The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of carisoprodol metabolite (meprobamate) in human urine at a cutoff value of 100 ng/mL when calibrated against meprobamate. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for verification by a confirmatory method such as GC/MS, LC/MS or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical confirmatory method (e.g., gas or liquid chromatography and mass spectrometry) must be used to obtain a confirmed analytical result. Clinical consideration and professional judgment must be exercised with any drug of abuse test, particularly when the preliminary test result is positive.

Device Description

The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is a kit comprised of two reagents (antibody/substrate reagent R1 and enzyme-drug conjugate reagent R2), which are bottled separately but sold together within the kit. The Ri solution contains mouse monoclonal anti-meprobamate antibody, glucose-6- phosphate (G6P), nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains meprobamate-labeled glucose-6-phosphate dehydrogenase (G6PDH) in buffer with sodium azide (0.09 %) as a preservative.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay, based on the provided document:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria (Inferred from study results and regulatory requirements)	Reported Device Performance
Accuracy (Qualitative Mode)	High agreement with confirmatory method (LC/MS or GC/MS) for positive and negative samples, particularly around the cutoff.	Qualitative Analysis Agreement: - Positive Agreement: 98.5% - Negative Agreement: 96.6% 2 false positives in "Near Cutoff Negative" (92 and 98 ng/mL, both identified as Negative by GC/MS/LC/MS) 1 false negative in "Near Cutoff Positive" (103 ng/mL, identified as Positive by GC/MS/LC/MS)
Accuracy (Semi-Quantitative Mode)	High agreement with confirmatory method (LC/MS or GC/MS) for positive and negative samples, particularly around the cutoff.	Semi-Quantitative Analysis Agreement: - Positive Agreement: 98.5% - Negative Agreement: 98.3% 1 false positive in "Near Cutoff Negative" (98 ng/mL, identified as Negative by GC/MS/LC/MS) 1 false negative in "Near Cutoff Positive" (103 ng/mL, identified as Positive by GC/MS/LC/MS)
Reproducibility/Precision (Qualitative Mode)	Consistent results at specific concentrations, especially near the cutoff.	At cutoff (100 ng/mL, GC/MS confirmed 94.9 ng/mL): 40 Negative / 48 Positive out of 88 determinations. At -25% Cutoff (75 ng/mL, GC/MS confirmed 76.8 ng/mL): 88 Negative / 0 Positive. At +25% Cutoff (125 ng/mL, GC/MS confirmed 122.3 ng/mL): 0 Negative / 88 Positive.
Reproducibility/Precision (Semi-Qualitative Mode)	Consistent results at specific concentrations, especially near the cutoff.	At cutoff (100 ng/mL, GC/MS confirmed 94.9 ng/mL): 60 Negative / 28 Positive out of 88 determinations. At -25% Cutoff (75 ng/mL, GC/MS confirmed 76.8 ng/mL): 88 Negative / 0 Positive. At +25% Cutoff (125 ng/mL, GC/MS confirmed 122.3 ng/mL): 0 Negative / 88 Positive.
Linearity/Reportable Range	Acceptable recovery across a range of concentrations.	Mean Recovery: 66.6% to 109.2% for expected concentrations from 10 ng/mL to 400 ng/mL. (Note: 10 ng/mL showed lower recovery, but higher concentrations were generally good).
Analytical Specificity (Endogenous Compounds)	No interference from common endogenous compounds at specified concentrations.	No positive or negative interference observed for the listed endogenous compounds when meprobamate was at -25% or +25% of the cutoff.
Analytical Specificity (Urine Preservatives)	No significant interference from common urine preservatives.	Sodium azide and sodium fluoride: No interference. Boric acid: Caused false negative results at +25% cutoff (125 ng/mL) and up to +125% cutoff (225 ng/mL). Labeling mitigation required.
Analytical Specificity (pH)	No interference across a physiological pH range.	No positive or negative interference observed at urine pH values ranging from 3 to 11.
Analytical Specificity (Specific Gravity)	No interference across a physiological specific gravity range.	No positive or negative interference observed at urine specific gravities ranging from 1.002 to 1.029.
Cross-Reactivity (Structurally Related Compounds)	Acceptable cross-reactivity profile.	Carisoprodol (90.9%), Felbamate (25.0%), Meprobamate-N-Glucuronide (0.5%), Hydroxymeprobamate (0.2%). Other listed compounds showed <0.1% cross-reactivity.
Interference (Structurally Unrelated Compounds)	No interference from common structurally unrelated drugs.	No positive or negative interference observed from a wide range of common drugs/substances (e.g., Acetaminophen, Codeine, Ibuprofen) at high concentrations (e.g., 100,000 ng/mL) when meprobamate was at -25% or +25% of the cutoff.
Clinical Validity of Cutoff	Meprobamate levels measurable for a relevant post-dose period.	Pharmacokinetic studies of carisoprodol and meprobamate in plasma, and meprobamate elimination in urine, indicated levels above 100 ng/mL are present for "up to a few days" post-single dose.

