FREND PSA PLUS (REAGENT CARTRIDGE)

• K Number: K124056
• Device Name: FREND PSA PLUS (REAGENT CARTRIDGE)
• Manufacturer: NANOEN TEK, INC.
• Date Cleared: 2013-05-29 ( 149 days)
• Product Code: LTJ KHO
• Regulation Number: 866.6010

Intended Use

The FREND™ PSA Plus as performed on the FREND™ system, is a quantitative in vitro diagnostic test which measures total Prostate Specific Antigen (PSA) in human serum and plasma. The NanoEnTek FREND™ PSA Plus is designed for in vitro DIAGNOSTIC USE ONL Y for the quantitative measurement of total Prostate Specific Antigen (PSA) in human serum, heparinized plasma, and EDTA plasma using the FREND™ System. This device is indicated for the serial measurement of total PSA in serum, heparinized plasma and EDTA plasma to be used as an aid in the management of patients with prostate cancer. The FREND™ PSA Plus is indicated for use in clinical laboratories upon prescription by the attending physician as an aid to clinicians in managing patients with prostate cancer. The information provided from this test may supplement decision-making and should only be used in conjunction with routine monitoring by a physician and the use of other diagnostic procedures. Because of the variability in the effects of various medications used in the treatment of prostate cancer, clinicians should use professional judgment in the interpretation of PSA results as an indicator of disease status.

Device Description

The FREND™ PSA Plus is a rapid fluorescence immunoassay that measures prostate specific antigen (PSA) in human serum and in lithium heparin and EDTA plasma using the FREND™ system. The FREND™ PSA Plus is intended for use as an aid for prostate cancer management. The FREND™ PSA Plus Test is a single use fluorescence immunoassay designed to quantify the concentration of total PSA in serum and lithium heparin and EDTA plasma samples. The specimen is added by the operator to the sample inlet with a transfer pipet, allowing the appropriate volume of sample (30 µL) to be delivered into the FREND™ PSA Plus Test Cartridge. The Cartridge is then placed into the FREND™ System, which is programmed to begin analysis once the sample has reacted with the reagents. The reaction and analysis time is approximately 6 minutes. The PSA quantification is based on the amount of fluorescence detected by the FREND™ System at the FREND™ PSA Plus Test Cartridge window. A higher level of fluorescence is indicative of a higher PSA concentration. In other words, the magnitude of the fluorescent signal is directly proportional to the amount of total PSA in the sample. The FREND™ System is a bench top fluorescence reader containing a touchscreen user interface. The System has a slot that accepts the FREND™ PSA Plus Test Cartridge (which contains the reagents and sample), and is programmed to analyze the Test when the sample has fully reacted with the on-board in cartridge reagents. Results of the test are displayed on the screen and can be printed on an optional printer through the RS232C interface.

Predicate Devices

TOSOH ST AIA-PACK PA (P910065/S004)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details a fluorescence immunoassay system that quantifies PSA based on fluorescence intensity. There is no mention of AI, ML, or complex algorithms beyond standard signal processing for quantification. The performance studies focus on analytical and clinical validation using traditional statistical methods.

Therapeutic

No

The device is an in vitro diagnostic test designed to measure Prostate Specific Antigen (PSA) levels, and it is indicated for "in vitro DIAGNOSTIC USE ONLY" as an aid in the management of prostate cancer. It does not provide any therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device is "in vitro diagnostic ONL Y" and is designed to "aid in the management of patients with prostate cancer," which demonstrates its diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device description clearly states that the FREND™ PSA Plus is a rapid fluorescence immunoassay that measures PSA using the FREND™ system, which is a bench top fluorescence reader containing a touchscreen user interface and a slot for the test cartridge. This indicates the device includes significant hardware components beyond just software.

IVD (In Vitro Diagnostic)

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

Here's why:

• Intended Use/Indications for Use: The document explicitly states: "The FREND™ PSA Plus as performed on the FREND™ system, is a quantitative in vitro diagnostic test..." and "The NanoEnTek FREND™ PSA Plus is designed for in vitro DIAGNOSTIC USE ONLY". It also describes its use in measuring total Prostate Specific Antigen (PSA) in human serum and plasma, which are biological samples taken from the body for analysis outside the body.
• Device Description: The description details a "rapid fluorescence immunoassay that measures prostate specific antigen (PSA) in human serum and in lithium heparin and EDTA plasma". This describes a test performed on biological samples outside the body.
• Clinical Testing: The document describes clinical studies involving the analysis of "evaluable clinical serum samples" and "Serial samples collected longitudinally from patients previously diagnosed with prostate cancer". This further confirms the use of the device for testing biological samples.

