ARCHITECT Active-B12 (Holotranscobalamin)
Device Facts
| Record ID | K233541 |
|---|---|
| Device Name | ARCHITECT Active-B12 (Holotranscobalamin) |
| Applicant | Axis-Shield Diagnostics, Ltd. |
| Product Code | CDD · Clinical Chemistry |
| Decision Date | Jul 31, 2024 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1810 |
| Device Class | Class 2 |
Intended Use
The ARCHITECT Active-B12 (Holotranscobalamin) assay is a chemiluminescent microparticle immunoassay (CMIA) 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.
Device Story
The ARCHITECT Active-B12 is a two-step chemiluminescent microparticle immunoassay (CMIA) used on the ARCHITECT i System. It measures Holotranscobalamin (HoloTC) in human serum. In the first step, sample and anti-HoloTC coated paramagnetic microparticles are combined; HoloTC binds to the microparticles. After washing, an anti-transcobalamin acridinium-labeled conjugate is added. Following a second wash, pre-trigger and trigger solutions are added, producing a chemiluminescent reaction measured as relative light units (RLUs). The RLU signal is directly proportional to the HoloTC concentration. The device is used in clinical laboratory settings by trained personnel. Results assist clinicians in diagnosing and managing vitamin B12 deficiency. The assay provides quantitative data within a measuring interval of 5.0 to 128.0 pmol/L.
Clinical Evidence
No clinical trials were performed. Evidence is based on analytical bench testing, including precision (CLSI EP05-A3), linearity (CLSI EP06-Ed2), interference (CLSI EP07-ED3), and method comparison (CLSI EP09c-ED3) against the predicate. Precision studies showed total %CV ≤ 6.2%. Method comparison (n=108) yielded a slope of 0.9 (95% CI: 0.85, 0.94) and correlation coefficient of 0.95. Reference range transference was verified using 40 normal donor samples.
Technological Characteristics
Chemiluminescent microparticle immunoassay (CMIA) using paramagnetic microparticles coated with anti-holotranscobalamin and acridinium-labeled conjugate. Operates on the ARCHITECT i System. Measuring interval: 5.0–128.0 pmol/L. Reagent storage: 2-8°C; on-board stability: 30 days. Calibration interval: 30 days. Sample type: serum.
Indications for Use
Indicated for the quantitative determination of Holotranscobalamin 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
- ARCHITECT Active-B12 (Holotranscobalamin) (K112443)
Related Devices
- K112443 — ARCHITECT ACTIVE B-12 (HOLOTRANSCOBALAMIN) · Axis-Shield Diagnostics, Ltd. · Dec 19, 2011
- K121946 — AXIS-SHIELD ACVTIVE-B12 · Axis-Shield Diagnostics, Ltd. · Mar 22, 2013
Submission Summary (Full Text)
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FDA U.S. FOOD & DRUG ADMINISTRATION
July 31, 2024
Axis-Shield Diagnostics Ltd.
Claire Dora
Associate Director, Regulatory Affairs
Luna Place, The Technology Park
Dundee, DD2 1XA, Scotland, UK
Re: K233541
Trade/Device Name: ARCHITECT Active-B12 (Holotranscobalamin)
Regulation Number: 21 CFR 862.1810
Regulation Name: Vitamin B12 test system
Regulatory Class: Class II
Product Code: CDD
Dated: June 28, 2024
Received: July 1, 2024
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov
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K233541 - Claire Dora
Page 2
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D.
Deputy Director
Division of Chemistry
and Toxicology Devices
OHT7: Office of In Vitro Diagnostics
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Enclosure
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FORM FDA 3881 (8/23)
Page 1 of 1
PSC Publishing Services (301) 443-6740
EF
| DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use | Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below. |
| --- | --- |
| 510(k) Number (if known) K233541 | |
| Device Name ARCHITECT Active-B12 (Holotranscobalamin) | |
| Indications for Use (Describe) The ARCHITECT Active-B12 (Holotranscobalamin) assay is a chemiluminescent microparticle immunoassay (CMIA) 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 | |
| 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) | |
| CONTINUE ON A SEPARATE PAGE IF NEEDED. | |
| This section applies only to requirements of the Paperwork Reduction Act of 1995. *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* | |
| The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov | |
| "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." | |
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
# 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.
A. 510(k) number:
K233541
B. 510(k) Preparation Date:
31st July 2024
C. Applicant and Correspondent:
Axis-Shield Diagnostics Ltd.
The Technology Park
Dundee, DD2 1XA,
Scotland, UK
Establishment # 8032314
Dr Claire Dora
Associate Director, Regulatory Affairs
Telephone: +44(0) 1382 422000
Fax: +44(0) 1382 422088
D. Device Name:
ARCHITECT Active-B12 (Holotranscobalamin) Reagents
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
# E. Regulatory Information:
Trade Name: ARCHITECT Active-B12 (Holotranscobalamin)
Common Name: Vitamin B12 Radioassay
Classification Name: Vitamin B12 test system
Governing Regulation: 21CFR 862.1810
Product Code: CDD
Device Classification: Class II
Classification Panel: Clinical Chemistry
# F. Legally marketed device to which equivalency is claimed:
ARCHITECT Active-B12 (Holotranscobalamin), K112443.
