this question is not applicable. For an ELISA kit, development involves optimizing reagents and protocols against known positive and negative samples, but this isn't typically referred to as "training" in the same way as AI/ML.

Ask a specific question about this device

Ask a specific question about this device