The definition of an In Vitro Diagnostic (IVD) is a medical device that is used to perform tests on samples such as blood, urine, or tissues to detect diseases or other conditions. The information provided clearly aligns with this definition.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The FREND™ PSA Plus as performed on the FREND™ system, is a quantitative in vitro diagnostic test which measures total Prostate Specific Antigen (PSA) in human serum and plasma. The NanoEnTek FREND™ PSA Plus is designed for in vitro DIAGNOSTIC USE ONL Y for the quantitative measurement of total Prostate Specific Antigen (PSA) in human serum, heparinized plasma, and EDTA plasma using the FREND™ System. This device is indicated for the serial measurement of total PSA in serum, heparinized plasma and EDTA plasma to be used as an aid in the management of patients with prostate cancer.

The FREND™ PSA Plus is indicated for use in clinical laboratories upon prescription by the attending physician as an aid to clinicians in managing patients with prostate cancer.

The information provided from this test may supplement decision-making and should only be used in conjunction with routine monitoring by a physician and the use of other diagnostic procedures. Because of the variability in the effects of various medications used in the treatment of prostate cancer, clinicians should use professional judgment in the interpretation of PSA results as an indicator of disease status.

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

LTJ, KHO

Device Description

The FREND™ PSA Plus is a rapid fluorescence immunoassay that measures prostate specific antigen (PSA) in human serum and in lithium heparin and EDTA plasma using the FREND™ system. The FREND™ PSA Plus is intended for use as an aid for prostate cancer management. The FREND™ PSA Plus Test is a single use fluorescence immunoassay designed to quantify the concentration of total PSA in serum and lithium heparin and EDTA plasma samples. The specimen is added by the operator to the sample inlet with a transfer pipet, allowing the appropriate volume of sample (30 µL) to be delivered into the FREND™ PSA Plus Test Cartridge. The Cartridge is then placed into the FREND™ System, which is programmed to begin analysis once the sample has reacted with the reagents. The reaction and analysis time is approximately 6 minutes. The PSA quantification is based on the amount of fluorescence detected by the FREND™ System at the FREND™ PSA Plus Test Cartridge window. A higher level of fluorescence is indicative of a higher PSA concentration. In other words, the magnitude of the fluorescent signal is directly proportional to the amount of total PSA in the sample.

Material Provided - FREND™ PSA Plus - Catalog Number FRPS 025

• 25 FREND™ PSA Plus cartridges The Test Cartridge is a disposable plastic device that . houses the reagents and contains an opening where the sample is applied. Once the sample is applied, it will mix with the reagents and travel towards the detection area via capillary action. The sample is dropped into the specimen inlet located on the top left corner of the Test Cartridge. Sample and reagents interact before being analyzed by the FREND System fluorescence reader. The shelf-life of FREND PSA Plus cartridges is 12 months. One Cartridge contains:
  Monoclonal anti-PSA1 48 ± 9.6 ng
  Monoclonal anti-PSA2 144 ± 28.8 ng
  Fluorescent particle 2.4 ± 0.48 µg
• 30 Disposable pipette tips (micro-pipettor optional) .
• 1 FREND™ PSA Plus Code Chip The OC Code Chip contains data to ensure the . performance of the FREND System's power, optical, and software systems when the QC Cartridge is inserted into the System. The QC Code Chip is inserted into the code chip port at the rear of the System. Each QC Code Chip is specific to its accompanying QC Cartridge. Each time a new lot is used, the PSA Code Chip that corresponds to that new lot must be inserted into the instrument and the previous PSA Code Chip must be removed. If the PSA Code Chip and the PSA Cartridge are not from the same lot, an error message will appear.
• 1 FREND™ PSA Plus Package Insert .
• 1 Product Certificate .
• QC Case Storage box for the QC Cartridge and QC Code Chip .
• Optional FREND™ System Pipettor device sheathed in a disposable single use plastic tip . used to transfer samples to the Cartridge.
• Adaptor & Power cable used to supply power to the System .
• FREND™ System User Manual .
• FRENDIM System Quick Manual .
• . USB drive 1.1
• Optional printer Results of the test can be printed out using the optional printer. . Otherwise, they are displayed on the screen.

