Predicate Devices

Not Found

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on a standard immunoassay technique and spectrophotometric measurement, with no mention of AI or ML algorithms for data analysis or interpretation.

Therapeutic

No.

This device is an in vitro diagnostic (IVD) assay designed to quantitatively measure clozapine levels in human serum. It is intended to aid in the management of individuals prescribed clozapine, not to directly treat a disease or condition.

Diagnostic

Yes

The device is intended for the in vitro quantitative measurement of clozapine in adult human serum, and these measurements are used to aid in the management of individuals prescribed clozapine for treatment-resistant schizophrenia. This directly implies its use in diagnosing or monitoring a medical condition.

SaMD (Software as a Medical Device)

No

The device is a physical assay kit containing reagents for a chemical reaction, not a software program.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states that the kit is "intended for the in vitro quantitative measurement of clozapine in adult human serum". "In vitro" means "in glass" or "outside the body," which is a key characteristic of IVDs.
Measurement of Analyte: The device measures the concentration of clozapine, an analyte, in a biological sample (human serum).
Clinical Purpose: The results are intended to "aid in the management of individuals prescribed clozapine for treatment-resistant schizophrenia," indicating a clinical purpose for the measurement.
Device Description: The description details a laboratory assay using reagents and nanoparticles to detect and quantify clozapine in a sample.

All of these points align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The MyCare Psychiatry Clozapine Assay Kit is intended for the in vitro quantitative measurement of clozapine in adult human serum using automated clinical chemistry analyzers. Measurements obtained can be used to aid in the management of individuals prescribed clozapine for treatment-resistant schizophrenia. This assay should be used in conjunction with other clinical and laboratory findings and results from this test alone should not be used to make treatment decisions.

Product codes

QKT

Device Description

The MyCare Psychiatry Clozapine Assay Kit is a homogenous two reagent nanoparticle agglutination assay used for detection of clozapine in human serum. It is based on competition between drug and drug-conjugates for binding to drug-specific antibodies covalently bound to nanoparticles. The extent of particle aggregation can be followed spectrophotometrically on clinical chemistry analyzers. This aggregation is measured at a wavelength of around (b)(4) by automated clinical chemistry analyzers.

The assay contains:

Reagent 1 (R1) reaction buffer that contains drug-conjugate in a buffered protein . solution
. Reagent 2 (R2) - nanoparticle reagent that contains clozapine-specific monoclonal antibody bound to nanoparticles in a buffered solution

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

adult

Intended User / Care Setting

Not Found

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)

Precision/Reproducibility Study:

Study Type: Precision study conducted according to CLSI EP05-A3.
Sample Size: 4 human serum sample pools (clinical samples from patients taking clozapine therapy, serum pools spiked with clozapine), and 3 levels of controls. Each sample assessed in replicates of (b)(4) for (b)(4) days.
Key Results:
- Serum pool 1 (Mean 148 ng/mL): Within-Run CV 4.6%, Total CV 5.6%
- Serum pool 2 (Mean 338 ng/mL): Within-Run CV 3.3%, Total CV 4.0%
- Serum pool 3 (Mean 577 ng/mL): Within-Run CV 3.3%, Total CV 4.0%
- Serum pool 4 (Mean 926 ng/mL): Within-Run CV 3.5%, Total CV 4.8%
- Spiked Serum 1 (Mean 98 ng/mL): Within-Run CV 6.0%, Total CV 7.8%
- Spiked Serum 2 (Mean 1,094 ng/mL): Within-Run CV 4.4%, Total CV 6.6%
- Control 1 (Mean 156 ng/mL): Within-Run CV 4.5%, Total CV 5.4%
- Control 2 (Mean 474 ng/mL): Within-Run CV 3.7%, Total CV 4.4%
- Control 3 (Mean 945 ng/mL): Within-Run CV 3.8%, Total CV 4.5%

Linearity/Assay Reportable Range Study:

Study Type: Linearity study following CLSI EP06-A guideline.
Sample Size: 11 different clozapine levels (55 to 1554 ng/mL). Each sample tested in five replicates using three lots of reagents and two analyzers.
Key Results:
- Claimed Range: 68-1500 ng/mL
- Slope: 0.920 (0.910 to 0.930)
- Intercept: 4.1 (1.4 to 6.8)
- R: 0.9985
- Supports claimed measuring range of 68 to 1500 ng/mL.

