The RapidFRET Oral Fluid Assay for PCP is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Phencyclidine at 10 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid PCP Calibrator Set and RapidFRET Oral Fluid PCP Control Set are intended for use only with the RapidFRET Oral Fluid Assay for PCP and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

Device Description

The RapidFRET Oral Fluid Assay for PCP is an In Vitro Diagnostic competitive immunoassay used to detect PCP in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy. The assay is performed on the RapidFRET Integrated Workstation.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Biophor Diagnostics, Inc. RapidFRET Oral Fluid Assay for PCP, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Acceptance Criteria	Reported Device Performance
Precision	Demonstrates consistent and reproducible results across various PCP concentrations (0% to 200% of cutoff).	Successfully demonstrated across three lots over a minimum of 20 days. Results were consistently positive at and above 125% of cutoff and consistently negative at and below 100% of cutoff, with some variability around the 100% cutoff (2 positive, 277 negative).
Correlation with GC/MS (Accuracy)	High agreement with a confirmed analytical method (GC/MS).	Overall Agreement: >99% - RapidFRET POS / GC/MS POS: 119 - RapidFRET NEG / GC/MS NEG: 126 - RapidFRET POS / GC/MS NEG: 1 (Sample was 9 ng/mL PCP by GC/MS, which is below the 10 ng/mL assay cutoff) - RapidFRET NEG / GC/MS POS: 0
Cross-Reactivity	Minimal false positive results due to structurally related or unrelated compounds, OTC/prescription medications, and drugs of abuse.	Only 4-HydroxyPCP (620 ng/mL) and PCM (310 ng/mL) were found to cross-react below 10,000 ng/mL at concentrations equivalent to the cutoff in the absence of PCP, indicating high specificity.
Analytical Specificity (Interfering Substances)	No significant interference from common substances (foods, dental products, pH variations, biological components, medications).	All tested compounds and pH variations (HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, IgA, IgG, IgM, mouthwash, cough syrup, cranberry juice, orange juice, toothpaste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee, tea) at specified concentrations resulted in NEG when spiked with 5 ng/mL PCP and POS when spiked with 15 ng/mL PCP, indicating no significant interference.

Study Details

Sample sizes used for the test set and the data provenance:
- Precision Study: The table shows totals of 279-294 samples per PCP concentration level for evaluating precision across different lots and days. This implies several hundred unique test measurements.
- Correlation with GC/MS: n = 246 neat oral fluid samples.
- Cross-Reactivity & Analytical Specificity: Not explicitly stated as one single test set size, but involves:
  - 175 different compounds for cross-reactivity.
  - A list of common substances and pH levels for analytical specificity.
- Data Provenance:
  - "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for PCP." This indicates prospective collection from volunteers.
  - Country of origin is not explicitly stated, but the submission is to the U.S. FDA, typically implying data relevant to the U.S. market.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable/mentioned for this type of in vitro diagnostic device study. The ground truth for drug concentration is established analytically, not through expert interpretation of images or clinical findings.
Adjudication method for the test set:
- Not applicable/mentioned for this type of in vitro diagnostic device study. Ground truth (PCP concentration) is determined by an objective, gold-standard chemical method (GC/MS or LC/MS/MS).
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 performed. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that relies on human readers interpreting output. The read-out and interpretation (positive/negative) is automated based on the assay's cutoff.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies described are essentially standalone for the device. The RapidFRET Oral Fluid Assay for PCP, when run on the RapidFRET Integrated Workstation, provides an automated qualitative screen (positive/negative) for PCP. Human intervention is limited to sample collection, loading, and interpreting the instrument's P/N result (with subsequent confirmation by GC/MS or LC/MS/MS). The assay itself is an "algorithm only" in the sense that it mechanically and chemically determines the result based on a pre-defined cutoff.
The type of ground truth used:
- Analytical Confirmation (GC/MS): For the "Correlation with GC/MS" study, Gas Chromatography/Mass Spectrometry (GC/MS) was used as the confirmatory method to establish the true PCP concentration in the samples. The text also mentions LC/MS/MS as another specific alternate chemical method for confirmation. This represents a gold-standard analytical method.
The sample size for the training set:
- Not explicitly stated for a training set in the context of machine learning. This is an immunoassay, not a machine learning algorithm that requires a distinct training set. The development of the assay, its reagents, and its cutoff would be optimized through internal research and development, which implicitly involves testing various formulations and parameters to achieve desired performance characteristics.
How the ground truth for the training set was established:
- Not applicable in the context of a "training set" for a traditional immunoassay. The performance of the assay (e.g., sensitivity, specificity, cutoff) is established empirically through experimentation, using precisely prepared samples with known concentrations of PCP (spiked samples) and confirmed clinical samples (by GC/MS). The cutoff (10 ng/mL) is a predefined analytical threshold, not learned from a dataset.

