2 x 1 mL ST AIA-PACK C-Peptide II Calibrator (1) 0 ng/mL Protein matrix containing no detectable concentration of C-peptide with sodium azide as a preservative (Liquid).
2 x 1 mL ST AIA-PACK C-Peptide II Calibrator (2) 0.5 ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (3) 2 ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (4) 6 ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (5) 15 ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (6) 33 ng/mL (approx.)
Protein matrix containing the assigned concentration of C-peptide (described on each vial) (Lyophilized).
The ST AIA-PACK C-Peptide II Calibrator Set is designed specifically for use on the Tosoh AIA Svstem Analyzers which have been previously cleared as a family of instruments under K971103. Only materials obtained from Tosoh should be used. Materials obtained elsewhere should not be substituted since assay performance is characterized based strictly on Tosoh materials.
The ST AIA-PACK C-Peptide II Calibrator Set is designed for use with ST AIA-PACK C-Peptide II, ST AIA-PACK C-Peptide Sample Diluting Solution, AIA-PACK C-Peptide Control Set.

AI/ML Overview

Here's an analysis of the provided text regarding the ST AIA-PACK C-Peptide II Calibrator Set, focusing on acceptance criteria and supporting studies.

Based on the provided 510(k) Summary, this document primarily discusses the substantial equivalence of a calibrator set, not a diagnostic device with performance metrics like accuracy, sensitivity, or specificity in relation to a disease state. Therefore, many standard questions about AI device performance (like MRMC studies, standalone performance, training set details, expert qualifications for ground truth, etc.) are not applicable to this type of submission.

The "acceptance criteria" and "device performance" in this context refer to the stability and reproducibility of the calibrator set itself, not its diagnostic accuracy in patients.

1. Table of Acceptance Criteria and Reported Device Performance

This calibrator set's "performance" is assessed based on its stability and reproducibility rather than diagnostic accuracy.

Performance Metric	Acceptance Criteria	Reported Device Performance
Shelf-Life Stability	Recovery: 100 ± 10%	Recovery: Within 100 ± 10%
(Unopened vial, 2-8°C)	Reproducibility (CV%): ≤ 10%	Reproducibility (CV%): ≤ 10% at 13 months
In-Use Stability	Recovery: 100 ± 10%	Recovery: Met criteria for 2 days at refrigerator temperature
(Opened/Reconstituted vial,	Reproducibility (CV%): ≤ 10%	Reproducibility (CV%): Met criteria for 2 days at refrigerator temperature
2-8°C)

The conclusions from these studies allowed the manufacturer to set:

Shelf-life: 12 months at 2-8°C (based on 13-month data meeting criteria)
In-use stability: 1 day (24 hours) after reconstitution at 2-8°C (based on 2-day data meeting criteria)

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

Test Set (Stability Studies) Sample Size:
- Shelf-Life Stability: Three different lots of calibrator set. Each specimen (presumably from each lot at each time point) was assayed in 5 replicates. This refers to the number of lots tested, not patient samples.
- In-Use Stability: One lot of calibrator material. Three sets of calibrator material were opened and reconstituted. Urine, serum, and EDTA plasma specimens were chosen for this study. Each specimen was assayed in 5 replicates. The number of patient specimens (urine, serum, EDTA plasma) is not explicitly stated, only that such specimens were chosen.
Data Provenance: Not specified, but generally for such in-vitro diagnostic (IVD) calibrators, the studies are conducted internally by the manufacturer. The text does not mention country of origin or whether the studies were external. The nature of the study (stability of a reagent) suggests it's prospective testing in a lab setting.

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

Not applicable. This device is a calibrator set, not a diagnostic device requiring expert interpretation of results to establish a "ground truth" for clinical performance. Its "ground truth" (assigned C-peptide concentrations) is established through an analytical traceability chain to international standards (WHO 1ª IRP 84/510).

4. Adjudication Method for the Test Set

Not applicable. There is no "adjudication" in the context of stability and reproducibility testing for a calibrator. The performance is assessed against predefined recovery and CV% criteria.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This is not an AI-powered diagnostic device, and thus MRMC studies are not relevant.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

No. This is a calibrator product for an in-vitro diagnostic assay, not an algorithm.

7. The Type of Ground Truth Used

Analytical Traceability to International Standard complemented by Internal Referencing: The assigned value of C-peptide in the primary reference material (which is then used to assign values to the calibrators) was based on WHO 1ª IRP 84/510. This is an internationally recognized reference preparation for C-peptide. Subsequent secondary reference materials and product calibrators are assigned values using Tosoh AIA instruments, comparing measured results with those obtained with previous lots or a primary reference.

