Predicate Devices

No predicate device exists

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a laboratory-based analytical method using LC/MS/MS for chemical quantitation, with no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No.
The device is intended for the quantitation of specific organophosphate metabolites for diagnostic purposes, not for treating or preventing a disease or condition.

Diagnostic

Yes

The device is intended for the "quantitation of specific organophosphate metabolites by LC/MS/MS" in human urine to "confirm exposure, identify the causative agent, and distinguish exposed from the unexposed patients" following an exposure or suspected exposure event. This direct measurement of biomarkers to identify and differentiate patient states aligns with the definition of a diagnostic device.

SaMD (Software as a Medical Device)

No

The device description explicitly mentions hardware components like a solid phase extraction cartridge, tandem mass spectrometer, and HPLC system, indicating it is not software-only.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use: The device is intended for the "quantitation of specific organophosphate metabolites by LC/MS/MS" in "human urine". This clearly indicates it's used to examine specimens derived from the human body.
Purpose: The data obtained is used to "confirm exposure, identify the causative agent, and distinguish exposed from the unexposed patients" based on the presence and concentration of these metabolites. This is a diagnostic purpose, providing information about a patient's health status (exposure to organophosphates).
Components: The device includes "organophosphate metabolite calibrators" and "organophosphate metabolite controls," which are standard components of IVD systems used for calibration and quality control.
Methodology: The use of LC/MS/MS to measure specific substances in a biological sample is a common technique in in vitro diagnostics.

The definition of an IVD generally includes devices intended for use in the collection, preparation, and examination of specimens taken from the human body for the purpose of providing information for the diagnosis, prevention, monitoring, treatment, or alleviation of disease or injury. This device fits that description.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

This device is intended for the quantitation of specific organophosphate metabolites by LC/MS/MS. The device system includes organophosphate metabolite calibrators to calibrate the system and organophosphate metabolite controls for quality control monitoring of the system. This device is intended for use in a single laboratory to detect and measure the concentration of specific organophosphate metabolites in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device will be used following an exposure or suspected exposure event to confirm exposure, identify the causative agent, and distinguish exposed from the unexposed patients.

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

PDY

Device Description

The device comprises internal standards which serve as the basis for the calibrators and quality control materials. A solid phase extraction cartridge is initially used to extract the metabolites for further separation and analysis on a tandem mass spectrometer and HPLC system.

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

This device is intended for use in a single laboratory and its distribution is limited to laboratories with experienced personnel who are trained to measure and evaluate organophosphate exposure and guide public health response.

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)

Analytical performance:

Precision/Reproducibility: Precision and repeatability were determined through analysis of quality control materials in synthetic urine at 15 and 75 ng/mL concentrations of five organophosphate metabolites (OP-1, 2, 3, 4, 5). Samples were prepared, analyzed, and processed by three different operators over 14 days, with no more than 4 QC samples prepared and analyzed in one 24-hour period. Within-day and between-day studies were performed on a single instrument (AU23771008).
- Within Day (n=4): %CV ranged from 2.4% to 5.8%.
- Between Day (n=20, days=14): %CV ranged from 2.8% to 4.2%.
Linearity/assay reportable range: The claimed measuring range is 2 – 200 ng/mL. Recovery studies were conducted for each organophosphate metabolite using spiked pooled urine samples at various concentrations, analyzed in triplicate. Recovery percentages generally ranged from 81.1% to 112.9%.
Detection limit: LoD for the five metabolites were determined by measuring spiked synthetic urine samples at 1, 2, and 5 ng/mL, and a blank synthetic urine sample. The claimed measuring range is 2 - 200 ng/mL.
- LoD values: OP-1 (0.40), OP-3 (0.35), OP-2 (0.13), OP-4 (0.20), OP-5 (0.69).
- LoQ values: 2 ng/mL for all five metabolites.
Analytical specificity: 200 individual unexposed urine samples were extracted. No peaks above the LoQ were detected for all five metabolites. Six non-specific pesticide metabolites (dialkylphosphates) were spiked into samples, and no interfering peaks were detected.
Assay cut-off: Not applicable.
Comparison studies: Not applicable (No predicate device exists).
Clinical studies: Not applicable.
Clinical cut-off: All values ≥ 2 ng/mL indicate exposure to an organophosphate metabolite. A value

Regulation Number and Section

§ 862.3652 Organophosphate test system.