Summary

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Biophor Diagnostics, Inc. Traditional Premarket Notification 510(k) Submission: K122703 _ RapidFRET Oral Fluid Assay for PCP

510(k) Summary for the RapidFRET Oral Fluid Assay for PCP

APR 2 5 2013

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

The assigned 510(k) number is:

807,92(a)(1); Contact Information

Name: Biophor Diagnostics, Inc. 1201 Douglas Avenue Address: Redwood City, CA 94063
Nathaniel G. Butlin, Ph.D. Contact: Phone: 650-367-4954 650-364-4985 Fax:

Date prepared: April 23, 2013

807,92(a)(2); Device Name, Common Name and Classification

RapidFRET Oral Fluid Assay for PCP (Enzyme Immunoassay for Phencyclidine) RapidFRET Oral Fluid PCP Calibrator Set (Clinical Toxicology Calibrator) RapidFRET Oral Fluid PCP Control Set (Drug Mixture Control Materials) RapidEASE Oral Fluid Collector RapidFRET Integrated Workstation

Product	Code	Class	RegulationSection	Panel
RapidFRET Oral Fluid Assay for PCP	LCM	II	862.3100	91 - Toxicology
RapidFRET Oral Fluid PCP Calibrator Set	DKB	II	862.3200	91 - Toxicology
RapidFRET Oral Fluid PCP Control Set	DIF	I	862.3280	91 - Toxicology

807.92(a)(3): Identification of Legally Marketed Predicate Devices

Thermo Scientific CEDIA® Phencyclidine (PCP) OFT Assay (K101746).

807,92(a){4): Device Description

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Biophor Diagnostics, Inc.

Traditional Premarket Notification 510(k) Submission: K122703-S002

RapidFRET Oral Fluid Assay for PCP proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy. The assay is performed on the RapidFRET Integrated Workstation.

807,92(a){5): Intended Use

The RapidFRET Oral Fluid PCP Calibrator Set and RapidFRET Oral Fluid PCP Control Set are intended for use only with theRapidFRET Oral Fluid Assay for PCP and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

	Thermo PCP	RapidFRET PCP
Indications for Use	Qualitative determination ofphencyclidine in human oralfluid.	Same
Methodology	Homogeneous competitiveimmunoassay.	Same
Kit Components	1 PCP specific antibody reagent(marketed in combination as alyophilized reagent andreconstitution buffer).1 PCP drug conjugate reagent(marketed in combination as alyophilized reagent andreconstitution buffer).	1 PCP specific antibody reagent inliquid, ready to use format.1 PCP drug conjugate reagent in liquid,ready to use format.
Controls	4 different Control andCalibrator concentrations areavailable for qualitative screens.	Same
Calibrators	2 Calibration levels are available.	Same

807-92(a){6): Technological Similarities and Differences to the Predicate

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Biophor Diagnostics, Inc.

Traditional Premarket Notification 510(k) Submission: K122703-S002 RapidFRET Oral Fluid Assay for PCP

	PerformanceCharacteristics
	Precision, accuracy, crossreacting/interfering studies aresimilar to the RapidFRET OralFluid Assay for PCP	Precision, accuracy, crossreacting/interfering studiesdemonstrate equivalence to thepredicate devices
Safety andEffectiveness	Demonstrated in bench testingand described in PI.	Demonstrated in bench testing anddescribed in PI, equivalent topredicate.
Neat Oral FluidCutoff Level	3 ng/mL neat oral fluid.	10 ng/mL neat oral fluid.
Platform	MGC240 analyzer	RapidFRET IntegratedWorkstation
Sample Collection	Oral fluid is collected with theOral-Eze Saliva CollectionSystem. This device uses anabsorbent swab and diluent.Sample is stored in plastic tubewith snap cap.	Neat oral fluid is collected with theRapidEASE Oral Fluid Collector viadirect expectoration. No diluent isused and sample is stored in glasssample tube with inert screw cap.
Principle andProcedure	The assay is based on the sampleanalytes competing with analyteconjugates to one inactivefragment of β- galactosidase forantibody binding sites.The amount of drug in thespecimen is inverselyproportional to the assay signalas measured by absorbance.	Drugs in the oral fluid sample competewith the PCP conjugate donorfluorophore for a fixed number ofbinding sites on the individual drugantibody acceptor reagents. Whenacceptor and donor fluorophores arebrought into close proximity, throughthe binding event, fluorescent energytransfer is measured.The amount of drug in the specimensample is inversely proportional to theassay signal as measured by timeresolved fluorescence.
Controls andCalibrator Levels	Calibrators are available at 0ng/mL, 1 ng/mL, 3 ng/mL and 20ng/mL	Calibrators are available at 0 ng/mLand 10 ng/mL. Controls are availableat 5 ng/ml and 15 ng/ml

807.92(b)(1): Brief Description of Study Data:

A series of studies were performed that evaluated the device performance characteristics including precision and analytical sensitivity, correlation with GC/MS, cross reactivity, and analytical specificity that are summarized below.

