K Number

Device Name

BIOPLEX(R) 2200 25-OH VITAMIN D KIT, BIOPLEX(R) 2200 25-OH VITAMIN D CALIBRATOR SET, AND BIOPLEX(R) 2200 25-OH VITAMIN D

Manufacturer

Bio-Rad Laboratories

Date Cleared

2015-01-09

(254 days)

Product Code

MRG JIT JJX

Regulation Number

862.1825

Intended Use

The BioPlex® 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25-OH Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency. The BioPlex® 2200 25-OH Vitamin D kit is intended for use with the Bio-Rad BioPlex 2200 System. The BioPlex® 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex® 2200 25-OH Vitamin D Reagent Pack. The BioPlex® 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 System and the corresponding BioPlex® 25-OH Vitamin D Reagent Packs in the clinical laboratory. The performance of the BioPlex® 25-OH Vitamin D Control Set has not been established with any other 25-hydroxyvitamin D assays.

Device Description

BioPlex® 2200 25-OH Vitamin D kit includes the following components: - One (1) 10 mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 (< 1.0%) and sodium azide (< 0.1%) as preservatives. - One (1) 10 mL vial of Release Buffer containing 25-OH Vitamin D releasing reagents in citrate and trisodium citrate acid buffer at pH 4.1 and ProClin 950 (<1.0%) as preservative. - One (1) 5 mL vial of Conjugate 1 containing biotinylated 25-OH Vitamin D conjugate and biotinylated anti-human FXIII antibody conjugate (murine) in buffer with protein stabilizers (bovine). ProClin 950 (< 1.0%) and 5-bromo-5nitro-1. 3-dioxane (<0.1%) as preservatives and chemical blockers. - One (1) 5 mL vial of Conjugate 2 containing phycoerythrin conjugated streptavidin (SA -PE) in a buffer comprising protein stabilizers (bovine). ProClin 950 (< 1.0%) and sodium azide (< 0.1%) as preservatives, chemical blockers and detergent (Tween 20). BioPlex® 2200 25-OH Vitamin D Calibrator set contains six (6) 0.5 mL 25-OH Vitamin D vials. Calibrator level 1 contains 25% horse serum without 25-OH Vitamin D. The calibrator levels 2 to 6 are provided in a Vitamin D depleted human serum matrix supplemented with known concentration of 25-hydroxyvitamin D3. All calibrators contain ProClin 950 (≤ 0.3%), sodium benzoate (≤ 0.1%) and 5-bromo-5-nitro-1, 3dioxane (<0.1%) as preservatives. BioPlex® 2200 25-OH Control set contains two (2) 1.5 mL Level 1 and two (2) 1.5 mL Level 2 Control vials, each containing 25-OH Vitamin D in human serum matrix. All controls contain ProClin 950 (< 0.3%), sodium benzoate (< 0.1%) and 5-bromo-5-nitro-1, 3-dioxane (<0.1%) as preservatives. Additional materials required but not supplied include BioPlex® 2200 Sheath Fluid containing Phosphate Buffered Saline (PBS), ProClin 300 (0.03%) and sodium azide (<0.1%) as preservatives; and BioPlex® 2200 Wash Solution containing Phosphate Buffered Saline (PBS) and Tween 20. ProClin 300 (0.03%) and sodium azide (<0.1%) as preservatives.

More Information

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Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

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ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K123660

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay kit and system for measuring vitamin D levels. There is no mention of AI or ML in the intended use, device description, or performance studies. The performance studies focus on traditional analytical validation metrics.

Therapeutic

No
The device is an in vitro diagnostic (IVD) kit used for the quantitative determination of 25-hydroxyvitamin D in human serum to aid in the assessment of vitamin D sufficiency. It does not provide treatment or directly manage a condition, which is characteristic of a therapeutic device.

Diagnostic

Yes

The device is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum, and is used as an aid in the assessment of vitamin D sufficiency, which implies a diagnostic purpose.

SaMD (Software as a Medical Device)

The device description clearly lists multiple physical components including vials of beads, buffers, and conjugates, which are not software. The intended use also describes a flow competitive immunoassay, which is a laboratory test involving physical reagents and equipment.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "quantitative determination of 25-hydroxyvitamin D in human serum" and is used "as an aid in the assessment of vitamin D sufficiency." This involves testing a sample taken from the human body (serum) in vitro (outside the body) to provide information about a physiological state (vitamin D sufficiency).
Device Description: The description details the components of a kit designed to perform a laboratory test on a biological sample.
Performance Studies: The document describes various performance studies (precision, linearity, detection limit, analytical specificity, method comparison) which are typical for IVD devices to demonstrate their analytical performance.
Predicate Device: The mention of a "Predicate Device" (EUROIMMUN 25-OH Vitamin D ELISA) is common in regulatory submissions for IVD devices, indicating a comparison to a previously cleared device.
Intended User/Care Setting: The intended user is a "Clinical laboratory," which is where IVD tests are performed.

All these elements strongly indicate that the BioPlex® 2200 25-OH Vitamin D kit is an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The BioPlex® 2200 25-OH Vitamin D kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex® 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex® 2200 25-OH Vitamin D Reagent Pack.