Study Details

2. Sample size used for the test set and the data provenance

Sample Size for Test Set:
- Precision Study: 88 determinations per concentration level for
  each of 8 concentrations (a total of 704 determinations for qualitative and 704 for semi-quantitative).
- Method Comparison Study: 127 clinical urine samples.
- Linearity Study: Each sample run in 10 replicates across 11 concentrations.
- Analytical Specificity (Endogenous, Preservatives, pH, Specific Gravity, Unrelated Compounds): Samples tested in duplicate.
- Cross-reactivity (Structurally Related Compounds): Not explicitly stated, but typically involves multiple runs.
Data Provenance: Retrospective clinical urine samples "from subjects that were (b) (4) taking prescribed or nonprescribed Carisoprodol." The origin country is not explicitly stated, but given this is an FDA submission, it's likely primarily US-based or from regions with comparable medical practices.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth for the test set was established by Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are established analytical methods for drug confirmation. There is no mention of "experts" in the sense of medical professionals (e.g., radiologists) establishing ground truth, as this is an in vitro diagnostic device. The "experts" in this context would be the technicians/scientists operating and interpreting the GC/MS/LC/MS results, who are implied to be qualified in their field based on the use of these validated methods.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

There was no human adjudication process described. The reference method (GC/MS or LC/MS) provided the definitive "ground truth" for each sample.

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

No, this was not a multi-reader multi-case (MRMC) comparative effectiveness study. This device is an automated enzyme immunoassay for chemical analysis, not an imaging-based AI system that would typically involve human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

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

Yes, this was a standalone (algorithm only) performance study. The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is an automated system designed to provide a preliminary analytical result without human interpretation of the assay itself. Human involvement comes in confirming positive results with alternative chemical methods and clinical judgment, as stated in the intended use.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth used was confirmatory analytical methods, specifically Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These methods are considered the gold standard for drug quantification and identification in urine.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" for the device. As an enzyme immunoassay, the "training" (calibration) involves using known calibrator concentrations (0, 50, 100, 200, and 400 ng/mL meprobamate, as mentioned in the linearity section) to establish the standard curve against which unknown samples are measured. There isn't an "algorithm" in the conventional AI sense that undergoes training with a large dataset. The performance characteristics described are related to the analytical validation of the assay itself.

9. How the ground truth for the training set was established

As there isn't a traditional "training set" in the AI sense, the concept of ground truth for it doesn't directly apply. The "ground truth" for the calibrators used in the assay system would be their known, precisely manufactured concentrations of meprobamate, traceable to a commercially available meprobamate source material with 99% analytical purity (as mentioned in section L.1.c).

Summary

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EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay

DECISION SUMMARY

A. DEN Number:

DEN170010

B. Purpose for Submission:

De Novo request for evaluation of automatic class III designation for the LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay

C. Measurand:

Meprobamate

D. Type of Test:

Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative

E. Applicant:

Lin-Zhi International, Inc.

F. Proprietary and Established Names:

LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay

G. Regulatory Information:

1. Regulation: 21 CFR 862.3590
1. Classification: Class II
1. Product code: QBK
1. Panel: Toxicology (91)

H. Intended Use:

1. Indications for use:
  The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is intended for

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the qualitative and semi-quantitative determination of carisoprodol metabolite (meprobamate) in human urine at a cutoff value of 100 ng/mL when calibrated against meprobamate. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

1. Special conditions for use statement(s):
- For in vitro diagnostic use only.
- For prescription use only. ●
1. Special instrument requirements:

The assay was validated on the Beckman AU400e automated clinical chemistry analyzer. Clinical chemistry analyzers capable of maintaining a constant temperature, pipetting samples, mixing reagents, measuring enzyme rates at 340 nm and timing the reaction accurately can be used to perform this assay.

