ACON OPI ONE STEP OPIATE TEST STRIP AND ACON OPI ONE STEP OPIATE TEST DEVICE

K040274 · ACON Laboratories, Inc. · DJG · May 3, 2004 · Clinical Toxicology

Device Facts

• Record ID: K040274
• Device Name: ACON OPI ONE STEP OPIATE TEST STRIP AND ACON OPI ONE STEP OPIATE TEST DEVICE
• Applicant: ACON Laboratories, Inc.
• Product Code: DJG · Clinical Toxicology
• Decision Date: May 3, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

The ACON® OPI II One Step Opiate Test Strip and ACON OPI II One Step Opiate Test Device are rapid chromatographic immunoassays for the qualitative detection of Opiate in urine at a cutoff concentration of 2,000 ng/mL. These tests are used to provide only a preliminary analytical result. All positive test results obtained with these devices must be confirmed by another test method, preferably GC/MS analysis. They are intended for healthcare professionals including professionals at point-of-care sites.

Device Story

Lateral flow, competitive binding immunochromatographic assay; detects opiates in urine. Principle: mouse monoclonal antibody-antigen interaction. Input: urine sample; Output: visual colored line on test strip/device. No instrumentation required. Used at point-of-care sites by healthcare professionals. Positive result: absence of colored line in test region; Negative result: presence of colored line. Procedural control line confirms proper sample volume and wicking. Preliminary screening only; requires GC/MS confirmation. Assists clinicians in identifying potential opiate presence to guide further diagnostic or clinical decision-making.

Clinical Evidence

Clinical evaluation of 300 urine specimens compared ACON OPI II devices against an FDA-cleared predicate and GC/MS. Overall agreement with predicate was >99% (95% CI: 98%-99%). Agreement with GC/MS at 2,000 ng/mL cutoff showed 98% positive agreement and 97% negative agreement. Study included specimens with concentrations ranging from -25% to +25% of the cutoff. Additional bench testing verified analytical sensitivity, specificity, cross-reactivity, interference, precision, and environmental robustness.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding format. Utilizes mouse monoclonal antibodies. Qualitative visual readout. No external energy source or instrumentation required. Standalone test strip or cassette device. Sterilization not specified.

Indications for Use

Indicated for the qualitative detection of opiates in human urine at a 2,000 ng/mL cutoff. Intended for use by healthcare professionals, including those at point-of-care sites, as a preliminary screening test. Requires confirmation by an alternate chemical method, preferably GC/MS.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Submission Summary (Full Text)

{0}

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
K040274

B. Analyte:
Opiates

C. Type of Test:
Qualitative immunoassay

D. Applicant:
ACON Laboratories, Inc.

E. Proprietary and Established Names:
ACON OPI II One Step Opiate Test Strip
ACON OPI II One Step Opiate Test Device

F. Regulatory Information:
1. Regulation section:
§ 862.3650 Opiate Test System
2. Classification:
Class II
3. Product Code:
DJG
4. Panel:
Toxicology (91)

G. Intended Use:
1. Intended use(s):
Refer to Indications for use.

2. Indication(s) for use:
The ACON OPI II One Step Opiate Test Strip and ACON OPI II One Step Opiate Test Device are chromatographic immunoassay for the qualitative detection of opiate levels in urine at a designated cut-off concentration of 2,000 ng/mL. These assays provide only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

For in vitro diagnostic use only.

{1}

2

3. Special condition for use statement(s):

These assays provide only the preliminary analytical test results. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

The assays are intended for use in point-of-care settings. The assays were evaluated in point-of-care settings.

4. Special instrument Requirements:

Not applicable. The devices are visually read single-use devices.

H. Device Description:

The ACON OPI II One Step Opiate Test Strip and ACON OPI II One Step Opiate Test Device are immunoassays based on the principle of competitive binding. Drugs which may be present in the urine specimen compete against the drug conjugate for binding sites on the antibody.

