← Product Code [DJG](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJG) · K101195

# 6-ACETYLMORPHINE ENZYME IMMUNOASSAY WITH 6-ACETYLMORPHINE CALIBRATORS AND CONTROLS (K101195)

_Lin-Zhi International, Inc. · DJG · Jul 6, 2010 · Clinical Toxicology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DJG/K101195

## Device Facts

- **Applicant:** Lin-Zhi International, Inc.
- **Product Code:** [DJG](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJG.md)
- **Decision Date:** Jul 6, 2010
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.3650
- **Device Class:** Class 2
- **Review Panel:** Clinical Toxicology

## Indications for Use

The 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of 6-Acetylmorphine in human urine, at a cutoff value of 10 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers. The 6-Acetylmorphine Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the 6-Acetylmorphine Enzyme Immunoassay. The 6-Acetylmorphine Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the 6-AcetyImorphine Enzyme Immunoassay. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method). Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

## Device Story

Homogenous enzyme immunoassay for 6-Acetylmorphine in human urine; utilizes automated clinical chemistry analyzers. Input: urine sample; Reagent 1 (mouse monoclonal anti-6-Acetylmorphine antibody, G6P, NAD); Reagent 2 (6-Acetylmorphine-labeled G6PDH). Principle: competitive binding between sample drug and enzyme-labeled drug for antibody; enzyme activity inhibited when bound to antibody; free drug displaces labeled conjugate, increasing enzyme activity. Output: absorbance change measured at 340 nm, proportional to drug concentration. Used in clinical toxicology settings by professional laboratory staff. Results are preliminary; require GC/MS or LC/MS confirmation. Assists clinicians in identifying 6-Acetylmorphine presence for drug abuse screening.

## Clinical Evidence

Bench testing only. Precision evaluated with 88 determinations per concentration level; total precision %CV ranged from 2.9% to 12.6%. Limit of detection determined as 2 ng/mL. Linearity demonstrated with correlation coefficient (r) of 0.9961. Method comparison using 80 clinical unaltered samples showed 100% agreement with positive samples and 93% agreement with negative samples at 10 ng/mL cutoff.

## Technological Characteristics

Homogenous enzyme immunoassay. Reagents: mouse monoclonal antibody, G6P, NAD, 6-Acetylmorphine-labeled G6PDH, sodium azide preservative. Measurement: spectrophotometric absorbance at 340 nm. Form factor: liquid ready-to-use reagents. Storage: 2-8 °C. Standard: CLSI EP5-A2 for precision.

## Regulatory 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).

## Predicate Devices

- Microgenics CEDIA® DAU 6-Acetylmorphine Assay ([K001178](/device/K001178.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k101195

B. Purpose for Submission:
New device

C. Measurand:
6-Acetylmorphine

D. Type of Test:
Qualitative and semi-quantitative enzyme immunoassay

E. Applicant:
Lin-Zhi International, Inc.

F. Proprietary and Established Names:
6-Acetylmorphine Enzyme Immunoassay
6-Acetylmorphine Calibrators
6-Acetylmorphine Controls

G. Regulatory Information:

|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  DJG- Opiate test system | II | 862.3650 | 91-Toxicology  |
|  DLJ -Clinical toxicology calibrator | II | 862.3200 | 91- Toxicology  |
|  LAS -Clinical toxicology control material | I, reserved | 862.3280 | 91- Toxicology  |

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H. Intended Use:

1. Intended use(s):

See indications for use below

2. Indication(s) for use:

The 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in human urine, at a cutoff value of 10 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The 6-Acetylmorphine Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the 6-Acetylmorphine Enzyme Immunoassay.

The 6-Acetylmorphine Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the 6-Acetylmorphine Enzyme Immunoassay.

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

3. Special conditions for use statement(s):

For professional use only

4. Special instrument requirements:

Analyzers capable of maintaining a constant temperature, pipetting samples, mixing reagents, measuring enzymatic rates at 340 nm and timing the reaction accurately can be used to perform this assay.

