(264 days)
Not Found
No
The device description and performance studies focus on a standard immunofluorescence assay and the calculation of analyte concentration based on fluorescence. There is no mention of AI/ML algorithms for image processing, data interpretation, or risk stratification beyond simple thresholding.
No
The device is an in vitro diagnostic (IVD) assay designed to semi-quantitatively determine the concentration of pancreatic stone protein (PSP) in blood. This measurement is used to aid in the early detection of sepsis, which is a diagnostic purpose, not a therapeutic one. It does not treat or alleviate a condition.
Yes
The device is described as an "in vitro diagnostic immunofluorescence assay" in the "Intended Use / Indications for Use" section and its purpose is to aid in the early detection of sepsis by measuring pancreatic stone protein (PSP) levels. This clearly indicates its role in diagnosis.
No
The device description clearly outlines physical components like a capsule, pipette, vial, desiccant bag, and an RFID tag, which are hardware. It also describes the abioSCOPE analyzer, a tabletop diagnostic device with a microscope and tray, which is also hardware. While software is involved in the abioSCOPE for calculation, the device as a whole is not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly Stated in Intended Use: The very first sentence of the "Intended Use / Indications for Use" section clearly states: "The IVD CAPSULE PSP is a single-use, rapid in vitro diagnostic immunofluorescence assay..."
- Analyzes Biological Sample: The device is designed to determine the concentration of pancreatic stone protein (PSP) in human whole blood, which is a biological sample.
- Used for Diagnostic Purposes: The test is used "to aid in the early detection of sepsis," which is a diagnostic purpose.
- Performed Outside the Body: The analysis of the blood sample is performed using the IVD CAPSULE PSP and the abioSCOPE analyzer, which are external to the patient's body.
- Intended for Professional Use in Clinical Laboratory Settings: This aligns with the typical use case for IVD devices.
N/A
Intended Use / Indications for Use
The IVD CAPSULE PSP is a single-use, rapid in vitro diagnostic immunofluorescence assay for the semi-quantitative determination of the concentration of pancreatic stone protein (PSP) in human K2-EDTA (arterial and K3-EDTA (venous) anticoagulated whole blood.
The IVD CAPSULE PSP is to be used on the abioSCOPE in vitro diagnostic analyzer. This diagnostic test is used in conjunction with other clinical assessments and laboratory findings to aid in the early detection of sepsis manifesting within the first 3 days after testing. IVD CAPSULE PSP generates PSP values that fall within one of three discrete Interpretation bands based on increasing likelihood of sepsis.
The test is intended for professional use in clinical laboratory settings. It is indicated for use in adult patients at high risk of sepsis presenting to intensive care units (ICUs).
Product codes (comma separated list FDA assigned to the subject device)
SCX
Device Description
IVD CAPSULE PSP (diagnostic assay kit)
The IVD CAPSULE PSP is a single-use, semi-quantitative immunofluorescence assay used to determine the concentration of the pancreatic stone protein (PSP) in a human whole blood sample. The test kit contains the following components:
- . Capsule
- . Special pipette (abioPIPETTE)
- Vial containing a detection reagent (abioMIX) ●
- . Desiccant bag (auxiliary item to reduce moisture within the blister)
The main component of the test kit is the capsule is a high impact polystyrene plastic cartridge similar in shape to a domino tile albeit smaller. The capsule allows the user to dispense the blood-abioMIX solution onto the loading port with the aid of the abioPIPETTE. The loading port has a membrane separator that excludes cells and other large particulates from the capsule interior. A second membrane drives the sample by capillary force to the entrance of nanofluidic biosensors containing a read-out area where the PSP is captured by specific antibodies and fluorescently detected.
The concentration of the captured PSP is proportional to the fluorescence generated by the fluorophore conjugated to the detection antibody. Therefore, the measured fluorescence signal is proportional to the concentration of PSP within the sample. The capsule also contains a RFID tag that is programmed with the capsule biosensor configuration and lot-specific information.
abioSCOPE (reading platform, analyzer)
The abioSCOPE is a tabletop diagnostic device that measures analytes in biological samples, using test-specific capsules (IVD CAPSULE) intended for use with this instrument. It is operated easily through a high-resolution touchscreen.