I. Device Description:

J. Standard/Guidance Documents Referenced:

CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition.

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K. Test Principle:

The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is based on competition between meprobamate in the sample and the enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled with meprobamate for a fixed amount of antibody in the reagent. G6PDH enzyme activity decreases upon binding to the antibody, and thus meprobamate concentration in the sample is proportional to enzyme activity. In the absence of meprobamate in the sample, meprobamate-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. When meprobamate is present in the sample competes with drug-labeled G6PDH for binding to antibody; the unbound meprobamatelabeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.

L. Performance Characteristics (if/when applicable):

The following performance characteristics were obtained on the Beckman AU400e automated clinical chemistry analyzer.

1. Analytical performance:

a. Reproducibility/Precision

A precision study was performed over 22 days, with 2 runs per day in duplicate (n = 88) using pooled negative urine samples spiked with meprobamate to concentrations of 25, 50, 75, 100, 125, 150, 175, and 200 ng/mL. All concentrations for precision studies were confirmed by Gas Chromatography/Mass Spectrometry (GC/MS) testing. The results from samples assaved using the qualitative and semi-quantitative modes are summarized below.

Targetmeprobamateconcentration(ng/mL)	GC/MSmeprobamateconcentration(ng/mL)	% ofCutoff	# ofDeterminations	Result
0	notdetermined	-100%	88	88 Neg / 0Pos
25	24.7	-75%	88	88 Neg / 0Pos
50	51.7	-50%	88	88 Neg / 0Pos
75	76.8	-25%	88	88 Neg / 0Pos
100	94.9	Cutoff	88	40 Neg / 48Pos

Qualitative Analysis

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Targetmeprobamateconcentration(ng/mL)	GC/MSmeprobamateconcentration(ng/mL)	% ofCutoff	# ofDeterminations	Result
125	122.3	+25%	88	0 Neg / 88Pos
150	149.4	+50%	88	0 Neg / 88Pos
ા તર	176.8	+75%	88	0 Neg / 88Pos
200	211.0	+100%	88	0 Neg / 88Pos

Semi-Quantitative Analysis

Sampleconcentration(ng/mL)	GC/MSmeprobamateconcentration(ng/mL)	% of Cutoff	# ofDeterminations	Result
0	notdetermined	-100%	88	88 Neg / 0Pos
25	24.7	-75%	88	88 Neg / 0Pos
50	51.7	-50%	88	88 Neg / 0Pos
75	76.8	-25%	88	88 Neg / 0Pos
100	94.9	Cutoff	88	60 Neg / 28Pos
125	122.3	+25%	88	0 Neg / 88Pos
150	149.4	+50%	88	0 Neg / 88Pos
175	176.8	+75%	88	0 Neg / 88Pos
200	211.0	+100%	88	0 Neg / 88Pos

b. Linearity/assay reportable range:

A recovery study was performed by spiking a pool of negative urine with a high dose of meprobamate and generating serial dilutions to achieve the following concentrations: 10, 40, 80, 120, 160, 200, 240, 280, 320, 360, and 400 ng/mL meprobamate. Each sample was run in replicates of 10 in semi-quantitative mode with a calibration curve established with five meprobamate calibrators (0, 50, 100, 200, and 400 ng/mL). Percent recovery was calculated using the mean concentration of the 10 replicates relative to the expected concentration as shown below.

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ExpectedConcentration(ng/mL)	Mean ObservedConcentration(ng/mL)	Mean Recovery(%)	Range ofRecovery (%)
0	2.2	N/A	N/A
10	6.7	66.6	38.0 - 87.0
40	39.9	99.7	93.8 - 104.8
80	81.8	102.2	98.0 - 108.4
120	123.3	102.8	99.9 - 107.3
160	163.7	102.3	98.3 - 107.5
200	195.3	97.7	95.4 - 99.7
240	251.6	104.8	95.3 - 110.5
280	305.7	109.2	102.0 - 114.3
320	348.9	109.0	105.5 - 111.9
360	386.6	107.4	102.3 - 111.8
400	412.5	103.1	100.3 - 105.4

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

The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is traceable to a commercially available meprobamate source material having 99% analytical purity as determined by LC/MS.

