The Psychemedics Microplate EIA for Opiates is an enzyme immunoassay (EIA) for the preliminary qualitative detection of opiates in human head and body hair using a morphine calibrator at 2 ng /10 mg hair cutoff for the purpose of identifying opiate use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone.

The Psychemedics Microplate EIA opiate 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 Chromatography/Mass Spectrometry (GC/MS or LC/MS/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.

Device Description

The test consists of two parts; a pre-analytical hair treatment procedure (to convert the solid matrix of hair to a measurable liquid matrix) and the screening assay, the Psychemedics Microplate EIA for Opiates. The drug is recovered from the hair using a patented method (U.S. Patent #8,084.215).The screening portion of the test system consists of (1) microplate wells coated with multiple drugs including morphine conjugated to bovine serum albumin (BSA) (patent pending), polyclonal sheep anti-morphine, rabbit anti-goat secondary antibody conjugated to HRP (horseradish peroxidase), substrate [3, 3', 5, 5' tetramethylbenzidine (TMB)}, HCl to acidify the final reaction, and wash buffer for washing the plates. Absorbance in the wells is read with a microplate reader.

AI/ML Overview

The provided text describes the performance testing of the Psychemedics Microplate EIA for Opiates in Hair. However, it does not explicitly state "acceptance criteria" as a separate, pre-defined set of metrics. Instead, the study aims to demonstrate substantial equivalence to a predicate device (Psychemedics RIA Assay for Opiates) and correlation with a confirmatory method (LC/MS/MS).

The "acceptance criteria" can be inferred from the reported performance results, particularly the low discordance with the predicate device and the high agreement with LC/MS/MS, especially for confirmed positive and negative samples.

Here's an analysis of the requested information based on the provided text:

Acceptance Criteria and Reported Device Performance

Inferred Acceptance Criteria:

Low discordance with predicate device (RIA Assay for Opiates): The device should show strong agreement with the established predicate method.
High agreement with LC/MS/MS confirmation: For definitive positive and negative cases, the EIA result should align with the LC/MS/MS results.
Robustness to cosmetic treatments: Cosmetic treatments should not significantly alter the test results for both negative and positive samples.
Effective contamination control: The wash procedure should effectively remove external contamination, preventing false positives.
Limited cross-reactivity and no interference: The assay should be specific to opiates and not significantly affected by common interfering substances.

Reported Device Performance:

Performance Metric	Reported Device Performance
Discordance with Predicate (RIA Assay)	< 0.2%
Agreement with LC/MS/MS (Negative Samples)	86 negative EIA samples confirmed negative by LC/MS/MS. 14 EIA negative samples were between ≥10% and < -50% of cutoff by LC/MS/MS. 2 EIA negative samples were between ≥ -50% and < Cutoff by LC/MS/MS. (This indicates strong agreement for clearly negative samples, with expected variations near the cutoff).
Agreement with LC/MS/MS (Positive Samples)	126 EIA positive samples confirmed ≥ +100% of cutoff by LC/MS/MS. 8 EIA positive samples were between ≥ +50% and < +100% of cutoff by LC/MS/MS. 9 EIA positive samples were between ≥ Cutoff, and < +50% of cutoff by LC/MS/MS. 8 EIA positive samples were between ≥ -50% and < Cutoff by LC/MS/MS. (This shows strong agreement for clearly positive samples, with some near-cutoff discrepancies).
Impact of Cosmetic Treatments (Negative Samples)	No significant differences observed; all 20 negative samples remained negative after bleach, permanent wave, dye, relaxer, and shampoo treatments.
Impact of Cosmetic Treatments (Positive Samples)	No opiate-positive samples became negative after bleach, permanent wave, dye, relaxer, and shampoo treatments. Average B/Bo x 100 values and ranges for positive samples before and after treatment showed consistent positivity.
Contamination Study (Washing Effectiveness)	For samples soaked in 1000 ng morphine/mL of water (high contamination): reduced from 67.9-265.2 ng/10 mg hair to 0.8-3.4 ng/10 mg hair. After wash criterion, all were determined contaminated, not positive. For samples soaked in 1000 ng morphine/mL of saline: reduced from 9.6-61.1 ng/10 mg hair to 0.3-1.3 ng/10 mg hair (all below cutoff without wash criterion).
Cross-reactivity	Codeine (111%), Hydromorphone (5.2%), Hydrocodone (41.7%), Acetylcodeine (57.1%), 6-Acetylmorphine (43.5%), Morphine Glucuronide (15%) showed cross-reactivity. 65 other compounds showed no cross-reactivity.
Interference	156 compounds tested for interference at +/-50% of the cutoff showed no interference.
Precision (Intra-Assay/Inter-Assay)	Detailed tables show consistent negative and positive results across various concentration levels (-100% to +100% relative to cutoff) for both intra-assay (15 repeats) and inter-assay (75 repeats) studies, suggesting good precision and reproducibility.