It is composed of a fully automated fluorescence microscope and a tray onto which is placed a single-use disposable IVD CAPSULE. The abioSCOPE uses a laser to excite the molecular complexes inside the biosensors which leads to the emission of a fluorescence signal. The abioSCOPE then calculates the concentration of the analyte in the patient sample.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult patients
Intended User / Care Setting
professional use in clinical laboratory settings. It is indicated for use in adult patients at high risk of sepsis presenting to intensive care units (ICUs).
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
The performance of the PSP was evaluated by comparing it to the assessment of an External Independent Review Committee (EIRC) consisting of three medical doctors who are experts in critical care medicine and the assessment of infection and sepsis, but who were not otherwise involved in the study. Based on the Sepsis-3 definition the EIRC independently adjudicated all subjects, determining whether each was with or without sepsis at each day within the first 3 days of ICU stay while remaining blinded to the PSP results. Clinical performance data from a multicentric, prospective, observational clinical study (AB-PSP-002; NCT04105699) conducted across six ICU centers in the U.S., involving 497 patients. The primary study population consisted of the intention-to-diagnose (ITD) group. A sensitivity analysis was conducted on the ITD population, using cut-off values established from a previous international multicentric observational clinical study, ensuring no influence from this study's patient data on the defined cut-off values and subsequent calculations.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance Data
The analytical performance characteristics of the IVD CAPSULE PSP were investigated and validated using a series of dedicated individual studies.
- Analytical sensitivity: Limit of Blank (LoB) 2.6 ng/ml; Limit of Detection (LoD) 9.4 ng/ml; Lower Limit of Quantification (LLoQ) 17.0 ng/ml.
- Analytical specificity: 8 endogenous substances assessed, total protein showed doses outside acceptance limits of ±10% at medium and highest PSP concentrations. 29 exogenous substances assessed, fentanyl showed doses outside acceptance limits of ±10% at the highest PSP concentration. No sample carryover observed.
- Analytical measuring range: The measuring range was established to be from 20 ng/ml to 600 ng/ml. The product showed linearity for the device measuring interval. No hook effect observed at 10'000 ng/ml.
- Accuracy: Trueness of measurement (method comparison) not evaluated due to no established reference method.
- Precision: Within clinical laboratory settings, Between-run and between-day CV% met acceptance criteria (all = 300 ng/ml: Predictive Value 70.10%, Likelihood Ratio 2.49 (95% CI: 1.83-3.38). Result interpretation: Increased risk of sepsis.
- PSP Concentration 100-299 ng/ml: Predictive Value 55.30%, Likelihood Ratio 1.32 (95% CI: 1.02-1.7). Result interpretation: Slightly increased sepsis risk.
- PSP Concentration = 300 ng/ml: 70.10%
- 100-299 ng/ml: 55.30%
- = 300 ng/ml: 2.49
- 100-299 ng/ml: 1.32
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
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September 25, 2024
Abionic SA Iwan Märki Chief Technology Officer Route de la Corniche 5 Epalinges, 1066 Switzerland
Re: K240041
Trade/Device Name: IVD CAPSULE PSP; abioSCOPE Regulation Number: 21 CFR 866.3215 Regulation Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis Regulatory Class: Class II Product Code: SCX Dated: January 3, 2024 Received: January 5, 2024
Dear Iwan Märki:
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, Drug, and Cosmetic Act (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
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 can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
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Sincerely,
Bryan M. Grabias -S Digitally signed by Bryan M. Grabias -S Date: 2024.09.25 14:03:14 -04'00'
Bryan Grabias, Ph.D. Acting Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K240041
Device Name IVD CAPSULE PSP / abioSCOPE
Indications for Use (Describe)
The IVD CAPSULE PSP is a single-use, rapid in vitro diagnostic immunofluorescence assay for the semi-quantitative determination of the concentration of pancreatic stone protein (PSP) in human K2-EDTA (arterial and K3-EDTA (venous) anticoagulated whole blood.
