ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) Assay

K172133 · Axis-Shield Diagnostics, Ltd. · CDD · Oct 27, 2017 · Clinical Chemistry

Device Facts

• Record ID: K172133
• Device Name: ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) Assay
• Applicant: Axis-Shield Diagnostics, Ltd.
• Product Code: CDD · Clinical Chemistry
• Decision Date: Oct 27, 2017
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1810
• Device Class: Class 2

Intended 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.

Device Story

The ADVIA Centaur Active-B12 (AB12) assay is a fully automated, two-step direct chemiluminescent immunoassay used on the ADVIA Centaur XP/XPT system. It measures holotranscobalamin (holoTC) in human serum samples. The assay uses an acridinium ester-labeled anti-transcobalamin antibody as the Lite Reagent and biotinylated anti-holotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles as the Solid Phase. The device is used in clinical laboratory settings by trained technicians. The output is a quantitative concentration of holoTC (pmol/L), which healthcare providers use to assist in diagnosing and managing vitamin B12 deficiency. The modification in this submission updates the calibration traceability to the WHO International Standard (NIBSC Code 03/178).

Clinical Evidence

Bench testing only. Verification and validation activities performed to confirm impact of calibration modification against WHO International Standard (03/178).

Technological Characteristics

In vitro diagnostic immunoassay; automated system-based; calibration traceable to WHO International Standard (03/178).

Indications for Use

Indicated for the quantitative measurement of holotranscobalamin (holoTC) in human serum to aid in the diagnosis and treatment of vitamin B12 deficiency in patients.

Regulatory Classification

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.

Predicate Devices

• ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay (k160757)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 27, 2017

AXIS-SHIELD DIAGNOSTICS LTD. CLAIRE DORA REGULATORY AFFAIRS MANAGER LUNA PLACE THE TECHNOLOGY PARK DUNDEE, SCOTLAND DD2 1XA UK

Re: K172133

Trade/Device Name: ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay Regulation Number: 21 CFR 862.1810 Regulation Name: Vitamin B12 test system Regulatory Class: II Product Code: CDD Dated: September 26, 2017 Received: September 28, 2017

Dear Dr. 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 as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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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 [phone] or [phone] 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 [phone] or [phone] or at its Internet address

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

Sincerely yours,

Kellie B. Kelm -S

Courtney H. Lias, Ph.D. for 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) k172133

Device Name

ADVIA Centaur Active-B12 (Holotranscobalamin)(AB12) assay

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.

| Type of Use (Select one or both, as applicable) | |
|--------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| <span style="font-size: 10pt;">☑ Prescription Use (Part 21 CFR 801 Subpart D)</span> | <span style="font-size: 10pt;">☐ Over-The-Counter Use (21 CFR 801 Subpart C)</span> |

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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 k172133

#### Submission correspondent:

Dr Claire Dora Regulatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee, DD2 1XA, Scotland, UK Telephone: [phone] Fax: [phone] 510k summary prepared date: 25th October 2017

#### Device Name:

ADVIA Centaur® Active-B12 (Holotranscobalamin) (AB12) Assay

#### Reagents:

Classification Name: Vitamin B12 test system Trade Name: ADVIA Centaur® Active-B12 (Holotranscobalmin) (AB12) assay Common Name: B12 test Governing Regulation: 21CFR 862.1810 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: CDD

### Legally marketed device to which equivalency is claimed:

ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, K160757

### 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.

#### Description of Device:

Centaur AB12 assay is a fully automated, two-step direct immunoassay The ADVIA using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-transcobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated anti-holotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.

### Comparison of Technological Characteristics:

The modified ADVIA Centaur AB12 assay is being compared to the cleared ADVIA Centaur AB12 assay (k160757) for the quantitative measurement of holotranscobalamin (holoTC) in human serum.

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## Modification of Device:

The special 510k modification ADVIA Centaur AB12 assay consisted of a change to the calibration to be traceable to the WHO International Standard for Holotranscobalamin.

