(59 days)
Not Found. This is a De Novo request.
Not Found
No
The summary describes a standard LC-MS/MS system for quantitative determination of vitamin D. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis focuses on analytical performance metrics typical of laboratory assays.
No.
This device is an in vitro diagnostic (IVD) device used to quantitatively determine total 25-hydroxyvitamin D in human serum. It is intended to assist clinicians in making patient management decisions by providing diagnostic information, not to directly treat or prevent a disease or condition.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states "The Vitamin D 200M Assay for the Topaz System is intended for in vitro diagnostic use". This phrase directly labels the device as a diagnostic tool.
No
The device description explicitly states it employs LC-MS/MS technology (Topaz System) in conjunction with reagents and sample preparation components, which are hardware and chemical components, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states "intended for in vitro diagnostic use".
- Purpose: The device is designed to quantitatively determine total 25-hydroxyvitamin D in human serum, which is a diagnostic measurement used to assist clinicians in assessing vitamin D sufficiency.
- Specimen Type: It uses human serum, which is a biological specimen.
- Technology: It employs LC-MS/MS technology, a common method used in clinical laboratories for diagnostic testing.
- User and Setting: It is intended for use by a "trained laboratory professional in a clinical laboratory," which is typical for IVD devices.
N/A
Intended Use / Indications for Use
The Vitamin D 200M Assay for the Topaz System is intended for in vitro diagnostic use in the quantitative determination of total 25-hydroxyvitamin D (25-OH-D) through the measurement of 25-hydroxyvitamin D3 (25-OH-D3) and 25-hydroxyvitamin D2 (25-OH-D2) in human serum using LC-MS/MS technology by a trained laboratory professional in a clinical laboratory. The Assay is intended for use with the Topaz System. The Vitamin D 200M Assay for the Topaz System is intended to be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population in the assessment of vitamin D sufficiency.
Product codes (comma separated list FDA assigned to the subject device)
PSL
Device Description
The Vitamin D 200M Assay for the Topaz System employs LC-MS/MS technology (Topaz System) in conjunction with reagents and sample preparation components to extract, separate by chromatography, detect, and quantify total Vitamin in human serum.
The Topaz System is a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system intended to for use in a clinical laboratory environment to identify inorganic or organic compounds in human specimens by ionizing the compound under investigation and separating the resulting ions by means of an electrical and magnetic field according to their mass.
Each assay kit contains enough material for 1000 tests, and includes reagents, sample extraction and purification components, calibrators, controls and the Vitamin D 200M Assay specific file which contains all necessary parameters to process the assay.
The assay contains calibrators to calibrate the Vitamin D 200M Assay for the Topaz System. The matrix base of the calibrators is human serum. Human source material is tested for the presence of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) and Type 2 (HIV-2), Hepatitis B Surface Antigen and antibodies to Hepatitis C Virus (HCV) and found to be negative/non-reactive.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult population
Intended User / Care Setting
trained laboratory professional in a clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility/Precision:
Study type: Multi-site evaluation study outlined in CLSI EP05-A3 guideline.
Sample size: Five serum samples (two diluted/spiked to approximate low and high levels/medical decision points, one native patient sample).
Key results:
- Sample 1: Mean 14.9 ng/mL, Repeatability SD 0.57 (%CV 3.8%), Within-Laboratory SD 1.05 (%CV 7.0%), Reproducibility SD 1.10 (%CV 7.3%)
- Sample 2: Mean 13.7 ng/mL, Repeatability SD 0.65 (%CV 4.7%), Within-Laboratory SD 0.80 (%CV 5.8%), Reproducibility SD 0.80 (%CV 5.8%)
- Sample 3: Mean 31.0 ng/mL, Repeatability SD 1.28 (%CV 4.1%), Within-Laboratory SD 2.03 (%CV 6.5%), Reproducibility SD 2.03 (%CV 6.5%)
- Sample 4: Mean 67.5 ng/mL, Repeatability SD 3.58 (%CV 5.3%), Within-Laboratory SD 3.99 (%CV 5.9%), Reproducibility SD 5.85 (%CV 8.7%)
- Sample 5: Mean 100 ng/mL, Repeatability SD 6.37 (%CV 6.3%), Within-Laboratory SD 6.46 (%CV 6.4%), Reproducibility SD 10.4 (%CV 10.4%)
- Native Patient Sample: Mean 28.4 ng/mL, Repeatability SD 1.44 (%CV 5.1%), Within-Laboratory SD 2.04 (%CV 7.2%), Reproducibility SD 2.10 (%CV 7.4%)
Linearity/assay reportable range:
Study type: Linearity study according to CLSI EP06-A.