The IVD CAPSULE PSP is to be used on the abioSCOPE in vitro diagnostic analyzer. This diagnostic test is used in conjunction with other clinical assessments and laboratory findings to aid in the early detection of sepsis manifesting within the first 3 days after testing. IVD CAPSULE PSP generates PSP values that fall within one of three discrete Interpretation bands based on increasing likelihood of sepsis.
The test is intended for professional use in clinical laboratory settings. It is indicated for use in adult patients at high risk of sepsis presenting to intensive care units (ICUs).
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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abionic
510(k) SUMMARY
IVD CAPSULE PSP on abioSCOPE®
This summary has been prepared in accordance with the requirements of 21 CFR 807.92.
1. 510(k) Number: K240041
2. Submitter
Abionic SA Route de la Corniche 5 CH-1066 Epalinges Switzerland
Contact Person: Iwan Märki Function: Chief Technology Officer at Abionic SA Phone: +41 21 353 33 88 Email: iwan.maerki@abionic.com
Date of Summary preparation: September 25, 2024
3. Regulatory Information
Subject Device
| Device Trade Name: | IVD CAPSULE PSP |
|---|---|
| Device Reference Number: | P02.00026 |
| Device Common Name: | Pancreatic Stone Protein biomarker for sepsis detection |
| Regulation Number: | 21 CFR 866.3215 |
| Classification Name: | Device to detect and measure non-microbial analyte(s) in |
| human clinical specimens to aid in assessment of patients | |
| with suspected sepsis. | |
| FDA Classification: | Class II |
| Product Code: | SCX |
| Name of reading platform: | abioSCOPE® |
| Reference number of platform: | P01.00007 |
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Predicate Device
| Device Name: | B.R.A.H.M.S PCT sensitive KRYPTOR® Test System |
|---|---|
| 510(k) Number: | K070310 |
| Applicant: | B.R.A.H.M.S Aktiengesellschaft |
| Manufacturer: | B.R.A.H.M.S GmbH, part of Thermo Fisher Scientific |
4. Device Description
IVD CAPSULE PSP (diagnostic assay kit)
The IVD CAPSULE PSP is a single-use, semi-quantitative immunofluorescence assay used to determine the concentration of the pancreatic stone protein (PSP) in a human whole blood sample. The test kit contains the following components:
- . Capsule
- . Special pipette (abioPIPETTE)
- Vial containing a detection reagent (abioMIX) ●
- . Desiccant bag (auxiliary item to reduce moisture within the blister)
The main component of the test kit is the capsule is a high impact polystyrene plastic cartridge similar in shape to a domino tile albeit smaller. The capsule allows the user to dispense the blood-abioMIX solution onto the loading port with the aid of the abioPIPETTE. The loading port has a membrane separator that excludes cells and other large particulates from the capsule interior. A second membrane drives the sample by capillary force to the entrance of nanofluidic biosensors containing a read-out area where the PSP is captured by specific antibodies and fluorescently detected.
The concentration of the captured PSP is proportional to the fluorescence generated by the fluorophore conjugated to the detection antibody. Therefore, the measured fluorescence signal is proportional to the concentration of PSP within the sample. The capsule also contains a RFID tag that is programmed with the capsule biosensor configuration and lot-specific information.
abioSCOPE (reading platform, analyzer)
The abioSCOPE is a tabletop diagnostic device that measures analytes in biological samples, using test-specific capsules (IVD CAPSULE) intended for use with this instrument. It is operated easily through a high-resolution touchscreen.
It is composed of a fully automated fluorescence microscope and a tray onto which is placed a single-use disposable IVD CAPSULE. The abioSCOPE uses a laser to excite the molecular complexes inside the biosensors which leads to the emission of a fluorescence signal. The abioSCOPE then calculates the concentration of the analyte in the patient sample.