Specimen stability information was provided to support the following specimen storage conditions: storage at 2-8℃ for up to 1 week and at -20℃ for up to 17 months.

d. Detection limit
Not applicable.
e. Analytical specificity:
Endogenous Compounds: Potential interference from endogenous compounds was evaluated in the qualitative and semi-quantitative modes by spiking these compounds (at the test concentrations shown in the table below) into urine containing either 75 ng/mL or 125 ng/mL meprobamate (±25% of the assay cutoff). Samples were tested in duplicate. The results, which were the same for the qualitative and semiquantitative modes, are shown below.

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Endogenous	Concentration	-25% Cutoff	+25% Cutoff
Compound	Tested (mg/dL)	(75 ng/mL)	(125 ng/mL)
Acetone	1000	Negative	Positive
Ascorbic acid	1500	Negative	Positive
Beta-hydroxybutyricacid sodium salt	100	Negative	Positive
Bilirubin	2	Negative	Positive
Calcium chloridedihydrate	300 (saturatedsolution)	Negative	Positive
Citric acid	800	Negative	Positive
Creatinine	500	Negative	Positive
Ethanol	1000	Negative	Positive
Galactose	10	Negative	Positive
γ-Globulin	500	Negative	Positive
Glucose	3000	Negative	Positive
Hemoglobin	300	Negative	Positive
Human SerumAlbumin	500	Negative	Positive
Oxalic Acid	100	Negative	Positive
Potassiumchloride	6000	Negative	Positive
Riboflavin	0.3	Negative	Positive
Urea	6000	Negative	Positive
Uric acidmonosodium salt	10	Negative	Positive
Sodium Chloride	6000	Negative	Positive
Sodium phosphatedibasic salt	300	Negative	Positive

Urine sample preservatives: To evaluate potential interference from common urine sample preservatives, device performance in qualitative and semi-quantitative modes was tested by spiking sodium azide (1% w/v), sodium fluoride (1% w/v), or boric acid (1% w/v) into negative urine to ± 25% of the 100 ng/mL meprobamate cutoff (75 ng/mL and 125 ng/mL). Samples were tested in duplicate. Boric acid was found to cause false negative results at +25% of the 100 ng/mL cutoff (125 ng/mL) and up to +125% of the 100 ng/mL cutoff (225 ng/mL) in both the qualitative and semiquantitative modes. The following statement is provided in the limitations section of the labeling: Boric Acid at 1% w/v may cause false negative results. Boric Acid is not recommended as a preservative for urine.

pH: To evaluate potential interference from the pH of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (3, 4, 5, 6, 7, 8, 9, 10, and 11). Test samples were prepared in negative urine, which was spiked to ±25% of the 100 ng/mL meprobamate cutoff (75 ng/mL and 125 ng/mL), and tested in duplicate. No positive or negative interference was observed at

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urine pH values ranging from 3 to 11 for the qualitative and semi-quantitative modes.

Specific Gravity: To evaluate potential interference from the specific gravity of urine. device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravities (1.002, 1.003, 1.006, 1.007, 1.008, 1.012, 1.014, 1.015, 1.019, 1.025, and 1.029). These 12 negative urine samples were spiked with meprobamate to ±25% of the 100 ng/mL meprobamate cutoff (75 ng/mL and 125 ng/mL), and tested in duplicate. No positive or negative interference was observed at urine specific gravities ranging from 1.002 to 1.029 for the qualitative and semi-quantitative modes.

Cross-reactivity of structurally related compounds: The cross-reactivity of various structurally related drugs was evaluated in qualitative and semi-quantitative modes by spiking each substance into negative urine. The following table shows the quantity of each potential cross-reacting compound that produced assay reactivity equivalent to the 100 ng/mL meprobamate cutoff, or the maximum concentration tested (concentration tested), and calculated cross-reactivity for each compound (% crossreactivity). The results were the same for the qualitative and semi-quantitative modes.

