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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, Li-heparinized plasma, and K3-EDTA plasma using the FREND™ System. This device is indicated for the serial measurement of total PSA to be used as an aid in the management of patients with prostate cancer.

The FREND™ PSA Plus is a rapid fluorescence immunoassay that measures prostate specific antigen (PSA) in human serum and in lithium heparin and K3-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 K3-EDTA plasma samples. The specimen is added by the operator to the sample inlet with a transfer pipet, allowing the appropriate volume of sample (35 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 4 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 total PSA detection range of the FREND™ PSA Plus Test System is 0.08 to 25 ng/mL. Results are determined via a lot-specific calibration curve which is generated by the manufacturer using a six-point calibration determined from values averaged from five replicates at each level. The established curve is uploaded to the FREND™ via the PSA Plus Code-chip and is valid until the lot expiration date. The established curve is saved in the code-chip and valid until the expiration date of the test cartridge lot.

The FREND™ PSA Plus Test cartridge is a disposable plastic device that houses the reagents and contains a port or opening (inlet) 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 FREND™ System is a portable, automated FREND™ cartridge reader. The FREND™ System is based on quantitative immunoassay technology capable of quantifying single or multiple analytes by measuring laser-induced fluorescence in a single-use disposable reagent cartridge. The FREND™ cartridge utilizes micro-fluidics lateral flow technology where the analyte of interest in the sample forms immune complexes while moving through the fluidics pathway in the cartridge. The concentration of the analyte of interest in an unknown sample is calculated using the ratio of the fluorescent intensity of the test zone and the reference zone.

FREND™ System is a bench top fluorescence reader containing a touchscreen user interface. The System has a slot that accepts the sample loaded FREND™ PSA Plus Test Cartridge, 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.

The FREND™ System software controls the graphical user interface, communication with hardware, database management and data analysis. The software also controls the functions of the mechanical components including the motor, laser, printer control and acquisition of data from the sensor. The user can set the time and date and enter patient ID through the graphic user interface. The user cannot make any changes to the software.

The FREND™ PSA Plus includes the following in the kit:

• 25 FREND™ PSA Plus cartridges
• · 30 Disposable pipette tips
• 1 FREND™ PSA Plus Code Chip
• 1 FREND™ PSA Plus Package Insert

The FREND™ System (previously cleared in K124056, K131928, K152422, K153577, and K162754) is not provided with the kit but is required for the use of the FREND™ PSA Plus test cartridge.

Here's a breakdown of the requested information regarding the acceptance criteria and study for the NanoEnTek FREND™ PSA Plus device:

The provided text describes a 510(k) submission for a modified version of the FREND™ PSA Plus, comparing it to its predicate device (the previously cleared FREND™ PSA Plus assay, K124056). Therefore, the "acceptance criteria" are implicitly the performance of the predicate device, and the "study" aims to demonstrate that the modified device's performance is substantially equivalent to this predicate.

1. Table of Acceptance Criteria and Reported Device Performance

For the purpose of this analysis, the "acceptance criteria" are based on the performance of the predicate device (FREND™ PSA Plus, K124056), and the "reported device performance" refers to the modified FREND™ PSA Plus.

2. Sample Size Used for the Test Set and Data Provenance

• Test Set Sample Size:

  • Precision/Reproducibility: 4 clinical samples, assayed in replicates of two, two times per day for twenty days (implies 4 samples * 2 replicates * 2 times/day * 20 days = 320 measurements per lot for within-lot precision, across 3 lots).
  • Multi-site Precision: 3 samples (C, D, E), N=25 for each sample at each of 3 sites (3 samples * 25 runs/sample/site * 3 sites = 225 runs for within-laboratory, and 75 for each sample for overall reproducibility).
  • Linearity: Samples tested in quadruplicate or quintuplicate per dilution level across a range of 0.05 ~ 25.53 ng/mL. (Exact number of unique samples or total measurements not specified, but multiple dilutions were used.)
  • High Dose Hook Effect: One concentrated sample of purified PSA antigen, neat and on dilution.
  • Interference: Two PSA levels (1ng/mL and 4ng/mL) tested with various interferents/cross-reactants. Data presented as average %Recovery.
  • Sample Volume Comparison: 64 serum samples.
  • Matrix Comparison: 40 sample pairs (serum, lithium heparin plasma, K3-EDTA plasma aliquots for each patient).
  • Method Comparison (vs. FDA Approved Assay): 207 samples.
  • Clinical Studies (Serial Monitoring): 194 determinations (each representing a point-to-point change in tPSA concentration compared to clinical status). Longitudinal samples from patients.