(a)
Identification. An organophosphate test system is a device intended to measure organophosphate metabolites quantitatively in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device is intended to aid in the confirmation and investigation of organophosphate exposure.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The distribution of these devices is limited to laboratories with experienced personnel who are trained to measure and evaluate organophosphate exposure and guide public health response.
(2) Analytical testing must demonstrate the device has appropriate performance characteristics, including adequate precision and accuracy across the measuring range and near medical decision points.

Summary

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EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR QUANTITATION OF ORGANOPHOSPHATE METABOLITES IN URINE BY LC/MS/MS

DECISION SUMMARY

Correction Date: March 10, 2017 This Decision Summary contains corrections to the August 8, 2013 Decision Summary

A. 510(k) Number:	K122282
B. Purpose for Submission:	De novo request for evaluation of automatic class
III designation of the Quantitation of
Organophosphate Metabolites in Urine by
LC/MS/MS new assay
C. Measurand:	Selected Organophosphate Metabolites
D. Type of Test:	Quantitative LC/MS/MS
E. Applicant:	Centers for Disease Control and Prevention (CDC)

F. Proprietary and Established Names:

Quantitation of Organophosphate Metabolites in Urine by LC/MS/MS

G. Regulatory Information:

FDA identifies this type of device as: Organophosphate test system

An organophosphate test system is a device intended to measure organophosphate metabolites quantitatively in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device is intended to aid in the confirmation and investigation of organophosphate exposure.

1. New Regulation Number:
  21 CFR 862.3652
1. Classification:
  Class II (special controls)
1. Product code:
  PDY

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4. Panel:

Clinical Chemistry and Clinical Toxicology Devices

H. Intended Use:

1. Intended use(s):
  This device is intended for the quantitation of specific organophosphate metabolites by LC/MS/MS. The device system includes organophosphate metabolite calibrators to calibrate the system and organophosphate metabolite controls for quality control monitoring of the system. This device is intended for use in a single laboratory to detect and measure the concentration of specific organophosphate metabolites in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device will be used following an exposure or suspected exposure event to confirm exposure, identify the causative agent, and distinguish exposed from the unexposed patients.
1. Indication(s) for use:
  Same as intended use.
1. Special conditions for use statement(s):
  For in vitro diagnostic use.

For prescription use only, in a single laboratory.

1. Special instrument requirements:
  AB Sciex Qtrap 5500 - Serial number (S/N) AU23771008

Agilent HPLC - (Degasser 1100 Series: S/N JP32750555: FC/ALS Therm Series: S/N DE60556845; HiP-ALS 1200 Series: S/N DE63055552; Bin Bump 1200 Series: S/N DE63057946; Degasser 1200 Series: S/N JP63705336)

Caliper Life Sciences - (Sciclone i1000 Workstation: S/N SS0712N0548 and SS739N0661; Twister II Microplate Handler: S/N T20838N0168)

Clearance of this assay is limited only to the instrument systems with the serial numbers as specified above. Any additional systems will require a validation panel to be reviewed and approved prior to use with the assay.

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I. Device Description:

The device comprises internal standards which serve as the basis for the calibrators and quality control materials. A solid phase extraction cartridge is initially used to extract the metabolites for further separation and analysis on a tandem mass spectrometer and HPLC system.

J. Substantial Equivalence Information:

1. Predicate device name(s):
  No predicate device exists
1. Predicate 510(k) number(s):
  Not applicable
1. Comparison with predicate:
  Not applicable

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

1. CLSI EP17-A, Protocol for Determination of Limits of Detection and Limits of Ouantitation: Approved Guideline, Vol. 24, No. 34, modified
1. CLSI EP6-A. Evaluation of the linearity of Quantitative Measurement Procedures: A Statistical approach; Approved Guideline, Vol. 23, No. 16

L. Test Principle:

This assay detects the presence of organophosphate metabolites in human urine. This is achieved through the separation, identification, and quantitation of the specific metabolites resulting from exposure to selected organophosphates by LC/MS/MS.