Commercially available controls from a variety of manufacturers are available that contain total PSA as a measured analyte. These controls are not provided with the assay cartridge.

The FREND™ System is not provided with the kit but is required for utilization of the FREND™ PSA Plus assay cartridge.

FREND™ System is a bench top fluorescence reader containing a touchscreen user interface. The System has a slot that accepts the FREND™ PSA Plus Test Cartridge (which contains the reagents and sample), and is programmed to analyze the Test when the sample has fully reacted with the on-board in cartridge reagents. Results of the test are displayed on the screen and can be printed on an optional printer through the RS232C interface.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Prostate

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Clinical laboratories, attending physician

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Performance Data Summary - Analytical Testing
To determine the analytical validity of the FREND™ PSA Plus, a series of studies have been performed.

1. Intra-assay, inter-assay and complex imprecision analyses were generated at three sites (NanoEnTek, Inc. facility, CLIA licensed facilities in US). Imprecision was found to be acceptable. Precision data was determined as described in the CLSI protocol EP5-A2. Three clinical samples were assayed in replicates of two at two separated times per day for twenty days using a single lot cartridge. Repeatability and Within-laboratory precision on samples with measured concentrations from 0.1 to 1.0 ng/mL was less than 15%. At concentrations >1.0 ng/mL but 8.5%. Disease status for the patients was determined by the physician.
   Concordance FREND™ PSA Plus and TOSOH ST AIA-PACK™ PSA:
   Confidence Intervals are based on 10,000 resamples of the patient data.
   Concordance tables for FREND™ PSA Plus and another FDA Cleared PSA Assay showed similar distribution of progression vs. no progression based on % change in PSA value relative to clinical progression/no progression.
   Based on the 95% confidence intervals, there are no differences between the concordances for the FREND™ PSA Plus assay and TOSOH ST AIA-PACK™ PSA assay. Positive, negative and overall concordances determined on the serial sets of samples for the two methods showed no significant difference in the ability of the assay to mirror the patient clinical status.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found (Accuracy metrics not explicitly called out in these terms, rather performance characteristics such as precision, linearity, recovery, and concordance are provided)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

TOSOH ST AIA-PACK PA (P910065/S004)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Summary

0

510(k) Summary

510(k) Number:

FREND™ PSA Plus on the FREND™ system K124056:

Summary Preparation Date:

December 28, 2012

Submitted by:

NanoEnTek, Inc. 12F, Ace High-end Tower, 235-2, Guro3-dong, Guro-gu Seoul, 152-740, Korea

Jimmy Chen

Owner/Operator Jimmy Chen ([e-mail])

Contact:

Judith E Loebel Director, Clinical and Regulatory Affairs DOCRO, Inc. (CRO assigned as contact with the FDA)

Proprietary Names:

For the assay: FREND™ PSA Plus

For the instrument: FREND™ system

Common Names:

For the assay: Quantitative PSA immunoassay

For the instrument: Bench-top fluorometer with microprocessor

Regulatory Information:

Regulation section:

866.6010 Tumor Associated Antigen Immunologic Test System 862.2560 Fluorometer

Classification:

Class II

Panel:

1

Immunology

Product Code(s):

LTJ Tumor Associated Antigen Immunologic Test System For the assay: For the instrument:

Predicate Device: TOSOH ST AIA-PACK PA (P910065/S004)

Intended Use:

The FREND™ PSA Plus performed on the FREND™ system, is a quantitative in vitro diagnostic test which measures total Prostate Specific Antigen (PSA) in human serum and plasma. The NanoEnTek FREND™ PSA Plus is designed for in vitro DIAGNOSTIC USE ONLY for the quantitative measurement of total Prostate Specific Antigen (PSA) in human serum, heparinized plasma, and EDTA plasma using the FREND™ System. This device is indicated for the serial measurement of total PSA in serum, heparinized plasma and EDTA plasma to be used as an aid in the management of patients with prostate cancer.