Study Details:

Sample sizes used for the test set and the data provenance:
- Agreement Testing: 383 head hair samples and 90 body hair samples (total 473 hair samples).
- LC/MS/MS Confirmation: 253 of the above samples were confirmed by LC/MS/MS.
- Cosmetic Treatments (Negative): 20 opiate-negative hair samples per treatment type (bleach, permanent wave, dye, relaxer, shampoo) for a total of 100 samples.
- Cosmetic Treatments (Positive): 12 opiate-positive hair samples per treatment type (bleach, permanent wave, dye, relaxer, shampoo) for a total of 60 samples.
- Contamination Study: 8 hair samples soaked in morphine/water, 8 hair samples soaked in morphine/saline.
- Data Provenance: Not explicitly stated, but typically these samples would be collected in a controlled or clinical environment for regulatory submissions. Given the context of a US submission, it's highly likely to be originating from the US. The type seems to be retrospective as they are described as "samples" rather than "patients undergoing a diagnostic pathway".
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 primarily established by LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry), which is described as the "preferred confirmatory method." LC/MS/MS results are considered the gold standard for drug detection in hair, not expert consensus. Therefore, no human experts were explicitly used for establishing the primary ground truth.
Adjudication method for the test set:
- Not applicable in the traditional sense, as the ground truth was established by LC/MS/MS, a quantitative analytical method, not human interpretation requiring adjudication. For discrepancies between the EIA and RIA, the LC/MS/MS method was used as the arbiter: "The samples were negative by LC/MS/MS, demonstrating that the EIA negative results, although discordant with the predicate, are correct."
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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that involves human readers interpreting images or data for improvement. The study focuses on the analytical performance of the assay itself.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this study represents a standalone performance evaluation of the Psychemedics Microplate EIA for Opiates. The "algorithm" here refers to the EIA assay's chemical and optical detection mechanism. The performance is assessed purely on its analytical results against a gold standard (LC/MS/MS) and a predicate device (RIA), without human interpretation influencing the primary outcome or a human-in-the-loop component for improved performance. The device provides "preliminary analytical test results," which are then confirmed by other chemical methods.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The primary ground truth used was LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry), which is a highly sensitive and specific chemical method considered the "gold standard" for confirming the presence and concentration of drugs in biological samples like hair.
The sample size for the training set:
- The document does not provide information about a separate training set. The data presented appears to be from a validation or test set to demonstrate the device's performance. For in vitro diagnostic assays, the "training" (development and optimization) phase often involves internal experiments and is generally not documented in the same way as a machine learning model's training set in regulatory submissions.
How the ground truth for the training set was established:
- As no training set is explicitly mentioned or described, this information is not available in the provided text.