Detection Limit Study:

Study Type: Detection limits assessed according to CLSI EP17-A2.
Key Results:
- Limit of Blank (LOB): (b)(4)
- Limit of Detection (LOD): 39 ng/mL
- Limit of Quantitation (LOQ): 68 ng/mL

Analytical Specificity (Cross-Reactivity and Interference) Study:

Study Type: Evaluation of cross-reactivity with metabolites and interference from endogenous and exogenous substances.
Key Results:
- No cross-reactivity exceeding ±10% for Clozapine-N-oxide (3%), 8-Hydroxy-8-deschloro-clozapine (9%), Norclozapine (1%).
- No clinically significant interference (> ±10%) from listed endogenous substances (e.g., Bilirubin, Hemolysate) and exogenous substances (e.g., Acetaminophen, Alprazolam).

Method Comparison Study:

Study Type: Comparison of MyCare Psychiatry Clozapine Assay Kit results to a validated clozapine LC-MS/MS method.
Sample Size: (b)(4) clinical samples collected at six different U.S. clinical sites from patients receiving clozapine therapy.
Key Results:
- Deming regression line equation: y = 1.037 (0.939 to 1.135) x - 27.8 (-78.3 to +22.7); R = 0.9269
- Accuracy compared to LC-MS/MS:
  - 68-350 ng/mL: Within 10% (30%), Within 15% (42%), Within 20% (60%), Within 30% (78%), Within 40% (84%)
  - 350-1000 ng/mL: Within 10% (34%), Within 15% (56%), Within 20% (75%), Within 30% (93%), Within 40% (96%)
  - 1000-1500 ng/mL: Within 10% (50%), Within 15% (50%), Within 20% (100%)

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

Not Applicable (Analytical performance metrics provided instead for an IVD kit)

Predicate Device(s)

Not Found

Reference Device(s)

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

§ 862.3245 Clozapine test system.

(a)
Identification. A clozapine test system is a device intended to measure clozapine in human specimens. Measurements obtained by this device are used in monitoring levels of clozapine to ensure appropriate therapy in patients with treatment-resistant schizophrenia.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) Precision study data that demonstrates precision that is clinically appropriate, as determined by FDA, for the clozapine test system. Precision studies must include a minimum of three samples containing different concentrations of clozapine including near medical decision points and throughout the expected therapeutic range of clozapine. Samples near the medical decision points must be clinical specimens collected from patients taking clozapine;
(ii) Method comparison data that demonstrates accuracy that is clinically acceptable, as determined by FDA, for the clozapine test system;
(iii) Data from studies that demonstrate that the device is free from clinically significant interference, as determined by FDA, from commonly co-administered medications that are used in patients with treatment-resistant schizophrenia; and
(iv) Data from studies that demonstrate that the device is free from clinically significant cross-reactivity, as determined by FDA, from major circulating metabolites found in the intended use population.
(2) The labeling required under § 809.10 of this chapter must include a limiting statement conveying that the assay should only be used in conjunction with information available from clinical evaluations and other diagnostic procedures and that results from the assay alone should not be used in making treatment decisions.

Summary

0

EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR MyCare Psychiatry Clozapine Assay Kit DECISION SUMMARY

A. DEN Number:

DEN190028

B. Purpose for Submission:

De Novo request for evaluation of class III designation of the MyCare Psychiatry Clozapine Assay Kit

C. Measurand:

Clozapine (8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine)

D. Type of Test:

Homogeneous nanoparticle agglutination immunoassay

E. Applicant:

Saladax Biomedical, Inc.

F. Proprietary and Established Names:

MyCare Psychiatry Clozapine Assay Kit

G. Regulatory Information:

1. Regulation section:
  21 CFR 862.3245
1. Classification:
  Class II (Special Controls)
1. Product code:
  QKT

1

1. Panel:
- 91- Toxicology

H. Intended Use:

1. Intended use(s):
  See indications for use
1. Indication(s) for use:
  The MyCare Psychiatry Clozapine Assay Kit is intended for the in vitro quantitative measurement of clozapine in adult human serum using automated clinical chemistry analyzers. Measurements obtained can be used to aid in the management of individuals prescribed clozapine for treatment-resistant schizophrenia. This assay should be used in conjunction with other clinical and laboratory findings and results from this test alone should not be used to make treatment decisions.
1. Special conditions for use statement(s):
  For prescription use only For In Vitro Diagnostic Use Only
1. Special instrument requirements:
  The assay was validated on the Beckman Coulter AU480 Clinical Analyzer