Compound	Concentration Tested (ng/mL)	% Cross-Reactivity
Carisoprodol	110	90.9
Darunavir	200,000	<0.1
Efavirenz	200,000	<0.1
Felbamate	400	25.0
Hydroxymeprobamate	65,000	0.2
Meprobamate	100	100.0
Meprobamate-N-Glucuronide	20,000	0.5
Methocarbamol	200,000	<0.1
Mitocycin C	200,000	<0.1
Neostigmine bromide	200,000	<0.1
Retigabine	200,000	<0.1
Ritonavir	100,000	<0.1
Rivastigmine tartrate	200,000	<0.1
Zafirlukast	200,000	<0.1

Interference by structurally unrelated compounds: The potential for positive or negative interference by various structurally unrelated compounds was evaluated by spiking these compounds (at the test concentrations shown in the table below) into urine containing either 75 ng/mL or 125 ng/mL meprobamate (±25% of the assay cutoff). Samples were tested in duplicate. The results, which are the same for the qualitative and semi-quantitative modes, are shown below.

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		-25%	+25%
		Cutoff	Cutoff
	Concentration	(75	(125
Compound	Tested (ng/mL)	ng/mL)	ng/mL)
Acetaminophen	100,000	Negative	Positive
6-Acetylmorphine	10,000	Negative	Positive
Acetylsalicylic Acid	100,000	Negative	Positive
Albuterol(Salbutamol)	100,000	Negative	Positive
Amitriptyline	100,000	Negative	Positive
d-Amphetamine	100,000	Negative	Positive
Benzoylecgonine	100,000	Negative	Positive
Buprenorphine	15,000	Negative	Positive
Bupropion	100,000	Negative	Positive
Caffeine	100,000	Negative	Positive
Carbamazepine	100,000	Negative	Positive
Cetirizine	20,000	Negative	Positive
Chlorpheniramine	100,000	Negative	Positive
Chlorpromazine	100,000	Negative	Positive
Clomipramine	100,000	Negative	Positive
Codeine	100,000	Negative	Positive
Cyclobenzaprine	100,000	Negative	Positive
Desipramine	100,000	Negative	Positive
Diphenhydramine	100,000	Negative	Positive
Ephedrine	100,000	Negative	Positive
Fentanyl	10,000	Negative	Positive
Fluoxetine	100,000	Negative	Positive
Fluphenazine	100,000	Negative	Positive
Hydrocodone	100,000	Negative	Positive
Hydromorphone	100,000	Negative	Positive
Ibuprofen	100,000	Negative	Positive
Imipramine	100,000	Negative	Positive
Lidocaine	100,000	Negative	Positive
Loratadine	100,000	Negative	Positive
Maprotiline	30,000	Negative	Positive
MDA (3,4-methylenedioxyamphetamine)	100,000	Negative	Positive
MDEA	100,000	Negative	Positive
MDMA (3,4-methylenedioxymethamphetamine)	100,000	Negative	Positive
Meperidine	100,000	Negative	Positive
Methadone	100,000	Negative	Positive
d-Methamphetamine	100,000	Negative	Positive
Methapyrilene	100,000	Negative	Positive
Methaqualone	100,000	Negative	Positive
		-25%Cutoff(75ng/mL)	+25%Cutoff(125ng/mL)
Compound	ConcentrationTested (ng/mL)
Metronidazole	100,000	Negative	Positive
Morphine	100,000	Negative	Positive
Nicotine	100,000	Negative	Positive
Nortriptyline	100,000	Negative	Positive
Oxazepam	100,000	Negative	Positive
Oxycodone	100,000	Negative	Positive
Oxymorphone	100,000	Negative	Positive
PCP (phencyclidine)	10,000	Negative	Positive
Pentazocine	20,000	Negative	Positive
Phenobarbital	100,000	Negative	Positive
d-Propoxyphene	100,000	Negative	Positive
Propranaolol	100,000	Negative	Positive
Ranitidine	100,000	Negative	Positive
Sertraline	100,000	Negative	Positive
THC-COOH (11-Nor-Delta-9-THC-9-carboxylic acid)	1,000	Negative	Positive
Thioridazine	100,000	Negative	Positive
Tramadol	100,000	Negative	Positive
Valproic Acid	100,000	Negative	Positive

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f. Assay cut-off:

Characterization of how the device performs analytically around the claimed cutoff concentrations of 100 ng/mL is described in the precision section, M.1.a. above.

