Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies detail a standard homogeneous enzyme immunoassay and its analytical performance characteristics. There is no mention of AI or ML in the intended use, device description, or performance summaries.

Therapeutic

No.
This device is an immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma to aid in the management of patients treated with lamotrigine. It is a diagnostic device for measuring drug levels, not a therapeutic device that treats or prevents disease.

Diagnostic

Yes

The device quantitatively determines lamotrigine in human serum or plasma, and these concentrations can be used "as an aid in management of patients treated with lamotrigine," which aligns with the definition of a diagnostic device providing information for the diagnosis, treatment, or prevention of disease.

SaMD (Software as a Medical Device)

No

The device is a homogeneous enzyme immunoassay consisting of reagents (R1 and R2), calibrators, and controls, which are physical components used in a laboratory setting. It is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers." This is a classic description of an in vitro diagnostic test performed on biological samples.
Indications for Use: The indications state that the results "can be used as an aid in management of patients treated with lamotrigine." This indicates the test provides information used for medical purposes.
Device Description: The description details a "homogeneous enzyme immunoassay" that measures a substance in a biological specimen (serum or plasma). This is a common type of IVD technology.
Components: The device includes reagents, calibrators, and controls, which are typical components of an IVD kit used for performing a diagnostic test.
Performance Studies: The document includes detailed performance studies (Limit of Quantitation, Assay Range, Recovery, Linearity, Method Comparison, Precision, Interfering Substances, Specificity, Sample Stability, On-Board Stability, Traceability) which are required for demonstrating the analytical performance of an IVD.
Intended User / Care Setting: The intended user is a "Routine clinical laboratory," which is where IVD tests are typically performed.
Predicate Device: The mention of a predicate device (K062966; QMS® Lamotrigine, calibrators and controls) is a strong indicator that this device is being submitted for regulatory clearance as an IVD, as predicate devices are used for demonstrating substantial equivalence to legally marketed IVDs.

All of these factors align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers. Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.

The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.

The ARKTM Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.

Product codes (comma separated list FDA assigned to the subject device)

ORH, DLJ, LAS

Device Description

The ARK Lamotrigine Assay is a homogeneous immunoassay based on competition between drug in the specimen and lamotrigine labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Lamotrigine Assay consists of reagents R1 anti-lamotrigine polyclonal antibody with substrate and R2 lamotrigine labeled with bacterial G6PDH enzyme. The ARK Lamotrigine Calibrator consists of a six-level set to calibrate the assay, and the ARK Lamotrigine Control consists of a three-level set used for quality control of the assay.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Routine clinical laboratory

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

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Limit of Quantitation (LOQ)
The LOQ of the ARK Lamotrigine Assay was determined according to CLSI EP17-A and is defined as the lowest concentration for which acceptable inter-assay precision and recovery is observed (40.00 ug/mL or above the analyzer-specific upper LOQ established in your laboratory.

Specimens testing initially above the assay range may be diluted in Calibrator A and retested. Multiply the assay result by the dilution factor to obtain the concentration of lamotrigine in the undiluted specimen.

Recovery
Accuracy (analytical recovery) was performed by adding concentrated lamotrigine drug into human serum negative for lamotrigine. A stock concentrate of highly pure lamotrigine was added volumetrically to human serum negative for lamotrigine, representing drug concentrations across the assay range. Six replicates of each sample were assayed on an automated clinical chemistry analyzer. The results were averaged and compared to the target concentration and percent recovery calculated. Mean percent recovery: 99.2.

Linearity
Linearity studies were performed as suggested in CLSI/NCCLS Protocol EP6-A. A 48.00 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for lamotrigine. Lamotrigine concentrations ranged from 1.00 to 48.00 ug/mL. Linearity at specific dilutions was considered acceptable if the percent difference was ±10% between the predicted 155 and 2nd order regressed values.

Method Comparison
Correlation studies were performed using CLSI/NCCLS Protocol EP9-A2. Results from the ARK Lamotrigine Assay on the Roche/Hitachi 917 system were compared with results from high performance liquid chromatography (HPLC, Study 1) and a turbidimetric immunoassay (Study 2).

