(127 days)
The BioPlex® 2200 MMRV IgG kit is a multiplex flow immunoassay intended for the qualitative detection of IgG antibodies to Measles, Mumps, Rubella and Varicella-zoster virus (VZV) in human serum and EDTA or heparinized plasma.
The BioPlex 2200 MMRV IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.
This kit is intended as an aid in the determination of serological status to Measles, Mumps, Rubella, and VZV. This kit is not intended for use in screening blood or plasma donors.
The performance of this assay has not been established for use in neonatal, pediatrics and immunocompromised patients, or for use at point of care facilities.
The BioPlex 2200 MMRV IgG kit uses multiplex flow immunoassay for simultaneous detection and identification of many antibodies in a single tube. Four (4) different populations of magnetic dyed beads are coated with antigens to identify the presence of IgG class antibodies against Measles. Mumps. Rubella and Varicella-zoster. The BioPlex 2200 System combines an aliquot of patient sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37℃. After a wash cycle, anti-human IgG antibody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector.
The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI). Three additional control beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB), and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum to the reaction vessel, and the absence of significant non-specific binding in serum.
The instrument is calibrated using a set of three (3) distinct calibrator vials, supplied separately by Bio-Rad Laboratories.
The BioPlex 2200 MMRV IgG system is designed to detect IgG antibodies for Measles, Mumps, Rubella, and Varicella-zoster virus (VZV) in human serum and plasma. The acceptance criteria and supporting studies for this device, specifically focusing on the modification of QC testing frequency, are outlined below.
1. Table of Acceptance Criteria and Reported Device Performance
| Feature | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Equivalence of Modified QC Procedure | The modified QC procedure (once per day or per new reagent pack lot) must fulfill the requirements of the specifications of the design control process. | Based on the conclusion of the risk management report and the FMEA, the performance of the modified QC test frequency is considered substantially equivalent to the current cleared kit. |
| Risk Assessment for Low Signal Pack (LSP) Occurrence | Potential impacts of LSP occurrence should be identified, quantified (using Risk Priority Number - RPN), and specific mitigations recommended if the RPN exceeds a chosen threshold. | An FMEA was used, and the modified OC procedure was deemed to fulfill design control requirements, implying that identified risks were adequately addressed or were within acceptable thresholds. |
| Intended Use/Indications For Use, Kit components, Technical Specifications, Fundamental Scientific Technology | No change from the legally marketed predicate device (K091616). | No change. |
2. Sample Size Used for the Test Set and Data Provenance
The provided document does not contain details regarding a specific test set, its sample size, or data provenance. The submission is a Special 510(k) for a modification (QC testing frequency) to an already cleared device, not for the initial clearance of the device itself. The evidence presented focuses on a risk analysis rather than a clinical performance study with patient samples to demonstrate equivalence for the modified aspect.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. The document does not describe a clinical study with a test set requiring expert-established ground truth for performance evaluation of the modified QC procedure. The assessment was based on risk analysis and design control activities.
4. Adjudication Method for the Test Set
Not applicable, as no described test set requiring adjudication of results from clinical samples is present in the document.
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. The BioPlex 2200 MMRV IgG is an in vitro diagnostic (IVD) assay designed for automated detection of antibodies, not an AI-assisted diagnostic tool that involves human reader interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
The BioPlex 2200 MMRV IgG operates as a standalone automated system for detecting antibodies. The original device's performance, which this modification refers to, would have been established as standalone as per the nature of the device. The current submission focuses on a procedural change (QC frequency) rather than re-evaluating the core standalone performance.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
For the original BioPlex 2200 MMRV IgG system, ground truth for establishing performance (sensitivity, specificity) would typically be based on:
- Reference laboratory methods: Comparison with established, validated serological tests (e.g., IFA, EIA) from reference laboratories.
- Clinical status: Correlation with patient vaccination history, known infection status, or immune response.
- Known positive/negative panels: Use of well-characterized serum panels with known antibody status.
However, the provided Special 510(k) document for the modification does not detail the ground truth used for the initial device or for evaluating the impact of the QC frequency change. The current submission relies on a risk assessment rather than a clinical performance study against a ground truth.
8. The Sample Size for the Training Set
Not applicable. This is an in vitro diagnostic device, not an AI/ML model that typically undergoes specific "training" with a dataset in the same way. The development of such assays involves optimization and calibration using characterized samples, but not a "training set" in the context of machine learning.
9. How the Ground Truth for the Training Set Was Established
Not applicable, for the reasons stated in point 8.
§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.