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5. Intended use
The IVD CAPSULE PSP is a single-use, rapid in vitro diagnostic immunoflyorescence assay for the semi-quantitative determination of the concentration of pancreatic stone protein (PSP) in human K₂-EDTA (arterial and venous) and K₃-EDTA (venous) anticoagulated whole blood.
The IVD CAPSULE PSP is to be used on the abioSCOPE in vitro diagnostic analyzer. This diagnostic test is used in conjunction with other clinical assessments and laboratory findings to aid in the early detection of sepsis manifesting within the first 3 days after testing. IVD CAPSULE PSP generates PSP values that fall within one of three discrete Interpretation bands based on increasing likelihood of sepsis.
The test is intended for professional use in clinical laboratory settings. It is indicated for use in adult patients at high risk of sepsis presenting to intensive care units (ICUs).
6. Technological Characteristics Comparison
The following table describes the similarities and differences between the IVD CAPSULE PSP (subject device), and the BRAHMS PCT sensitive KRYPTOR (predicate device).
| Item | Subject Device | Predicate Device |
|---|---|---|
| Intended Use | IVD CAPSULE PSP on abioSCOPE | |
| The IVD CAPSULE PSP is a single- use, rapid in vitro diagnostic immunofluorescence assay for the semi-quantitative determination of the concentration of pancreatic stone protein (PSP) in human K2-EDTA (arterial and venous) and K3-EDTA (venous) anticoagulated whole blood. The IVD CAPSULE PSP is to be used on the abioSCOPE in vitro diagnostic analyzer. This diagnostic test is used in conjunction with other clinical assessments and laboratory findings to aid in the early detection of sepsis manifesting within the first 3 days after testing. IVD CAPSULE PSP generates PSP values that fall within one of three discrete Interpretation bands based on increasing likelihood of sepsis. The test is intended for professional use in clinical laboratory settings. It is indicated for use in adult patients at high risk of sepsis presenting to intensive care units (ICUs). | BRAHMS PCT sensitive KRYPTOR® | |
| The BRAHMS PCT sensitive KRYPTOR® is an immunofluorescent assay used to determine the concentration of PCT (procalcitonin) in human serum and plasma. The BRAHMS PCT sensitive KRYPTOR® is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock. |
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| Subject Device | Predicate Device | |
|---|---|---|
| Item | IVD CAPSULE PSP on abioSCOPE | BRAHMS PCT sensitive KRYPTOR |
| Detection | ||
| Method | Immunofluorescence assay based on | |
| specific nanofluidic biosensor design | Immunofluorescence assay with measuring | |
| principle based on Time-Resolved | ||
| Amplified Cryptate Emission (TRACE) | ||
| technology which measures the signal | ||
| emitted from an immunocomplex with time | ||
| delay | ||
| Assay Type | Semi-quantitative | Quantitative |
| Result Output | Fluorescent signal is converted with | |
| the use of a calibration curve to a | ||
| concentration that falls within one of | ||
| three discrete interpretation bands | ||
| based on likelihood of sepsis within | ||
| three (3) days of testing. | Fluorescent signal is converted to | |
| concentration with the use of a calibration | ||
| curve. | ||
| Sample Volume | 50 μl | 50 μl |
| Analyte | PSP (Pancreatic Stone Protein) | PCT (Procalcitonin) |
| Specimen type | K2-EDTA (arterial and venous) and K3- | |
| EDTA (venous) anticoagulated whole | ||
| blood | EDTA anticoagulated serum and plasma | |
| from venous blood | ||
| Measuring | ||
| Range | 20-600 ng/ml | 0.02-50 μg/L |
| Assay Time | 7.5 minutes | 19 minutes |
| Operating | ||
| conditions for | ||
| instrument | Operating temperature (18-28 °C). | |
| Relative humidity: 20-80% | Instrument-controlled, 37 °C | |
| Controls | One level (medium concentration at | |
| approximately 200 ng/ml)) | Two levels (low and high) |
Table 1| Comparison table of subject and predicate device for establishing substantial equivalence.