Study 1 (HPLC Comparison)
- Lamotrigine concentrations by HPLC ranged 1.00 to 36.70 µg/mL.
- ARK lamotrigine values ranged 0.97 to 36.32 µg/mL.
- Results of Passing-Bablok regression analysis: Slope = 1.01 (0.99 to 1.03), y-intercept = 0.37 (0.22 to 0.55), Correlation Coefficient (r2) = 0.97 (0.96 to 0.98).
- Number of Samples = 193.
Study 2 (Turbidimetric Immunoassay Comparison)
- Lamotrigine concentrations by the turbidimetric immunoassay ranged from 2.28 µg/mL to 37.70 µg/mL.
- ARK lamotrigine values ranged 2.51 to 36.32 µg/mL.
- Results of Passing-Bablok regression analysis: Slope = 0.93 (0.89 to 0.97), y-intercept = 0.41 (0.07 to 0.74), Correlation Coefficient (r2) = 0.96 (0.94 to 0.97).
- Number of Samples = 77.

Precision
Precision was determined as described in CLSI/NCCLS Protocol EP5-A2. Tri-level controls and three human serum pooled specimens containing lamotrigine were used in the study. Each level was assayed in quadruplicate twice a day for 20 days. Each of the runs per day was separated by at least two hours. The within run, between day, total SD, and percent CVs were calculated. Acceptance criteria: ≤10% total CV. All results shown were within acceptance criteria.

Interfering Substances
Interference studies were conducted using CLSI/NCCLS Protocol EP7-A2. Clinically high concentrations of potentially interfering substances in serum with known levels of lamotrigine (approximately 3 and 15 µg/mL) were evaluated. Measurement of lamotrigine resulted in ≤10% error in the presence of interfering substances at the levels tested.

Specificity
Lamotrigine's major metabolite (2-N-glucuronide), minor metabolites (2-N-methyl, 2-N-oxide), and co-administered anti-epileptic drugs were tested for cross-reactivity. High levels of these compounds were spiked into serum pools containing low (3 µg/mL) and high (15 µg/mL) therapeutic levels of lamotrigine. The samples were analyzed and cross-reactivity percentages were determined. Lamotrigine-selective antibody did not cross-react with most anti-epileptic or co-administered drugs tested. Due to structural similarities with lamotrigine, high trimethoprim levels may interfere (e.g., 40.0 µg/mL trimethoprim resulted in 156.0% recovery for 3 µg/mL lamotrigine and 108.0% recovery for 15 µg/mL lamotrigine).

Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing lamotrigine. The results indicate that there is no significant difference between the recovery of lamotrigine in serum or plasma.

Sample Stability
Serum specimens were shown to be stable for at least six (6) months frozen, at least fifty (50) hours at room temperature (22°C), at least thirty-seven (37) days when refrigerated (2-8°C) and after three (3) successive freeze/thaw cycles.

On-Board Stability
Calibration Curve Stability: Calibration curve stability for a period of 30 days is supported by data.
Reagent on-board stability: Reagents were effective when stored after transfer to analyzer specific reagent containers for up to at least 30 days as supported data. In-use stability of calibrator and controls was also demonstrated.
Accelerated OPEN stability of calibrators and controls: Calibrators and controls were shown to be stable OPEN in accelerated stability at 37℃ for seven (7) days. Once opened vials may be stored at 2-8℃ for 12 months.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Limit of Quantitation (LOQ): 0.85 µg/mL
Assay Range: 0.85 to 40.00 µg/mL
Mean percent recovery: 99.2%
Precision: Total CV ≤ 10%
Interference: ≤ 10% error in presence of interfering substances.

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.

QMS® Lamotrigine, calibrators and controls (K062966)

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

Regulation Number and Section

§ 862.3350 Diphenylhydantoin test system.

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

Summary

0

K/01305

પુદા 2 પુ ટેપાર

510(k) SUMMARY

ARK™ Lamotrigine Assay ARK™ Lamotrigine Calibrator ARK™ Lamotrigine Control

ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay

page 1 of 15

1

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 K101305.

