MAGLUMI 2000 25-OH Vitamin D

K191499 · Shenzhen New Industries Biomedical Engineering Co., Ltd. · MRG · Aug 1, 2019 · Clinical Chemistry

Device Facts

• Record ID: K191499
• Device Name: MAGLUMI 2000 25-OH Vitamin D
• Applicant: Shenzhen New Industries Biomedical Engineering Co., Ltd.
• Product Code: MRG · Clinical Chemistry
• Decision Date: Aug 1, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1825
• Device Class: Class 2

Intended Use

MAGLUMI 2000 25-OH Vitamin D is an in vitro chemiluminescence immunoassay for the quantitative determination of 25-OH Vitamin D in human serum using Maglumi 2000 Fully-auto chemiluminescence immunoassay analyzer. The measurement of 25-OH Vitamin D is to be used as an aid in the assessment of vitamin D sufficiency.

Device Story

MAGLUMI 2000 25-OH Vitamin D is an in vitro diagnostic assay used on the Maglumi 2000 Fully-auto chemiluminescence immunoassay analyzer. It utilizes a two-step competitive chemiluminescence immunoassay (CLIA) principle. Human serum samples are incubated with magnetic microbeads coated with 25-OH Vitamin D monoclonal antibody and a displacing reagent to release 25-OH Vitamin D from binding proteins. After a second incubation with ABEI-labeled 25-OH Vitamin D antigen and a wash cycle, starter reagents are added to trigger a flash chemiluminescent reaction. The resulting relative light units (RLUs) are inversely proportional to the 25-OH Vitamin D concentration. The device is intended for use in clinical laboratory settings by trained personnel. Results assist clinicians in assessing vitamin D sufficiency, potentially guiding patient management for vitamin D deficiency or monitoring.

Clinical Evidence

No clinical diagnostic studies were performed. Evidence consists of analytical bench testing: precision (CLSI EP5-A3), linearity (CLSI EP6-A), interference/cross-reactivity, and limit of detection/quantitation (CLSI EP17-A2). Method comparison against the predicate (N=241) showed a correlation coefficient of 0.9739. Reference range study (N=302) established a 2.5th–97.5th percentile range of 9.99–49.3 ng/mL.

Technological Characteristics

Two-step competitive chemiluminescence immunoassay (CLIA). Reagents: magnetic microbeads coated with 25-OH Vitamin D monoclonal antibody, ABEI-labeled 25-OH Vitamin D antigen, acidic displacing buffer. Measuring range: 5.371-143 ng/mL. Connectivity: automated analyzer (Maglumi 2000). Traceability: ID-LC-MS/MS to NIST RMP 2972.

Indications for Use

Indicated for the quantitative determination of total 25-hydroxyvitamin D in human serum to aid in the assessment of vitamin D sufficiency in adult populations.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Liaison 25 Oh Vitamin D Total Assay (K112725)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo has the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

August 1, 2019

Shenzhen New Industries Biomedical Engineering Co., Ltd % Joe Shia. Director LSI International Inc 504E Diamond Ave., Suite F Gaithersburg, MD 20877

Re: K191499

Trade/Device Name: MAGLUMI 2000 25-OH Vitamin D Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: Class II Product Code: MRG Dated: June 2, 2019 Received: June 6, 2019

Dear Joe Shia:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) k191499

Device Name MAGLUMI 2000 25-OH Vitamin D

#### Indications for Use (Describe)

MAGLUMI 2000 25-OH Vitamin D is an in vitro chemiluminescence immunoassay for the quantitative determination of 25-OH Vitamin D in human serum using Maglumi 2000 Fully-auto chemiluminescence immunoassay analyzer. The measurement of 25-OH Vitamin D is to be used as an aid in the assessment of vitamin D sufficiency.

| Type of Use (Select one or both, as applicable) | |
|---------------------------------------------------------------|-------------------------------------------------------------|
| <div> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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### K191499

#### 510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is submitted in accordance with the
requirements of 21 CFR 807.92

- 1. Date: July 26, 2019
- 2. Submitter: Shenzhen New Industries Biomedical Engineering Co., Ltd. No.16, Jinhui Road, Pingshan New District, Shenzhen China 518122
- 3. Contact person: Joe Shia LSI International Inc. 504 East Diamond Ave., Suite F Gaithersburg, MD 20878 Telephone: [phone] Fax: [phone] Email:shiajl(@yahoo.com
- 4. Device Name: MAGLUMI 2000 25-OH VITAMIN D