Sample size: Nine serially diluted serum samples.
Key results: Linear regression: y = 0.9974x + 1.1737, R2 = 0.9984. Supports claimed measuring range of 4.0 to 140 ng/mL.
Detection limit:
Study type: Low level determinations.
Key results: LLMI for total 25-OH-Vitamin D was 2.9 ng/mL.
Analytical specificity:
Study type: Analytical specificity study based on CLSI EP07-A2 guideline.
Sample size: 79 potential interferents spiked into samples.
Key results: No potential endogenous and exogenous interfering substances or collection tubes tested caused interference greater than a 10% difference between test and control samples. A table lists the highest concentrations tested that did not demonstrate significant interference for various substances.
Method comparison with reference method:
Study type: Accuracy study to the CDC Vitamin D Standardization-Certification Program (VDSCP).
Sample size: 118 unique natural patient serum samples (with 12 contrived specimens, 10.2%).
Key results:
n = 118
Slope = 1.008 (Passing-Bablok regression)
Intercept = -0.3949 (Passing-Bablok regression)
Correlation Coefficient = 0.991
Range (ng/mL) = 5.6 – 133 ng/mL
Expected Values (Reference Range Study):
Study type: Reference range study with reference to the CLSI EP28-A3 guideline.
Sample size: 404 serum samples.
Data source: Apparently healthy male and female adults 21 years of age and older from 3 different geographic regions.
Key results: The inner 95% Reference interval of 25(OH) vitamin D concentrations found in this population was 8.6 to 49 ng/mL.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Precision (%CV, SD) and linearity (R2) are reported.
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.
Not Found. This is a De Novo request.
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
§ 862.1840 Total 25-hydroxyvitamin D mass spectrometry test system.
(a)
Identification. A total 25-hydroxyvitamin D mass spectrometry test system is a device intended for use in clinical laboratories for the quantitative determination of total 25-hydroxyvitamin D (25-OH-D) in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in part 807, subpart E, of this chapter subject to the limitations in § 862.9. The device must comply with the following special controls:(1) The device must have initial and annual standardization verification by a certifying vitamin D standardization organization deemed acceptable by FDA.
(2) The 21 CFR 809.10(b) compliant labeling must include detailed descriptions of performance testing conducted to evaluate precision, accuracy, linearity, interference, including the following:
(i) Performance testing of device precision must, at a minimum, use intended sample type with Vitamin D concentrations at medically relevant decision points. At least one sample in the precision studies must be an unmodified patient sample. This testing must evaluate repeatability and reproducibility using a protocol from an FDA-recognized standard.
(ii) Performance testing of device accuracy must include a minimum of 115 serum or plasma samples that span the measuring interval of the device and compare results of the new device to results of a reference method or a legally marketed standardized mass spectrometry based vitamin D assay. The results must be described in the 21 CFR 809.10(b)(12) compliant labeling of the device.
(iii) Interference from vitamin D analogs and metabolites including vitamin D2, vitamin D3, 1-hydroxyvitamin D2, 1-hydroxyvitamin D3, 3-Epi-25-Hydroxyvitamin D2, 3-Epi-25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D2, 1,25-Dihydroxyvitamin D3, 3-Epi-1,25-Dihydroxyvitamin D2, and 3-Epi-1,25-Dihydroxyvitamin D3, 25, 26-Dihydroxyvitamin-D3, 24 (R), 25-dihydroxyvitamin-D3, 23 (R), 25-dihydroxyvitamin-D3 must be described in the 21 CFR 809.10(b)(7) compliant labeling of the device.
(3) The 21 CFR 809.10(b) compliant labeling must be supported by a reference range study representative of the performance of the device. The study must be conducted using samples collected from apparently healthy male and female adults at least 21 years of age and older from at least 3 distinct climatic regions within the United States in different weather seasons. The ethnic, racial, and gender background of this study population must be representative of the U.S. population demographics.