807.92 (a)(1): Name: ARK Diagnostics, Inc. Address: 1190 Bordeaux Drive Sunnyvale, CA 94089 Owner Operator Number: 10027663 Establishment Registration: 3005755244 (400) スイフ 0700 n.

Phone:	(408) 747-0700
FAX:	(408) 747-0783
Contact:	Johnny Valdez – (408) 747-0706
President

Date prepared: October 20, 2010

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name:	ARK TM Lamotrigine Assay
	ARK TM Lamotrigine Calibrator
	ARK TM Lamotrigine Control
Common Name:	Homogeneous Enzyme Immunoassay
Classification:	21 CFR 862.3350 NWM Diphenylhydantoin Test System; Class II (21 CFR 862.3200 DLJ, 21 CFR 862.3280 LAS)

807.92 (a)(3): Identification of the legally marketed predicate device

QMS® Lamotrigine, calibrators and controls (K062966)

ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay

page 2 of 15

2

807.92 (a)(4): Device Description

The ARK Lamotrigine Assay is a homogeneous immunoassay based on competition between drug in the specimen and lamotrigine labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Lamotrigine Assay consists of reagents R1 anti-lamotrigine polyclonal antibody with substrate and R2 lamotrigine labeled with bacterial G6PDH enzyme. The ARK Lamotrigine Calibrator consists of a six-level set to calibrate the assay, and the ARK Lamotrigine Control consists of a three-level set used for quality control of the assay.

807.92 (a)(5): Intended Use / Indications for Use

The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers. Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.

The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.

The ARKTM Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.

3

807.92 (a)(6): Technological Similarities and Differences to the Predicate

:

SUBSTANTIAL EQUIVALENCE COMPARATIVE CHART

Characteristic	Device	Predicate
	ARK™ Lamotrigine Assay	QMS® Lamotrigine K062966
Intended Use	The ARK™ Lamotrigine Assay is
intended for the quantitative
determination of lamotrigine in human
serum or plasma on automated clinical
chemistry analyzers.	The QMS Lamotrigine is intended for
the quantitative determination of
lamotrigine in human serum or plasma
on automated clinical chemistry
analyzers.
Indications for
Use	Lamotrigine concentrations can be used
as an aid in management of patients
treated with lamotrigine.	Lamotrigine concentrations can be used
as an aid in management of patients
treated with lamotrigine.
Sample	Serum or plasma	Serum or plasma
Methodology	Homogenous enzyme immunoassay
(EIA)	Homogeneous particle-enhanced
turbidimetric immunoassay (particle
agglutination)
Reagent
Components	Two (2) reagent system:
Anti-Lamotrigine
Antibody/Substrate Reagent
(R1) containing rabbit
polyclonal antibodies to
lamotrigine, glucose-6-
phosphate, nicotinamide adenine
dinucleotide, bovine serum
albumin, preservatives, and
stabilizers Enzyme Reagent (R2)
containing lamotrigine labeled
with bacterial G6PDH, buffer,
bovine serum albumin,
preservatives, and stabilizers	Two (2) reagent system:
Anti-Lamotrigine Antibody
Reagent (R1) in buffers
containing stabilizers with
sodium azide Lamotrigine-coated
Microparticle Reagent (R2) in
buffer containing
stabilizers with sodium azide
Platform required	Automated clinical chemistry analyzer	Automated clinical chemistry analyzer
Accessory
reagents	Calibrators (six levels) and controls
(three levels)	Calibrators (six levels) and controls
(three levels)
Testing
environment	Routine clinical laboratory	Routine clinical laboratory
Reagent
condition and
storage	Liquid, 2-8° C	Liquid, 2-8° C

.

Comparison between the ARK™ Lamotrigine Assay and the OMS® Lamotrigine Assay

ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay

page 4 of 15

4

807.92 (b)(1) and 807.92 (b)(2): Brief Description of Nonclinical and Clinical Data

Limit of Quantitation (LOO)

The LOQ of the ARK Lamotrigine Assay was determined according to CLSI EP17-A and is defined as the lowest concentration for which acceptable inter-assay precision and recovery is observed (40.00 ug/mL or above the analyzer-specific upper LOQ established in your laboratory.

Specimens testing initially above the assay range may be diluted in Calibrator A and retested. Multiply the assay result by the dilution factor to obtain the concentration of lamotrigine in the undiluted specimen.

