The ARCHITECT i Vancomycin assay is an in vitro chemiluminescent microparticle immunoassay (CMIA) for the quantitative measurement of vancomycin in human serum or plasma on the ARCHITECT i System with STAT protocol capability. The ARCHITECT i Vancomycin assay is used in the diagnosis and treatment of vancomycin overdose and in monitoring levels of vancomycin to help ensure appropriate therapy.

Device Description

The ARCHITECT i Vancomycin assay is a one-step STAT immunoassay for the quantitative measurement of vancomycin in human serum or plasma using CMIA technology, with flexible assay protocols, referred to as Chemiflex.

Sample, anti-vancomycin coated paramagnetic microparticles, and vancomycin acridinium-labeled conjugate are combined to create a reaction mixture. The anti-vancomycin coated microparticles bind to vancomycin present in the sample and to the vancomycin acridinium-labeled conjugate. After washing, pre-trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An indirect relationship exists between the amount of vancomycin in the sample and the RLUs detected by the ARCHITECT i System optics.

AI/ML Overview

The ARCHITECT i Vancomycin assay is a device for the quantitative measurement of vancomycin in human serum or plasma. The device is a chemiluminescent microparticle immunoassay (CMIA) for in vitro diagnostic use, intended to aid in the diagnosis and treatment of vancomycin overdose and in monitoring its levels to ensure appropriate therapy.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria	Reported Device Performance
Precision	Total run %CV ≤ 10%	Total run %CV was ≤ 10%
Recovery	Not explicitly stated, but implied to be near 100% and within a reasonable range.	Overall percent recovery was 100.2%. Ranged from 98.0% to 105.4% for 5-45 ug/mL, and 86.4% for 3.2 µg/mL.
Interferences	Not explicitly stated, but implied that substances should not significantly impact recovery.	The mean recovery ranged from 93.0% to 104.5% for supplemented samples within specific interfering concentrations.
Linearity	Not explicitly stated, but implied to demonstrate a linear range across the assay's intended use.	Established linear range of 3.0 ug/mL to 50.0 ug/mL.
Sensitivity	Not explicitly stated, but values for LoB, LoD, and LoQ are provided.	Limit of Blank (LoB) was 0.27 ug/mL. Limit of Detection (LoD) was 0.42 ug/mL. Limit of Quantitation (LoQ) was 2.50 ug/mL.
Matrix Comparison	Not explicitly stated, but verified for various human serum and plasma types.	Verified for human serum and human plasma collected in Lithium heparin, Dipotassium EDTA, Sodium Citrate, Sodium Heparin, and Sodium Fluoride/Potassium Oxalate.
Specificity (Cross-reactivity)	Different criteria for CDP-1 (less than 0.42 µg/mL in absence of vancomycin, but interferes > 5 µg/mL in measurement range) and other compounds (less than 0.42 µg/mL for cross-reactivity, 100±10% recovery for interference).	CDP-1 at 10 ug/mL showed cross-reactivity < 0.42 µg/mL in the absence of vancomycin. CDP-1 at > 5 µg/mL interferes with samples containing vancomycin in the measurement range. Isoniazid at > 300 ug/mL interferes with samples containing vancomycin in the measurement range. Other tested compounds showed cross-reactivity < 0.42 µg/mL and no interference (100 ± 10% recovery).
Method Comparison (Correlation with predicate)	Not explicitly stated, but implied strong correlation (e.g., r close to 1, slope close to 1, intercept close to 0).	Correlation Coefficient (r) = 0.99 (95% CI: 0.99, 0.99). Slope = 1.04 (95% CI: 1.01, 1.07). Intercept = -0.23 (95% CI: -0.87, 0.36).
Measuring Interval	Not explicitly stated, but a defined range is established.	Measuring interval range: 3.0 µg/mL to 50.0 µg/mL.

2. Sample Sizes Used for the Test Set and Data Provenance

Precision: The document states that "Vancomycin samples were tested for precision." It does not specify the exact sample size.
Recovery: "Serum samples were spiked with vancomycin at concentrations across the assay range." The exact number of samples is not provided.
Interferences: "Serum specimens with vancomycin levels from 4.4 to 48.8 µg/mL were supplemented with the following potentially interfering compounds." The exact number of specimens or replicates is not provided.
Linearity: "Samples were tested to demonstrate linearity." The exact number of samples is not provided.
Sensitivity: "In this study," no specific sample size is mentioned.
Matrix Comparison: Specific number of samples or details on how many of each type of matrix were tested are not provided.
Specificity: Specific numbers of samples for each compound tested are not provided.
Method Comparison: 107 observations were used for the method comparison study between the new and predicate devices.

Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given the nature of in vitro diagnostic device testing for regulatory submission, it is typically conducted prospectively at controlled laboratory sites.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of device (in vitro diagnostic for quantitative measurement) does not typically rely on human expert interpretation to establish ground truth for performance studies like precision, recovery, linearity, and interference. Instead, the "ground truth" for these studies is established through:

Known concentrations: For studies like recovery and linearity, samples are spiked with known, precise concentrations of vancomycin or its analogues.
Reference methods/predicate devices: For method comparison, the "ground truth" for the test samples is derived from measurements by a legally marketed predicate device (ARCHITECT i Vancomycin [LN 1P30-25] in this case) or a traceable reference method.

Therefore, there were no "experts" in the sense of radiologists or pathologists to establish ground truth for this device's performance characteristics.

4. Adjudication Method for the Test Set

Not applicable for this type of quantitative in vitro diagnostic device. Adjudication methods (like 2+1, 3+1) are typically used in image-based diagnostic studies where human readers interpret results and consensus is needed to establish ground truth or resolve discrepancies. Here, the measurements are quantitative chemical analyses performed by an automated system.

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 for quantitative chemical measurement, not an AI-assisted diagnostic imaging or interpretation system that requires human readers.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

This entire submission describes the standalone performance of the ARCHITECT i Vancomycin assay (an automated immunoassay system). There is no "human-in-the-loop" component in the direct measurement and quantitation of vancomycin levels. The device itself performs the assay and provides a quantitative result.

7. The Type of Ground Truth Used

The ground truth for the performance studies was established using:

Known concentrations: For precision, recovery, linearity, sensitivity, and specificity studies, samples were prepared with precisely known concentrations of vancomycin or potential interfering/cross-reacting substances.
Predicate device results: For the method comparison study, the results from the legally marketed predicate ARCHITECT i Vancomycin assay (LN 1P30-25) were used as the comparative "ground truth" to demonstrate substantial equivalence.

8. The Sample Size for the Training Set

Not applicable. This is not a machine learning or AI-based device that requires a "training set" in the conventional sense. The device is a traditional immunoassay system with established chemical and optical principles.

However, if "training set" refers to the samples used during the development and optimization phases of the assay before formal validation, that information is not provided in this 510(k) summary. The provided details pertain to the formal validation studies.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" for an AI algorithm described in this submission. For the development and optimization of the immunoassay, ground truth would have been established through a combination of using known calibrators, controls, and potentially reference methods to ensure the assay's chemical and performance characteristics were appropriately tuned.

Summary

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KI23947

510(k) Summary

The summary of the 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:

Company and Contact Name

Mr. Joan Guixer, Director of Quality Assurance and Regulatory Affairs Biokit S.A. Llica d'Amunt Barcelona, Spain 08186 Phone: +34657883347/+34 93 860 9000 Fax: +34 93 860 9029

AUG 2 9 2013

Date Prepared: August 27, 2013

Regulatory Declarations

Common/Usual Name	Vancomycin Test
Trade/Proprietary Name	ARCHITECT i Vancomycin
Classification Regulation	21 CFR 862.3950
Device Class	Class II
Device Regulation Panel	Toxicology
Product Code	LEH

Indications for Use

Legally Marketed Device to Which Equivalency is Claimed

The ARCHITECT i Vancomycin assay (LN 1P30-28) is substantially equivalent to the previously cleared ARCHITECT i Vancomycin assay (LN 1P30-25, K072036).

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Device Description

Comparison of Technological Characteristics

Both the submission (ARCHITECT i Vancomycin [LN 1P30-28]) and predicate (ARCHITECT i Vancomycin [LN 1P30-25]) device use a chemiluminescent microparticle immunoassay (CMIA) technology for the quantitative measurement of vancomycin in human serum and plasma.

Summary of Performance Testing

Precision

Vancomycin samples were tested for precision following the CLSI protocol EPS-A2. In the study, the total run %CV was ≤ 10% and meets the design acceptance criteria.

Recovery

Serum samples were spiked with vancomycin at concentrations across the assay range. The overall percent recovery of the ARCHITECT i Vancomycin assay was 100.2%. The percent recovery ranged from 98.0% to 105.4% for vancomycin concentrations from 5 to 45 ug/mL. The percent recovery was 86.4% for vancomycin concentration 3.2 µg/mL.

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Interferences

Serum specimens with vancomycin levels from 4.4 to 48.8 µg/mL were supplemented with the following potentially interfering compounds. The mean recovery observed during the study ranged from 93.0% to 104.5%.

. Triglycerides, 2500 mg/dL
. Hemoglobin, 400 mg/dL
Bilirubin, 20 mg/dL .
Low Protein, 3 g/dL .
High Protein, 12 g/dL •
. HAMA, 1000 ng/mL
Rheumatoid Factor, 500 IU/mL

Linearity

Samples were tested to demonstrate linearity throughout the assay range. A linear range of

3.0 ug/mL to 50.0 ug/mL was established for the ARCHITECT i Vancomycin assay.