The BioPlex® 2200 25-OH Vitamin D Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 System and the corresponding BioPlex® 25-OH Vitamin D Reagent Packs in the clinical laboratory. The performance of the BioPlex® 25-OH Vitamin D Control Set has not been established with any other 25-hydroxyvitamin D assays.

Product codes (comma separated list FDA assigned to the subject device)

MRG, JIT, JJX

Device Description

BioPlex® 2200 25-OH Vitamin D kit includes the following components:

One (1) 10 mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead (SVB) in buffer with protein stabilizers (bovine). ProClin 950 ( 125.0 ng/mL.

Detection limit:
Study type: Determined Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) in accordance with CLSI EP17-A2 guideline.
Sample size: Five blank samples for LoB. Six human samples with low levels of 25-OH vitamin D for LoD and LoQ.
Key results:

LoB	LoD	LoQ
0.8	2.5	6.5

Analytical specificity (Interfering Substances):
Study type: Evaluation of potential interference of specific endogenous and exogenous substances in accordance with CLSI EP7-A2 guideline.
Key results: No interference was observed with any of the substances tested if the percent difference is ≤ 10%. Hemoglobin > 150 mg/dL may interfere. Do not use visibly hemolyzed samples.

Analytical specificity (Cross-Reactivity):
Study type: Cross-reactivity study in accordance with CLSI EP17-A2.
Sample size: 2 human serum pools.
Key results: Paricalcitol (Zemplar) has been found to cross-react and interfere with the BioPlex 2200 25-OH Vitamin D assay.

Method comparison with predicate device:
Study type: Method comparison studies following CLSI EP09-A2-IR guideline.
Sample size: 204 human samples (185 unaltered, 19 spiked). Eight samples were excluded from analysis. Total of 196 BioPlex 25-0H Vitamin D results were plotted.
Key results:

Number of Results Analyzed	Slope (95% CI)	Intercept (95% CI)	Correlation Coefficient (r) (95% CI)	Test Range (ng/mL)
196	1.0039 (0.9365 to 1.0712)	-0.2256 (-2.4121 to1.9608)	0.9553 (0.9412 to 0.9661)	BioPlex: 6.6 to 124.9 Comparator: 4.3 to118.1

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

EUROIMMUN 25-OH Vitamin D ELISA, K123660

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1825 Vitamin D test system.

(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.

Summary

Image /page/0/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle. Inside the circle is a stylized image of a caduceus, which is a symbol of medicine. The caduceus is made up of three lines that form the shape of a snake wrapped around a staff.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 9, 2015

BIO-RAD LABORATORIES JUANG WANG REGULATORY AFFAIRS REPRESENTATIVE 5500 E. 2ND STREET BENICIA CA 94510

Re: K14114

Trade/Device Name: BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set, BioPlex® 2200 25-OH Vitamin D Control Set Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: II Product Code: MRG, JJX, JIT Dated: November 25, 2014 Received: November 25, 2014

Dear Juang 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Stayce Beck -S

For :Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

Indications for Use

510(k) Number (if known) K141114

Device Name BioPlex® 2200 25-OH Vitamin D Kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set

Indications for Use (Describe)

The BioPlex® 2200 25-OH Vitamin D kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex® 2200 25-OH Vitamin D Calibrator Set is intended for the BioPlex® 2200 25-OH Vitamin D Reagent Pack.

Type of Use (Select one or both, as applicable)

	Prescription Use (Part 21 CFR 801 Subpart D)
	Over-The-Counter Use (21 CFR 801 Subpart C)

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BioPlex® 2200 25-OH Vitamin D 510(k) Summary

Bio-Rad Laboratories hereby submits this 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 25-OH Vitamin D kit.

510(k) Number:

K141114

Summary Preparation Date:

December 30, 2014

Applicant:

Bio-Rad Laboratories

Contact:

Juang Wang Regulatory Affairs Representative 5500 E. Second Street Benicia, CA 94510 Tel:510-741-4609 FAX: 510-741-3941 Juang wang@bio-rad.com

Purpose for Submission:

New Device

Measurand:

25-hydroxyvitamin D

Type of Test:

Quantitative multiplexed flow immunoassay

Proprietary and Established Names:

BioPlex® 2200 25-OH Vitamin D kit BioPlex® 2200 25-OH Vitamin D Calibrator Set BioPlex® 2200 25-OH Vitamin D Control Set

Regulatory Information:

Regulation section: 21 CFR §862.1825 – Vitamin D test system 21 CFR §862.1150 - Calibrator 21 CFR §862.1660 - Quality Control Material (assayed and unassayed)

Classification:

Class II (Assays, Calibrator) Class I (Controls)

Product code:

MRG, System, Test, Vitamin D JIT, Calibrator, Secondary JJX, Single (specified) Analyte Controls (Assayed and Unassayed)

Panel:

Clinical Chemistry (75)

Intended Use:

1. Intended use(s):
  The BioPlex® 2200 25-OH Vitamin D kit is a flow competitive immunoassay intended for the quantitative determination of 25-hydroxyvitamin D in human serum. The BioPlex 2200 25-OH Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency.