Discussion of main differences:
The main technological differences between the IVD CAPSULE PSP on abioSCOPE and its predicate are not critical and include the following:
- The biomarkers (PSP vs PCT) are different. Reference values as normal range, cut-offs, etc. . are different but diagnostic performance is equivalent as shown in clinical studies.
- . Both test systems deliver as result biomarker concentration values, but an international reference standard has not yet been established for PSP, therefore, different test methods using PSP may have a certain bias between them and the measurement is indicated as "semiquantitative".
- . The IVD CAPSULE PSP is currently limited to adult patients since sufficient clinical data is not yet available for younger populations. The indications of use for the subject device fall within the intended use of the predicate device.
- The IVD CAPSULE PSP uses a special nanofluidic biosensor design to shorten the time-to-. result and concentrate the labelled measurand proteins, thereby increasing the fluorescence signal. The performance of the (subject and predicate) devices has been validated to be substantially equivalent.
8
- The systems use different (closed) reading instruments with similar methods . (immunofluorescence) to work with specific test kits for measurements. The performance of the devices has been validated to be substantially equivalent.
- The collected specimen types (whole blood vs serum/plasma) are different but do not impact . the effectiveness of the device since whole blood (arterial and venous) is easily available by the standard of care in ICUs and the used matrices were properly validated.
7. Analytical Performance Data
The analytical performance characteristics of the IVD CAPSULE PSP were investigated and validated using a series of dedicated individual studies, each of those looking at a particular aspect of the assay. The findings are summarized in the table below.
| Inputs | Results |
|---|---|
| Analytical sensitivity | |
| Limit of Blank (LoB) | 2.6 ng/ml |
| Limit of Detection (LoD) | 9.4 ng/ml |
| Lower Limit of | |
| Quantification (LLoQ) | 17.0 ng/ml |
| Analytical specificity | |
| Endogenous | |
| interferences | 8 endogenous substances were assessed for their effect on the assay's performance. |
| All but one (total protein) exhibited an average bias across all three PSP levels below the | |
| acceptance limit set at 10% although individual bias was above the limit for 2 substances | |
| (HAMA and hemoglobin) at the highest PSP concentration. | |
| Following these results, dose-response experiments were conducted on these 3 | |
| substances. Only total protein showed doses that were outside the acceptance limits of | |
| ±10% at the medium and highest PSP concentrations. | |
| Exogenous | |
| interferences | 29 exogenous substances were assessed for their effect on the assay's performance. In |
| the initial assessment, all substances exhibited an average bias across all three PSP | |
| levels below the acceptance limit set at 10% although some individual biases were above | |
| the limit for 10 substances (acetaminophen, dopamine, doxycycline, ethanol, fentanyl, | |
| furosemide, heparin, imipenem, salmeterol and tiotropium) at certain PSP concentration. | |
| Following these results, dose-response experiments were conducted on these | |
| substances. Among the 10 substances tested in these experiments, only fentanyl showed | |
| doses that were outside the acceptance limits of ±10% at the highest PSP concentration. | |
| It was concluded that all the other interferents are not affecting the assay's performance. | |
| Interference by sample | |
| Carryover | By alternating low-dose and high dose samples, the study showed that PSP measurement |
| is not impacted by the previous test and no sample carryover was observed. | |
| Analytical measuring range | |
| Measuring range | The measuring range of the assay was established and spans from 20 ng/ml to 600 ng/ml. |
| Linearity | The product showed linearity for the device measuring interval (20 to 600 ng/ml). |
| High-dose hook effect | No hook effect was observed at 10'000 ng/ml. Of important note, no PSP value above |
| 5'000 ng/ml has been observed so far in clinical samples. | |