Sensitivity

In this study, the Limit of Blank (LoB) was 0.27 ug/mL, Limit of Detection (LoD) was

0.42 ug/mL and Limit of Quantitation (LoQ) was 2.50 ug/mL.

Matrix Comparison

The specimen collection tubes listed below were verified to be used with the ARCHITECT i Vancomycin assay.

Human serum .
. Human plasma collected in:
- . Lithium heparin
- . Dipotassium EDTA
- . Sodium Citrate
- . Sodium Heparin
- . Sodium Fluoride/Potassium Oxalate

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Specificity

A study has demonstrated that vancomycin crystalline degradation product 1 (CDP-1) at a concentration of 10 ug/mL, has cross-reactivity less than 0.42 µg/mL in the absence of vancomycin. CDP-1 at ≥ 5 µg/mL demonstrated cross-reactivity with samples containing vancomycin in the measurement range. CDP-1 may accumulate in patients with impaired renal function.

The following compounds were tested in the absence of vancomycin after adding 500 ug/mL of each compound (except Methotrexate, Isoniazid and CDP-1) to human serum. Isoniazid was tested at 300 ug/mL. Methotrexate was tested at 227 ug/mL. Cross-reactivity of each compound was less than 0.42 µg/mL. The same compounds (except CDP-1 and Isoniazid) at the concentrations tested demonstrated no interference in the presence of vancomycin using the acceptance criteria of % recovery within 100 ± 10%. Interference was observed for CDP-1 and Isoniazid in the presence of vancomycin as follows:

. CDP-1 at > 5 µg/mL interferes with samples containing vancomycin in the measurement range.
. Isoniazid at > 300 ug/mL interferes with samples containing vancomycin in the measurement range.

Acetaminophen	Clindamycin	Heparin	Nitrofurantoin	Sulfamethoxazole
Amikacin	Chloramphenicol	Hydrocholorothiazide	Penicillin G	Tetracycline
Amphotericin B	Chlorothiazide	Ibuprofen	Penicillin V	Ticarcillin
Ampicillin	Ciprofloxacin	Isoniazid	Prednisolone	Tobramycin
Caffeine	Erythromycin	Kanamycin B	Rifampin	Trimethoprim
CDP-1	Ethambutol	Methotrexate	Salicylic acid
Cefotaxime	5-Fluorocytosine	Methylprednisolone	Spectinomycin
Cephalexin	Furosemide	Naproxen	Streptomycin
Cephalothin	Gentamicin	Neomycin	Sulfadiazine

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Method Comparison

The new ARCHITECT i Vancomycin assay (LN 1P30-28) correlated with the predicate ARCHITECT i Vancomycin assay (LN 1P30-25) as shown in the table below:

Specimen Concentration Range(µg/mL)		Number ofObservations	CorrelationCoefficient (r)(95% CI)	Slope(95% CI)	Intercept(95% CI)
LN 1P30-25	LN 1P30-28
7.34-47.49	7.69-48.60	107	0.990.99, 0.99	1.041.01, 1.07	-0.23-0.87, 0.36

Measuring Interval

For the verification studies described in the reagent package insert, the measuring interval range is 3.0 µg/mL to 50.0 µg/mL.

Conclusion

Substantial equivalence of the proposed device to the previously cleared ARCHITECT i Vancomycin assay (K072036) has been demonstrated through performance testing to verify that the device functions as intended and design specifications have been satisfied.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G6(19 Silver Spring, MD 20993-0002

August 29, 2013

Biokit S.A. C/O Joan Guixer Can Malé S/N Llica d'Amunt, Barcelona, 08186, SPAIN

Re: K123947

Trade/Device Name: ARCHITECT iVancomycin Regulation Number: 21 CFR 862.3950 Regulation Name: Vancomycin test system Regulatory Class: II Product Code: LEH Dated: July 23, 2013 Received: July 25, 2013

Dear Mr. Guixer:

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 Part 801); 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 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 regulation (21 CFR Part 801), please go to http://www.fda.gov/AhoutFDA/CentersOffices/CDRH/CDRHOffices/uem115809.htm for

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Page 2-Mr. Guixer

the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance 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,

Carol C. Benson -S for

Courtney H. 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): K123947

Device Name: ARCHITECT i Vancomycin

Indications for Use:

Reagents

For in vitro diagnostic use.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR) Denise Johnson-lyles -S 2013.08.28 13:21:25 -04'00'

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k) K123947

Regulation Number and Section

§ 862.3950 Vancomycin test system.

(a)
Identification. A vancomycin test system is a device intended to measure vancomycin, an antibiotic drug, in serum. Measurements obtained by this device are used in the diagnosis and treatment of vancomycin overdose and in monitoring the level of vancomycin to ensure appropriate therapy.(b)
Classification. Class II.