ST AIA-PACK BNP Assay by Tosoh Bioscience, Inc.

The Tosoh ST AIA-PACK BNP assay is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of BNP in human (K2EDTA) plasma on Tosoh AIA System Analyzers. BNP is used as an aid in the diagnosis of heart failure (HF) in patients presenting to the emergency department (ED) with clinical suspicion of new onset HF, acutely decompensated or exacerbated HF.

Device Description

The ST AIA-PACK BNP is a two-site immunoenzymometric assay which is performed entirely in the ST AIA-PACK BNP test cups. BNP present in the test sample is bound with monoclonal antibody immobilized on magnetic beads and enzyme-labeled monoclonal antibody. The magnetic beads are washed to remove unbound enzyme-labeled monoclonal antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled monoclonal antibody that binds to the beads is directly proportional to the BNP concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using the curve.

AI/ML Overview

The Tosoh ST AIA-PACK BNP Assay aims to extend its measuring interval beyond 2,000 pg/mL through manual and automated 1:5 and 1:10 dilutions. This is a special 510(k) submission, meaning it refers to a device that has already been cleared (K192380) and modifications were made to it that do not significantly alter its performance or safety (e.g., modified firmware, revised labeling, minor material changes, etc.). Since this is a Special 510(k) and not a de novo submission, this document is a justification for substantial equivalence to its predicate device (K192380), and does not contain detailed information for how the predicate device was evaluated.

Therefore, the study summary below only refers to the performance of the modified device compared to its predicate device, and not a full evaluation of the predicate device's performance.

1. Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Manual Dilution
Recovery value	102% for 1:5 dilution
Recovery value	100% for 1:10 dilution
On-board (automated) Dilution
Recovery value	95% for 1:5 dilution
Recovery value	95% for 1:10 dilution

2. Sample size used for the test set and data provenance

The document does not specify the sample sizes used for the manual and automated dilution studies, nor does it specify the country of origin or whether the data was retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. The ground truth method does not involve human experts; it relies on direct measurement.

4. Adjudication method for the test set

Not applicable. The ground truth method does not involve human experts.

5. 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 versus without AI assistance

Not applicable. This is not an AI-assisted diagnostic device, but an in vitro diagnostic assay.

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

Not applicable. This device is an in vitro diagnostic assay, not an algorithm.

7. The type of ground truth used

The ground truth used for both manual and automated dilution studies is the recovery value of the BNP concentration after dilution, indicating the accuracy of the dilution process. This is a direct measurement based on the expected concentration after dilution.

8. The sample size for the training set

Not applicable. This device is an in vitro diagnostic assay and does not involve machine learning or a training set.

9. How the ground truth for the training set was established

Not applicable. This device is an in vitro diagnostic assay and does not involve machine learning or a training set.

Summary

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November 8, 2021

Tosoh Bioscience, Inc. Louise Musante Regulatory Compliance Consultant 6000 Shoreline Court. Suite 101 South San Francisco, CA 94080

Re: K211199

Trade/Device Name: ST AIA-PACK BNP Assay Regulation Number: 21 CFR 862.1117 Regulation Name: B-Type Natriuretic Peptide Test System Regulatory Class: Class II Product Code: NBC Dated: April 20, 2021 Received: April 22, 2021

Dear Louise Musante:

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 (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 located 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.

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

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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).

Sincerely,

Kellie B. Kelm, Ph.D. Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K211199

Device Name ST AIA-PACK BNP Assay

Indications for Use (Describe)

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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510(k) Summary Tosoh Bioscience, Inc.'s ST AIA-PACK BNP Assay

DATE PREPARED: April 20, 2021

1. COMPANY NAME/CONTACT Tosoh Bioscience, Inc. 6000 Shoreline Court, Suite 101 South San Francisco, CA 94080
1. CONTACT: Louise Musante Regulatory Compliance Consultant Email: louise.musante@tosoh.com Cell Phone: (650) 242-5563

3. DEVICE INFORMATION

Device Trade Name: ST AIA-PACK BNP Assay Regulation Number: 21 CFR Part 862.1117 Regulation Name: Test, Natriuretic Peptide Product Code: NBC, B-Type natriuretic peptide test system Device Class: Class II 510(k) Review Panel: Clinical Chemistry

