(130 days)
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.
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.
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.
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.
This document describes the ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, a device for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum to aid in the diagnosis and treatment of vitamin B12 deficiency.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance:
| Performance Characteristic | Acceptance Criteria (from predicate or general principles) | Reported Device Performance (ADVIA Centaur AB12) |
|---|---|---|
| Linearity | Not explicitly stated (evaluated according to CLSI protocol EP6-A) | 5.00 - 146.00 pmol/L |
| Dilution Linearity | Not explicitly stated (recovery and parallelism assessed) | Average recovery: 93.77% (Range: 90.86% - 98.61%) |
| Measuring Interval | Not explicitly stated (range of measurable concentrations) | 5.00 - 146.00 pmol/L |
| Limit of Blank (LoB) | Not explicitly stated (determined as per CLSI Document EP17-A2) | 0.74 pmol/L |
| Limit of Detection (LoD) | Not explicitly stated (determined as per CLSI Document EP17-A2, 95% probability) | 1.08 pmol/L |
| Limit of Quantitation (LoQ) | Not explicitly stated (determined as per CLSI Document EP17-A2, total CV of 8%) | 5.00 pmol/L |
| High Dose Hook Effect | No significant hook effect (specifically, assaying greater than 146.00 pmol/L) | No hook effect observed up to 1867.80 pmol/L |
| Cross-reactivity | ≤ 10% cross-reactivity with specified substances | Apotranscobalamin: 0.2% / -0.1%Haptocorrin: -0.4% / -0.4% |
| Interference | ≤ 10% interference with specified substances at indicated concentrations | All tested substances (Biotin, Cholesterol, Conjugated Bilirubin, Hemoglobin, Human IgG, Methotrexate, Perimethamine, Rheumatoid Factor, Silwet L720, Total Protein, Unconjugated Bilirubin, Triglyceride) demonstrated ≤ 10% interference at the specified highest concentrations. |
| Precision (Within-Lab %CV) | Not explicitly stated (compared to predicate, which has Total %CV ≤ 5.8%) | Within-Lab (Total) %CV ≤ 4.7% (Range: 4.0% - 4.7%) |
| Precision (Repeatability %CV) | Not explicitly stated (compared to predicate, which has Within-run %CV ≤ 4.4%) | Repeatability (Within-run) %CV ≤ 3.2% (Range: 1.8% - 3.2%) |
| Method Comparison (Correlation with Predicate) | Not explicitly stated (substantially equivalent performance expected) | r = 0.95 (Passing-Bablok regression: ADVIA Centaur AB12 = 0.97 (CMIA) - 0.99 pmol/L) |
| Expected Values (Reference Interval) | Not explicitly stated (established for the assay) | 95% central reference interval from 28.96 – 168.90 pmol/L |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Linearity: The number of samples used is not explicitly stated, but it involved "Two samples containing high levels of active-B12" mixed with "a pool of artificial serum matrix."
- Dilution Linearity: Five samples were used.
- Detection Capability (LoB, LoD, LoQ): The raw sample sizes for these determinations are not specified but are described as being determined according to CLSI Document EP17-A2, which typically involves multiple replicates and measurements.
- High Dose Hook: Patient samples with "active-B12 levels as high as 1867.80 pmol/L" were tested. The exact number of samples is not stated.
- Cross-reactivity: Populations evaluated included "other B12 proteins apotranscobalamin and haptocorrin" at two different concentrations each. The number of samples per concentration is not stated.
- Interference: The number of unique samples or runs for each interfering substance is not explicitly stated.
- Precision: Five serum precision panel members were used. Each sample was tested in replicates of 2 in two runs per day over 20 days, resulting in 80 observations per sample for each reagent lot.
- Method Comparison: 104 serum samples were used.
- Expected Values (Reference Range): 241 apparently healthy males (n = 103) and females (n = 138) were used. The age range was 21 - 67 years.
The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective, beyond stating that the device is manufactured by Axis-Shield Diagnostics Ltd. in Scotland, UK. The reference range study involved "apparently healthy males and females," suggesting prospective collection for that specific study.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
This device is an in-vitro diagnostic assay for quantitative measurement of holotranscobalamin. The "ground truth" for such assays is typically established by established reference methods, calibrated standards, or the concentration values determined by a legally marketed predicate device. Experts are not directly involved in establishing "ground truth" for individual test results in the same way they would be for image interpretation.
- For method comparison, the "ground truth" reference values were obtained from the ARCHITECT Active-B12 (Holotranscobalamin) assay (K112443), which is the legally marketed predicate device.