Recovery

Accuracy (analytical recovery) was performed by adding concentrated lamotrigine drug into human serum negative for lamotrigine. A stock concentrate of highly pure lamotrigine was added volumetrically to human serum negative for lamotrigine, representing drug concentrations across the assay range. Six replicates of each sample were assayed on an automated clinical chemistry analyzer. The results were averaged and compared to the target concentration and percent recovery calculated. Results are shown below.

| Theoretical
Concentration
(µg/mL) | Mean Recovered
Concentration
(µg/mL) | Percent
Recovery |
|-----------------------------------------|--------------------------------------------|---------------------|
| 0.85 | 0.84 | 98.2 |
| 1.00 | 0.99 | 99.2 |
| 2.50 | 2.48 | 99.3 |
| 5.00 | 5.25 | 105.1 |
| 11.00 | 10.97 | 99.7 |
| 15.00 | 14.80 | 98.7 |
| 30.00 | 29.16 | 97.2 |
| 40.00 | 38.33 | 95.8 |

		% Recovery = 100 X Mean recovered concentration
		Theoretical concentration

Mean percent recovery: 99.2

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Linearity

Linearity studies were performed as suggested in CLSI/NCCLS Protocol EP6-A. A 48.00 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for lamotrigine. Lamotrigine concentrations ranged from 1.00 to 48.00 ug/mL. Linearity at specific dilutions was considered acceptable if the percent difference was ±10% between the predicted 155 and 2nd order regressed values. Results are shown below.

| Estimated
Value (µg/mL) | Results
(ug/mL) | 1st Order
Predicted
Results | 2nd Order
Predicted
Results | % Difference
(Acceptance
Criteria:
+10%) |
|----------------------------|--------------------|-----------------------------------|-----------------------------------|---------------------------------------------------|
| 1.00 | 0.96 | 1.13 | 1.21 | 7.1 |
| 2.00 | 2.08 | 2.11 | 2.17 | 3.1 |
| 4.00 | 4.16 | 4.06 | 4.10 | 0.9 |
| 8.00 | 8.18 | 7.97 | 7.96 | -0.1 |
| 12.00 | 12.01 | 11.88 | 11.83 | -0.4 |
| 16.00 | 16.18 | 15.78 | 15.72 | -0.4 |
| 24.00 | 22.78 | 23.60 | 23.53 | -0.3 |
| 32.00 | 30.84 | 31.41 | 31.39 | -0.1 |
| 40.00 | 40.13 | 39.23 | 39.30 | 0.2 |
| 48.00* | 46.88 | 47.04 | 47.27 | 0.5 |

*Concentration exceeds the reportable limit.

Method Comparison

Correlation studies were performed using CLSI/NCCLS Protocol EP9-A2. Results from the ARK Lamotrigine Assay on the Roche/Hitachi 917 system were compared with results from high performance liquid chromatography (HPLC, Study 1) and a turbidimetric immunoassay (Study 2).

6

Study 1

Lamotrigine concentrations by HPLC ranged 1.00 to 36.70 µg/mL. ARK lamotrigine values ranged 0.97 to 36.32 µg/mL. Results of the Passing-Bablok' regression analysis for the study are shown below (with 95% confidence limits).

Slope	1.01	(0.99 to 1.03)
y-intercept	0.37	(0.22 to 0.55)
Correlation Coefficient (r2)	0.97	(0.96 to 0.98)
Number of Samples	193

Image /page/6/Figure/3 description: This image is a scatter plot comparing two different methods of measuring Lamotrigine concentration. The x-axis represents the concentration measured by HPLC in micrograms per milliliter, while the y-axis represents the concentration measured by ARK Lamotrigine Assay, also in micrograms per milliliter. The plot includes a line of identity and a Passing & Bablok fit line, which is described by the equation y = 0.37 + 1.01x.

ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay

page 7 of 15

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Study 2

Lamotrigine concentrations by the turbidimetric immunoassay ranged from 2.28 µg/mL to 37.70 µg/mL. ARK lamotrigine values ranged 2.51 to 36.32 µg/mL. Results of the Passing-Bablok" regression analysis for the study are shown below (with 95% confidence limits).