(4) The results of the device as provided in the 21 CFR 809.10(b) compliant labeling and any test report generated must be reported as only total 25-hydroxyvitamin D.
0
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR Vitamin D 200M Assay
DECISION SUMMARY
A. DEN Number:
B. Purpose for Submission:
De Novo request for evaluation of automatic class III designation for the Vitamin D 200M Assay for the Topaz System
C. Measurand:
Total 25-hydroxyvitamin D
D. Type of Test:
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
E. Applicant:
AB SCIEX
F. Proprietary and Established Names:
Vitamin D 200M Assay
G. Regulatory Information:
-
- Regulation:
21 CFR 862.1840
- Regulation:
-
- Classification:
Class II (special controls)
- Classification:
-
- Product code(s):
PSL
- Product code(s):
1
-
- Panel:
Clinical Chemistry (75)
- Panel:
H. Indications For Use:
-
- Indications for Use:
The Vitamin D 200M Assay for the Topaz System is intended for in vitro diagnostic use in the quantitative determination of total 25-hydroxyvitamin D (25-OH-D) through the measurement of 25-hydroxyvitamin D3 (25-OH-D3) and 25-hydroxyvitamin D2 (25-OH-D2) in human serum using LC-MS/MS technology by a trained laboratory professional in a clinical laboratory. The Assay is intended for use with the Topaz System. The Vitamin D 200M Assay for the Topaz System is intended to be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population in the assessment of vitamin D sufficiency.
- Indications for Use:
-
- Special conditions for use statement(s):
For in vitro diagnostic use only. For prescription use only.
- Special conditions for use statement(s):
-
- Special instrument requirements:
Topaz System
- Special instrument requirements:
I. Device Description:
The Vitamin D 200M Assay for the Topaz System employs LC-MS/MS technology (Topaz System) in conjunction with reagents and sample preparation components to extract, separate by chromatography, detect, and quantify total Vitamin in human serum.
The Topaz System is a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system intended to for use in a clinical laboratory environment to identify inorganic or organic compounds in human specimens by ionizing the compound under investigation and separating the resulting ions by means of an electrical and magnetic field according to their mass.
Each assay kit contains enough material for 1000 tests, and includes reagents, sample extraction and purification components, calibrators, controls and the Vitamin D 200M Assay specific file which contains all necessary parameters to process the assay.
2
The assay contains calibrators to calibrate the Vitamin D 200M Assay for the Topaz System. The matrix base of the calibrators is human serum. Human source material is tested for the presence of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) and Type 2 (HIV-2), Hepatitis B Surface Antigen and antibodies to Hepatitis C Virus (HCV) and found to be negative/non-reactive.
J. Standard/Guidance Documents Referenced:
CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents
CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory
CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
CLSI EP9-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples
CLSI EP07-A2 Interference Testing in Clinical Chemistry
CLSI EP06-A Evaluation of the Linearity of the Quantitative Measurement Procedures: A Statistical Approach
CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods
CLSI C62-A Liquid Chromatography-Mass Spectrometry Methods
IEC 61010-1:2001 IEC Safety Requirements for Electrical Equipment for Measurement, Control, and Laboratory Use - Part 1: General Requirements
IEC 61010-2-101:2002 IEC Safety Requirements for Electrical Equipment for Measurement, Control. and Laboratory Use - Part 2-101: Particular Requirements for In Vitro Diagnostic (IVD) Medical Equipment
IEC 61010-2-061: 2005 IEC Safety Requirements for Electrical Equipment for Measurement, Control, and Laboratory Use - Part 2-061: Particular Requirements for Laboratory Atomic Spectrometers with Thermal Atomization and Ionization 2005 8-28
K. Test Principle:
The Vitamin D 200M Assay for the Topaz System employs LC-MS/MS technology in conjunction with reagents and sample preparation components to extract, separate by chromatography, detect and quantify total Vitamin D in human serum.
3
During the sample preparation stage, an isotopic 25-hydroxyvitamin D3 analog is used as an internal standard and is added to the sample. The analytes of interest are extracted from the sample matrix by protein precipitation and centrifugation.