- For reference range establishment, the "ground truth" is derived from the statistical analysis of results from a healthy population, following established protocols (EP28-A3c).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This is not a study involving human interpretation or subjective assessment that would require adjudication. The performance is based on quantitative measurements.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is an in-vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the studies presented are standalone performance evaluations of the ADVIA Centaur Active-B12 assay. The performance characteristics (linearity, precision, detection capability, interference, cross-reactivity, method comparison) are intrinsic to the device and do not involve human intervention in the interpretive output generation. The assay quantitatively measures holotranscobalamin levels.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The ground truth used depends on the specific performance characteristic:
- Assay values for clinical samples: The ARCHITECT Active-B12 (Holotranscobalamin) assay (CMIA) was used as the comparator or "reference" for method comparison studies.
- Known concentrations: For studies like linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, and interference, the "ground truth" is based on known spiked concentrations of substances or defined samples with expected values (e.g., precision panel members with established active-B12 concentrations).
- Population statistics: For expected values (reference range), the "ground truth" is derived from statistical analysis of a healthy reference population, following CLSI guidelines.
8. The sample size for the training set:
Not applicable. This device is an in-vitro diagnostic assay, not a machine learning or AI model that requires a distinct training set in the conventional sense. The "training" or development of such assays involves reagent formulation, optimization, and calibration based on known standards and samples, but not a "training set" like that used for algorithms.
9. How the ground truth for the training set was established:
Not applicable. As explained in point 8, there isn't a "training set" for an in-vitro diagnostic assay in the same way there is for an AI algorithm. The assay is developed and optimized using known standards and calibrated samples, where the "ground truth" for these is established through highly accurate reference methods or certified reference materials. The calibration of the device itself relies on "Master Curve Material" (MCM) with established values.
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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
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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
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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
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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.
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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 thequantitative measurement ofholotranscobalamin (holoTC) in humanserum using the ADVIA Centaur XPsystem. Active-B12 (holotranscobalamin)is used as an aid in the diagnosis andtreatment of vitamin B12 deficiency. | For the quantitative determination ofHolotranscobalamin in human serum onthe ARCHITECT i System.Active-B12 (Holotranscobalamin) is usedas an aid in the diagnosis and treatment ofvitamin B12 deficiency. |
| Assay Technology | Chemiluminescent microparticleimmunoassay (CMIA) | Chemiluminescent microparticleimmunoassay (CMIA) |
| Substrate / SignalGeneration | 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 at2-8ºC. | Reagent Pack must be stored at2-8ºC. |
| 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 dilutionprotocol | 1:2 autodilute withADVIA Centaur Multi-Diluent 13 | 1:2 autodilute or manual with ARCHITECT iMulti-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 levelcalibrators | 6-point calibration curve.4PLC Y-weighted |
| Expected Values inAsymptomaticPopulation | The mean holoTC concentration forthe group was established at 81.91pmol/L with a 95% central referenceinterval from 28.96 to 168.90 pmol/L | The mean Holotranscobalaminconcentration was 71.9 pmol/L with a rangefrom 20.6 to 196.7 pmol/L. The central 95%of the population defined the expectedrange 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/dLMethotrexate at 91 mg/dLPerimethamine at 75 µg/mL | ||
| Cross- Reactivity | No detectable cross-reactivity with;Apotranscobalamin at 500 pmol/LHaptocorrin at 5000 pmol/L | No detectable carryover with;Apotranscobalamin at 500 pmol/LHaptocorrin 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 ReagentStability | Reagents can be stored onboard theCentaur XP instrument for a maximumof 44 days. | Reagents can be stored onboard theARCHITECT instrument for a maximum of 30days. |
| CalibrationFrequency | 44 days | 30 days |
| Sample Stability | Separated specimens are stable for 16hours at room temperature, 3 days at2-8°C | Up to 16 hours at room temperatureUp to 3 days at 2-8°C (for longer than 3 daysstore at -20°C or colder for up to 6 months). |
| For longer storage, specimens may befrozen for 3 months at -20 °C orcolder. Avoid more than 1 freeze/thawcycle. Do not store in a frost-freefreezer | Avoid more than 3 freeze-thaw cycles. | |
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Differences
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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 andexogenous potentialinterferents | Highest concentration at which nosignificant interference (≤10%) wasobserved |
|---|---|
| *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 andexogenous potentialinterferents | Highest concentration at which nosignificant interference (≤10%) wasobserved |
|---|---|
| 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.
§ 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.