During testing, a urine specimen migrates upward by capillary action. Morphine, if present in the urine specimen below 2,000 ng/mL, will not saturate the binding sites of antibody-coated particles in the test strip. The morphine conjugate will be captured by antibody and visible color line will show up in the test line region. The colored line will not form in the test line region if the morphine level exceeds 2,000 ng/mL because it will saturate all the binding sites of anti-benzoylecgonine antibodies.

A drug-positive urine specimen will not generate a colored line in the test line region because of drug competition, while a drug-negative urine specimen or a specimen containing the target drug in a concentration less than the cut-off level of the assay will generate a line in the test line region.

To serve as a procedural control, a colored line will always appear at the control line region, indicating that proper volume of specimen has been added and membrane wicking has occurred.

I. Substantial Equivalence Information:

1. Predicate device name(s): ACON OPI One Step Opiate
2. Predicate K number(s): K011353
3. Comparison with predicate:

{2}

3

Both devices are for the qualitative determination of the same analyte(s) in the same matrix, and utilize the same cutoff concentration. Both are visually-read single use devices.

The difference between the new tests and the predicate is in the components of the mobile phase and capture reagents used in the new devices. The new devices employ a particle membrane immunoassay using the mouse anti-drug monoclonal antibody-colored particle complex embedded in the conjugate pad as part of the mobile phase and drug-protein conjugate strip on the membrane as the capture reagent; while the predicate device employs a particle membrane immunoassay using a drug-protein-colored particle complex embedded in the conjugated pad as part of the mobile phase and mouse anti-drug monoclonal antibody strip on the membrane as the capture reagent.

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

The sponsor did not reference any standards in their submission.

## K. Test Principle:

The tests employ lateral flow immunochromatographic technology.

Drug in the sample and drug-labeled conjugate (containing a chromagen) compete for antibody binding sites in the test area of the test strip. Binding of drug in the sample causes the absence of a line at the test area, i.e., a positive result. When drug is not present in the sample, the drug-labeled conjugate binds at the test line, resulting in formation of a line, i.e., a negative result. The absence or presence of the line is determined visually by the operator.

The devices also have an internal process controls which indicate that adequate volume of sample has been added and that the immunochromatographic strip is intact.

The test strip and device contain monoclonal anti-morphine antibody-coupled particles and morphine-protein conjugates. A gold anti-rabbit antibody is employed in the control line system.

## L. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

For ACON OPI II One Step Opiate Test Strip, A study was conducted at 3 physician's offices by untrained operators using 3 different lots of product to demonstrate the within run, between run and between operator precision. An identical panel of coded specimens were blind labeled and tested at each site. The results are given below:

{3}

4

| Morphine conc (ng/mL) | n per site | Site A | | | Site B | | | Site C | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | - | + | Invalid | - | + | Invalid | - | + | Invalid |
| 0 | 15 | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 | 0 |
| 1,000 | 15 | 15 | 0 | 0 | 14 | 1 | 0 | 15 | 0 | 0 |
| 1,500 | 15 | 14 | 1 | 0 | 11 | 4 | 0 | 6 | 9 | 0 |
| 2,500 | 15 | 0 | 15 | 0 | 1 | 14 | 0 | 0 | 15 | 0 |
| 3,000 | 15 | 0 | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 |
| Invalid | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 | 0 | 15 |

For ACON OPI II One Step Opiate Test Device, a study was conducted at 3 physician's offices by untrained operators using 3 different lots of product to demonstrate the within run, between run and between operator precision. An identical panel of coded specimens were blind labeled and tested at each site. The results are given below:

| Morphine conc (ng/mL) | n per site | Site A | | | Site B | | | Site C | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | - | + | Invalid | - | + | Invalid | - | + | Invalid |
| 0 | 15 | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 | 0 |
| 1,000 | 15 | 15 | 0 | 0 | 14 | 1 | 0 | 15 | 0 | 0 |
| 1,500 | 15 | 14 | 1 | 0 | 10 | 5 | 0 | 6 | 9 | 0 |
| 2,500 | 15 | 0 | 15 | 0 | 1 | 14 | 0 | 0 | 15 | 0 |
| 3,000 | 15 | 0 | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 |
| Invalid | 15 | 0 | 0 | 15 | 0 | 0 | 15 | 0 | 0 | 15 |

b. Linearity/assay reportable range:
Not applicable. The assay is intended for qualitative use.