# G. Description of Device:
The ARCHITECT Active-B12 (Holotranscobalamin) assay is a two-step immunoassay for the quantitative determination of Holotranscobalamin in human serum using CMIA technology, with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and anti-holotranscobalamin coated paramagnetic microparticles are combined. Holotranscobalamin present in the sample binds to the anti-holotranscobalamin coated microparticles. After washing, anti-transcobalamin acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of Holotranscobalamin in the sample and the RLUs detected by the ARCHITECT i System optics.
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
# H. Intended Use of Device:
The ARCHITECT Active-B12 (Holotranscobalamin) assay is a chemiluminescent microparticle immunoassay (CMIA) 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.
# I. Comparison with Predicate Device:
The modified (candidate) ARCHITECT Active-B12 (Holotranscobalamin) assay is substantially equivalent to the predicate device previously cleared under 510(k) premarket notification, K112443. The function and intended use of the device are equivalent to the predicate device. The table below provides a comparison of the technological characteristics of the proposed and predicate devices.
| Attribute | Original Device (Predicate)
ARCHITECT Active-B12
(Holotranscobalamin), K112443 | Candidate Device (New)
ARCHITECT Active-B12
(Holotranscobalamin) |
| --- | --- | --- |
| SIMILARTITIES | | |
| FDA Product Code | CDD | Same |
| Intended Use | The ARCHITECT Active-B12
(Holotranscobalamin) assay is a
chemiluminescent microparticle immunoassay
(CMIA) for the quantitative determination of
Holotranscobalamin in human serum on the
ARCHITECT iSystem. Active-B12
(Holotranscobalamin) is used as an aid in the
diagnosis and treatment of vitamin B12
deficiency. | Same |
| Intended Use Environment | Rx Only | Same |
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
| Attribute | Original Device (Predicate)
ARCHITECT Active-B12
(Holotranscobalamin), K112443 | Candidate Device (New)
ARCHITECT Active-B12
(Holotranscobalamin) |
| --- | --- | --- |
| Instrument | ARCHITECT i 2000SR system | Same |
| Assay Technology | Chemiluminescent microparticle immunoassay
(CMIA) | Same |
| Units of Measure | pmol/L | Same |
| Measuring Interval
(Reportable Range) | 5.0 – 128.0 pmol/L | Same |
| Sample type | Serum (serum and SST) | Same |
| Storage Requirements
for reagents, calibrators
and controls | 2-8°C until expiration date | Same |
| Onboard Storage | System temperature up to 30 days | Same |
| Stored Calibration | Calibration frequency 30 days | Same |
| Expected values | Central 95%: 25.1 to 165.0 pmol/L | Same |
| Limit of Quantitation
(LoQ) | 5.0 pmol/L | Same |
| Linear range | Across the measuring interval, 5.0 to 128.0
pmol/L | Same |
| Cross-reactivity | ≤ 10% Cross-reactivity observed in presence of;
• Apotranscobalamin at 500 pmol/L
• Haptocorrin at 5000 pmol/L | Same |
| Interference | ≤10% bias in the presence of the following
substances;
• Triglycerides 850 mg/dL
• Rheumatoid Factor 70 IU/mL | Same |
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
| DIFFERENCES | | |
| --- | --- | --- |
| Sample volume | 110μL | 70μl with 40μL buffer chase |
| Calibrator value assignment | Calibrator values: 0.0, 8.0, 16.0, 32.0, 64.0, 128.0 pmol/L | Calibrator Values: 0.0, 7.4, 16.8, 35.7, 73.5, 149.1 pmol/L |
| Lot-to-Lot | No Lot-to-lot data | Maximum % difference from target to observed concentration was 9.1% |
| Precision | Total %CV ≤ 5.8 %
Within-run %CV ≤ 4.4 % | For samples with holotranscobalamin concentrations ≥ 20 pmol/L:
• Total %CV ≤ 6.2 %
• Within-run %CV ≤ 5.8 %
For samples with holotranscobalamin concentrations <20 pmol/L:
• Total SD observed was 0.62 and 1.50
• Within-run SD observed was 0.49 and 1.37 |
| Interference | ≤10% bias in the presence of the following substances;
• Bilirubin 20 mg/dL
• Hemoglobin 200 mg/dL
• Total Protein 10 g/dL
• Biotin -Not tested | ≤10% bias in the presence of the following substances;
• Bilirubin (unconjugated) 40 mg/dL
• Bilirubin (conjugated) 40 mg/dL
• Hemoglobin 1000 mg/dL
• Total Protein 15 g/dL
• Biotin 4250 mg/dL |
## J. Summary of Non-Clinical Performance:
The ARCHITECT Active-B12 (Holotranscobalamin) assay demonstrated substantially equivalent performance to the predicate, ARCHITECT Active-B12 (Holotranscobalamin) assay, K112443. A summary of the non-clinical performance data included in this 510(k) submission has been presented below for the candidate device, ARCHITECT Active-B12 (Holotranscobalamin) assay.