Assigned Special 510(k) number: K211199

4. PREDICATE DEVICE

Trade name: ST AIA-PACK BNP Assay

510(k) submitter/holder:	Tosoh Bioscience, Inc.6000 Shoreline Court, Suite 101South San Francisco, CA 94080
--------------------------	--------------------------------------------------------------------------------------------

510(k) Number:

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K192380

5. DEVICE DESCRIPTION

ST AIA-PACK BNP (Cat. No. 025228)

The ST AIA-PACK BNP set consists of 5 trays x 20 test cups. Each kit contains plastic test cups containing twelve magnetic lyophilized beads coated with anti-BNP mouse monoclonal antibody and 100 µL of anti-BNP mouse monoclonal antibody conjugated to alkaline phosphatase with sodium azide as a preservative.

Other Materials/Equipment Required (not Provided):

Tosoh AIA Analyzer 2000

AIA PACK

AIA-PACK Substrate Set II AIA-PACK Substrate Reagent II AIA-PACK Substrate Reconstituent II AIA-PACK Wash Concentrate AIA-PACK Diluent Concentrate Sample Cups AIA-PACK Detector Standardization Test Cups AIA-PACK Sample Treatment Cups Pipette Tips (1000/pkg) Tip Rack (empty) Preloaded Pipette Tips (96 tips x 50 racks) Preloaded Pipette Tips (96 Tips x 5 Racks)

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6. INDICATION FOR USE STATEMENT

The Tosoh ST AIA PACK BNP assay is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement of BNP in human (K2EDTA) plasma on Tosoh AIA System Analyzers. BNP is used as an aid in the diagnosis of heart failure (HF) in patients presenting to the emergency department (ED) with clinical suspicion of new onset HF, acutely decompensated or exacerbated HF.

7. INTENDED USE STATEMENTS:

(See above Indications For Use Statement).

The Tosoh ST AIA PACK BNP assay is intended for prescription use only, on Tosoh AIA Analyzer 2000.

8. REASON FOR SUBMISSION

This Special 510(k) is being filed to seek FDA clearance for the ST AIA-PACK BNP assay, a modified version of the existing ST AIA-PACK BNP assay, which is currently cleared (K192380, FDA cleared on August 24, 2020).

9. DESCRIPTION OF DEVICE MODIFICATION

The ST AIA-PACK BNP device is being modified to add a manual and automated dilution claim to the existing ST AIA-PACK BNP assay 510(k) clearance (K192380).This modification does not change the Intended Use/Indications for Use. the fundamental scientific technology, reagent formulation, assay configuration, manufacturing procedures, principle of operation, or safety and effectiveness of the device.

A summary of the modifications and the rationale for the changes between the current cleared Device: ST AIA-PACK BNP assay (K192380) and the ST AIA-PACK BNP assay with the dilution claims (modified device) are provided in Table 1 below.

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Table 1 - Summary of Modifications to Subject Device Compared to Predicate Device

Cleared Device (K192380)	Candidate Device(Modification)	Rationale
No sample dilution claim	Addition of a 1:5 and 1:10manual & automateddilution claim for the STAIA-PACK BNP Assay	To allow a clinician to extend the measuring intervalof the ST AIA-PACK BNP assay (above theanalytical measurement interval of 2,000pg/mL)through specimen dilution, prepared both manuallyor onboard (automated) by the analyzer, for higherconcentration BNP specimens.

10. SUBSTANTIAL EQUIVALENCE COMPARISON

The Tosoh ST AIA PACK BNP assay is substantially equivalent to the claimed predicate device; the Tosoh ST AIA PACK BNP (K192380), based on comparisons of the intended use and technological characteristics.

