(130 days)
Not Found
No
The summary describes a standard immunoassay technology and does not mention any AI or ML components in the device description, performance studies, or intended use.
No
This device is an in vitro diagnostic assay used to measure holotranscobalamin levels in human serum, which aids in the diagnosis and treatment of vitamin B12 deficiency. It does not directly treat a condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay "is used as an aid in the diagnosis and treatment of vitamin B12 deficiency."
No
The device description explicitly states it is a "fully automated, two-step direct immunoassay using chemiluminescent technology" and describes physical components like "acridinium ester-labeled antitranscobalamin antibody" and "biotinylated antiholotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles," indicating it is a hardware-based in vitro diagnostic device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states "for in vitro diagnostic use" multiple times for the assay, the quality control, and the master curve material. It also specifies that the assay is used "as an aid in the diagnosis and treatment of vitamin B12 deficiency," which is a diagnostic purpose.
- Device Description: The description details a laboratory test that measures a substance (holotranscobalamin) in a human sample (serum) using chemical and immunological methods. This is characteristic of an in vitro diagnostic device.
- Intended User/Care Setting: The mention of "in vitro diagnostic use" further reinforces its classification as an IVD, indicating it's used in a laboratory setting for diagnostic purposes.
N/A
Intended Use / Indications for Use
The ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.
Quality Control
The ADVIA Centaur® Active-B12 (AB12) quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
Master Curve Material (MCM)
The ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
Product codes (comma separated list FDA assigned to the subject device)
CDD, JJX
Device Description
The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled antitranscobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated antiholotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
human serum
Indicated Patient Age Range
The age range was 21 - 67 years.
Intended User / Care Setting
Not Found
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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Linearity: Linearity was evaluated according to the CLSI protocol EP6-A. Two samples containing high levels of active-B12 were mixed with a pool of artificial serum matrix. The ADVIA Centaur AB12 assay is linear from 5.00-146.00 pmol/L.
Dilution Linearity: Five samples containing high levels of active-B12 (96.64-135.51 pmol/L) were diluted 1:2 (1 part sample plus 1 part diluent) with Multi-Diluent 13 and assayed for recovery and parallelism correcting the diluted sample by the dilution factor.
Detection Capability: The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI Document EP17-A2. LoB of 0.74 pmol/L, an LoD of 1.08 pmol/L and an LoQ of 5.00 pmol/L.
High Dose Hook: Patient samples with active-B12 levels as high as 1867.80 pmol/L are not subject to a hook effect and will assay greater than 146.00 pmol/L.
Cross-reactivity: Cross-reactivity was tested in the presence and absence of active-B12 according to CLSI EP7-A2 using the ADVIA Centaur AB12 assay. Populations evaluated in the study included other B12 proteins apotranscobalamin and haptocorrin. The results for apotranscobalamin were 0.2% at 250 pmol/L and -0.1% at 500 pmol/L. The results for haptocorrin were -0.4% at 2500 pmol/L and -0.4% at 5000 pmol/L.
Interference: Potential interference in the ADVIA Centaur AB12 assay is designed to be less than or equal to 10%. Interfering substances at the levels indicated in the table below were tested as described in CLSI Document EP7-A2 using the ADVIA Centaur AB12 assay.
Precision: Precision was evaluated according to the CLSI protocol EP5-A2. Five serum precision panel members were prepared with active-B12 concentrations spanning the measuring interval. Each sample was tested in replicates of 2 in two runs per day over 20 days. One ADVIA Centaur XP system was used and 2 reagent lots giving a total of 80 observations per sample for each reagent lot. The Within-Laboratory (Total) %CV ranged from 4.0% to 4.7%.
Method Comparison: For 104 serum samples in the range of 5.56 – 142.58 pmol/L, the relationship of the ADVIA Centaur AB12 assay (y) and the Abbott ARCHITECT Chemiluminescent Microparticle Immunoassay (CMIA) Active-B12 (Holotranscobalamin) assay (x) is described using Passing-Bablok regression. ADVIA Centaur AB12 = 0.97 (CMIA) - 0.99 pmol/L (intercept), r = 0.95.