M. Performance Characteristics (if/when applicable):

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

Precision and repeatability were both determined through analysis of quality control materials in synthetic urine at 15 and 75 ng/mL concentrations of five organophosphate metabolites (identified as OP-1, 2, 3, 4, 5). The samples were prepared, analyzed, and processed by three different operators over a

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period of 14 days, with no more than 4 QC samples prepared and analyzed in one 24-hour period. Within-day and between-day studies were performed on a single instruments. The data are summarized in the tables below.

| | | Within Day, n=4, operators = 1 | | | Between Day, n=20, days = 14,
operators = 3 | | |
|---------|--------------------------|--------------------------------|----------|-----|------------------------------------------------|----------|-----|
| Analyte | Concentration
(ng/mL) | Mean | St. Dev. | %CV | Mean | St. Dev. | %CV |
| OP-1 | 15 | 15.2 | 0.8 | 5.4 | 14.9 | 0.6 | 4.2 |
| | 75 | 75.7 | 2.2 | 2.9 | 75.6 | 2.3 | 3.0 |
| OP-2 | 15 | 15.0 | 0.4 | 2.4 | 15.0 | 0.5 | 3.4 |
| | 75 | 76.3 | 1.8 | 2.4 | 76.2 | 2.1 | 2.8 |
| OP-3 | 15 | 15.4 | 0.4 | 2.7 | 15.0 | 0.6 | 4.1 |
| | 75 | 76.8 | 3.5 | 4.1 | 75.7 | 2.1 | 2.7 |
| OP-4 | 15 | 15.5 | 0.9 | 5.8 | 15.0 | 0.6 | 4.0 |
| | 75 | 76.1 | 1.5 | 1.9 | 75.9 | 2.3 | 3.1 |
| OP-5 | 15 | 14.9 | 0.5 | 3.1 | 14.8 | 0.6 | 4.2 |
| | 75 | 75.2 | 3.3 | 4.0 | 75.3 | 2.2 | 2.9 |

Instrument AU23771008

b. Linearity/assay reportable range:

The claimed measuring range is 2 – 200 ng/mL.

Recovery studies were conducted for each organophosphate metabolite. Spiked pooled urine samples at various concentrations were prepared and analyzed in triplicate.

| Conc.

ng/mL	OP-3		OP-4		OP-5
	Mean,
ng/mL	%
Recovery	Mean,
ng/mL	%
Recovery	Mean,
ng/mL	%
Recovery
2	1.7	86.5	1.9	96.0	1.9	94.0
3	2.8	92.3	2.4	81.1	3.4	112.9
7	6.8	96.4	6.3	90.1	7.2	103.1
9	7.9	87.6	8.5	94.5	8.3	92.2
22	20.2	92.0	20.4	92.9	20.4	92.6
30	n/a	n/a	n/a	n/a	n/a	n/a
45	40.7	90.5	40.5	90.1	42.3	94.0
65	60.5	93.0	59.5	91.5	60.4	93.0
80	72.9	91.2	71.2	89.0	74.5	93.2
95	86.7	91.3	87.5	92.1	90.1	94.9
115	106.3	92.5	103.7	90.1	107.5	93.5
130	120.0	92.3	118.2	90.9	123.2	94.7
145	n/a	n/a	n/a	n/a	n/a	n/a

Instrument AU23771008

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180	183.8	102.1	155.3	86.3	182.5	101.4
200	210.3	105.2	173.7	86.8	207.3	103.7

| Conc.

ng/mL	OP-1		OP-2
	Mean,
ng/mL	%
Recovery	Mean,
ng/mL	%
Recovery
2	1.9	93.0	1.9	95.5
3	2.5	82.6	2.9	97.3
7	6.7	95.2	6.8	96.6
9	8.4	93.2	8.9	98.9
22	21.2	96.3	20.8	94.6
30	28.6	95.4	n/a	n/a
45	42.9	95.5	43.7	97.1
65	63.1	97.1	n/a	n/a
80	n/a	n/a	74.8	93.5
95	90.2	95.0	88.0	92.6
115	n/a	n/a	107.3	93.3
130	125.8	96.8	122.3	94.1
145	140.2	96.7	136.3	94.0
180	177.7	98.3	173.8	96.6
200	203.2	101.6	199.8	99.9

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

Traceability and Value assignment

Calibrators are prepared at the assigned levels by a vendor using a dilution scheme. Assigned values are verified according to precision, accuracy, and linear response.