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
# Precision
Precision was evaluated according to the CLSI guideline EP05-A3, 3rd Ed.
The candidate device demonstrated a ≤ 8% within-laboratory (total) %CV for samples with HoloTC concentrations ≥ 20.0 pmol/L and a total standard deviation (SD) of ≤ 1.6 pmol/L for samples with HoloTC concentrations < 20.0 pmol/L.
# Detection Capability
Limit of Quantitation was evaluated according to the CLIS guideline EP17-A2, 2nd Ed.
10 low-level HoloTC samples at concentration levels ranging from 0.6 to 5.5 pmol/L were prepared. These samples were tested over 3 days using 2 reagent lots and 1 instrument. The LoQ was determined to be 0.7 pmol/L.
In the same study, the Limit of Blank (LoB) and Limit of Detection (LoD) were determined. The LoB was 0.1 pmol/L and the LoD was 0.2 pmol/L.
# Linearity
Linearity was evaluated according to the CLSI guideline EP06-Ed2:2020, 2nd Ed.
One dilution series was prepared as follows: a high HoloTC sample was combined in specific ratios with a low HoloTC sample. The dilution series, including the low level and high-level sample, was tested using the ARCHITECT Active-B12 (Holotranscobalamin) assay. The ARCHITECT Active-B12 (Holotranscobalamin) assay demonstrated linearity across the measuring interval from 5.0 to 128.0 pmol/L (actual range observed: 2.26 to 134.17 pmol/L).
# High Sample Dilution Verification
High Sample dilution capabilities (Autodilution and manual dilution) was evaluated using the 1:2 assay protocol using human serum samples diluted with assay specific mulit-diluent.
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
The observed percent recovery for individual samples for when comparing manual to auto dilution met the study design as defined as 90 – 110% recovery for auto vs manual.
## Reactivity
Reactivity was evaluated following according to the CLSI guideline EP07, 3rd Ed.
No reactivity was observed as defined by ≤ 10% reactivity for B₁₂ binding proteins apotranscobalamin at 500 pmol/L and haptocorrin at 5000 pmol/L.
## Interference
Interference was evaluated following according to the CLSI guideline EP07, 3rd Ed.
No interference was observed as defined by ≤ 10% bias ≤10% in the presence of the following substances;
- Bilirubin (conjugated and unconjugated), 40 mg/dL
- Hemoglobin, 1000 mg/dL
- Total Protein, 15 g/dL
- Triglycerides, 850 mg/dL
- Rheumatoid Factor, 70 IU/mL
- Biotin, 4250 ng/mL
## On-Board Stability
On-Board stability and Calibration Interval were evaluated based on guidance from the CLSI guideline EP25-A, 1st Ed.
For the on-board stability study, three native serum pools targeted at the medical decision points of the assay were assessed in fresh and reference reagent kits (stored at intended storage of 2-8°C) and test reagent kits (stored on-board the instrument) over a period of 31 days. Ten testing time-points were spread out over this testing period. All samples demonstrated suitable stability through linear regression analysis detailing delta values
Section 5 - 510(k) SUMMARY
Confidential
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ARCHITECT ActiveB12 (Holotranscobalamin)
Pre-market Notification
AXIS-SHIELD
Innovation for Life
(pmol/L) versus Test Day over the 31 days; therefore supporting reagent on-board stability of 30 days.
For calibration interval, 3 testing time-points were performed up to 31 days. All samples demonstrated % difference <10% to Day 0 over the 31 days; therefore supporting reagent calibration interval of 30 days.
## K. Comparison Studies
The ARCHITECT Active-B12 (Holotranscobalamin) assay demonstrated substantially equivalent performance to the predicate, ARCHITECT Active-B12 (Holotranscobalamin) assay as indicated by a method comparison.
## Method Comparison
A correlation study was performed based on guidance from the CLSI EP09c.
Using two candidate lots and one predicate lot, 108 samples ranging from 5.4 to 128.0 pmol/L were evaluated using the Pearson correlation coefficient (r) and the Passing-Bablok regression method where by a slope of 0.9 and r value of 0.95 was demonstrated.
## L. Conclusion:
Based on the performance characteristics, the ARCHITECT Active-B12 (Holotranscobalamin) assay is substantially equivalent to the predicate device cleared in K112443. The modifications to the assay have not changed the intended use, as described in the labelling, nor have the changes altered the fundamental assay technology of the device.
Section 5 - 510(k) SUMMARY
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