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I. Device Description:

The assay consists of ready-to-use liquid reagents. Reagent 1 contains mouse monoclonal anti-6-Acetylmorphine antibody, glucose-6-phosphate (G6P), nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide as preservative. Reagent 2 contains 6-Acetylmorphine-labeled glucose-6-phosphate dehydrogenase (G6PDH) in buffer and sodium azide as preservative. The calibrators and controls are sold separately

J. Substantial Equivalence Information:

1. Predicate device name(s):

Microgenics CEDIA DAU 6-Acetylmorphine Assay, Microgenics Corporation
Microgenics DAU 6-Acetylmorphine Calibrators, Microgenics Corporation
Microgenics DAU 6-Acetylmorphine Controls, Microgenics Corporation

2. Predicate 510(k) number(s):

K001178

3. Comparison with predicate:

|  Similarities/Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended Use | Intended for the qualitative and semi-quantitative determination of 6-acetylmorphine in human urine, at a cutoff value of 10 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers. | Same  |
|  Analyte | 6-Acetylmorphine | Same  |
|  Cutoff | 10 ng/mL | Same  |
|  Matrix | Human Urine | Same  |
|  Calibrators | 5 levels (0, 5, 10, 20, 40 ng/mL) | 3 levels (0, 10, 20 ng/mL)  |
|  Controls | 2 levels (7.5 ng/mL, 12.5 ng/mL) | 2 levels (7.5 ng/mL, 12.5 ng/mL)  |
|  Storage | 2-8 °C until expiration date | 2-8 °C until expiration date  |

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

CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods

L. Test Principle:

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The 6-Acetylmorphine assay is a homogenous enzyme immunoassay with ready-to-use liquid reagent. The assay is based on competition between drug in the sample and dug labeled with enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measures in terms of enzyme activity. In the absence of drug in the sample, 6-Acetylmorphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound 6-Acetylmorphine-labeled 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  $340~\mathrm{nm}$ .

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

# 1. Analytical performance:

Performance testing was conducted on the Hitachi 717

# a. Precision/Reproducibility:

Precision was determined by spiking 6-Acetylmorphine into drug free urine at various concentrations (-75%, -50%, -25%, at the cutoff, 125% and 150%, 175% and 200% of the cutoff). Concentrations were confirmed by LC/MS. Testing for the intra-assay was performed once a day for 22 days. The between run testing was performed in replicate twice a day for 22 day. The qualitative and semi-quantitative results are presented below:

Qualitative:

|   |   | Within Run |  | Between Run  |
| --- | --- | --- | --- | --- |
|  Sample concentration (ng/mL) | No. Observations |  | No. Observations |   |
|   |   |  # Neg/#Pos |   | # Neg/#Pos  |
|  0 (negative) | 22 | 22/0 | 88 | 88/0  |
|  2.5 (-75% c/o) | 22 | 22/0 | 88 | 88/0  |
|  5.0 (-50% c/o) | 22 | 22/0 | 88 | 88/0  |
|  7.5 (-25% c/o) | 22 | 22/0 | 88 | 88/0  |
|  10 (cutoff) | 22 | 12/10 | 88 | 47/41  |
|  12.5 (+25% c/o) | 22 | 0/22 | 88 | 0/88  |
|  15.0 (+50% c/o) | 22 | 0/22 | 88 | 0/88  |
|  17.5 (+50% c/o) | 22 | 0/22 | 88 | 0/88  |
|  20 (+100% c/o) | 22 | 0/22 | 88 | 0/88  |

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Semi-Quantitative:

|   |   | Within Run |  | Between Run  |
| --- | --- | --- | --- | --- |
|  Sample concentration (ng/mL) | No. Observations |  | No. Observations |   |
|   |   |  # Neg/#Pos |   | # Neg/#Pos  |
|  0 (negative) | 22 | 22/0 | 88 | 88/0  |
|  2.5 (-75% c/o) | 22 | 22/0 | 88 | 88/0  |
|  5.0 (-50% c/o) | 22 | 22/0 | 88 | 88/0  |
|  7.5 (-25% c/o) | 22 | 22/0 | 88 | 88/0  |
|  10 (cutoff) | 22 | 16/6 | 88 | 66/22  |
|  12.5 (+25% c/o) | 22 | 0/22 | 88 | 0/88  |
|  15.0 (+50% c/o) | 22 | 0/22 | 88 | 0/88  |
|  17.5 (+50% c/o) | 22 | 0/22 | 88 | 0/88  |
|  20 (+100% c/o) | 22 | 0/22 | 88 | 0/88  |

b. Linearity/assay reportable range:

Linearity across the range was confirmed by serially diluting a spiked urine pool containing  $100\mathrm{ng / mL}$  of 6-Acetylmorphine in to concentration levels listed in the table below. Each sample was assayed in the semi-quantitative mode. The results were averaged and compared to the expected result and the percent recovery was calculated. The claimed range is  $2 - 40\mathrm{ng / mL}$ . Results are presented in the table below:

|  Expected Concentration | Mean Observed Concentration | Recovery (%)  |
| --- | --- | --- |
|  Negative | 0.36 | not applicable  |
|  2 | 2.47 | 123.5  |
|  5 | 5.48 | 109.6  |
|  10 | 9.77 | 97.7  |
|  15 | 14.22 | 94.8  |
|  20 | 19.18 | 95.9  |
|  30 | 29.14 | 97.1  |
|  35 | 32.34 | 92.4  |
|  40 | 40.51 | 101.3  |

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

A commercially available 6-Acetylmorphine standard solution from Cerolliant Analytical Reference Standards is used and traceable to NIST standard. This standard solution is made into a secondary (lower concentration) stock solution. The secondary stock solution is then spiked into the calibrators and controls to the desired concentration. The concentrations are confirmed by GC/MS.

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Stability Studies:

Real time and accelerated studies for both controls and calibrators have been conducted. Protocols and acceptance criteria were described and found to be acceptable. The manufacturer claims the following expiration date for both controls and calibrators:

When stored at 2-8 °C unopened product is stable until expiration date which is 18 months.

On board stability is good for 14 days when stored at 2-8 °C.

d. Detection limit:

Performance at low drug concentrations in the semi-quantitative assay was characterized by determination of recovery (see section b above).

e. Analytical specificity:

Cross-reactivity was established by spiking various concentrations of structurally related and unrelated into drug-free urine. Results are expressed as a minimum concentration of metabolite or compound required to produce a response approximately equivalent to the cutoff concentration of the assay. The percent cross-reactivity of those compounds are presented below:

Structurally related

|  Compound | Equivalent to 10 ng/mL | % Cross reactivity  |
| --- | --- | --- |
|  Codeine | 500,000 | 0  |
|  Dextromethorphan | 100,000 | 0  |
|  Dihydrocodine | 500,000 | 0  |
|  Heroin | 10 | 67.5  |
|  Hudrocodone | 300,000 | 0  |
|  Hydromorphone | 100,000 | 0  |
|  Imipramine | 200,000 | 0  |
|  Levorphanol | 100,000 | 0  |
|  Meperidine | 800,000 | 0  |
|  Morphine | 100,000 | 0  |
|  M3G | 600,000 | 0  |
|  M6G | 600,000 | 0  |
|  Nalorphine | 100,000 | 0  |
|  Naloxone | 500,000 | 0  |
|  Naltrexone | 300,000 | 0  |
|  Norcodeine | 600,000 | 0  |
|  Normorphine | 100,000 | 0  |
|  Oxycodone | 500,000 | 0  |

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|  Compound | Equivalent to 10 ng/mL | % Cross reactivity  |
| --- | --- | --- |
|  Oxymorphone | 100,000 | 0  |