Attributes	ST AIA-PACK BNPCandidate	ST AIA-PACK BNPPredicate(K192380)	Differences	Differencesraise anyadditionalsafetyissues?
General Information
Regulation #	21 CFR 862.1117	21 CFR 862.1117	Same	N/A
RegulationName	B-type natriuretic peptide testsystem	B-type natriuretic peptide testsystem	Same	N/A
RegulatoryClass	Class II	Class II	Same	N/A
Product Code	NBC	NBC	Same	N/A
Indicationsfor Use	The Tosoh ST AIA PACK BNPassay is designed for IN VITRODIAGNOSTIC USE ONLY for thequantitative measurement of BNPin human (K2EDTA) plasma onTosoh AIA System Analyzers.BNP is used as an aid in thediagnosis of heart failure (HF) inpatients presenting to theemergency department (ED) withclinical suspicion of new onsetHF, acutely decompensated orexacerbated HF.	The Tosoh ST AIA PACK BNPassay is designed for IN VITRODIAGNOSTIC USE ONLY for thequantitative measurement of BNPin human (K2EDTA) plasma onTosoh AIA System Analyzers.BNP is used as an aid in thediagnosis of heart failure (HF) inpatients presenting to theemergency department (ED) withclinical suspicion of new onsetHF, acutely decompensated orexacerbated HF.	Same	N/A

Table 2 - Comparison Table of Subject Device to Predicate Device

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Attributes	ST AIA-PACK BNPCandidate	ST AIA-PACK BNPPredicate(K192380)	Differences	Differencesraise anyadditionalsafetyissues?
Intended UseSetting	For use on patients presenting tothe Emergency Department (ED).	For use on patients presenting tothe Emergency Department (ED).	Same	N/A

Table 3 – Comparison Table of Technological Characteristics: Subject Device to Predicate Device

Attributes	ST AIA-PACK BNPCandidate	ST AIA-PACK BNPPredicate(K192380)	Differences	Differencesraise anyadditionalsafety issues?
Product Specifications
InstrumentPlatform	Tosoh AIA Analyzer 2000	Tosoh AIA Analyzer 2000	Same	N/A
DetectionMethod	Fluorescence	Fluorescence	Same	N/A
AssayPrinciple	Immunoenzymometric Assay	Immunoenzymometric Assay	Same	N/A
TestPrinciple	On-step sandwich assay	On-step sandwich assay	Same	N/A
SpecimenTypes	Human EDTA plasma	Human EDTA plasma	Same	N/A
SpecimenCollectionMethodology	Routine Phlebotomy Techniques	Routine Phlebotomy Techniques	Same	N/A
Analyte	Human B-type Natriuretic Peptide(BNP)	Human B-type Natriuretic Peptide(BNP)	Same	N/A
MeasuringRange	4.0 – 2000 pg/mL	4.0 – 2000 pg/mL	Same	N/A
Cut-off	100 pg/mL	100 pg/mL	Same	N/A
Manual &AutomatedDilution	Manual dilution study had arecovery value of 102% for 1:5and 100% for 1:10 dilution.On-board (automated) dilutionstudy had a recovery value of 95%for 1:5 and 95% for 1:10 dilution.	Not previously cleared	Different	No

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11. RISK MANAGEMENT

The Risk Management was performed in compliance with EN ISO 14971:2012 Medical Devices - Application of Risk Management to Medical Devices. The Failure Modes Effects Analysis (FMEA) methodology was used to systematically identify, estimate, evaluate, control and report risks to ensure the development and maintenance of a safe and effective product that meets its intended use.

12. VERIFICATION AND VALIDATION SUMMARY

All verification and validation activities were performed in accordance with relevant standards, established plans, protocols, and Design Control procedures, Testing verified all acceptance criteria were met. Verification of the changes did not raise any new items of safety and effectiveness.

13. SUMMARY OF PERFORMANCE DATA

Refer to Table 3 - Comparison Table of Technological Characteristics: Subject Device to Predicate Device for the summary results of the verification and validation testing.

14. SUBSTANTIAL EQUIVALENCE STATEMENT

All verification and validation testing conducted with the ST AIA-PACK BNP assay demonstrate that the modified device met the predetermined acceptance criteria, supporting the determination of substantial equivalence to the predicate device.

The modifications to the predicate device to provide a manual and automated dilution claim do not substantially change the device. The validation and verification data demonstrate that the performance of the ST AIA-PACK BNP assay to detect BNP is substantially equivalent to the predicate device.

15. CONCLUSION

Tosoh Bioscience, Inc. believes that the ST AIA-PACK BNP, is substantially equivalent in intended use and technological characteristics to the previously cleared ST AIA-PACK BNP (K192083). The ST AIA-PACK BNP, therefore, meets the Federal Food, Drug and Cosmetic Act criteria for 510(k) clearance of this device.

Regulation Number and Section

§ 862.1117 B-type natriuretic peptide test system.

(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”