Expected Values: The ADVIA Centaur AB12 assay results were obtained on 241 apparently healthy males (n = 103) and females (n = 138), age range 21 - 67 years. The mean holoTC concentration was 81.91 pmol/L with a 95% central reference interval from 28.96–168.90 pmol/L.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Linearity Range: 5.00-146.00 pmol/L
- Limit of Blank (LoB): 0.74 pmol/L
- Limit of Detection (LoD): 1.08 pmol/L
- Limit of Quantitation (LoQ): 5.00 pmol/L (at a total CV of 8%)
- High-Dose Hook Effect: No hook effect detected up to 1867.80 pmol/L
- Cross-reactivity: Apotranscobalamin ≤ 0.2%, Haptocorrin ≤ -0.4%
- Interference Tolerance: ≤ 10% for listed substances (Biotin (100 mg/dL), Cholesterol (500 mg/dL), Conjugated Bilirubin (40 mg/dL), Hemoglobin (500 mg/dL), Human IgG (12 g/dL), Methotrexate (91 mg/dL), Perimethamine (75 µg/mL), Rheumatoid Factor (200 IU/mL), Silwet L720 (0.2 mg/dL), Total Protein (12 g/dL), Unconjugated Bilirubin (60 mg/dL), Triglyceride (1000 mg/dL))
- Within-Laboratory (Total) %CV (Precision): Ranged from 4.0% to 4.7% across different samples.
- Method Comparison Regression (vs. Abbott ARCHITECT CMIA): ADVIA Centaur AB12 = 0.97 (CMIA) - 0.99 pmol/L, r = 0.95
- 95% Central Reference Interval: 28.96–168.90 pmol/L
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.
ARCHITECT Active-B12 (Holotranscobalamin) Assay (K112443)
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
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
AXIS-SHIELD DIAGNOSTICS LIMITED CLAIRE DORA REGULATORY AFFAIRS MANAGER THE TECHNOLOGY PARK LUNA PLACE DUNDEE DD2 1XA Great Britain
July 26, 2016
Re: K160757
Trade/Device Name: ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) Assay, ADVIA Centaur Active-B12 (AB12) Quality Control, ADVIA Centaur Active-B12 (AB12) Master Curve Materials (MCM) Regulation Number: 21 CFR 862.1810 Regulation Name: Vitamin B12 test System Regulatory Class: II Product Code: CDD, JJX Dated: June 23, 2016 Received: June 27, 2016
Dear Claire Dora:
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
1
as set forth in the quality systems (OS) 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,
Katherine Serrano -S
For: Courtney C. 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
2
Indications for Use
510(k) Number (if known) K160757
Device Name
ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay ADVIA Centaur® Active-B12 (AB12) Quality Control ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM).
Indications for Use (Describe)
The ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.
Quality Control
The ADVIA Centaur® Active-B12 (AB12) quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
Master Curve Material (MCM)
The ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of callbration and reportable range of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
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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510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is K160757
Submission correspondent:
Dr Claire Dora Regulatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee DD2 1XA, Scotland, UK Telephone: +44(0) 1382 422000 Fax: +44(0) 1382 422088 510k summary prepared date: 22nd July 2016
Device Name:
ADVIA Centaur® Active-B12 (Holotranscobalamin) (AB12) Assay Quality Control Master Curve Material (MCM)
Reagents:
Classification Name: Vitamin B12 test system Trade Name ADVIA Centaur® Active-B12 (Holotranscobalamin) (AB12) assay Common Name: B12 test Governing Regulation: 21CFR 862.1810 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: CDD
Quality Control:
Classification Name: Single (Specified) Analyte Control Trade Name: ADVIA Centaur® Active-B12 (AB12) quality control material Common Name: Control Governing Regulation: 862.1660 Device Classification: Class I, reserved Classification Panel: Clinical Chemistry Product Code: JJX
4
Master Curve Material:
Classification Name: Single (Specified) Analyte Control Trade Name: ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) Common Name: Control Governing Regulation: 862.1660 Device Classification: Class I, reserved Classification Panel: Clinical Chemistry Product Code: JJX
Legally marketed device to which equivalency is claimed:
ARCHITECT Active-B12 (Holotranscobalamin) Assay (K112443)
Intended Use of Device:
The ADVIA Centaur® Active-B12 (Holotranscobalamin) (AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.
Quality Control
The ADVIA Centaur® Active-B12 (AB12) quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
Master Curve Material (MCM)
The ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
Description of Device:
The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled antitranscobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated antiholotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.