I. Device Description:

The MyCare Psychiatry Clozapine Assay Kit is a homogenous two reagent nanoparticle agglutination assay used for detection of clozapine in human serum. It is based on competition between drug and drug-conjugates for binding to drug-specific antibodies covalently bound to nanoparticles. The extent of particle aggregation can be followed spectrophotometrically on clinical chemistry analyzers. This aggregation is measured at a wavelength of around (b)(4) by automated clinical chemistry analyzers.

The assay contains:

Reagent 1 (R1) reaction buffer that contains drug-conjugate in a buffered protein . solution
. Reagent 2 (R2) - nanoparticle reagent that contains clozapine-specific monoclonal antibody bound to nanoparticles in a buffered solution

2

J. Standard/Guidance Document Referenced (if applicable):

. CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition, October 2014.
CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A ● Statistical Approach; Approved Guideline, April 2003.
CLSI EP17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement ● Procedures; Approved Guideline - second edition, June 2012.
CLSI EP25-A Evaluation of Stability of In vitro Diagnostic Reagents; Approved ● Guideline, September 2009.

K. Test Principle:

Drug-conjugates serve as binding partners to antibodies selective for clozapine which are covalently attached to the surface of nanoparticles. In the absence of free clozapine, this reaction creates large aggregates, resulting in a solution that scatters incident light and leads to an increase in the observed absorption of the solution. When incubated with a sample containing clozapine, the free clozapine in the sample binds to the reagent antibodies, and those antibody-nanoparticle conjugates are no longer available to aggregate, resulting in less scattering of incident light and lower observed absorption of the solution. Thus, maximum absorption occurs with low levels of drug, and minimum absorption occurs with high levels of drug.

L. Performance Characteristics (if/when applicable):

1. Analytical performance:
- a. Precision/Reproducibility:

A precision study was conducted according to recommendations in CLSI EP05-A3 using 4 human serum sample pools, which were prepared from clinical samples from patients taking clozapine therapy, serum pools spiked with clozapine, and 3 levels of controls. Each sample was assessed in replicates of (b)(4) a day, for (b)(4) days. Samples were assessed using three lots of reagents, calibrators, and controls on two Beckman Coulter AU480 Clinical Analyzers. The results are summarized below.

Sample Results Across All Reagent Lots and Analyzers

| Sample | N | Mean
(ng/mL) | Within - Run | Total |
|--------------|-----|-----------------|--------------|-------|
| | | | CV | CV |
| Serum pool 1 | 480 | 148 | 4.6% | 5.6% |
| Serum pool 2 | 480 | 338 | 3.3% | 4.0% |

3

Sample	N	Mean	Within - Run	Total
		(ng/mL)	CV	CV
Serum pool 3	480	577	3.3%	4.0%
Serum pool 4	480	926	3.5%	4.8%
Spiked Serum 1	480	98	6.0%	7.8%
Spiked Serum 2	480	1,094	4.4%	6.6%
Control 1	480	156	4.5%	5.4%
Control 2	480	474	3.7%	4.4%
Control 3	480	945	3.8%	4.5%

b. Linearity/assay reportable range:

A study was conducted to evaluate linearity across the measuring range of the assay following the CLSI EP06-A guideline. Samples with 11 different clozapine levels were evaluated: 55, 132, 169, 352, 491, 588, 821, 1003, 1214, 1467, and 1554 ng/mL. Two samples were prepared by pooling human serum specimens that were then spiked with clozapine to low and high clozapine concentrations, which were then mixed to produce samples with the concentrations tested. Each sample was tested in five replicates using three lots of reagents, calibrators, and controls and two Beckman Coulter AU480 clinical analyzers. The observed values were plotted against the expected values and linear regression analysis was performed. The linear regression results from the worst performing lot of three lots are shown below.

| Claimed

Range	Slope	Intercept	R
68-1500 ng/mL	0.920
(0.910 to
0.930)	4.1
(1.4 to 6.8)	0.9985

The 95% confidence intervals are shown for slope and intercept.