Structurally unrelated

|  Compound | Equivalent to 10 ng/mL | % Cross reactivity  |
| --- | --- | --- |
|  11-nor—THC-COOH | 100,000 | 0  |
|  Acetaminophen | 500,000 | 0  |
|  Acetylsalicylic | 500,000 | 0  |
|  Amitriptyline | 500,000 | 0  |
|  Benzoylecgonine | 500,000 | 0  |
|  Brompheniramine | 100,000 | 0  |
|  Caffeine | 500,000 | 0  |
|  Chlorpomazine | 250,000 | 0  |
|  Desipramine | 500,000 | 0  |
|  Diazepam | 100,000 | 0  |
|  Digoxin | 100,000 | 0  |
|  Diphenhydramine | 100,000 | 0  |
|  Doxepin | 100,000 | 0  |
|  Fluoxetine | 500,000 | 0  |
|  Hydroxyzine | 500,000 | 0  |
|  Ibuprofen | 500,000 | 0  |
|  Methadone | 500,000 | 0  |
|  Methamphetamine | 500,000 | 0  |
|  Oxazepam | 500,000 | 0  |
|  Phencyclidine | 100,000 | 0  |
|  Phenobarbital | 500,000 | 0  |
|  Propoxyphene | 100,000 | 0  |
|  Ranitidine | 500,000 | 0  |
|  Secobarbital | 500,000 | 0  |
|  Triprolidine | 100,000 | 0.001  |

Endogenous Compounds

The following endogenous compounds were added into drug-free urine, urine sample spiked to  $7.5\mathrm{ng / mL}$  of 6-Acetylmorphine and one urine spiked to 12.5  $\mathrm{ng / mL}$  of 6-Acetylmorphine at various concentrations. The substances listed in the table below were determined not to interfere at the concentration shown:

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|  Interfering Substance | Concentration Tested mg/dL | Interfering Substance | Concentration Tested mg/dL  |
| --- | --- | --- | --- |
|  Acetone | 1000 | Glucose | 1500  |
|  Ascorbic Acid | 400 | Hemoglobin | 300  |
|  Creatinine | 500 | Human Serum Albumin (HSA) | 500  |
|  Ethanol | 100 | Oxalic Acid | 100  |
|  Galactose | 10 | NaCl | 3000  |
|  r-Globulin | 500 | Urea | 2000  |

There is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results, e.g., technical or procedural errors.

## pH and Specific Gravity

To test for possible positive and/or negative interference from pH urine samples having pH from 4, 5, 7, 8, 9 and 10 were used. Each of these samples were divided into two aliquots for each drug and spiked to -25% of the cutoff and 125% of the cutoff. No positive or negative interference due to pH was observed.

To test for possible positive and/or negative interference from specific gravity urine samples having specific gravity from 1.0025, 1.005, 1.0075, 1.010, 1.015, 1.017, 1.025 and 1.030 were used. Each of these samples were divided into two aliquots for each drug and spiked to -25% of the cutoff and 125% of the cutoff. No positive or negative interference due to specific gravity was observed.

## f. Assay cut-off:

Analytical performance of the device around the claimed cutoff is described in precision section (1 a.) above

## 2. Comparison studies:

a. Method comparison with predicate device:

Eighty unaltered clinical urine samples (40 negative and 40 positive) were evaluated by the LZI 6-Acetylmorphine assay and compared to a LC/MS. Results from the study are presented below:

Qualitative

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|  Candidate Device Results | Negative | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration)  |
| --- | --- | --- | --- | --- | --- |
|  Positive | 0 | 0 | 0 | 6 | 31  |
|  Negative | 10 | 14 | 16 | 3 | 0  |

Semi-quantitative

|  Candidate Device Results | Negative | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration)  |
| --- | --- | --- | --- | --- | --- |
|  Positive | 0 | 0 | 0 | 6 | 31  |
|  Negative | 10 | 14 | 16 | 3 | 0  |

% Agreement among positives is 93% (37/40)
% Agreement among negatives is 100% (40/40)

Discordant

|  Cutoff Value (ng/mL) | LZI 6-Acetylmorphine Assay (POS/NEG) | Drug/Metabolite LC/MS value (ng/mL)  |
| --- | --- | --- |
|  10 | Negative | 10.0  |
|  10 | Negative | 11.0  |
|  10 | Negative | 13.0  |

b. Matrix comparison:

Test is for urine samples only

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

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Not applicable

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

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DJG/K101195](https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DJG/K101195)

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