Slope	0.93	(0.89 to 0.97)
y-intercept	0.41	(0.07 to 0.74)
Correlation Coefficient (r2)	0.96	(0.94 to 0.97)
Number of Samples	77

Image /page/7/Figure/3 description: This figure is a scatter plot comparing two different assays for measuring Lamotrigine. The x-axis represents the Turbidimetric Immunoassay in μg/mL, while the y-axis represents the ARK Lamotrigine Assay in μg/mL. The plot includes a Passing & Bablok fit line, represented by the equation (0.41 + 0.93x), along with an identity line for reference.

page 8 of 15

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Precision

Precision was determined as described in CLSI/NCCLS Protocol EP5-A2. Tri-level controls and three human serum pooled specimens containing lamotrigine were used in the study. Each level was assayed in quadruplicate twice a day for 20 days. Each of the runs per day was separated by at least two hours. The within run, between day, total SD, and percent CVs were calculated. Results are shown below. Acceptance criteria: ≤10% total CV.

			Within Run			Between Day		Total
Sample	N	Mean
(µg/mL)	SD	CV
(%)	SD	CV
(%)	SD	CV
(%)
ARK Lamotrigine Control
LOW	160	2.08	0.07	3.4	0.05	2.5	0.08	4.1
MID	160	11.70	0.42	3.6	0.28	2.4	0.49	4.2
HIGH	160	24.23	0.99	4.1	1.06	4.4	1.47	6.1
Calibrator/Control
Matrix	40	38.04	2.05	5.4	0.95	2.5	2.27	6.0
Human Serum
LOW	160	2.41	0.08	3.5	0.09	3.7	0.12	5.2
MID	160	10.75	0.41	3.8	0.42	3.9	0.59	5.5
HIGH	160	25.84	1.33	5.2	1.12	4.3	1.88	7.3
Pooled Human
Serum	40	38.24	2.78	7.3	0.61	1.6	3.38	8.8

9

Interfering Substances .

Interference studies were conducted using CLSI/NCCLS Protocol EP7-A2 as a guideline. Clinically high concentrations of the following potentially interfering substances in serum with known levels of lamotrigine (approximately 3 and 15 µg/mL) were evaluated. Each sample was assayed using the ARK Lamotrigine Assay, along with a serum control of lamotrigine. Measurement of lamotrigine resulted in ≤10% error in the presence of interfering substances at the levels tested.

			Percentage Recovery
Interfering
Substance	Interferent
Concentration	3 $\mu$ g/mL
Lamotrigine	15 $\mu$ g/mL
Lamotrigine
Albumin	12 g/dL	101.5	103.4
Bilirubin - conjugated	70 mg/dL	93.6	102.6
Bilirubin - unconjugated	70 mg/dL	97.1	105.0
Cholesterol	623 mg/dL	98.9	103.8
Gamma-Globulin	12 g/dL	106.8	104.4
Hemoglobin	1000 mg/dL	98.2	97.0
Intralipid®	1000 mg/dL	94.5	94.3
Rheumatoid Factor	1100 IU/mL	107.3	108.9
Triglycerides	618 mg/dL	101.7	104.0
Uric Acid	30 mg/dL	101.0	99.6

Specificity

Lamotrigine's major metabolite, medications that may be routinely co-administered with lamotrigine and other anti-evileptic drugs were tested to determine whether these compounds affect the quantitation of lamotrigine concentrations using the ARK Lamotrigine Assay. High levels of these compounds were spiked into serum pools containing low (3 µg/mL) and high (15 µg/mL) therapeutic levels of lamotrigine. The samples were analyzed and the lamotrigine concentrations of samples containing interferent were compared to the serum control.