2. Comparison studies:

a. Method comparison:

A method comparison study was performed using 127 unaltered clinical urine samples from subjects that were (b) (4) taking prescribed or nonprescribed Carisoprodol. Each sample was run in singlicate using the LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay on the AU400e automated clinical analyzer and the result was compared to that obtained by LC/MS or GC/MS. Samples with meprobamate concentrations < 100 ng/mL by LC/MS or GC/MS were defined as "negative." Samples with meprobamate concentrations > 100 ng/mL by LC/MS or GC/MS were defined as "positive." The results are summarized below.

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Qualitative analysis

Candidatedeviceresults	Negative(Drug-free orless than 50%of the cutoffconcentration)	Near CutoffNegative(Between50% belowthe cutoff andthe cutoffconcentration)	Near CutoffPositive(Between thecutoff and50% abovethe cutoffconcentration)	High Positive(Greater than50% abovethe cutoffconcentration)	%Agreement
Positive	0	2*	11	56	98.5
Negative	43	14	1**	0	96.6

Sample#	LC/MS or GC/MSMeprobamate (ng/mL)	LC/MS orGC/MS result	Candidate deviceresult
58*	92	Negative	Positive
59*	98	Negative	Positive
60**	103	Positive	Negative

Semi-Quantitative analysis

Candidatedeviceresults	Negative(Drug-free orless than 50%of the cutoffconcentration)	Near CutoffNegative(Between50% belowthe cutoff andthe cutoffconcentration)	Near CutoffPositive(Between thecutoff and50% abovethe cutoffconcentration)	High Positive(Greater than50% abovethe cutoffconcentration)	%Agreement
Positive	0	1*	11	56	98.5
Negative	43	15	1**	0	98.3

Sample#	LC/MS Meprobamate(ng/mL)	LC/MSresult	Candidate deviceresult
59*	98	Negative	Positive
60**	103	Positive	Negative

b. Matrix comparison:
Not applicable. Urine is the only claimed matrix for the candidate device.
1. Clinical studies:
- a. Clinical Sensitivity: Not applicable.
- b. Clinical Specificity: Not applicable.

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c. Other clinical supportive data (when a. and b. are not applicable): Not applicable.
1. Clinical cut-off:

The assay has a clinical cut-off of 100 ng/mL meprobamate in human urine. To support the clinical validity of this cut-off, the sponsor submitted information from pharmacokinetic studies of carisoprodol and meprobamate in plasma following single dose administration and detailed information about meprobamate elimination in urine as a first-order elimination. This information indicates that meprobamate levels above the cutoff of this assay (100 ng/mL) are present in the urine for up to a few days following a single dose of drug. The information provided supported the clinical validity of the claimed cutoff of this device.

1. Expected values/Reference range:
  Not applicable.

M. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Not applicable.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and the special controls for this device type.

O. Patient Perspectives:

This submission did not include specific information on patient perspectives for this device. In general, patients benefit from reliable tests to screen for the presence of drugs of abuse.

P. Identified Risks to Health and Required Mitigations

Identified Risks to Health	Required Mitigations
Clinical action based on incorrect test results(false positive results, false negative results)may lead to inappropriate clinical decisionmaking.	Special controls (1), (2), and (3)
Incorrect understanding of the device,including the results, may lead toinappropriate clinical decision making.	Special controls (2) and (3)

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Q. Benefit/Risk Analysis

Summary
Summary ofthe Benefit(s)	There are benefits related to the detection of the presence of the carisoprodol metabolite ormeprobamate drug in human urine. While the test is not indicated for acute clinicalmanagement of patients it may have value in settings of drug treatment programs,including decreasing the risk of potentially dangerous medication interactions. Forexample, identifying the presence of meprobamate may help prevent drug interactions withother sedating drugs that could potentiate the sedating effect. The test also has benefit foruse in substance abuse programs to monitor the illicit use of carisoprodol or meprobamatewhich have abuse potential and are categorized as Schedule IV controlled substances bythe Drug Enforcement Administration (DEA).
Summary ofthe Risk(s)	The risk of the test is limited to false negative or false positive test results and the incorrectunderstanding of how to interpret the results.
	A false positive result could result in the misidentification of a patient as having takencarisoprodol or meprobamate; however, device labelling states that positive results must beconfirmed with a more specific analytical testing method; and when performed thisconfirmatory testing mitigates the risk of false positive results.
	A false negative result could increase the risk of drug interactions if other drugs whichcontribute to or potentiate the side effects are prescribed. However, the analyticalperformance of the test appears mitigates the risk of false negative results. Negativeagreement among the 127 samples tested was 96.6% and the one false negative result inthe study showed a level of meprobamate (established by a confirmatory analyticalmethod) that was very near the cut-off.
	Misinterpretation of a positive test as indicative of toxicity, when the test is used in anacute care setting, could delay appropriate treatment if the result leads to confusion in thediagnosis of another acute condition that is present. This risk is mitigated by labelling ofthe device which specifically limits against the use of the test in being used for diagnosingdrug intoxication or for the purposes of determining appropriate therapy.
Summary ofOtherFactors	The studies conducted included assessment of the accuracy, specificity, and precisionaround the cutoff of the device.
ConclusionsDo the probable benefits outweigh the probable risks?
Given the device's indications for use, required general controls and special controls established for this device,the probable benefits outweigh the probable risks.