Comparison of Technological Characteristics:
The ADVIA Centaur AB12 assay and the ARCHITECT Active-B12 are both automated immunoassays for the quantitative measurement of holotranscobalamin (holoTC) in human serum.
The ADVIA Centaur System and ARCHITECT i System share similar detection methods both utilizing chemiluminescent microparticle immunoassay (CMIA) technology. Both assays also demonstrated substantial equivalence in terms antibodies employed, detection method and the units of measure.
5
Comparison of the subject device with the predicate device:
| Similarities |
|---|
| Parameter | ADVIA Centaur® AB12 | ARCHITECT Active-B12 |
|---|---|---|
| Intended use | For in vitro diagnostic use in the | |
| quantitative measurement of | ||
| holotranscobalamin (holoTC) in human | ||
| serum using the ADVIA Centaur XP | ||
| system. Active-B12 (holotranscobalamin) | ||
| is used as an aid in the diagnosis and | ||
| treatment of vitamin B12 deficiency. | For the quantitative determination of | |
| Holotranscobalamin in human serum on | ||
| the ARCHITECT i System. | ||
| Active-B12 (Holotranscobalamin) is used | ||
| as an aid in the diagnosis and treatment of | ||
| vitamin B12 deficiency. | ||
| Assay Technology | Chemiluminescent microparticle | |
| immunoassay (CMIA) | Chemiluminescent microparticle | |
| immunoassay (CMIA) | ||
| Substrate / Signal | ||
| Generation | Acridinium Tracer | Acridinium Tracer |
| Specimen type | Serum and Serum Separator | Serum and Serum Separator |
| Conjugate antibody | Murine monoclonal antibody 3-11 | Murine monoclonal antibody 3-11 |
| Storage conditions | Reagent Pack must be stored at | |
| 2-8ºC. | Reagent Pack must be stored at | |
| 2-8ºC. | ||
| Unit of Measure | pmol/L | pmol/L |
| Cross- Reactivity | ≤ 10% with; | |
| Apotranscobalamin (500 pmol/L) | ||
| Haptocorrin (5000 pmol/L) | ≤ 10% with; | |
| Apotranscobalamin (500 pmol/L) | ||
| Haptocorrin (5000 pmol/L) | ||
| Assay dilution | ||
| protocol | 1:2 autodilute with | |
| ADVIA Centaur Multi-Diluent 13 | 1:2 autodilute or manual with ARCHITECT i | |
| Multi-Assay manual diluent | ||
| Sensitivity | Limit of Quantitation of ≤ 5.0 pmol/L | Limit of Quantitation of ≤ 5.0 pmol/L |
| Parameter | ADVIA Centaur®AB12 | ARCHITECT Active-B12 |
| Calibration | 2-point Calibration using 2 level | |
| calibrators | 6-point calibration curve. | |
| 4PLC Y-weighted | ||
| Expected Values in | ||
| Asymptomatic | ||
| Population | The mean holoTC concentration for | |
| the group was established at 81.91 | ||
| pmol/L with a 95% central reference | ||
| interval from 28.96 to 168.90 pmol/L | The mean Holotranscobalamin | |
| concentration was 71.9 pmol/L with a range | ||
| from 20.6 to 196.7 pmol/L. The central 95% | ||
| of the population defined the expected | ||
| range of 25.1 to 165.0 pmol/L | ||
| Imprecision | Within-Laboratory (Total) %CV ≤ 4.7% | |
| Within-run %CV ≤ 3.2% | Total %CV ≤ 5.8% | |
| Within-run %CV ≤ 4.4% | ||
| Interference | ≤ 10% with; | |
| Bilirubin at 40 mg/dL | ≤ 10% with; | |
| Bilirubin at 20 mg/dL | ||
| Unconjugated bilirubin at 60 mg/dL | Haemoglobin at 200 mg/dL | |
| Haemoglobin at 500 mg/dL | Triglycerides at 850 mg/dL | |
| Triglyceride at 1000 mg/dL | Rheumatoid Factor at 70 IU/mL | |
| Rheumatoid Factor at 200 IU/mL | Total protein at 10 g/dL | |
| Total protein at 12 g/dL | ||
| Biotin at 100 mg/dL | ||
| Human IgG at 12 g/dL | ||
| Cholesterol at 500 mg/dL | ||
| Silwet L720 at 0.2 mg/dL | ||
| Methotrexate at 91 mg/dL | ||