• Data Provenance:

  • The primary analytical performance studies (Precision/Reproducibility, Linearity, LoD, LoQ, High Dose Hook Effect, Analytical Specificity, Sample Volume Comparison, Matrix Comparison) were performed at the NanoEnTek, Inc. facility (manufacturer's site) in Korea.
  • The Multi-site precision study was performed at three different sites. (Locations not specified beyond 'different sites').
  • The Method Comparison with an FDA-approved assay (ARCHITECT total PSA) was done in a CLIA-certified laboratory testing facility (CentraState Medical Center).
  • The Clinical Studies (Serial Monitoring) involved patients with prostate cancer. The sample collection was described as "longitudinally from patients previously diagnosed with prostate cancer and treated in a variety of ways over the clinical course of their disease". The geographical origin of these patients/samples is not specified but given the manufacturer's location, samples from Korea or other Asian countries are possible, as well as potentially US samples if the CLIA lab was involved in recruitment. These were retrospective samples in the sense that they were "previously diagnosed" and "collected longitudinally."

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

• Analytical Studies: For most analytical studies (Precision, Linearity, LoD, Hook Effect, Interference, Method Comparisons), the "ground truth" is typically established by established reference methods, spiked samples with known concentrations, or comparison to a cleared predicate device or gold standard assay. It doesn't inherently involve human "experts" in the same way clinical image reviews would.
• Clinical Studies (Serial Monitoring): The "clinical status" (NED, Responding, Stable, Progression) used as ground truth for serial monitoring was determined for the patients based on "other laboratory tests, patient interviews, physical examinations, and imaging studies of a variety of types." This implies a clinical review by attending physicians or a clinical team. The number and qualifications of these specific clinicians/experts are not specified in the provided text.

4. Adjudication Method for the Test Set

• Not applicable in the context of this type of IVD device submission. Adjudication methods like "2+1" (two readers agree, third is tie-breaker) are typically used for subjective assessments, such as reviewing medical images where there can be inter-reader variability. For quantitative invitro diagnostic tests like PSA measurement, the result is a numerical value, and the comparison is statistical against a reference or clinical outcome.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

• No, an MRMC comparative effectiveness study was not done. This type of study (MRMC) is primarily applicable to diagnostic imaging devices, especially those incorporating AI, where the performance of human readers with and without AI assistance is evaluated. The FREND™ PSA Plus is an in vitro diagnostic (IVD) immunoassay, not an imaging device, and does not involve AI assistance for human readers in its direct use.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

• Yes, this is effectively a standalone device. The FREND™ PSA Plus assay, run on the FREND™ System, provides a quantitative result for total PSA. While an operator loads the sample, the system itself interprets the fluorescent signal and calculates the PSA concentration. There isn't a human "in-the-loop" who re-interprets or modifies the assay's output based on their own judgment in the way that an AI-assisted diagnostic imaging system might require. Its performance is evaluated entirely on its independent ability to measure PSA accurately and consistently.

7. The Type of Ground Truth Used

• Analytical Studies:
  • Traceability: WHO International Standard Prostate Specific Antigen (90:10) NIBSC code: 96/670.
  • Linearity, LoD, LoQ: Spiked samples with known concentrations or dilutions of highly concentrated samples.
  • Method Comparison: Comparison to the predicate device (FREND™ PSA Plus, K124056) and an FDA-approved commercial assay (Abbott ARCHITECT total PSA assay) as external reference methods.
• Clinical Studies (Serial Monitoring):
  • Clinical Status: A composite judgment based on patient outcomes data and expert clinical assessment, including "other laboratory tests, patient interviews, physical examinations, and imaging studies of a variety of types." This represents a form of clinical diagnosis/outcome.

8. The Sample Size for the Training Set

• Not applicable / Not explicitly specified as a "training set" in the context of machine learning. This device is a fluorescence immunoassay, not a machine learning or AI-based diagnostic tool that would typically have a distinct "training set" for an algorithm. All samples mentioned in the performance characteristics section (precision, linearity, method comparison, clinical evaluation) would be considered part of the overall analytical and clinical validation, not segregated into typical ML training/test sets. The lot-specific calibration curve used for quantification is generated by the manufacturer using a six-point calibration from five replicates at each level, but this is a traditional calibration process, not an AI training set.

9. How the Ground Truth for the Training Set was Established

• Not applicable. As explained above, there isn't a "training set" in the machine learning sense for this device. The closest equivalent is the process of generating the lot-specific calibration curve, which uses known concentrations of PSA standards (traced to WHO International Standard) that are measured multiple times to establish the relationship between fluorescence signal and PSA concentration.

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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.

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.

Here's a summary of the acceptance criteria and study findings for the FREND™ PSA Plus on the FREND™ system, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

| Performance Metric | Acceptance Criteria (Stated or Implied) | Total (Total CV%) | |
| Site-to-Site Value) | 3.50% | 1.57% | 1.67% | 3.47% | 1.61% | 2.06% | |
| Inter-cartridge | 18.45% | 6.81% | 7.94% | 20.03% | 6.17% | 7.49% | |
| Total (Total CV%) | 20.87% | 7.74% | 10.79% | 21.22% | 7.69% | 9.81% | |

Note: The document explicitly states "acceptance criteria" for some tests (e.g., dilution linearity, spiked recovery, interference) but for others (e.g., imprecision, method comparison), it describes the results and concludes they are "acceptable" or "compared well," implying that the performance met internal thresholds comparable to predicate devices.