Classification: Class II (assay)

| Product Code | CFR # | Product Name |
|--------------|----------|-----------------------|
| MRG | 862.1825 | Vitamin D Test System |

- 5. Predicate Devices:
K 112725, DiaSorin LIAISON 25-OH VITAMIN D Total Assay

- 6. Device Description:
MAGLUMI 2000 25-OH VITAMIN D kit consists of the following reagents: Magnetic Microbeads- coated with 25-OH Vitamin D monoclonal antibody, containing BSA, NaN3 (<0.1%) Calibrator Low-Containing BSA and 25-OH Vitamin D antigen, NaN3(<0.1%) Calibrator High- Containing BSA and 25-0H Vitamin D antigen, NaN3(<0.1%) Displacing Reagent- Acidic buffer ABEI Label- 25-OH Vitamin D antigen labeled with ABEI Control 1- Containing BSA and 25-OH Vitamin D antigen, NaN3 (<0.1%) Control 2- Containing BSA and 25-OH Vitamin D antigen, NaN3 (<0.1%)

- 7. Intended Use:
MAGLUMI 2000 25-OH Vitamin D is an in vitro chemiluminescence immunoassay for the

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quantitative determination of 25-OH Vitamin D in human serum using Maglumi 2000 Fully-auto chemiluminescence immunoassay analyzer. The measurement of 25-OH Vitamin D is to be used as an aid in the assessment of vitamin D sufficiency.

- 8. Standard/Guidance Documents
Clinical and Laboratory Standards Institute EP5-A2 - Evaluation of Precision Performance of Clinical Chemistry Devices-Approved Guideline-Second Edition.

Clinical and Laboratory Standards Institute EP6-A - Evaluation of the Linearity of Quantitative Analytical

Clinical and Laboratory Standards Institute EP17-A2: Evaluation of detection Capability for Clinical Laboratory Measurement Procedures

Clinical and Laboratory Standards Institute EP7-A2 - Interference Testing in Clinical Chemistry Clinical and Laboratory Standards Institute EP9-A2 - Method Comparison and Bias Estimation Using Patient Samples

- 9. Substantial Equivalence Information

| Item | Predicate Device | Candidate Device |
|----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------|
| Intended Use/<br>Indication for<br>Use | For the quantitative determination of 25-<br>hydroxyvitamin D and other hydroxylated<br>vitamin D metabolites to be used in the<br>assessment of vitamin D sufficiency using<br>the LIAISON® Analyzer family. | Same |
| Specimen | Serum (plain serum tubes and serum<br>separator tubes) | Same |
| Measurement | Quantitative | Same |
| Calibration | 2 points | Same |
| Calibrator | Calibrator 1 and Calibrator 2 | Calibrator Low and Calibrator High |
| Automated | Yes | Same |

# Assay Similarities

# Assay Differences

| Item | Predicate Device | Candidate Device |
|----------------|-----------------------------------------------------------------|-----------------------------------------------------------------|
| Test principle | Direct competitive chemiluminescence<br>immunoassay (CLIA) | Two-step Competitive<br>chemiluminescence immunoassay<br>(CLIA) |
| Traceability | Calibrators are traceable to concentrations<br>determined by UV | ID-LC-MS/MS traceable to<br>NIST RMP 2972 |

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| | spectrophotometric analysis | |
|------------------|-----------------------------------------------------------------|---------------------------------------------------------------------|
| Measuring range | 4-150 ng/ml | 5.371-143 ng/ml |
| Capture antibody | Magnetic particles coated with antibody against 25 OH Vitamin D | Magnetic microbeads coated with 25-OH Vitamin D monoclonal antibody |
| Detection | 25 OH Vitamin D conjugated to an isoluminol derivative | ABEI-labeled 25-OH Vitamin D antigen |
| Sample size | 25 ul | 100 ul |

# 10. Test Principle

The 25-OH VITAMIN D assay is a competitive chemiluminescence immunoassay using FDA previously cleared MAGLUMI 2000 instrument (k162698).

The 25-OH Vitamin D assay is a two-incubation chemiluminescence immunoassay for the quantitative determination of total 25-OH vitamin D in human serum. In the first incubation, the 25-OH vitamin D is dissociated from its binding protein by the displacing reagent and binds to the 25-0H vitamin D antibody on the magnetic microbeads forming an antibodyantigen complex. Following a second incubation, the 25-OH Vitamin D labeled ABEI are added. The rest unbound material is removed during a wash cycle. Subsequently, the Starter 1+2 are added to initiate a flash chemiluminescent reaction. The resulting chemiluminescent reaction is measured as relative light units (RLUs), which is inversely proportional to the concentration of 25-OH Vitamin D present in the sample (or calibrator/control, if applicable).