10

Metabolites

Lamotrigine is metabolized predominantly by UDP-glucuronyltransferase to form a pharmacologically inactive metabolite, 2-N-glucuronide. Lamotrigine-2-N-methyl has been detected in human plasma by HPLC and capillary electrophoresis. Other minor metabolites, lamotrigine-2-N-oxide, and lamotrigine-5-N-glucuronide have been proposed. Lamotrigine-2-N-glucuronide, Lamotrigine-2-N-methyl and Lamotrigine-2-N-oxide metabolites were tested for cross-reactivity. These metabolites were spiked into two separate samples each containing low and high lamotrigine concentrations of 3 and 15 µg/mL, respectively.

| Metabolite* | Metabolite
Concentration
(\u03bcg/mL) | Percentage Cross-Reactivity | |
|---------------------------------|---------------------------------------------|-------------------------------|--------------------------------|
| | | Lamotrigine
(3 \u03bcg/mL) | Lamotrigine
(15 \u03bcg/mL) |
| Lamotrigine-2-N-
glucuronide | 50.0 | 2.41 | 1.86 |
| Lamotrigine-2-N-
glucuronide | 25.0 | 2.57 | 1.09 |
| Lamotrigine-2-N-
glucuronide | 12.5 | 2.91 | 1.92 |
| Lamotrigine-2-N-
glucuronide | 9.0 | 2.15 | 1.57 |
| Lamotrigine-2-N-methyl | 400.0 | 0.04 | 0.21 |
| Lamotrigine-2-N-methyl | 200.0 | 0.07 | 0.02 |
| Lamotrigine-2-N-methyl | 80.0 | 0.10 | 0.24 |
| Lamotrigine-2-N-oxide | 80 | 3.69 | 3.63 |
| Lamotrigine-2-N-oxide | 40 | 3.94 | 3.64 |
| Lamotrigine-2-N-oxide | 20 | 3.72 | 3.14 |
| Lamotrigine-2-N-oxide | 10 | 3.88 | 1.30 |

The literature suggests there is weak evidence for the presence of minor metabolites in human plasma.

Drug Interference

Lamotrigine-selective antibody did not crossreact with most other anti-epileptic or coadministered drugs tested. Due to structural similarities with lamotrigine, high trimethoprim levels may interfere. A high concentration of each compound was spiked into normal human serum with known levels of lamotrigine (approximately 3 and 15 ug/mL) and assayed along with a serum control of lamotrigine. Measurement of lamotrigine resulted in ≤10% error in the presence of drug compounds at the levels tested.

