(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.
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Bio-Rad Laboratories, Inc Special 510(k): Device Modification BioPlex 2200 MMRV IgG
AUG 2 3 2011
Confidential
BioPlex 2200 MMRV IgG 510(k) Summary
510(k) Number _ K 11/072 _____________________________________________________________________________________________________________________________________________________ : Date Prepared: March 25, 2011
Introduction
Bio-Rad Laboratories hereby submits this Special 510(k) in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. This summary of 510(k) safety and effectiveness information provides detail as a basis for a determination of substantial equivalence for the BioPlex 2200 MMRV IgG.
Submitter name, address and contact
| Submitter | Contact Person |
|---|---|
| Bio-Rad Laboratories, Inc | Juang Wang |
| BioPlex Division | Regulatory Affairs Representative |
| 5500 E. Second Street | Phone: (510)741-4609 |
| Benicia, CA 94510 | Fax: (510)741-4650 |
Device name and Classification
| Product Trade Name | BioPlex 2200 MMRV IgG on the BioPlex 2200 Multi-Analyte Detection System |
|---|---|
| Common Name | Multi-Analyte Detection System – MMRV IgG |
| Classification name | Multiplex immunoassay for measles virus, mumps virus,rubella, and varicella-zoster virus |
| Device Class | Class II |
| Classification Panel | Microbiology |
| Registration Number | 886.3510 |
| Product Code | OPL |
Legally Marketed Predicate Device
BioPlex 2200 MMRV IgG, K091616
Intended Use/Indications For Use
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.
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Bio-Rad Laboratories, Inc Special 510(k): Device Modification BioPlex 2200 MMRV IgG
Confidential
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.
Device Description
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.
Similarities and Differences
Similarities
| Feature | Modified Device |
|---|---|
| Intended Use/Indications For Use | No Change |
| Kit components | No Change |
| Technical Specifications | No Change |
| Fundamental Scientific Technology | No Change |
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Differences
The only difference of the BioPlex 2200 MMRV IgG is to modify OC testing from each reagent pack to once per day as stated in the Instructions For Use (IFU) of the BioPlex 2200 MMRV IgG reagent kit.
| Feature | Modified | Predicate |
|---|---|---|
| Frequency ofReagent Pack QCTesting | QC once per day or per newreagent pack lot | QC once per pack and perday |
Summary of Design Control Activities
A Failure Mode and Effect Analysis (FMEA) was used to facilitate, capture, and quantify potential impacts of Low Signal Pack (LSP) occurrence. The Risk Priority Number (RPN) is a quantitative measure of the combined effects of severity, occurrence, and detection of potential risks. Specific mitigations are recommended that may include changes to the design or formulation if the RPN score exceeds a chosen threshold.
The Design Control Activities include Risk Analysis method to identify the verification and validation activities required, test used and acceptance criteria.
Based on the conclusion of the risk management report, the modified OC 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.
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES.USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Bio-Rad Laboratories, Inc. c/o Mr. Juang Wang Regulatory Affairs Representative BioPlex Division 5500 E. Second Street Benicia. CA 94510
AUG 2 3 2011
Re: K111072
Trade/Device Name: BioPlex 2200 MMRV IgG on the BioPlex 2200 Multi-Analyte Detection System Regulation Number: 21 CFR 866.3510 Regulation Name: Rubella Virus Serological Reagents Regulatory Class: Class II Product Code: OPL, LJB, LJB, LJY, LFY Dated: August 8, 2011 Received: August 16, 2011
Dear Mr. Wang:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the
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Page 2-Mr. Juang Wang
quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Nou, aotopon
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Devices Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication(s) for use
510(k) Number (if known): K111072
Device Name:BioPlex® 2200 MMRV IgG Kit on the BioPlex® 2200 Multi Analyte Detection
System
BioPlex® 2200 MMRV IgG Calibrator Set BioPlex® 2200 MMRV IgG Control Set
Indications for Use:
The BioPlex® 2200 MMRV IgG kit
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.
BioPlex® 2200 MMRV IgG Calibrator Set
The BioPlex® 2200 MMRV IgG Calibrator Set is intended for the calibration of the BioPlex® 2200 MMRV IgG Reagent Pack. -
BioPlex® 2200 MMRV IgG Control Set
The BioPlex® 2200 MMRV IgG Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 instrument and BioPlex 2200 MMRV IgG Reagent Pack in the clinical laboratory. The performance of the BioPlex 2200 MMRV IgG Control Set has not been established with any other Measles, Mumps, Rubella or VZV IgG assays.
For Prescription Use Only (Part 21 CFR 801 Subpart D)
AND/OR Over-the-Counter Use (21 CFR 801 Subpart C)
(Please do not write below this line-Continue on another page if needed)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Sign-Off
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)
Tamera Feldbolz
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K111072
§ 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.