# 11. Performance Characteristics

- 1. Analytical Performance
- a. Precision

The precision was determined using the CLSI EP5-A3 protocol as a guide. The study was conducted on three different instruments with three controls, two calibrators, three spiked patient serum pools and three native patient sample pools. The data was collected over 20 days in duplicate with 2 runs per day with a total of 80 samples analyzed per level on each instrument. The results (in ng/mL) obtained are summarized in the following tables:

| Sample | N | Mean<br>(ng/mL) | Repeatability | | Between-Run | | Between-Day | | Total<br>(within instrument) | | Reproducibility<br>(across instruments) | |
|--------------------|-----|-----------------|---------------|------|-------------|------|-------------|------|------------------------------|------|-----------------------------------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 240 | 30.077 | 1.039 | 3.45 | 0.389 | 1.29 | 1.546 | 5.14 | 1.903 | 6.33 | 1.944 | 6.46 |
| Control 2 | 240 | 60.362 | 1.625 | 2.69 | 0.487 | 0.81 | 2.590 | 4.29 | 3.096 | 5.13 | 3.096 | 5.13 |
| Control 3 | 240 | 119.953 | 1.741 | 1.45 | 1.842 | 1.54 | 3.971 | 3.31 | 4.711 | 3.93 | 4.930 | 4.11 |
| Calibrator<br>Low | 240 | 7.635 | 0.385 | 5.04 | 0.177 | 2.32 | 0.408 | 5.34 | 0.588 | 7.70 | 0.602 | 7.89 |
| Calibrator<br>High | 240 | 97.863 | 1.529 | 1.56 | 0.938 | 0.96 | 3.585 | 3.66 | 4.009 | 4.10 | 4.278 | 4.37 |

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| Spiked Serum<br>Pool 1 | 240 | 56.361 | 1.850 | 3.28 | 0.576 | 1.02 | 1.788 | 3.17 | 2.637 | 4.68 | 2.764 | 4.90 |
|------------------------|-----|---------|-------|------|-------|------|-------|------|-------|------|-------|------|
| Spiked Serum<br>Pool 2 | 240 | 80.795 | 1.800 | 2.23 | 0.705 | 0.87 | 1.972 | 2.44 | 2.762 | 3.42 | 2.812 | 3.48 |
| Spiked Serum<br>Pool 3 | 240 | 130.363 | 1.530 | 1.17 | 1.960 | 1.50 | 3.572 | 2.74 | 4.353 | 3.34 | 4.701 | 3.61 |
| Native Serum<br>Pool 1 | 240 | 8.387 | 0.458 | 5.46 | 0.235 | 2.80 | 0.578 | 6.89 | 0.774 | 9.23 | 0.778 | 9.28 |
| Native Serum<br>Pool 2 | 240 | 30.512 | 1.092 | 3.58 | 0.682 | 2.24 | 1.330 | 4.36 | 1.851 | 6.07 | 2.220 | 7.27 |
| Native Serum<br>Pool 3 | 240 | 106.049 | 1.353 | 1.28 | 1.971 | 1.86 | 2.068 | 1.95 | 3.161 | 2.98 | 3.313 | 3.12 |

#### b. Linearity

The linearity of the MAGLUMI 25-OH VITAMIN D method was determined following the CLSI EP6-A procedure. Eleven levels of linearity samples were prepared by blending a low serum sample pool and a high serum sample pool to span the whole measuring range with 25-OH VITAMIN D concentrations from 4.6 to 145.8 ng/mL. Each sample was measured in quadruple on 3 lots of reagent. Linearity was evaluated using regression analysis based on CLSI EP6-A.

The assays are linear between 4.6 and 145.8 ng/mL with the following relationship: Observed = 0.9885 (Expected) + 0.1192, R2 = 0.9986

- c. Stability
Accelerated stability study at 37°C showed that all controls are stable for 12 months at 2-8°C. Accelerated stability study at 37°C showed all that calibrators are stable for 12 months at 2-8°C. Accelerated stability study at 37°C showed that the reagent is stable for 12 months at 2-8°C. The real time stability at 2-8°C is on-going.