Summary

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K111926

MAY - 1 2012

510 K SUMMARY

Psychemedics Microplate EIA for Opiates in Hair

Psychemedics Opiates Assay, K000851

Submitted By:

Psychemedics Corporation 5832 Uplander Way Culver City, CA 90230 TEL: 310 216 7776 FAX: 310 216 6662

Submission Contact:

Virginia Hill April 25, 2012

DIG

Date Prepared:

Device Trade Name:

Predicate Device:

Product Code:

Device Classification/Name:

Intended Use:

Assay Description:

Sample Collection:

21 CFR 862.3650, Enzyme Immunoassay, Opiates; Classification II; The Psychemedics Microplate EIA for Opiates is an enzyme immunoassay (EIA) for the preliminary qualitative detection of opiates in human head and body hair using a morphine calibrator at 2 ng /10 mg hair cutoff for the purpose of identifying opiate use. This is an in vitro diagnostic device intended exclusively for Psychemedics use only and is not intended for sale to anyone.

The Psychemedics Microplate EIA opiate 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 Liguid Chromatography/Mass Spectrometry (GC/MS or LC/MS or LC/MS/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.

A sample of hair should be cut as close as possible to the skin. The hair is placed in a V-shaped aluminum foil sample holder with the root end of the hair protruding beyond the slanted edge of the foil. The aluminum

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foil is crimped around the sample, securing the hair specimen firmly into place within the foil. The hair samples crimped within the foil is placed in a sample acquisition card envelope and the envelope is sealed with a tamper-evident seal. Hair specimens are kept at ambient temperature in a secure location until they are shipped without refrigeration to the laboratory.

Materials required:

Hair sample collection kit, Microplate EIA for Opiates, Microplate washer and reader, LC/MS/MS for confirmation.

Comparison of Psychemedics Microplate ElA for Opiates with Psychemedics RIA Assay for Opiates

Item	Device	Predicate
Indications for Use	The Psychemedics Microplate EIA forOpiates is an enzyme immunoassay (EIA)for the preliminary qualitative detection ofopiates in human head and body hair using amorphine calibrator at 2 ng /10 mg haircutoff for the purpose of identifying opiateuse. This is an in vitro diagnostic deviceintended exclusively for Psychemedics useonly and is not intended for sale to anyone.The test is not intended for over the countersale to non-professionals.The Psychemedics Microplate EIA opiateassay provides only a preliminary analyticaltest result. A more specific alternativechemical method must be used in order toobtain a confirmed analytical result. Gas orLiquid Chromatography/Mass Spectrometry(GC/MS or LC/MS or LC/MS/MS) is thepreferred confirmatory method. Clinicalconsideration and professional judgmentshould be exercised with any drug of abusetest result, particularly when the preliminaryresult is positive.	The Psychemedics Opiate assay is aradioimmunoassay (RIA) for thepreliminary detection of morphine inhair using a 2 ng/10 mg hair cutofffor the purposes of identifying opiateuse. For a quantitative analyticalresults or to confirm positive resultsvia the presence of the heroinmetabolite, 6-monoacetylmorphine(6-MAM), a more specific alternatechemical method must be used inorder to obtain a confirmed analyticalresults
510k	K111926	K000851
Measurand	Opiates	Opiates
Matrix	Human head or body hair	Human head or body hair
Cutoffconcentration	2 ng morphine10 mg hair	2 ng morphine /10 mg hair
Type of Test	Enzyme Immunoassay	Radioimmunoassay
Method ofmeasurement	Microplate reader	Gamma counter
ExtractionMethod	Nonproteolytic Digestion	Proteolytic Digestion
Confirmation	LC/MS/MS	LC/MS/MS

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Summary of Performance Testing

	Summary -Intra-Assay			Summary-Inter-Assay
LEVEL	NEG	POS	LEVEL	NEG	POS
B₀ (-100%)	15	0	B₀ (-100%)	75	0
-75%	15	0	-75%	75	0
-50%	15	0	-50%	75	0
-25%	15	0	-25%	75	0
plus 25%	0	15	plus 25%	0	75
plus 50%	0	15	plus 50%	0	75
plus 75%	0	15	plus 75%	0	75
plus 100%	0	15	plus 100%	0	75

Precision Studies

Agreement Testing

The agreement studies included 383 head hair samples and 90 body hair samples. Four hundred-seventythree hair samples were assayed by the predicate device and by the Psychemedics Opiates EIA. The discordance between EIA and RIA was < 0.2%.