The FREND™ PSA Plus is indicated for use in clinical laboratories upon prescription by the attending physician as an aid to clinicians in managing patients with prostate cancer.

The information provided from this test may supplement decision-making and should only be used in conjunction with routine monitoring by a physician and the use of other diagnostic procedures. Because of the variability in the effects of various medications used in the treatment of prostate cancer, clinicians should use professional judgment in the interpretation of PSA results as an indicator of disease status.

Technological Characteristics:

The FREND™ PSA Plus is a rapid fluorescence immunoassay that measures prostate specific antigen (PSA) in human serum and in lithium heparin and EDTA plasma using the FREND™ system. The FREND™ PSA Plus is intended for use as an aid for prostate cancer management. The FREND™ PSA Plus Test is a single use fluorescence immunoassay designed to quantify the concentration of total PSA in serum and lithium heparin and EDTA plasma samples. The specimen is added by the operator to the sample inlet with a transfer pipet, allowing the appropriate volume of sample (30 µL) to be delivered into the FREND™ PSA Plus Test Cartridge. The Cartridge is then placed into the FREND™ System, which is programmed to begin analysis once the sample has reacted with the reagents. The reaction and analysis time is approximately 6 minutes. The PSA quantification is based on the amount of fluorescence detected by the FREND™ System at the FREND™ PSA Plus Test Cartridge window. A higher level of fluorescence is indicative of a higher PSA concentration. In other words, the magnitude of the fluorescent signal is directly proportional to the amount of total PSA in the sample.

Material Provided - FREND™ PSA Plus - Catalog Number FRPS 025

2

• 25 FREND™ PSA Plus cartridges The Test Cartridge is a disposable plastic device that . houses the reagents and contains an opening where the sample is applied. Once the sample is applied, it will mix with the reagents and travel towards the detection area via capillary action. The sample is dropped into the specimen inlet located on the top left corner of the Test Cartridge. Sample and reagents interact before being analyzed by the FREND System fluorescence reader. The shelf-life of FREND PSA Plus cartridges is 12 months. One Cartridge contains:
  Monoclonal anti-PSA1 48 ± 9.6 ng

Monoclonal anti-PSA2 144 ± 28.8 ng

Fluorescent particle 2.4 ± 0.48 µg

• 30 Disposable pipette tips (micro-pipettor optional) .
• 1 FREND™ PSA Plus Code Chip The OC Code Chip contains data to ensure the . performance of the FREND System's power, optical, and software systems when the QC Cartridge is inserted into the System. The QC Code Chip is inserted into the code chip port at the rear of the System. Each QC Code Chip is specific to its accompanying QC Cartridge. Each time a new lot is used, the PSA Code Chip that corresponds to that new lot must be inserted into the instrument and the previous PSA Code Chip must be removed. If the PSA Code Chip and the PSA Cartridge are not from the same lot, an error message will appear.
• 1 FREND™ PSA Plus Package Insert .
• 1 Product Certificate .
• QC Case Storage box for the QC Cartridge and QC Code Chip .
• Optional FREND™ System Pipettor device sheathed in a disposable single use plastic tip . used to transfer samples to the Cartridge.
• Adaptor & Power cable used to supply power to the System .
• FREND™ System User Manual .
• FRENDIM System Quick Manual .
• . USB drive 1.1
• Optional printer Results of the test can be printed out using the optional printer. . Otherwise, they are displayed on the screen.

Commercially available controls from a variety of manufacturers are available that contain total PSA as a measured analyte. These controls are not provided with the assay cartridge.

The FREND™ System is not provided with the kit but is required for utilization of the FREND™ PSA Plus assay cartridge.

FREND™ System is a bench top fluorescence reader containing a touchscreen user interface. The System has a slot that accepts the FREND™ PSA Plus Test Cartridge (which contains the reagents and sample), and is programmed to analyze the Test when the sample has fully reacted with the on-board in cartridge reagents. Results of the test are displayed on the screen and can be printed on an optional printer through the RS232C interface.

3

Performance Data Summary - Analytical Testing

ﺗ

To determine the analytical validity of the FREND™ PSA Plus, a series of studies have been performed as described below.