11

| Tested
(µg/mL) | Percentage Recovery | |--------------------------------------|---- | Compound | Lamotrigine |
| Acetaminophen | 200 | Acetazolamide | 100 | Acetylsalicylic acid | 1000 | Amikacin | 100 | Amitriptyline | 20 | Amoxapine | 40 | Amphotericin B | 100 | Ampicillin | 100 | Ascorbic Acid | 100 | Baclofen | 100 | Buproprion | 40 | Caffeine | 100 | Carbamazepine | 120 | Carbamazepine-10, 11
epoxide | 120 | 101.7 | 10-Hydroxy
carbamazepine | 100 | Chloramphenicol | 250 | Chlorpromazine | 20 | Citalopram | 20 | Clobazam | 100 | Clonazepam | 20 | Cyclosporin A | 40 | Diazepam | 20 | Digoxin | 80 | Doxepin | 20 | Erythromycin | 200 | Ethanol | 4000 | Ethotoin | 100 | Ethosuximide | 250 | Felbamate | 250 | Fluoxetine | 20 | Furosemide | 100 | Gentamicin | 100 | Tested
(µg/mL) | Percentage Recovery | | Compound | | Haloperidol | 20 | Heparin U/mL | 99.0 | 100.5 | Ibuprofen | 500 | Imipramine | 20 | Kanamycin B | 200 | Gabapentin | 200 | Levetiracetam | 400 | Lidocaine | 100 | Lincomycin | 1000 | Mephenytoin | 100 | Mesoridazine | 40 | Methicillin | 250 | Naproxen | 600 | Neomycin | 1000 | Niacin | 100 | Nitrazepam | 20 | Nortriptyline | 20 | Olanzapine | 20 | Oxcarbazepine | 200 | Paroxetine | 40 | 2-phenyl-ethyl-
malonamide (PEMA) | 1000 | Penicillin V | 100 | Perphenazine | 100 | Phenobarbital | 200 | Phenytoin | 200 | Pregabalin | 200 | Primidone | 100 | Procainamide | 100 | Prochlorperazine | 40 | Ranitidine | 100 | Rifampin | 100 | Risperidone | 20 | Sertraline | 100 | Compound Tested
(µg/mL) | Percentage Recovery | | | | Spectinomycin | 100 | Stiripentol | 100 | Sulfamethoxazole | 400 | Theophylline | 200 | Thioridazine | 20 | Tobramycin | 100 | Tiagabine | 200 | Topiramate | 250 | Valproic Acid | 600 | Vancomycin | 250 | Vigabatrin | 150 | Zonisamide | 400 | Conc.
|
------------------------|---------------------|-------------------------|
| 3 µg/mL Lamotrigine | 15 µg/mL
| 103.7 | 99.1 |
| 101.2 | 99.2 |
| 100.8 | 100.7 |
| 95.7 | 97.0 |
| 99.0 | 97.9 |
| 104.7 | 101.2 |
| 94.0 | 91.6 |
| 97.7 | 94.1 |
| 98.5 | 94.4 |
| 95.8 | 90.9 |
| 98.8 | 106.2 |
| 101.3 | 103.2 |
| 104.3 | 103.2 |
| 99.0 |
| 96.2 | 94.3 |
| 103.7 | 98.4 |
| 97.2 | 95.0 |
| 98.0 | 97.5 |
| 103.4 | 105.6 |
| 97.6 | 96.4 |
| 101.7 | 99.4 |
| 101.1 | 97.7 |
| 103.4 | 97.6 |
| 101.6 | 103.1 |
| 103.6 | 103.9 |
| 94.0 | 98.2 |
| 101.3 | 101.9 |
| 101.0 | 96.4 |
| 103.0 | 101.4 |
| 102.2 | 97.0 |
| 99.8 | 97.1 |
| 99.8 | 98.6 |
| Conc.
|
| 3 µg/mL Lamotrigine | 15 µg/mL Lamotrigine |
| 104.1 | 100.3 |
| 200
|
| 101.6 | 96.2 |
| 99.6 | 97.7 |
| 98.5 | 100.5 |
| 103.8 | 98.1 |
| 103.6 | 101.9 |
| 101.6 | 101.8 |
| 106.0 | 99.7 |
| 95.7 | 103.9 |
| 97.6 | 101.7 |
| 95.2 | 99.4 |
| 97.3 | 104.8 |
| 100.8 | 101.6 |
| 97.8 | 105.8 |
| 101.5 | 103.9 |
| 96.6 | 104.9 |
| 99.5 | 102.2 |
| 97.3 | 100.5 |
| 101.6 | 100.0 |
| 100.1 | 100.9 |
| 100.4 | 101.4 |
| 99.5 | 103.2 |
| 101.0 | 98.9 |
| 100.0 | 100.8 |
| 99.6 | 98.4 |
| 98.7 | 102.5 |
| 100.6 | 101.9 |
| 99.4 | 90.3 |
| 104.0 | 97.8 |
| 101.6 | 97.7 |
| 98.0 | 100.2 |
| 101.5 | 101.9 |
| Conc.
|
| 3 µg/mL Lamotrigine | 15 µg/mL Lamotrigine |
| 97.7 | 103.1 |
| 102.3 | 101.6 |
| 99.2 | 99.2 |
| 98.7 | 97.9 |
| 102.9 | 101.3 |
| 98.8 | 96.9 |
| 100.9 | 97.8 |
| 100.3 | 96.7 |
| 100.8 | 96.8 |
| 96.5 | 95.0 |
| 97.8 | 101.0 |
| 97.9 | 99.6 |

ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay

page 12 of 15

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ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay

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page 13 of 15

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Drug that Cross-Reacts

Cross-reactivity of the antibody to trimethoprim at the following concentration was tested. A high concentration was spiked into normal human serum with known levels of lamotrigine (approximately 3 and 15 ug/mL) and assayed along with a serum control of lamotrigine. The results are shown below.

| Trimethoprim

(µg/mL)	Percent Cross-Reactivity		Percent Recovery
Lamotrigine
(3 µg/mL)	Lamotrigine
(15 µg/mL)	Lamotrigine
(3 µg/mL)	Lamotrigine
(15 µg/mL)
40.0	4.4	3.0	156.0	108.0

Care should be taken when interpreting ARK Lamotrigine results if trimethoprim is also being administered to the patient.