Values assigned to the calibrators and quality control materials are traceable to the internal standards synthesized by a vendor. There are no certified reference materials available for these compounds.

Stability

Calibrator and quality control material storage stability was evaluated. All

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data met the acceptance criteria and support the shelf life claim of 2 years at -70 C.

d. Detection limit:
The LoD for the five metabolites were determined by measuring piked synthetic urine samples at 1, 2, and 5 ng/mL, as well as a blank synthetic urine sample. The LoB, LoD, and LoQ are summarized below. The claimed measuring range is 2 - 200 ng/mL.

	OP-1	OP-3	OP-2	OP-4	OP-5
LoB	0.229	0.192	0.029	0.090	0.406
LoD	0.40	0.35	0.13	0.20	0.69
LoQ	2	2	2	2	2

Instrument AU23771008

e. Analytical specificity:
200 individual unexposed urine samples were extracted for the presence of any peaks that would contribute to false positive results (i.e. the presence of any positive peaks). No peaks were detected in the samples that were above the LoQ for all five metabolites. Six non-specific pesticide metabolites, known as dialkylphosphates, were spiked into samples and the samples were analyzed for the presence of any positive peaks associated with the organophosphates. No interfering peaks were detected.
f. Assay cut-off:
Not applicable
1. Comparison studies:
- a. Method comparison with predicate device:

Not applicable

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

Not applicable

b. Clinical specificity:

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Not applicable

Other clinical supportive data (when a. and b. are not applicable): C.
Not applicable
1. Clinical cut-off:
  All values ≥ 2 ng/mL indicate exposure to an organophosphate metabolite. A value False positive: The risks to the individual of a false positive result include unnecessary anxiety related to long term impact of such exposure and possible unnecessary medical work up, evaluation and follow-up for exposure-related complications. Since no treatment decisions will be initiated based on test results, a false positive result will not lead to risk of inappropriate treatment. Treatment is initiated based on signs and symptoms of possible exposure in the immediate setting, prior to obtaining results of medical diagnostic tests. False negative: The risk to the individual of a false negative result is missed identification of exposure to organophosphate(s). Since no treatment decisions are expected to be initiated based on test results, a false negative result will not lead to missed opportunity to initiate appropriate treatment in the immediate setting. A false negative result may lead to a missed opportunity for additional medical evaluation and follow-up for exposure-related complications. Public Health Risk from Incorrect Test Results: The consequences to public health for both false positive and false negative results are similar and are related to inaccurate epidemiologic data leading to long term misconceptions and inaccurate conclusions related to exposure event. Missed opportunities for valuable information gathering that could lead to significant benefits to public health may occur. |
  | Summary of
  Other
  Factors | Not applicable |
  | Conclusions
  Do the probable benefits outweigh the probable risks? | Given robust analytical performance characteristics and risk mitigation (i.e. proper labeling and use in the Public Health response sector), the probable benefits to both the individual and public health outweigh the probable risks of this device. |

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T. Conclusion:

The information provided in this de novo submission is sufficient to classify this device into class II under regulation 21 CFR 862.3652. FDA believes that special controls, along with the applicable general controls, provide reasonable assurance of the safety and effectiveness of the device type. This device, and similar devices, are classified under the following:

Product Code: PDY

Device Type:	Organophosphate Test System
Class:	II (special controls)
Regulation:	21 CFR 862.3652

(a) Identification. An organophosphate test system is a device intended to measure organophosphate metabolites quantitatively in human urine from individuals who have signs and symptoms consistent with cholinesterase poisoning. The data obtained by this device is intended to aid in the confirmation and investigation of organophosphate exposure.

(b) Classification. Class II (special controls). Organophosphate test systems must comply with the following special controls:

1. The distribution of these devices is limited to laboratories with experienced personnel who are trained to measure and evaluate organophosphate exposure and guide public health response.
1. Analytical testing must provide a reasonable assurance of safety and effectiveness demonstrate the device has appropriate performance characteristics, including adequate precision and accuracy across the measuring range and near medical decision points.