Analyte separation, ionization, detection, and quantitation and reporting are achieved through LC-MS/MS technology on the Topaz System. The liquid chromatography (LC) component of the Topaz System separates chemicals by conventional chromatography on a column. The analyte separation method is reverse phase chromatography, where the analytes bind to the chromatography column by hydrophobic interactions in the presence of a hydrophilic solvent (for instance water) and are eluted off by a more hydrophobic solvent (methanol or acetonitrile). As the analytes elute from the end of the column they enter the mass spectrometer, where the solvent is removed and the analytes are ionized. The analytes must be ionized as the mass spectrometer can only detect ions. not neutral molecules. The mass spectrometer then scans the analytes of interest by mass and produces a full high-resolution spectrum, separating all ions that have different masses. The ions can be further fragmented to produce daughter ions (MS/MS). Monitoring the transitions of the original (parent) and daughter ions provides a highly specific identification of the desired analytes.
The parent ions of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 and major fragment ions are monitored and detected in the mass spectrometer. The concentration of 25hydroxyvitamin D3 and 25-hydroxyvitamin D2 is interpolated from a calibration curve established with calibrators of known standard concentrations. Total Vitamin D concentrations is calculated as a total of the concentrations of 25-hydroxyvitamin D3 and 25hydroxyvitamin D2.
L. Performance Characteristics:
-
- Analytical performance:
- a. Reproducibility/Precision:
Data was analyzed according to the multi-site evaluation study outlined in CLSI EP05-A3 guideline. The study was performed at three sites. Five serum samples were assayed on five calendar days, with one run per day and five replicates per sample. The analyte concentrations of the samples approximated both low (b) (4) and high (0) (4) levels, as well as medical decision points. The samples were either diluted with serum that did not contain vitamin D or spiked with 25-OH-vitamin D standards to achieve the low and high concentrations. The sixth sample was a native patient sample (unmodified).
Results obtained are summarized below:
| Sample | Mean | Repeatability | | Within-
Laboratory | | Reproducibility | |
|--------|---------|---------------|------|-----------------------|------|-----------------|------|
| | (ng/mL) | SD | %CV | SD | %CV | SD | %CV |
| 1 | 14.9 | 0.57 | 3.8% | 1.05 | 7.0% | 1.10 | 7.3% |
| 2 | 13.7 | 0.65 | 4.7% | 0.80 | 5.8% | 0.80 | 5.8% |
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| Sample | Mean
(ng/mL) | Repeatability | | Within-
Laboratory | | Reproducibility | |
|-----------------------------|-----------------|---------------|------|-----------------------|------|-----------------|-------|
| | | SD | %CV | SD | %CV | SD | %CV |
| 3 | 31.0 | 1.28 | 4.1% | 2.03 | 6.5% | 2.03 | 6.5% |
| 4 | 67.5 | 3.58 | 5.3% | 3.99 | 5.9% | 5.85 | 8.7% |
| 5 | 100 | 6.37 | 6.3% | 6.46 | 6.4% | 10.4 | 10.4% |
| Native
Patient
Sample | 28.4 | 1.44 | 5.1% | 2.04 | 7.2% | 2.10 | 7.4% |
b. Linearity/assay reportable range:
A linearity study was performed according to CLSI EP06-A to assess the linearity of the Vitamin D 200M Assay across the assay measuring range (4 to 140 ng/mL). A serum sample with a high concentration of vitamin D was serially diluted with a low concentration serum sample to generate nine samples with vitamin D concentration values of 3.4. 47.7, 91.9, 136, 180, 225, 269, 313, 357 ng/mL, respectively.
The results of the linear regression analyses are summarized below:
y = 0.9974x + 1.1737 R2 = 0.9984
The linearity study data support the claimed measuring range of 4.0 to 140 ng/mL.
- Traceability, Stability, Expected values: C.
Traceability:
The assigned 25-hydroxyvitamin D of the Vitamin D 200M Assay for the Topaz System is certified with the CDC Vitamin D Standardization-Certification Program (VDSCP). See VDSCP website for current certification at https://www.cdc.gov/labstandards/hs_standardization.html (last accessed on May 18, 2017; Note this website is not controlled by FDA).
Stability:
Unopened reagents are stable until the expiry date stipulated on the label, provided that the storage conditions indicated on the label are complied with.
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d. Detection limit:
Low level determinations were made for each of six samples that were prepared using two kits from different lots. The lower limit of the measuring interval (LLMI) for each lot was determined to be the lowest concentration of analyte that achieved both the bias and precision goals (