	Negative by Predicate	Positive by Predicate
EIA Positive	0	156
EIA Negative	316	1

Two-hundred fifty-three of the samples were confirmed by LC/MS/MS, with the results shown in the following table.

LC/MS/MS:	Negative	≥10% and < -50% of Cutoff	≥ -50% and < Cutoff	≥ Cutoff, and < +50% of cutoff	≥ +50% and < +100% of cutoff	≥ +100% of cutoff
EIA Positive	0	0	8	9	8	126
EIA Negative	86	14	2	0	0	0

Samples vary in the amount of contamination on the surface; in fact, contamination is, by its very nature, random in the way in which it may present on the hair sample. Therefore, it is not surprising that a sample might be positive in one screening assay and not in the next, even if the assays are the same technology. The samples were negative by LC/MS/MS, demonstrating that the EIA negative results, although discordant with the predicate, are correct.

Cosmetic Treatments

Twenty opiate-negative hair samples were treated with bleach, 20 with permanent wave, 20 with dye, 20 with relaxer, and 20 with shampoo, and the results compared to the same samples without the treatments. In each case of the 20 samples treated with a type of cosmetic treatment, 10 samples were treated with one brand of a particular product and 10 other samples with a second brand. No significant differences were observed for the negative hair samples before and after the treatments; all samples remained negative after the treatments.

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Twelve opiate-positive hair samples were treated with bleach, 12 with permanent wave, 12 with dye, 12 with relaxer, and 12 with shampoo, and the results compared to the same samples without the treatments. In each case of the 12 samples treated with a type of cosmetic treatment, 6 samples were treated with one brand of a particular product and 6 other samples with a second brand. The average of the EIA B/Bo x 100 values obtained for the samples in each set before treatment is shown, with the range following in parenthesis. In the second row of the table, the average of the EIA B/Bo x 100 values obtained for the samples in each set after treatment is shown, with the range following in parenthesis. No opiate-possitive samples became negative after the cosmetic treatments.

TreatmentStatus	Bleach	Dye	Perm	Relaxer	Shampoo
	Mean (Range) of B/Bo x 100 Values of 12 Opiate-Positive Samples in Opiate EIA
Before	23.3 (13.5 – 37.5)	24.0 (13.5 – 46.9)	22.2 (10.6 – 48.7)	23.8 (13.8 – 37.9)	24.4 (13.8 – 48.7)
After	28.9 (16.8 - 46.4)	28.6 (14.2 - 48.7)	26.7 (12.9 - 52.0)	26.9 (12.1 - 42.7)	25.5 (14.0 - 43.7)

Summary of Contamination Study

Potential environmental contamination of samples that are identified as presumptive positive in the screening assay is addressed by an extensive washing procedure prior to confirmation and application of a wash criterion following confirmation, as described below.

Contamination of 8 hair samples by soaking in 1000 ng morphine /mL of water resulted in a range of morphine on the hair of 67.9 to 265.2 ng of morphine /10 mg hair before washing. After washing by the procedure described below, the amount of morphine remaining on the hair samples ranged from 0.8 to 3.4 ng/10 mg hair, with 5 samples appearing to be positive before application of the wash criterion. After application of the wash criterion (see below), all of these samples containing morphine above the culoff were determined to be contaminated rather than positive and would not be reported as positive samples.

Contamination of 8 hair samples by soaking in 1000 ng morphine /mL of saline resulted in a range of morphine on the hair of 9.6 to 61.1 ng of morphine /10 mg hair before washing. After washing by the Psychemedics hair washing procedure described below, the amount of morphine remaining on the hair samples ranged from 0.3 to 1.3 ng/10 mg hair, with all samples negative (i.e., below the cutoff) even without application of the wash criterion.