c. Traceability (controls, calibrators, or method):
Procedural controls are included in the test strip and device. A red line appearing in the control region (C) is considered as an internal procedural control. It confirms sufficient specimen volume, adequate membrane wicking and correct procedural technique.
Control standards are not supplied with these kits; however, it is recommended that positive and negative controls be tested as a good laboratory practice to confirm the test procedure and to verify proper test performance. Users should follow local, state, and federal guidelines for testing QC materials.

d. Cutoff Studies:
For ACON OPI II One Step Opiate Test Strip, a drug-free urine pool was spiked with Morphine at the following concentrations: 0 ng/mL, 1,000 ng/mL, 1,500 ng/mL, 2,000 ng/mL, 2,500 ng/mL, 3,000 ng/mL and 4,000 ng/mL. The result demonstrates >99% analytical accuracy at 50% above and 50% below the cut-off concentration. The data are summarized below:

{4}

5

| Morphine Concentration (ng/mL) | Percent of Cutoff | n | Visual Result | |
| --- | --- | --- | --- | --- |
| | | | Negative | Positive |
| 0 | 0% | 30 | 30 | 0 |
| 1,000 | -50% | 30 | 30 | 0 |
| 1,500 | -25% | 30 | 24 | 6 |
| 2,000 | Cutoff | 30 | 14 | 16 |
| 2,500 | +25% | 30 | 7 | 23 |
| 3,000 | +50% | 30 | 0 | 30 |
| 4,000 | +100% | 30 | 0 | 30 |

For ACON OPI II One Step Opiate Test Device, a drug-free urine pool was spiked with Morphine at the following concentrations: 0 ng/ml, 1,000 ng/ml, 1,500 ng/ml, 2,000 ng/ml, 2,500 ng/ml, 3,000 ng/ml and 4,000 ng/ml. The result demonstrates >99% analytical accuracy at 50% above and 50% below the cut-off concentration. The data are summarized below:

| Morphine Concentration (ng/mL) | Percent of Cutoff | n | Visual Result | |
| --- | --- | --- | --- | --- |
| | | | Negative | Positive |
| 0 | 0% | 30 | 30 | 0 |
| 1,000 | -50% | 30 | 30 | 0 |
| 1,500 | -25% | 30 | 26 | 4 |
| 2,000 | Cutoff | 30 | 13 | 17 |
| 2,500 | +25% | 30 | 5 | 25 |
| 3,000 | +50% | 30 | 0 | 30 |
| 4,000 | +100% | 30 | 0 | 30 |

e. Analytical specificity:

Opiate and its related compounds listed in the following table were spiked to 100 ug/mL concentration in drug free urine, then serial diluted and tested with the ACON OPI II One Step Opiate Test Strip and Test Device until the concentrations at which initial negative results were obtained. The following table lists compounds that are positively detected in urine by the ACON OPI II One Step Opiate Test Strip at 5 minutes.

{5}

6

| Compound | Concentration (ng/mL) | % Cross Reactivity |
| --- | --- | --- |
| Morphine | 2,000 | 100% |
| Codeine | 2,000 | 100% |
| Hydrocodone | 100,000 | 2% |
| Levorphanol | 100,000 | 2% |
| Morphine-3-β-Glucuronide | 12,500 | 16% |
| Norcodeine | 50,000 | 4% |
| Thebaine | 100,000 | 2% |
| Nalorphine | 100,000 | 2% |
| Hydromorphone | 100,000 | 2% |
| 6-Monoacetylmorphine | 1,500 | 133% |
| Ethylmorphine | 6,250 | 32% |
| Heroin (Diacetylmorphine) | 20,000 | 10% |

## Effect of Urinary Specific Gravity

Fifteen (15) urine samples of normal, high, and low specific gravity ranges were spiked with 1,000 ng/ml and 3,000 ng/ml of Morphine respectively. The ACON OPI II One Step Opiate Test Strip was tested in duplicate using the fifteen neat and spiked urine samples. The results demonstrate that specific gravity ranges from 1.004 to 1.034 did not affect the expected results or accuracy of the test.