| Perimethamine at 75 µg/mL | ||
| Cross- Reactivity | No detectable cross-reactivity with; | |
| Apotranscobalamin at 500 pmol/L | ||
| Haptocorrin at 5000 pmol/L | No detectable carryover with; | |
| Apotranscobalamin at 500 pmol/L | ||
| Haptocorrin at 5000 pmol/L | ||
| Measurable Range | 5.0 to 146.0 pmol/L | 5.0 to 128.0 pmol/L |
| Calibration Range | 0 to 146.0 pmol/L | 0 to 128.0 pmol/L |
| Linearity | 5.0 to 146.0 pmol/L | 5.0 to 128.0 pmol/L |
| On-board Reagent | ||
| Stability | Reagents can be stored onboard the | |
| Centaur XP instrument for a maximum | ||
| of 44 days. | Reagents can be stored onboard the | |
| ARCHITECT instrument for a maximum of 30 | ||
| days. | ||
| Calibration | ||
| Frequency | 44 days | 30 days |
| Sample Stability | Separated specimens are stable for 16 | |
| hours at room temperature, 3 days at | ||
| 2-8°C | Up to 16 hours at room temperature | |
| Up to 3 days at 2-8°C (for longer than 3 days | ||
| store at -20°C or colder for up to 6 months). | ||
| For longer storage, specimens may be | ||
| frozen for 3 months at -20 °C or | ||
| colder. Avoid more than 1 freeze/thaw | ||
| cycle. Do not store in a frost-free | ||
| freezer | Avoid more than 3 freeze-thaw cycles. | |
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Differences
7
Summary of Non-Clinical Performance:
The ADVIA Centaur AB12 assay demonstrated substantially equivalent performance to the ARCHITECT Active-B12 assay. A summary of the non-clinical performance data included in this 510(k) submission has been presented.
Linearity
Linearity was evaluated according to the CLSI protocol EP6-A.Two samples containing high levels of active-B12 were mixed with a pool of artificial serum matrix. The resulting sample mixtures were assayed for active-B12. The ADVIA Centaur AB12 assay is linear from 5.00-146.00 pmol/L.
Dilution Linearity
Five samples containing high levels of active-B12 (96.64-135.51 pmol/L) were diluted 1:2 (1 part sample plus 1 part diluent) with Multi-Diluent 13 and assayed for recovery and parallelism correcting the diluted sample by the dilution factor. Representative data from the study is shown below.
| Sample | Dilution | Observed
(pmol/L) | Expected
(pmol/L) | Recovery % |
|----------|----------|----------------------|----------------------|------------|
| Sample 1 | 1:2 | 91.41 | 96.64 | 94.59 |
| Sample 2 | 1:2 | 112.61 | 114.20 | 98.61 |
| Sample 3 | 1:2 | 126.19 | 135.51 | 93.12 |
| Sample 4 | 1:2 | 110.09 | 121.17 | 90.86 |
| Sample 5 | 1:2 | 121.29 | 132.63 | 91.45 |
Measuring Interval
The ADVIA Centaur AB12 assay measures active-B12concentrations from 5.00-146.00 pmol/L.
Detection Capability
The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI Document EP17-A2. The ADVIA Centaur AB12 assay has an LoB of 0.74 pmol/L, an LoD of 1.08 pmol/L and an LoQ of 5.00 pmol/L.
The LoB is defined as the highest measurement result that is likely to be observed for a blank sample. The LoD is defined as the lowest concentration of active-B12 that can be detected with 95% probability. The LoQ is defined as the lowest concentration of active-B12 that can be detected at a total CV of 8%.
High Dose Hook
Patient samples with high active-B12 levels can cause a paradoxical decrease in the Relative Light Units (RLUs) (high-dose hook effect). In the ADVIA Centaur AB12 assay, patient samples with active-B12 levels as high as 1867.80 pmol/L are not subject to a hook effect and will assay greater than 146.00 pmol/L.