These results support the claimed measuring range of 68 to 1500 ng/mL for clozapine.

Traceability, Stability, Expected values (controls, calibrators, or methods): C.

Traceability

The MyCare Psychiatry Calibrator Kit is traceable to a certified USP clozapine reference standard. Master calibrators are prepared by (b) (4) of this

4

certified reference material in buffer and verified by LC-MS/MS.

d. Detection limit:
Detection limits were assessed according to recommendations in CLSI EP17-A2.

The limit of blank (LOB) was determined using the non-parametric "classical approach" using "individual normal(b) (4) serum samples containing no clozapine. Each of the serum samples were tested in duplicate on three different days on two different analyzers for n="", using" lots of reagents, calibrators and controls. The
95th percentile of each n = " data set was calculated, and the highest 95th percentile value from among the three n = data sets was determined. The sponsor determined the LOB to be (b) (4) (4) (4) (4) (4) (4) 1) 1) (4) 1) 1) (4) 1) 1) 1 (4) 1) 1 (4) 1) 1 (4) 1 1) 1 (4) 1 1) 1 (4) 1 1) 1 (4) 1 1) 1 (4) 1 1) 1 (4) 1 1 1 (4) 1 1 1 (4) 1 1 1 (

The limit of detection (LOD) was determined using the variant (non-parametric analysis) "classical approach" with a beta of (b) (4) individual normal human serum samples spiked with clozapine at 15, 20, 25, 30, and 35 ng/mL. Each of the serum samples were tested in duplicate on three different days on (0K4) different analyzers for n=""", using " lots of reagents, calibrators and controls. The LOD was determined using the highest median value observed at the lowest spiking level for which each of the three n = "" data sets associated with that spiking level had(b) (4) of results below the LOB. The sponsor determined the LOD to be 39 ng/mL.

The limit of quantitation (LOO) was determined by 4 individual normal human serum samples spiked with clozapine at " targeted concentrations: 40, 50, 60, 70 and 8 ng/mL. Each of the serum sample was tested n = "on(b) (4) different days on analyzer, using lots of reagents/calibrators/controls, for n=000 (results combined across all lots). The LOQ was defined as the specimen concentration where the total allowable error was ≤ 35% when calculated according to the Westgard model. The sponsor determined the LOO to be 68 ng/mL.

e. Analytical specificity:

Potentially Cross-Reacting Substances

Cross-reactivity was evaluated by adding each potentially cross-reacting clozapine metabolite into a human serum pool prepared from multiple individual human serum samples. The sponsor tested the three metabolites in the presence of clozapine at 350 ng/mL. Testing was conducted using one lot of reagents, one lot of calibrators, and two analyzers. Samples were tested in (0) (4) replicates. The formula used for calculating percent cross reactivity was:

(b) (4)

The results are summarized below. The sponsor did not observe cross-reactivity

5

exceeding ±10%:

Compound	Tested at (ng/mL)	% Cross-reactivity
Clozapine-N-oxide	250	3%
8-Hydroxy-8-deschloro-clozapine	100	9%
Norclozapine	2,700	1%

Endogenous and Exogenous Interfering Substances:

Interference studies were conducted based on the CLSI guideline EP07-A2. Potentially interfering substances (test sample) or solvent (control sample) were spiked into human serum sample pools with clozapine at 350 and 600 ng/mL. Each sample was tested at a minimum of 5 runs using one lot of reagent on two analyzers. The percentage difference between the measurement of clozapine in the test sample and the control sample was calculated. The sponsor considered a percent difference between test samples and control samples of > ±10% to be clinically significant interference. None of the substances in the following tables (endogenous or exogenous substances) were found to lead to clinically significant interference (> ±10%) for the device.