- d. Detection Limit
Detection limit studies were performed following CLSI EP17-A guidelines. The limit of blank (LOB) is the 95th percentile value from 60 measurements of 25-OH VITAMIN D depleted serum samples using 3 different lots of 25-OH VITAMIN D reagents over 5 days. The LOB corresponds to the concentration below which analyte-free samples are found with a probability of 95% and was determined to be 1.990 ng/mL (highest of the 3 lots). The limit of detection (LOD) is determined based on the LOB and the standard

deviation of low concentration samples. The LOD corresponds to the lowest analyte concentration which can be detected. Four level of low samples were measured in 60 replicates over 5 days per sample using 3 lots of reagents. LOD was determined to be 3.8 ng/mL (highest of the 3 lots).

The limit of quantitation (LOQ) was determined by measuring six low serum samples, in six replicates per run, one run per day, over 5 days, using 3 lots of reagents. LOQ is defined as the lowest analyte concentration that can be

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reproducibly measured with an intermediate precision CV of ≤ 20 % and was determined to be 5.371 ng/mL (highest of the 3 lots).

- Interference e.
A cross reactivity study was performed using two base serum samples containing total 25-OH VD 30 ng/mL and 60 ng/mL respectively. These samples were spiked with various cross reactants and measured for these solutions using 3 lots of reagents. The following table shows cross reactivity of potential cross reactant.

| Cross Reactant | %Cross-reactivity |
|-----------------------|-------------------|
| 25-OH Vitamin D2 | 98.10% |
| 25-OH Vitamin D3 | 96.13% |
| Vitamin D2 | 1.04% |
| Vitamin D3 | 1.98% |
| 1,25-(OH)2-Vitamin D3 | 8.12% |
| 1,25-(OH)2-Vitamin D2 | 8.77% |
| 3-epi-25OH D3 | 2.04% |

The effect of endogeous substances were evaluated using human serum pools. For each substance, three serum samples containing 20, 30 and 60ng/mL concentration of 25-OH VITAMIN D were analyzed, the highest concentration of interferents were listed below at which no significant interference was observed.

| Potential Interferent | Highest concentration tested at which no<br>significant interference is observed (mg/dL) |
|------------------------|------------------------------------------------------------------------------------------|
| Conjugated bilirubin | 60 |
| Unconjugated bilirubin | 42.5 |
| Hemoglobin | 250 |
| triglyceride | 500 |
| Uric acid | 20 |
| Cholesterol | 300 |

The effect of common drugs and interference substances were evaluated using human serum pools. For each substance, three serum samples containing 20, 30 and 60ng/mL concentration of 25-OH VITAMIN D were analyzed. For all substances tested, no significant interference was defined as recovery ± 10% of initial value. The substances and the highest concentration tested which did not cause significant interference are listed below.

| Potential Interferent | Highest concentration tested at which no<br>significant interference is observed (mg/dL) |
|---------------------------|------------------------------------------------------------------------------------------|
| Cefoxitin | 340 |
| Levodopa | 3.25 |
| Metronidazole | 12.3 |
| Ascorbic Acid (Vitamin C) | 16.95 |
| Acetaminophen | 15.6 |

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| Biotin | 5 |
|--------------|------|
| Cyclosporine | 0.6 |
| Rifampicin | 6.5 |
| Doxycycline | 3.2 |
| Theophylline | 11.4 |

The effect of human anti-mouse antibodies (HAMA), rheumatoid factor (RF) and human serum total protein was evaluated using human serum samples. Each potential interferent was added to 25-OH VITAMIN D human serum samples and tested using 3 lots of reagents. For all substances tested, no significant interference was defined as recovery ± 10% of initial value. The potential interferents and the highest concentration tested which did not cause significant interference are listed below.

| Potential Interferent | Highest concentration tested at which no significant interference is observed (mg/dL) |
|-----------------------|---------------------------------------------------------------------------------------|
| HAMA | 401 ng/mL |
| RF | 1745 IU/mL |
| Total protein | 6.25 g/dL |

### 2. Comparison Studies

A method comparison study was performed with 241 human serum samples with concentrations ranging from 5.371 to 143 ng/mL. The comparison of the MAGLUMI 25-OH VITAMIN D assay (y) with the predicate device, LIAISON 25-OH VITAMIN D total assay (x), produced the following

linear regression equation:

Y = 1.013X - 0.504, R2 =0.9739

- 3. Expected values/Reference range:
A total of 302 serum samples from normal, apparently healthy adult (20 years and older) individuals were tested according to the procedure in CLSI C28-A3. The expected normal range is 9.99 - 49.3 ng/dL based on the central 95% of the frequency distribution.

# 12. Conclusion

Based on the test principle and acceptable performance characteristics including precision. interference, specificity and method comparison of the device, it is concluded that the MAGLUMI 2000 25-OH VITAMIN D is substantially equivalent to the predicate.