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Cross-reactivity
Cross-reactivity was tested in the presence and absence of active-B12 according to CLSI EP7-A2 using the ADVIA Centaur AB12 assay. Populations evaluated in the study included other B12 proteins apotranscobalamin and haptocorrin. Percent cross-reactivity is calculated as:
% cross-reactivity = (concentration of spiked sample - concentration of unspiked sample) x100 concentration of cross-reactant
The following results were obtained:
| Cross-reactant | Concentration
(pmol/L) | Cross-reactivity
(%) |
|-------------------|---------------------------|-------------------------|
| Apotranscobalamin | 250 | 0.2 |
| | 500 | -0.1 |
| Haptocorrin | 2500 | -0.4 |
| | 5000 | -0.4 |
Interference
Potential interference in the ADVIA Centaur AB12 assay is designed to be less than or equal to 10%. Interfering substances at the levels indicated in the table below were tested as described in CLSI Document EP7-A2 using the ADVIA Centaur AB12 assay.
| Endogenous and
exogenous potential
interferents | Highest concentration at which no
significant interference (≤10%) was
observed |
|-------------------------------------------------------|--------------------------------------------------------------------------------------|
| *Biotin | 100 mg/dL |
| Cholesterol | 500 mg/dL |
| Conjugated Bilirubin | 40 mg/dL |
| Hemoglobin | 500 mg/dL |
| Human IgG | 12 g/dL |
| Methotrexate | 91 mg/dL |
| Perimethamine | 75 µg/mL |
| Rheumatoid Factor | 200 IU/mL |
| Silwet L720 | 0.2 mg/dL |
| Total Protein | 12 g/dL |
| Unconjugated Bilirubin | 60 mg/dL |
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| Endogenous and
exogenous potential
interferents | Highest concentration at which no
significant interference (≤10%) was
observed |
|-------------------------------------------------------|--------------------------------------------------------------------------------------|
| Triglyceride | 1000 mg/dL |
Precision
Precision was evaluated according to the CLSI protocol EP5-A2.
Five serum precision panel members were prepared with active-B12 concentrations spanning the measuring interval. Each sample was tested in replicates of 2 in two runs per day over 20 days. One ADVIA Centaur XP system was used and 2 reagent lots giving a total of 80 observations per sample for each reagent lot. Representative data from the study is shown in the following table.
A summary of the imprecision data is summarized below:
| Repeatability | Within-Lab | |||||
|---|---|---|---|---|---|---|
| Mean | SD | CV | SD | CV | ||
| Specimen | N | (pmol/L) | (pmol/L) | (%) | (pmol/L) | (%) |
| Sample 1 | 80 | 16.82 | 0.30 | 1.8 | 0.79 | 4.7 |
| Sample 2 | 80 | 38.12 | 1.12 | 2.9 | 1.66 | 4.4 |
| Sample 3 | 80 | 74.24 | 1.64 | 2.2 | 3.06 | 4.1 |
| Sample 4 | 80 | 104.76 | 1.92 | 1.8 | 4.16 | 4.0 |
| Sample 5 | 80 | 123.10 | 3.92 | 3.2 | 5.61 | 4.6 |
Summary of Clinical Performance:
The ADVIA Centaur AB12 assay demonstrated substantially equivalent performance to the ARCHITECT Active-B12 assay as indicated by method comparison and reference range studies.
Method Comparison
For 104 serum samples in the range of 5.56 – 142.58 pmol/L, the relationship of the ADVIA Centaur AB12 assay (y) and the Abbott ARCHITECT Chemiluminescent Microparticle Immunoassay (CMIA) Active-B12 (Holotranscobalamin) assay (x) is described using Passing-Bablok regression. Representative data from the study is shown below:
ADVIA Centaur AB12 = 0.97 (CMIA) - 0.99 pmol/L (intercept), r = 0.95.
Expected Values
The ADVIA Centaur AB12 assay results were obtained on 241 apparently healthy males (n = 103) and females (n = 138). The age range was 21 - 67 years. The mean holoTC concentration for the group was established at 81.91 pmol/L with a 95% central reference interval from 28.96–168.90 pmol/L according to EP28-A3c.
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As with all in vitro diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results. Consider these values as guidelines only.
Conclusion
The results presented in this 510(k) premarket submission demonstrate that the candidate assay (ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay, K160757) performance is substantially equivalent to the predicate assay (ARCHITECT Active-B12 (Holotranscobalamin) assay,K112443).
The similarities and differences between the candidate assay and the predicate assay are presented in the tables starting on page 3/8.