2. Sample Sizes and Data Provenance

• Clinical Samples: 1219 evaluable clinical serum samples.
  • Provenance: Prospectively collected stored samples were utilized for the clinical study. No specific country of origin is explicitly stated, but NanoEnTek is a Korean company with a CRO (DOCRO, Inc.) in the US, and testing was done at both NanoEnTek facilities and CLIA licensed facilities in the US.
• Precision (Analytical):
  • Intra-assay/inter-assay/complex imprecision: Three clinical samples (0.186, 2.757, 16.625 ng/mL) assayed in duplicates twice a day for 20 days using a single lot cartridge (total 80 measurements per sample).
  • Multi-Site, Multi-Lot Imprecision: Four replicates each of Material A, B, C and two replicates of QC 1, 2, 3 were evaluated in two runs performed for five days at each of three geographically diverse sites. This yielded a total of 40 results on each material per site, and 120 total replicates for each material across all sites.
• Dilution Linearity & Recovery: A serum pool with elevated PSA (34 ng/mL) was diluted to seven levels, plus neat and zero samples. Each level was tested in 6 replicates.
• Spiked Recovery: A serum pool from females (tPSA < 0.01 ng/mL) was spiked with 3 known PSA levels. Samples were assayed before and after spiking (number of replicates not explicitly stated, but table shows 3 replicates per spike level).
• Analytical Sensitivity (LOD/LOQ): 5 blank samples and 5 low PSA concentration samples were tested in 12 replicates each.
• High Dose Hook Effect: A concentrated sample of purified PSA antigen tested neat and on dilution (number of replicates not specified).
• Interfering Substances and Assay Specificity: Not explicitly stated, but samples were tested according to CLSI protocol EP7-A.
• Method Comparison:
  • Prostate cancer samples: Single point samples (n = 85) and earliest sample from serially monitored subjects (n = 75), for a total of 160 samples (tPSA < 25 ng/mL).
  • Serially Monitored Subjects: 75 subjects undergoing serial monitoring for prostate cancer. A total of 236 point-to-point determinations for each assay.
• Sample Matrix Comparison Study: 36 matched sets (serum, lithium heparin, EDTA plasma, sodium citrate) were collected, aliquoted, frozen, and run.
• Reagent Stability Studies: Three different lots of cartridges were tested over 15 months at three-month intervals using five standard specimens.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with X years of experience) for establishing the ground truth for the test set in the clinical performance section.

• For the serial monitoring study, "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." This implies a medical professional established the clinical ground truth. The nature of this determination included "other laboratory tests, patient interviews, physical examinations, and imaging studies of a variety of types."

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the clinical test set. The clinical status for serially monitored patients was determined by "the physician" and was used as the ground truth.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an in vitro diagnostic assay, not an imaging device or AI-assisted diagnostic tool that would typically involve human readers interpreting cases with and without AI assistance. The clinical study compares the device's performance to a predicate device and clinical status, but not the improvement of human reader performance.

6. Standalone (Algorithm Only) Performance

Yes, numerous standalone performance studies were done. The FREND™ PSA Plus is an automated immunoassay system, and its analytical and clinical performance is its standalone performance. The entire "Performance Data Summary - Analytical Testing" and "Performance Data Summary - Clinical Testing" sections detail the standalone performance of the assay and system without human intervention in the measurement process (though human input is required to operate the system and interpret results in a clinical context).

7. Type of Ground Truth Used

• Analytical Studies:
  • Precision, Dilution Linearity, Spiked Recovery, Sensitivity, Hook Effect, Interference: Ground truth was based on known concentrations of PSA, characterized reference materials, or clinically established levels of interfering substances. For example, for dilution linearity, the "Expected Value" was the ground truth based on known dilutions. For spiked recovery, the "Concentration Added" was the ground truth.
• Clinical Studies:
  • Disease Cohorts (Normal, Benign, Malignant): Ground truth was based on patient diagnoses (e.g., "Benign prostate disease," "Prostate Cancer") established through clinical assessment (including other diagnostic tests and potentially pathology results, though not explicitly detailed for this specific aspect).
  • Serial Monitoring: Ground truth for "Progression" or "No Progression" was based on "the clinical status of the patients as measured by other laboratory tests, patient interviews, physical examinations, and imaging studies of a variety of types." This is essentially patient outcomes data/clinical diagnosis as determined by a physician.

8. Sample Size for the Training Set

The document does not explicitly describe a separate "training set" for an algorithm in the way that would typically be detailed for an AI/ML device. This device is an immunoassay, and its performance characteristics (like linearity, precision, etc.) are established through traditional analytical and clinical validation studies, rather than machine learning model training on a distinct dataset. The "development" and "optimization" of the assay would typically involve internal samples and experiments, but these are not referred to as a "training set" in the context of this 510(k) submission.

9. How the Ground Truth for the Training Set Was Established

Since a "training set" for an AI/ML algorithm is not described, the method for establishing its ground truth is not applicable/provided. The analytical and clinical performance data presented here are for the validation and verification of the device's performance against established metrology principles and clinical outcomes.

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