Interfering Substance	Concentration Tested
Bilirubin	18.18 mg/dL
Hemolysate	1,050 mg/dL
Human IgG (HIgG)	12.5 g/dL
Human Serum
Albumin (HSA)	10.9 g/dL
Rheumatoid Factor (RF)	508 IU/mL
Triglycerides	2,585.87 mg/dL

Endogenous Substances

Exogenous Interferences

| Compound (ng/mL) | Compound (ng/mL) |
|--------------------------------|---- | Acetaminophen | 200,000 | Acetylsalicylic acid | 500,000 | Alendronate sodium | 1,000 | Alprazolam | 2,000 Hydrochloride | 10,000 | Compound (ng/mL) | Compound (ng/mL) |
| Amikacin sulfate | 144,000 dihydrate | 500 | Amisulpride | 1,200 | Amlodipine besylate | 100 amphetamine | 1,000 | Amoxapine | 2,900 | Aripiprazole | 1,400 | Asenapine | 500 | Atorvastatin calcium | 800 | Benztropine | 600 | Biotin | 3,600 | Blonanserin | 100 | Bromperidol | 100 | Bupropion | 3,000 | Caffeine | 108,000 | Cannabidiol | 100 | Carbamazepine | 45,000 | L-Carnosine | 100,000 | Celecoxib | 8,800 dihydrochloride | 4,400 | 8-chlorotheophylline | 3,000 HCl | 3,300 | Cimetidine | 30,000 | Citalopram HBr | 5,500 | Clonazepam | 300 | Clotrimazole | 50 | Cortisol | 300 | Cyclosporin A | 9,000 | Desvenlafaxine | 800 methorphan | 1,000 | Diazepam | 30,000 HCl | 6,000 | Divalproex Sodium | 400,000 acid ethyl ester | 150,000 | Donepezil | 50,000 | Droperidol | 200 | Duloxetine | 200 | Escitalopram | 200 | Compound | Eszopiclone | 300 | Famotidine | 2,500 | Fentanyl | 600 | Fluticasone propionate | 50 | Folic acid | 15 | Galantamine | 200 | Glyburide | 2,000 | Heparin sodium salt | 50 U/mL | Hyoscine (Scopolamine HBr) | 100 | Hypericin (St. John's Wort) | 100 | Iloperidone | 100 | Indinavir sulfate | 400 | Lamivudine | 10,500 | Lansoprazole | 9,400 | Lisinopril dihydrate | 350 | Lorazepam | 1,000 | Loxapine | 300 | Meclizine dihydrochloride | 500 | Methotrimeprazine | 600 | Metoclopramide HCl | 500 | Metronidazole | 123,000 | Milnacipran | 10,000 | Mometasone furoate | 50 | Naltrexone | 200 | Nateglinide | 30,000 | Nicotine | 1,000 | Nordiazepam | 5,000 | Olanzapine | 400 | Oxazepam | 5,000 | Oxycodone | 500 | Pantothenic acid | 1,800 | Penicillin V | 42,000 | Compound | Perlapine | 150 | Phenobarbital | 690,000 | Phenytoin | 60,000 | Pipamperone
dihydrochloride | 1,200 | Pravastatin sodium | 300 | Pregabalin | 22,500 | Promethazine | 1,200 pseudoephedrine | 10,000 | S,S-(+)-
pseudoephedrine | 10,000 | Quetiapine | 2,800 | Raloxifene | 50 | Retinol | 4,000 | Rifampicin | 65,000 | Rosuvastatin calcium | 200 | Sarcosine | 1,500 | Sertraline