The BioPlex® 2200 25-OH Vitamin D kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex® 2200 25-OH Vitamin D Calibrator Set is intended for the calibration of the BioPlex® 2200 25-OH Vitamin D Reagent Pack.

1. Indication(s) for use: Same as Intended Use
1. Special conditions for use statement(s): For prescription use only
Special instrument requirements: 4. Bio-Rad BioPlex® 2200 System

Device Description:

BioPlex® 2200 25-OH Vitamin D kit includes the following components:

One (1) 10 mL vial of Bead Set containing dyed beads coated with anti-25-OH D antibody (sheep), an Internal Standard bead (ISB), and a Serum Verification bead

(SVB) in buffer with protein stabilizers (bovine). ProClin 950 ( 125.0 ng/mL.

Traceability, Stability, Expected values (controls, calibrators, or methods): c.

Traceability:

The BioPlex 25-OH Vitamin D Calibrators are traceable to internal standards which are determined by UV spectrophotometric analysis using the extinction coefficient of 18,000 mL/mmol/cm at 264 nm wavelength.

The six levels of Master calibrators are manufactured volumetrically from the internal standards into the depleted human serum except level 1 (25hydroxyvitamin D free) in 25% horse serum. The Master calibrators are immediately frozen at 150 mg/dL may interfere. Do not use visibly hemolyzed samples.

Cross-Reactivity:

The study was conducted in accordance with CLSI EP17-A2 using 2 human serum pools at 25-hydroxyvitamin D concentrations of 20 and 35 ng/mL. Nine cross reactants at levels listed below were then spiked into the human serum pools. The spiked and non-spiked samples were then evaluated in replicates of five to calculate the cross reactivity as shown below.

% Cross Reactivity = (spiked vitamin D - non-spiked vitamin D) = Cross reactant concentration × 100%

The results of each potential cross reactant are listed below.

| Cross Reactant | Spiked
Concentration
(ng/mL) | % Cross
Reactivity |
|----------------------------|------------------------------------|-----------------------|
| 25-hydroxyvitamin D2 | 30 | 103% |
| 25-hydroxyvitamin D3 | 30 | 97% |
| Vitamin D2 | 1000 | 0.2% |
| Vitamin D3 | 1000 | 0.0% |
| 1,25-dihydroxyvitamin D2 | 30 | >100% |
| 1,25-dihydroxyvitamin D3 | 30 | 79% |
| 3-epi 25-hydroxyvitamin D3 | 30 | 59% |
| 24,25-dihydroxyvitamin D3 | 20 | 9% |
| Paricalcitol (Zemplar)* | 24 | >100% |

Paricalcitol (Zemplar) has been found to cross-react and interfere with the BioPlex 2200 25-OH Vitamin D assay

High dose hook effect: Not Applicable

f. Assay cut-off:

Not Applicable

2. Comparison studies:

a. Method comparison with predicate device: Method comparison studies were performed following CLSI EP09-A2-IR guideline.
A total of 204 human samples spanning the entire measuring assay range were tested in singlicate on both the BioPlex 2200 25-OH Vitamin D kit and the predicate assay. Of the 204 samples, there were 185 unaltered samples and 19 samples spiked with 25-hydroxyvitamin D3 to supplement the assay range. There are eight (8) samples with values lower or higher than the measuring range of the comparator method not including in the analysis. A total of 196 BioPlex 25-0H Vitamin D results were plotted using weighted Deming regression analysis for all samples spanning the measuring range of both assays. Results of the regression slope, intercept, and coefficient of correlation (r) are summarized in the table below:

| Number of
Results
Analyzed | Slope
(95% CI) | Intercept
(95% CI) | Correlation Coefficient (r)
(95% CI) | Test Range (ng/mL) |
|----------------------------------|------------------------------|-------------------------------|-----------------------------------------|--------------------------------------------------|
| 196 | 1.0039
(0.9365 to 1.0712) | -0.2256
(-2.4121 to1.9608) | 0.9553
(0.9412 to 0.9661) | BioPlex: 6.6 to 124.9
Comparator: 4.3 to118.1 |

b. Matrix comparison: Serum only
1. Clinical studies:
- a. Clinical Sensitivity: Not Applicable
- b. Clinical Specificity: Not Applicable
- c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable

4. Clinical cut-off: Not Applicable

5. Expected values/Reference range:

The Expected Values study was conducted following CLSI C28-A3c guideline.

Two hundred and eighty-seven (287) samples from apparently healthy donors including 160 males ranging in age from 21 to 79 and 127 females ranging in age from 21 to 66 were collected from three regions (North, Central, and South) in the US in spring, summer and winter, including African Americans, Hispanics and Caucasians.

The 287 samples from apparently healthy donors met the following inclusion/exclusion criteria as follows and tested with the BioPlex 25-OH Vitamin D kit in singlicate.

Age from 21 to 90 ●
Roughly 50% female and 50% male
20% from Northern. 20% from Central and 60% from Southern region
40% collected in Spring, 30% in Summer and 30% in Winter
At least 30% African Americans and 30% Caucasians
. 90% not taking Vitamin D supplements and