## Effect of Urinary pH

The pH of an aliquoted negative urine pool was adjusted to a pH range of 5 to 9 in 1 pH unit increments; four of the five aliquots were spiked with Morphine. Final morphine concentrations in the aliquots were 0, 1,000, 3,000 and 4,000 ng/ml. The spiked, pH-adjusted urine was tested with the ACON OPI II One Step Opiate Test Strip in duplicate and interpreted according to the package insert. The results demonstrate that varying ranges of pH does not interfere with the performance of the test.

## Cross-Reactivity

A study was conducted to determine the cross-reactivity of the test with compounds in either drug-free urine or morphine positive urine. The following compounds show no cross-reactivity when tested with the ACON OPI II One Step Opiate Test Strip at a concentration of 100 µg/mL.

## Non Cross-Reacting Compounds

4-Acetaminophenol
Acetophenetidin
6-Acetylcodeine
N-Acetylprocainamide
Acetylsalicylic acid
Aminopyrine

Fenoprofen
Furosemide
Gentisic acid
Hemoglobin
Hydralazine
Hydrochlorothiazide

Trans-2-Phenylcyclopropylamine
L-Phenylephrine
β-Phenylethylamine
Phenylpropanolamine
Prednisolone

{6}

7

| Amitryptyline | O-Hydroxyhippuric acid | Prednisone |
| --- | --- | --- |
| Amobarbital | p-OH-Amphetamine | Procaine |
| Amoxicillin | p-OH-Methamphetamine | Promazine |
| Ampicillin | 3-Hydroxytyramine | Promethazine |
| L-Ascorbic acid | Ibuprofen | DL-Propranolol |
| D-Amphetamine | Imipramine | D-Propoxyphene |
| DL-Amphetamine | Iproniazid | D-Pseudoephedrine |
| L-Amphetamine | (+/-)-Isoproterenol | Quinacrine |
| Apomorphine | Isoxuprine | Quinidine |
| Aspartame | Ketamine | Quinine |
| Atropine | Ketoprofen | Ranitidine |
| Benzilic acid | Labetalol | Salicylic acid |
| Benzoic acid | Loperamide | Secobarbital |
| Benzphetamine | Maprotiline | Serotonin |
| Bilirubin | Meperidine | Sulfamethazine |
| (±)-Brompheniramine | Mephentermine | Sulindac |
| Buspirone | Meprobamate | Sustiva (efavirenz) |
| Caffeine | D-Methamphetamine | Temazepam |
| Cannabidiol | Methadone | Tetracycline |
| Cannabinol | Methoxyphenamine | Tetrahydrocortisone, |
| Chloralhydrate | Methylphenidate | 3-acetate |
| Chloramphenicol | MDA* | Tetrahydrocortisone, |
| Chlordiazepoxide | MDMA** | 3-β-Glucuronide |
| Chlorothiazide | Nalidixic acid | Tetrahydrozoline |
| (±)-Chlorpheniramine | Naloxone | Theophylline |
| Chlorpromazine | Naltrexone | Thiamine |
| Chloroquine | Naproxen | Thioridazine |
| Cholesterol | Niacinamide | Tolbutamide |
| Clomipramine | Nifedipine | Trazodone |
| Clonidine | Nimesulide | DL-Tyrosine |
| Cortisone | Norethindrone | Triamterene |
| (-) -Cotinine | Normorphone | Trifluoperazine |
| Creatinine | D-Norpropoxyphene | Trimethoprim |
| Deoxycorticosterone | Noscapine | Trimipramine |
| Dextromethorphan | D,L-Octopamine | Tryptamine |
| Diazepam | Oxalic acid | DL-Tryptophan |
| Diclofenac | Oxazepam | Tyramine |
| Dicyclomine | Oxolinic acid | Uric acid |
| Diflunisal | Oxymetazoline | Verapamil |
| Digoxin | Oxycodone | Zomepirac |
| Diphenhydramine | Oxymorphone | |
| 5,5-Diphenylhydantoin | Papaverine | |
| Doxylamine | Penicillin-G | |
| (-) - Ψ-Ephedrine | Pentazocine HCl | |
| [1R, 2S]-(-)-Ephedrine | Pentobarbital | |
| L-Epinephrine | Perphenazine | |
| Erythromycin | Phencyclidine | |
| β-Estradiol | Phenelzine | |
| Estrone-3-sulfate | Phenobarbital | |
| Ethyl-p-aminobenzoate | Phentermine | *(+/-)3,4-Methylenedioxyamphetamine |
| | | ***(+/-)3,4-Methylenedioxymethamphetamine |