• 1. Estimates of imprecision: intra-assay, inter-assay and complex imprecision analyses were generated at three sites including the NanoEnTek, Inc. facility as well as at CLIA licensed facilities in the US. Imprecision was found to be acceptable at all three sites on all three lot numbers. The magnitude of the imprecision is not significantly different than that seen with other devices of this type.
     Precision data was determined as described in the CLSI protocol EP5-A2. Three clinical samples were assayed in replicates of two at two separated times per day for twenty days using a single lot cartridge. Results are shown below in table format. All elements of this testing process met the specifications set. Repeatability and Within-laboratory precision on samples with measured concentrations from 0.1 to 1.0 ng/mL was less than 15%. At concentrations >1.0 ng/mL but 40
     ng/mL |
     | Healthy Subjects | 196 | | | | | |
     | Men ≥ 50 yrs. | 196 | 100% | 0% | 0% | 0% | 0% |
     | Benign Disease/Cond* | 410 | | | | | |
     | Benign Prostate | 104 | 56.73% | 25.96% | 11.54% | 3.85% | 1.92% |
     | Diabetes | 97 | 95.88% | 3.09% | 1.03% | 0.00% | 0.00% |
     | HTN/Heart Disease | 102 | 95.10% | 4.90% | 0.00% | 0.00% | 0.00% |
     | Benign GI | 107 | 94.4% | 4.67% | 0.00% | 0.93% | 0.00% |
     | | | | | | | |
     | Malignant Diseases* | 302 | | | | | |
     | Prostate Cancer** | 85 | 40.00% | 38.82% | 12.95% | 2.35% | 5.88% |
     | Gleason Score 5-6 | 43 | 51.16% | 44.19% | 2.38% | 2.38% | 0% |
     | Gleason Score 7 | 31 | 35.48% | 38.72% | 19.35% | 0% | 6.45% |
     | Gleason Score 8-9 | 11 | 9.09% | 18.18% | 36.36% | 9.09% | 27.27% |
     | Lung/Liver Cancer | 52 | 98.08% | 0% | 1.92% | 0% | 0% |
     | GB,Gastric,Pancreatic | 31 | 100% | 0% | 0% | 0% | 0% |
     | Colorectal Cancer | 89 | 94.38% | 4.49% | 1.13% | 0% | 0% |
     | Other Cancers | 45 | 97.78% | 2.22% | 0% | 0% | 0% |

Distribution of Serum FRENDTM PSA Plus Concentrations in Healthy, Benign
and Various Malignant Disease States

*Treated and untreated subjects

TOTAL Subjects

** Serial samples are not included in this cohort.

Performance between the two assay systems did not show any clinically significant differences.

Serially monitored subjects: As an important part of the clinical studies performed to characterize the FREND™ PSA Plus, serial samples collected longitudinally from patients previously diagnosed with prostate cancer and treated in a variety of ways over the clinical

12

course of their disease (including prostatectomy, radioactive seeds, external beam radiation, chemotherapy, hormone therapy alone or in combination) were assayed for tPSA with the FREND™ PSA Plus on the FREND™ system. The same samples were also measured for tSA by the predicate PSA method.

For each point to point in a sample serial set, the change in the tPSA concentration was compared to the change in the clinical status of the patients as measured by other laboratory tests, patient interviews, physical examinations, and imaging studies of a variety of types.

These changes in the tPSA marker concentration were defined as significant or not by multiplying the overall %CV of the assay at the midrange (as determined by the test imprecision study) by a factor of 2.5 to define a percentage change difference higher than would be expected because of assay imprecision. For the FREND™ PSA Plus assay with an overall mid-range %CV of 8%, significance was set at a change in excess of 20%. Any increase in value from one time period to the next that did not exceed 20% was logged as ≤ 20% Change. For the predicate method, significant percentage change was set at a change > 8.5%. This was calculated using that method's published overall mid-range CV of 3.4% x 2.5.

Disease status for the patients was determined by the physician. This Disease Status was used to determine Progression or No Progression from a clinical perspective. The first table below shows the progressions and non-progressions as determined for the FREND™ PSA Plus results for all seventy five subjects compared to the Clinical Status changes. The second table shows the same comparison for the other FDA cleared assay. There are a total of 236 such determinations for each assay.

Point to Point for FRENDTM PSA Plus
% Change in PSA Value	Progression	No Progression	Total
Change≥ 20.0%	84	46	130
Change