(29 days)
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
| Acceptance Criteria | Reported Device Performance (with modified QC frequency) |
|---|---|
| No compromise in device performance or safety due to modified QC frequency (Implicit, derived from the purpose of a Special 510(k) for a QC change and the risk analysis). The essential implicit acceptance criterion for this Special 510(k) is that the change in QC frequency maintains the safety and effectiveness of the device as previously cleared (K093954), meaning its "performance" in terms of clinical utility (semi-quantitative detection of IgG antibodies to CCP as an aid in RA diagnosis) remains unaffected. This would typically be demonstrated by showing that the modified QC procedure effectively controls the process and prevents the release of incorrect results. | The document states: "Based on the conclusion of the risk management report, the modified QC procedure fulfills the requirements of the specifications of the design control process. Therefore, the performance of the modified QC test frequency is substantially equivalent to the current cleared kit." |
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
§ 866.5775 Rheumatoid factor immunological test system.
(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).