The Wash Procedure

Wash by Psychemedics' standard wash procedure: a.
- Add 2 mL of dry isopropanol and shake in waterbath for 15 minutes at 37°C with i. shaking @ 100 -120 oscillations/minute. Remove isopropanol.
- ii. Add 2 mL of Wash Buffer (0.01 M phosphate buffer, pH 6.0, containing 0.1% BSA) and shake in waterbath for 30 minutes at 37℃ with shaking @ 100 -120 oscillations/minute. Remove Buffer.
- iii. Repeat Step ii. two more times.
- iv. Add 2 mL of Wash Buffer, and shake in waterbath for 60minutes at 37°C with shaking @ 100 -120 oscillations/minute. Remove Buffer.
- Repeat Step iv. one more time. Remove Buffer. Save Wash. v.
b. Analyze last wash for opiates.

Confirmation and Interpretation

a. Perform confirmation procedures for opiates.
b. Calculate wash criterion:

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i. Multiply the last wash value x 5.
ii. Subtract the value of the parent drug in the last wash from the value of the parent drug in the digested hair.

iii. If the result is less than the cutoff for the parent drug, the sample is interpreted as contaminated. If the result is > the parent drug cutoff, in combination with other metabolite criteria, the sample is interpreted as positive due to ingestion. The confirmation cutoff values for the opiates is 2 ng/10 mg hair.

Summary of Cross-reactivity and Interference Studies

Six compounds, shown in the table below, showed cross-reactivity in the Opiate EIA assay. Sixty-five other compounds showed no cross-reactivity in the assay. One-hundred-fifty-six compounds tested for interference at +/-50% of the cutoff showed no interference in the assay.

Compound	Amount of Compound required to Producea positive test at the cutoff of 2 ngmorphine/10 mg hair	Percent Cross-reactivity*
Codeine	1.8	111
Hydromorphone	38	5.2
Hydrocodone	4.8	41.7
Acetylcodeine	3.5	57.1
6-Acetylmorphine	4.6	43.5
Morphine Glucuronide	13.3	15

of related Compo

Stability of Calibrator and Control Solutions

The morphine calibrator and control solutions are prepared in-house by the laboratory from certified standards. Stability of morphine in methanol in the presence of other drugs of abuse was shown to exceed 1 year.

Recovery

Recovery of opiates from hair of opiate users was shown to be substantially equivalent to that of the predicate device.

Conclusion:

The Psychemedics Microplate EIA for Opiates in Hair is substantially equivalent to the predicate device K000851, and the results are substantially equivalent to LC/MS/MS results.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a stylized eagle with its wings spread, facing to the right. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular fashion around the eagle. The text is in all capital letters and is evenly spaced around the circle.

Food and Drug Administration

10903 New Hampshire Avenue Silver Spring, MD 20993

PSYCHEMEDICS CORP. c/o Virginia Hill 5832 Uplander Way Culver City, CA 90230

MAY - 1 2012

Re: K111926

KT11220
Trade Name: PSYCHEMEDICS MICROPLATE EIA FOR OPIATES IN HAIR Regulation Number: 21 CFR §862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Codes: DJG Dated: March 9, 2012 Received: March 12, 2012

Dear Ms. Hill:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave roviewed your eee atermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device mensiale conments, or to devices that have been reclassified in accordance with the provisions of Amendinents, or to do resos that the Act (Act) that do not require approval of a premarket the rederal 1 000, Drug, und Commons , therefore, market the device, subject to the general approval upprisation () ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . controls provisions of the Fist - tion, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III II your device is classified (see as a roll additional controls. Existing major regulations affecting (I MA), it may of subject to tack active of Federal Regulations (CFR), Parts 800 to 895. your device can oc round in Title B2, Oncouncements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements mean that IDA has made a deceminations administered by other Federal agencies.
of the Act or any Federal statutes and regulations administered by other Federal spacies. of the Act of ally rederal statutes and rogulations, but not limited to: registration 1 ou must comply with an the Hot Hot eight store (21 CFR Parts 801 and 809); medical device and listing (21 CFR Part 607), laceming (21 CFR 803); and good reporting (reporting of medical device related daverse evening (
manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm

Sincerely vours,

signature

Counney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number: K111926

Device Name: Psychemedics Microplate EIA for Opiates in Hair

Indications For Use:

Prescription Use (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _ X (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

CARS

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) 1111926

Page 1 of 1

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
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.(b)
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).