Precision

Three lots of the RapidFRET Oral Fluid Assay for PCP were analyzed, four times daily, for a minimum of 20 days. Negative oral fluid pools were spiked with PCP at 0%, 25%, 50%, 75%, 100%, 125%, 150%, 175% and 200% of the cutoff level corresponding to approximately 0, 2.5, 5.0, 7.5, 10, 12.5, 15.0, 17.5 and 20 ng/mL. The aggregate data is summarized in the

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Biophor Diagnostics, Inc. Traditional Premarket Notification 510(k) Submission: K122703-S002 RapidFRET Oral Fluid Assay for PCP

table below:

РСР	0%	25%	50%	75%	100%	125%	150%	175%	200%
POS						278	263	294	278
NEG	279	278	279	279	277		0		0
2	279	278	279.	279	279	278	263	294	278

Correlation with GC/MS

Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for PCP. The samples (n=246) were randomized and blinded to the instrument operator and assayed using RapidFRET PCP reagents. Following screening, positive and negative samples were sent to a reference laboratory for confirmatory testing. The summarized data are shown below.

n = 246	GC/MS POS	GC/MS NEG
RapidFRET POS	119	1†
RapidFRET NEG	0	126
% Agreement	100%	99%

Sample contained 9 ng/mL PCP by GC/MS.

The data indicate that the RapidFRET Oral Fluid Assay for PCP was accurate >99% of the time in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector.

Cross Reactivity and Analytical Specificity

A compound library of 175 different structurally related and unrelated compounds including metabolites, OTC and prescription medications and drugs of abuse was used to evaluate the device cross reactivity and specificity. Compounds were spiked at 30,000 ng/mL into neat oral fluid pool aliquots with 0 ng/mL, 5 ng/mL and 15 ng/mL PCP, processed with the RapidEASE Collector, and tested with the RapidFRET PCP assay. Those compounds that gave an unexpected result were further titrated to determine the concentration at which the cross-reacting compound yielded a result approximately equivalent to the cutoff. Only 4-HydroxyPCP and PCM were found to cross react below 10,000 ng/mL with cutoff equivalent concentrations determined to be 620 and 310 ng/mL, respectively, in the absence of PCP.

A second study evaluated common substances such as foods and dental products as well as pH variations. HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, lgA, lgG and IgM were spiked into neat oral fluid pool aliquots that contained either 5 ng/mL or 15 ng/mL PCP. Neat oral fluid pool was titrated to pH values of 5, 6, 7, 8 and 9, spiked with PCP at 5 ng/mL or 15 ng/mL and assayed with the RapidFRET PCP Assay. The effects of antiseptic mouthwash, cough syrup, cranberry juice, orange juice, tooth paste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee and tea were evaluated by asking volunteers to use a specific item and provide an oral fluid

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Biophor Diagnostics, Inc.

Traditional Premarket Notification 510(k) Submission: K122703-S002 RapidFRET Oral Fluid Assay for PCP

sample. These samples were then spiked with PCP at 5 ng/mL or 15 ng/mL, processed with a RapidEASE Collector and assayed with the RapidFRET PCP assay. All compounds at the listed concentrations gave a NEG result when spiked with 5 ng/mL PCP and a POS result when spike with 15 ng/mL PCP.

807,92(b){3): Conclusions

The RapidFRET Oral Fluid Assay for PCP including the RapidFRET Oral Fluid Negative and Cutoff Calibrators, the RapidFRET Oral Fluid Negative and Positive Controls and the RapidEASE Oral Fluid Collector were determined to be safe and effective for their intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized emblem featuring a symbol that resembles a caduceus or a staff with a serpent entwined around it.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

Biophor Diagnostics, Inc. C/O Nathaniel G. Butlin 1201 Douglas Avenue REDWOOD CITY CA 94063

April 25, 2013

Re: K122703

Trade/Device Name: RapidFRET Oral Fluid Assay for PCP RapidFRET Oral Fluid PCP Calibrator Set RapidFRET Oral Fluid PCP Control Set RapidEASE Oral Fluid Collector RapidFRET Integrated Workstation Regulation Number: 21 CFR 862.3100

Regulatory Class: Unclassified Product Code: LCM, DKB, DIF Dated: April 09, 2013 Received: April 17, 2013

Dear Dr. Butlin:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined 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 Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drig, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, interne of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract lightlity warranties. We remind you, however, that device labeling must be truthful and not misleding.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device an be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA max publish further announcements 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 mauron wour not nection of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 100-1000.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/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) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely vours.

Katherine Serrano

For

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K122703

Device Names:

RapidFRET Oral Fluid Assay for PCP RapidFRET Oral Fluid PCP Calibrator Set RapidFRET Oral Fluid PCP Control Set RapidEASE Oral Fluid Collector RapidFRET Integrated Workstation

Indications for Use:

Prescription Use X (21 CFR Part 801 Subpart D)

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

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

And/Or

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Denise Johnson=lyles 2013.04.24 14:06:21 =04'00'

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

K122703 510(k)

Regulation Number and Section

N/A