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R. Conclusion:

The information provided in this de novo submission is sufficient to classify this device into class II under regulation 21 CFR 862.3590. FDA believes that the stated special controls, and applicable general controls, including design controls, provide reasonable assurance of the safety and effectiveness of the device type. The device is classified under the following:

Product Code:	QBK
Device Type:	Meprobamate test system
Class:	II (special controls)
Regulation:	21 CFR 862.3590

(a) Identification. A meprobamate test system is a device intended to measure meprobamate in human specimens. Measurements obtained by this device are used to detect the presence of meprobamate to diagnose the use or overdose of meprobamate or structurally-related drug compounds (e.g., prodrugs).

(b) Classification. Class II (special controls). The special controls for this device are:

1. Design verification and validation must include:
Robust data demonstrating the accuracy of the device when used in the intended (i) specimen matrix. The accuracy data must include a comparison between the meprobamate test system results and meprobamate results that are measured on an FDA-accepted measurement method that is specific and accurate (e.g., gas or liquid chromatography combined with tandem mass spectrometry).
(ii) Robust analytical data demonstrating the performance characteristics of the device, including, but not limited to, specificity, cross-reactivity to relevant endogenous and exogenous substances, and the reproducibility of analyte detection around the cutoff(s).
1. The intended use of the device must not include an indication for use in monitoring therapeutic drug concentrations or informing dosing adjustment decisions.
1. Your 21 CFR 809.10 labeling must include the following:
(i) If indicated for use as a screening test to identify preliminary results for further confirmation, the intended use must state "This assay provides only a preliminary analytical result. A more specific alternative chemical confirmatory method (e.g., gas or liquid chromatography and mass spectrometry) must be used to obtain a confirmed analytical result. Clinical consideration and professional judgment must be exercised with any drug of abuse test, particularly when the preliminary test result is positive."
(ii) A limiting statement that reads as follows: "This test should not be used to monitor therapeutic drug concentrations or to inform dosing adjustment decisions."

Regulation Number and Section

§ 862.3590 Meprobamate test system.

(a)
Identification. A meprobamate test system is a device intended to measure meprobamate in human specimens. Measurements obtained by this device are used to detect the presence of meprobamate to diagnose the use or overdose of meprobamate or structurally-related drug compounds (e.g., prodrugs).(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Robust data demonstrating the accuracy of the device when used in the intended specimen matrix. The accuracy data must include a comparison between the meprobamate test system results and meprobamate results that are measured on an FDA-accepted measurement method that is specific and accurate (e.g., gas or liquid chromatography combined with tandem mass spectrometry).
(ii) Robust analytical data demonstrating the performance characteristics of the device, including, but not limited to, specificity, cross-reactivity to relevant endogenous and exogenous substances, and the reproducibility of analyte detection around the cutoff(s).
(2) The intended use of the device must not include an indication for use in monitoring therapeutic drug concentrations or informing dosing adjustment decisions.
(3) Your 21 CFR 809.10 labeling must include the following:
(i) If indicated for use as a screening test to identify preliminary results for further confirmation, the intended use must state “This assay provides only a preliminary analytical result. A more specific alternative chemical confirmatory method (e.g., gas or liquid chromatography and mass spectrometry) must be used to obtain a confirmed analytical result. Clinical consideration and professional judgment must be exercised with any drug of abuse test, particularly when the preliminary test result is positive.”
(ii) A limiting statement that reads as follows: “This test should not be used to monitor therapeutic drug concentrations or to inform dosing adjustment decisions.”