hydrochloride | 1,000 | Sodium benzoate | 400,000 | Spironolactone | 600 | Sulpiride | 50,000 | Terbinafine | 9,000 | Thiamine HCl | 500 | Trazodone HCl | 14,700 acetonide | 300 | Triamterene | 9,000 | Valproic acid | 500,000 | Varenicline | 50 | Vitamin B12 | 50 | Vitamin K1 | 50 | Ziprasidone | 600 hemitartrate | 5,000 | Zonisamide | 120,000 | Zuclopenthixol | 300 | Tested at
| Tested at
------------------|-------------------------------------|----------------------|
| Acetazolamide | 60,000 |
| Albuterol | 1,000 |
| Alpha - tocopherol | 130,000 |
| Amantadine
|
| Tested at
| Tested at
| Amiloride HCl
|
| Amitriptyline | 1,000 |
| S (+)-
|
| Amoxicillin | 80,000 |
| L-ascorbic acid | 60,000 |
| Atomoxetine | 7,900 |
| Baclofen | 3,000 |
| Betamethasone | 400 |
| Biperiden | 300 |
| Brexpiprazole | 1,000 |
| Budesonide | 50 |
| Buspirone | 200 |
| Calcium carbonate | 315,000 |
| Cannabinol | 100 |
| Cariprazine | 50 |
| Cefalexin | 200,000 |
| Cetirizine
|
| Chlorpromazine
|
| Ciprofloxacin | 12,000 |
| Clindamycin | 51,000 |
| Clotiapine | 500 |
| Codeine | 2,000 |
| (-)-Cotinine | 2,000 |
| Desloratadine | 600 |
| Dextro-
|
| Diphenhydramine
|
| Docosahexaenoic
|
| Doxycycline HCl | 35,000 |
| D-Serine | 100,000 |
| Erythromycin | 138,000 |
| Estradiol | 10 |
| Tested at (ng/mL) | Compound | Tested at (ng/mL) |
| Ethanol | 10,000,000 |
| Fenofibrate | 50,000 |
| Fluoxetine HCl | 4,000 |
| Fluvoxamine | 2,000 |
| Furosemide | 60,000 |
| Gentamicin sulfate | 30,000 |
| Haloperidol | 1,000 |
| Hydrochlorothiazide | 6,000 |
| Hyperforin (St. John's Wort) | 200 |
| Ibuprofen | 500,000 |
| Imipramine | 700 |
| Lactulose | 10,000 |
| Lamotrigine | 42,000 |
| Levonorgestrel | 100 |
| Lithium carbonate | 250,000 |
| Lovastatin | 500 |
| Lurasidone | 400 |
| Metformin | 40,000 |
| Methylphenidate HCl | 350 |
| Metoprolol tartrate | 5,000 |
| Midazolam | 3,800 |
| Mirtazapine | 900 |
| Morphine | 7,800 |
| Naproxen sodium | 500,000 |
| Nefazodone HCl | 6,000 |
| Nicotinic acid | 27,900 |
| Nortriptyline | 1,200 |
| Omeprazole | 8,400 |
| Oxcarbazepine | 105,000 |
| Paliperidone | 60 |
| Paroxetine | 1,200 |
| Perazine | 1,400 |
| Tested at (ng/mL) | Compound | Tested at (ng/mL) |
| Perphenazine | 100 |
| Phentermine | 500 |
| Pimozide | 100 |
| Potassium EDTA | 1,000 |
| Prednisolone | 3,000 |
| Procyclidine | 1,900 |
| R,R-(-)-
|
| Pyridoxine HCl | 100 |
| Quinidine | 15,000 |
| Ranitidine | 10,500 |
| Riboflavin | 200 |
| Risperidone | 200 |
| Salicylic acid | 500,000 |
| Sertindole | 300 |
| Simvastatin | 1,700 |
| Sodium fluoride | 900 |
| Sulfamethoxazole | 400,000 |
| Temazepam | 5,000 |
| Theophylline | 60,000 |
| Topiramate | 75,000 |
| Triamcinolone
|
| Triazolam | 40 |
| Vancomycin HCl | 120,000 |
| Venlafaxine HCl | 700 |
| Vitamin D2 | 200 |
| Warfarin | 75,000 |
| Zolpidem
|
| Zopiclone | 200 |
| | |