| Accuracy | |
| Trueness of | |
| measurement (method | |
| comparison) | Not evaluated (there is no established reference method, therefore the test is indicated as |
| semi-quantitative) | |
| Precision | |
| In clinical laboratory | |
| settings | - Between-run and between-day CV% met acceptance criteria. Actual values are all below |
| or equal to 6%. |
- Reproducibility (device-to-device, lot-to-lot and operator precision) fulfilled |
| Inputs | Results |
| | the acceptance criteria exhibiting %CV values lower than 7% at the individual PSP
concentrations analyzed and with averages across all 5 levels of 3%, 2.2% and 1.8%
respectively. |
| | - instrument-to-instrument and user-to-user imprecision measured at 3 levels of PSP
(low/intermediate/high) proved to be acceptable overall with %CV values not higher than
8.4% at the individual PSP concentrations analyzed. |
| | - Whole blood between-run precision was also determined with samples covering the
reportable range (20 to 600 ng/ml) and yielded a %CV of 14.8%. |
| Stability | |
| Shelf-life | The current claimed shelf-life of the IVD CAPSULE PSP is 9 months at 2-8 °C. |
| In-Use | An open IVD CAPSULE PSP device can withstand at least 3 hours exposure to room
temperature with temperatures reaching up to 30 °C.
It is nevertheless recommended to use the device as soon as it is open and limit its
exposure to the elements as much as possible. |
| Shipping | The stability of IVD CAPSULE PSP during transportation was assessed using a simulation
approach where the kits were submitted to different temperature sequences to simulate a
transport by plane from the manufacturing site to a customer site with the kit's exposure
to either high or low temperature. It was shown that the benefit-risk ratio is not impacted
by the results of the study. |
| Calibration and metrological traceability | |
| Metrological traceability | - No internationally recognized reference standard is available at this point of time. - Abionic has established an in-house higher order calibrator to which the final result in the
patient's sample can be traced back through an unbroken chain of interdependence. |
| Specimen | |
| Type | The IVD CAPSULE PSP is an assay for the semi-quantitative determination of the
concentration of pancreatic stone protein (PSP) in K2-EDTA and K3-EDTA anticoagulated
venous and arterial whole blood. |
| Stability | PSP is stable in K2-EDTA anticoagulated whole blood for up to 24 hours at room
temperature and by extension at 2°C to 8°C. |
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Table 2 | Summary of analytical performance
The analytical performance of IVD CAPSULE PSP was established in accordance with the requirements for special controls imposed by the CFR regulation. The corresponding non-clinical studies were performed in compliance with the applicable CLSI standards, and the applied methods and performance characteristics of the device correspond to the current general state of the art for IVD devices. A direct analytical performance comparison with the predicate has only limited value as both devices use different biomarkers with individual cut-off values.
8. Clinical Performance Data
Normal reference range
The normal PSP concentration [ng/m]] range in adults was determined by the manufacturer on an US adult population. Results are provided in the following table.
| Mean | 97 ng/ml |
|---|---|
| 5-95% percentiles | 89 – 105 ng/ml |
| Median | 81 ng/ml |
| LRL / URL | 29 / 228 ng/ml |
Table 3 | Normal PSP values are from 211 healthy donors (Male/Female (%): 35/65, Caucasian/African American/Asian/Other (%): 77/15/7/1).
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The distribution of the normal reference values over the established risk interpretation bands is shown in Table 4.
| PSP concentration [ng/ml] | Distribution of (normal) reference values:
number of subjects (percentage) |
|---------------------------|-------------------------------------------------------------------------------|
| ≥ 300 | 4 (1.9%) |
| 100 – 299 | 69 (32.7%) |
| ≥200-299 | 11 (5.2%) |
| ≥100-200 | 58 (27.5%) |
| = 300 | 103 | 44 | 147 | 70.10% | 29.60% | 2.49 | 1.83 | 3.38 |
| 100-299 | 88 | 71 | 159 | 55.30% | 32.00% | 1.32 | 1.02 | 1.7 |
|