f. Assay cut-off:
The ACON OPI II One Step Opiate Test Strip and Device yield a positive result when the opiates in urine exceed $2,000\mathrm{ng/mL}$. At present, the recommended screening cutoff for opiates positive

{7}

specimens as set by the Substance Abuse and Mental Health Services Administration (SAMHSA) is 2,000 ng/mL. Characterization of how the device performs analytically around the claimed cutoff concentration appears in the detection limit section, above.

## 2. Comparison studies:

a. Method comparison with predicate device:

A side-by-side comparison was conducted using the ACON OPI II One Step Opiate Test Strip/Device and a commercially available OPI rapid test. Testing was performed on specimens previously collected from subjects presenting for Drug Screen Testing. Presumptive positive results were confirmed by GC/MS, and on samples diluted with negative urine to challenge the cutoff. A total of 116 pre-screened positive samples, 18 diluted positive samples near the cutoff, and 168 pre-screened negative samples were used. The following results were tabulated:

| Method | | Other OPI Rapid Test | | Total Results |
| --- | --- | --- | --- | --- |
| ACON OPI II One Step Test Strip | Results | Positive | Negative | |
| | Positive | 131 | 0 | 131 |
| | Negative | 1 | 168 | 169 |
| Total Results | | 132 | 168 | 300 |
| % Agreement with this commercial kit | | 99% | >99% | >99% |

When compared to GC/MS at the cut-off of 2,000 ng/mL, the following results were tabulated:

| Method | Specimen Cutoff Range by GC/MS Data | | | | |
| --- | --- | --- | --- | --- | --- |
| | Result | <-25% Cutoff | -25% to Cutoff | Cutoff to +25% | >+25% Cutoff |
| ACON OPI II Test Strip | Positive | 0 | 2 | 20 | 109 |
| | Negative | 0 | 14 | 3 | 2 |

A side-by-side comparison was conducted using the ACON OPI II One Step Opiate Test Device and a leading commercially available OPI rapid test. Testing was performed on specimens previously collected from subjects presenting for Drug Screen Testing. Presumptive positive results were confirmed by GC/MS. A total of 116 pre-screened positive samples, 18 diluted positive samples near the cutoff, and 168 pre-screened negative samples were used. The following results were tabulated:

{8}

9

| Method | | Other OPI Rapid Test | | Total Results |
| --- | --- | --- | --- | --- |
| ACON OPI II One Step Test Device | Results | Positive | Negative | |
| | Positive | 131 | 0 | 131 |
| | Negative | 1 | 168 | 169 |
| Total Results | | 132 | 168 | 300 |
| % Agreement with this commercial kit | | 99% | >99% | >99% |

When compared to GC/MS at the cut-off of 2,000 ng/mL, the following results were tabulated:

| Method | Specimen Cutoff Range by GC/MS Data | | | | |
| --- | --- | --- | --- | --- | --- |
| | Result | <-25% Cutoff | -25% to Cutoff | Cutoff to +25% | >+25% Cutoff |
| ACON OPI II Test Device | Positive | 0 | 2 | 20 | 109 |
| | Negative | 0 | 14 | 3 | 2 |

b. Matrix comparison:
Not applicable. The assay is intended for only one sample matrix.

3. Clinical studies:
a. Clinical sensitivity:
Not applicable. Clinical studies are not typically submitted for this device type.
b. Clinical specificity:
Not applicable. Clinical studies are not typically submitted for this device type.
c. Other clinical supportive data (when a and b are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:
Not applicable.

M. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalent decision.