### Comparison of the subject device with the predicate device:

The modified ADVIA Centaur® AB12 assay is being compared to the cleared ADVIA Centaur® AB12 assay (k160757).

| Parameter | NEW<br>ADVIA Centaur®AB12<br>(Modified Device) | PREDICATE<br>ADVIA Centaur®AB12<br>(K160757 cleared device) |
|--------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | Same | For in vitro diagnostic use in the quantitative<br>measurement of holotranscobalamin (holoTC) in<br>human serum using the ADVIA Centaur XP system.<br>Active-B12 (holotranscobalamin) is used as an aid in<br>the diagnosis and treatment of vitamin B12<br>deficiency. |
| Assay Technology /<br>System | Same | Chemiluminescent microparticle<br>immunoassay ADVIA Centaur XP/XPT system |
| Reagents | Same | Lite Reagent:<br>anti-transcobalamin (TC) monoclonal Ab 3-11<br>(0.5 µg/mL) labeled with acridinium ester in<br>buffer with surfactant and preservatives<br>Solid Phase Reagent:<br>streptavidin coated paramagnetic mP<br>preformed with biotinylated anti-holoTC<br>monoclonal antibody 3C4<br>(~0.4 mg/mL) in buffer with surfactant |
| Calibration | Same | 2-point Calibration using 2 level calibrators |
| Calibration Range | Same | 0 to 146.0 pmol/L |
| Calibration Frequency | Same | 44 days |
| Levels | Same | 2 Levels<br>Low – 19 pmol/L<br>High - 121 pmol/L |
| Fill volume | Same | 4.0 mL |
| Calibration Materials<br>Formulation/ Matrix | Same | recombinant holotranscobalamin, bovine<br>serum albumin and sodium azide (< 0.1%) |
| Standardization | World Health Organization<br>(WHO) International Standard for<br>holotranscobalamin; NIBSC Code<br>03/178 | Internal reference material; recombinant<br>holotranscobalamin and phosphate buffer<br>with protein (bovine) stabilizers |
| Traceability of<br>calibration materials | WHO International Standard<br>NIBSC Code 03/178 | Internal (in-house)<br>reference standard |
| Parameter | NEW<br>ADVIA Centaur®AB12<br>(Modified Device) | PREDICATE<br>ADVIA Centaur®AB12<br>(K160757 cleared device) |
| Expected Values in<br>Asymptomatic<br>Population | The mean holoTC<br>concentration for the group was<br>established at 90.24 pmol/L with a<br>95% central reference interval<br>from 27.24 to 169.62 pmol/L | The mean holoTC concentration for the group was<br>established at 81.91 pmol/L with a 95% central<br>reference interval from 28.96 to 168.90 pmol/L |
| Analytical measuring<br>range | Same | 5.0 to 146.0 pmol/L |
| Limit of Quantitation | Same | 5.0 pmol/L |
| Quality Controls:<br>Level 1 (Low) Control | Same | 15.60 pmol/L |
| Quality Controls:<br>Level 2 (High) Control | Same | 60.40 pmol/L |

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## Summary of Non-Clinical Performance

Based on the risk analysis, the modifications to the Active-B12 (Holotranscobalamin) (AB12) assay could affect the accuracy, linearity, precision, and detection limits of the assay as well as the reference range.

Verification, validation and testing activities were conducted to establish performance of the modified device, which included:

Accuracy by correlation Dilution Linearity 20-day precision – repeatability and within-run Detection capability - Limit of blank / detection / quantification Dilution recovery of WHO IRP (NIBSC 03/178) Proficiency sample testing Reference range / expected value for asymptomatic population

The device passed all of the tests based on pre-determined Pass/Fail criteria.

### Conclusion:

The results presented in this 510(k) premarket submission demonstrate that the candidate assay (ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay is substantially equivalent to the predicate device.

Substantial equivalence of the modified device, ADVIA Centaur AB12 assay is claimed to the predicate device cleared in k160757. The modification to the assay calibration has not changed use, as described in the labelling, nor has it altered the fundamental assay technology of the device.