Anticoagulants

Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing lamotrigine.

The results indicate that there is no significant difference between the recovery of lamotrigine in serum or plasma.

14

Sample Stability

Serum specimens were shown to be stable for at least six (6) months frozen, at least fifty (50) hours at room temperature (22°C), at least thirty-seven (37) days when refrigerated (2-8°C) and after three (3) successive freeze/thaw cycles.

On-Board Stability

Calibration Curve Stability: Calibration curve stability for a period of 30 days is supported by data.

Reagent on-board stability:

Reagents were effective when stored after transfer to analyzer specific reagent containers for up to at least 30 days as supported data. In-use stability of calibrator and controls was also demonstrated.

Accelerated OPEN stability of calibrators and controls: Calibrators and controls were shown to be stable OPEN in accelerated stability at 37℃ for seven (7) days. Once opened vials may be stored at 2-8℃ for 12 months.

Traceabiliity of Calibrators and Controls

There is no internationally recognized standard for lamotrigine. ARK Lamotrigine Calibrators and ARK Lamotrigine Controls are prepared by gravimetric dilution of high purity lamotrigine into a synthetic proteinaceous matrix free of lamotrigine.

The calibrator/control matrix was shown to be equivalent to human serum with supporting data.

807.92 (b)(3): Conclusions from Nonclinical Testing

The ARK Lamotrigine Assay, the ARK Lamotrigine Calibrator and the ARK Lamotrigine Control are substantially equivalent to the QMS Lamotrigine Assay system. The ARK Lamotrigine Assay system was shown to be safe and effective for its intended use based on performance studies.

15

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/15/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, rendered in a simple, stylized manner.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

ARK Diagnostics, Inc.
c/o Dr. Kenneth Kasper
Executive Director, Quality & Regulatory Affairs
1190 Bordeaux Drive
Sunnyvale, CA 94089

OCT 29 2010

Re: K101305 Trade Name: ARK™ Lamotrigine Assay, ARK™ Lamotrigine Calibrator, and ARK™ Lamotrigine Control

Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin Test System. Regulatory Class: Class II Product Codes: ORH, DLJ, LAS Dated: October 28, 2010 Received: October 29, 2010

Dear Dr. Kasper:

We have reviewed your Section 510(k) premarket notification of intent to market the we have reviewed your Bookers = exermined 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 m interslate commerce proof to may 20, 2014 11:55 am accordance with the provisions of Annemallens, or to do roos mar metic Act (Act) that do not require approval of a premarket the Federal I ood, Drag, and Ocomens , therefore, market the device, subject to the general approval apprication (1 Mr 1). controls provisions of the rictration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III II your device is classified (500 above) into controls. Existing major regulations affecting (PMA), II may be subject to such additional controllar controllations (CFR), Parts 800 to 895. your device can be found in This 21, Occo ecceming 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 mean that FDA has made a determination these and regulations administered by other requirements of the Act of any Podern stall the Act's requirements, including, but not Federal agencies. Tou must compry with an the 100 row would be (21 CFR Parts 801 and 809);
Imited to: registration and listing (21 CFR Part 807); labeling (21 CFR medical device reporting (reporting of medical device-related adverse events) (21 CFR)
medical device reporting (reporting of medical device-related adverse evelity avatems medical device reporting (reporting of medical device forth in the quality systems (QS) regulation (21 CFR Part 820).

16

Page 2 -

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 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/cdrh/industry/support/index.html.

Sincerely yours,

CJC.

Courtney Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

17

Indication for Use

510(K) Number (if known):

101305

OCT 2 9 2010

Device Name:

ARKTM Lamotrigine Assay ARKTM Lamotrigine Calibrator ARKTM Lamotrigine Control

Indications for Use:

The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers.

Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.

The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.

The ARK™ Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.

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 Diagnostic Device Evaluation and Safety (OVD)

Division Sign Off

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K101305

ARK Lamotrigine Assay - Indications/Intended Use ARK Diagnostics, Inc.