6

7

8

9

f. Assay cut-off:
Not applicable
1. Comparison studies:
- a. Method comparison study:

A method comparison study was conducted using the MyCare Psychiatry Clozapine Assay Kit on the Beckman Coulter AU480 by testing clinical samples that were collected at six different U.S. clinical sites from patients receiving clozapine therapy. Results from the MyCare Psychiatry Clozapine Assay Kit were compared to results from a validated clozapine LC-MS/MS method. Deming regression analysis was performed with (b)(4) samples, resulting in the following line equation (with 99% confidence intervals shown) from a representative lot:

y = 1.037 (0.939 to 1.135) x - 27.8 (-78.3 to +22.7); R = 0.9269

A summary of the device accuracy (compared to the LC-MS/MS comparator method) at different concentration ranges throughout the claimed measuring interval is shown below.

| | Difference Range Between the Serum Clozapine Level
by LC/MS-MS and the MyCare Psychiatry Clozapine
Assay | | | | |
|------------------------------------------|----------------------------------------------------------------------------------------------------------------|------------------------|------------------------|------------------------|------------------------|
| Concentration of
Clozapine
(ng/mL) | Within
10%
(n/N) | Within
15%
(n/N) | Within
20%
(n/N) | Within
30%
(n/N) | Within
40%
(n/N) |
| 68-350 | 30%
(15/50) | 42%
(21/50) | 60%
(30/50) | 78%
(39/50) | 84%
(42/50) |
| 350-1000 | 34%
(24/71) | 56%
(40/71) | 75%
(53/71) | 93%
(66/71) | 96%
(68/71) |
| 1000-1500 | 50% (1/2) | 50% (1/2) | 100% (2/2) | N/A | N/A |

b. Matrix comparison:
Not applicable
1. Clinical studies:
- a. Clinical Sensitivity:

Not applicable

10

b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
The sponsor provided a discussion of the clinical use of therapeutic drug monitoring for clozapine in patients with treatment-resistant schizophrenia, as provided in the U.S. clinical practice guideline, "The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia" (2020).
1. Clinical cut-off:
  Not applicable.
1. Expected values/Reference range:
  There is no definitive therapeutic range for clozapine, as this range may be different for each patient.

N. Proposed Labeling:

The labeling supports the decision to grant the De Novo request for this device.

O. Identified Risks to Health and Mitigation Measures

Identified Risks to Health	Mitigation Measures
Incorrect test results	Certain design verification and validation
activities
Certain labeling information
Incorrect interpretation of test results	Certain design verification and validation
activities
Certain labeling information

P. Benefit/Risk Determination

Patient Perspectives

This submission did not include specific information on patient perspectives for this device.

Summary of the Assessment of Benefit

There is currently no available FDA cleared or approved device for determining Clozapine

11

blood concentrations. Toxic side effects from Clozapine include seizures, myocarditis, agranulocytosis, and other severe adverse effects, and Clozapine currently requires a REMS (Risk Evaluation and Mitigation Strategy) to ensure the benefits of the drug outweigh the risk of severe neutropenia. The availability of the test may aid in the management of patients with treatment-resistant schizophrenia under various clinical scenarios as described in the American clinical practice guideline, "The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia" (2020) (e.g. "while the dose of clozapine is being titrated, it is useful to obtain blood levels of clozapine").

Summary of the Assessment of Risk

In the setting of poor or incomplete drug response, a falsely low clozapine level may increase the risk of a prescriber falsely concluding that the outcome is due to sub-therapeutic levels which may prompt an unnecessary increase in drug dose and increase the risk of adverse events such as seizures. In the setting of potential toxicity, a falsely low level may delay clozapine dose de-escalation, increasing the risk of persistent adverse events and severe adverse events. In the setting of poor or incomplete drug response, a falsely high level may increase the risk of a prescriber incorrectly assuming that the patient was receiving an adequate dose and continue a suboptimal dose or conclude that the patient was not responding to clozapine and prescribe alternate therapies that may be less effective for the patient, increasing the risk of continued psychological distress from persistent symptoms, poorer social and occupational functioning, hospitalization, or transfer to residential settings. Additionally, if a patient's clozapine level is falsely elevated, a prescriber may not fully investigate the possibility of suboptimal dosing, which could result in a missed opportunity to identify and rectify conditions that could lead to suboptimal dosing or to consider treatment alternatives that are more acceptable to the patient. Falsely elevated levels may lead to a prescriber deciding to decrease the dose or discontinue medication, even if the patient were tolerating the medication and had experienced benefit, which could increase the risk of relapse, functional impairment, or transition to higher levels of care.

Summary of the Assessment of Benefit-Risk

General controls are insufficient to mitigate the risks of the device. However, the probable clinical benefits outweigh the probable risks for the assay, considering the mitigation of the risks provided for in the special controls. Device design verification and validation, including precision, method comparison, interference, and cross-reactivity studies will help ensure that the device functions as intended and mitigate the risk of falsely high test results. A limitation statement conveying that results from the assay alone should not be used in making treatment decisions will be included in the labeling, as a mitigation against the risk of incorrect interpretation of results. Overall, the probable benefits outweigh the probable risks of incorrect test results or incorrect interpretation of test results for the proposed indications for use, in light of the special controls and general controls.

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Q. Conclusion

The De Novo request for the MyCare device is granted and the device is classified under the following and subject to the special controls identified in the letter granting the De Novo request:

Product Code: QKT Device Type: Clozapine test system Class: II (special controls) Regulation: 21 CFR 862.3245