8. The Sample Size for the Training Set

Not applicable. This is a calibrator set, not an AI or machine learning model that requires a training set. The values are assigned based on analytical methods and traceability, not learned from data.

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

Not applicable, as there is no "training set." The "ground truth" for the calibrator values is established through the analytical traceability described in point 7.

Summary

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Tosoh Bioscience, Inc.

K140648

510(k) Summary

ST AIA-PACK C-Peptide II Calibrator Set

Date: Submitter:

March 11, 2014 Tosoh Bioscience, Inc 3600 Gantz Road Grove City, OH 43123

Contact Person:

Robert L. Wick Regulatory Specialist 6000 Shoreline Ct., Ste. 101 South San Francisco, CA 94080 Phone: 650-636-8117 650-636-8121 Fax: Email: Robert.Wick@Tosoh.com

Device Name: Classification:

ST AIA-PACK C-Peptide II Calibrator Set Class II JIT Clinical Chemistry 21 CFR 862.1150

Predicate Device:

K951848 Tosoh Bioscience, Inc. (previously known as Tosoh Medics, Inc.) ST AIA-PACK C-Peptide (Calibrator Set)

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510(k) Summary

ST AIA-PACK C-Peptide II Calibrator Set

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Device Description:

2 x 1 mL

ST AIA-PACK C-Peptide II Calibrator (1) 0 ng/mL Protein matrix containing no detectable concentration of C-peptide with sodium azide as a preservative (Liquid).

2 x 1 mL

ST AIA-PACK C-Peptide II Calibrator (2)	0.5	ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (3)	2	ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (4)	ି	ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (5)	15	ng/mL (approx.)
ST AIA-PACK C-Peptide II Calibrator (6)	33	ng/mL (approx.)
Protein matrix containing the assigned concentration of C-peptide (described on
each vial) (Lyophilized).

ST AIA-PACK C-Peptide II Calibrator Set

P/N # 025383

The ST AIA-PACK C-Peptide II Calibrator Set is designed specifically for use on the Tosoh AIA Svstem Analyzers which have been previously cleared as a family of instruments under K971103. Only materials obtained from Tosoh should be used. Materials obtained elsewhere should not be substituted since assay performance is characterized based strictly on Tosoh materials.

The ST AIA-PACK C-Peptide II Calibrator Set is designed for use with ST AIA-PACK C-Peptide II, ST AIA-PACK C-Peptide Sample Diluting Solution, AIA-PACK C-Peptide Control Set.

Device Intended Use:

The ST AIA-PACK C-Peptide II Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK C-Peptide II assay.

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Tosoh Bioscience, Inc.

Substantial Equivalence:

Comparison between the Tosoh ST AIA-PACK C-Peptide II Calibrator Set and the Tosoh ST AIA-PACK C-Peptide Calibrator Set

Similarities

Characteristic	Tosoh AIA-PACK C-Peptide IICalibrator Set	PredicateTosoh AIA-PACK C-PeptideCalibrator Set (K951848)
Intended Use	The ST AIA-PACK C-Peptide IICalibrator Set is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACK C-Peptide II assay.	The AIA-PACK C-Peptide CalibratorSet is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACK C-Peptide Assays.
Analyte	C-Peptide	C-Peptide
Analyzer	Tosoh AIA Systems	Tosoh AIA Systems
Levels	Six(0, 0.5, 2, 6, 15, 33ng/mL approximately)	Six(0, 0.5, 2.0, 6.0, 15.0, 30ng/mL approximately)
Format	LyophilizedSix bottles, one foreach of the six calibratorlevels	LyophilizedSix bottles, one foreach of the six calibratorlevels
Storage	Store upright and refrigerate at2 to 8°C	Store upright and refrigerate at2 to 8°C
Stability(unopened vial)	Stable until the expiration datestated on the label when stored at2 - 8°C	Stable until the expiration datestated on the label when stored at2 -8°C
Shelf-life	12 months when stored unopenedand refrigerated at 2-8°C	12 months when stored unopenedand refrigerated at 2-8°C
Calibration Stability	Stable up to 90 days	Stable up to 90 days

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		Predicate
Characteristic	Tosoh AIA-PACK C-Peptide IICalibrator Set	Tosoh AIA-PACK C-PeptideCalibrator Set (K951848)
Base	Contains sucrose	Does not contain sucrose
Stability(opened vial)	Vial is stable at 2 - 8°C for1 day after initial use	Vial is stable at 2 - 8°C for7 days after initial use

Differences

Summary of Traceability

The ST AIA-PACK C-Peptide II Calibrator Set contains assigned concentrations of Cpeptide. The assigned value is determined on a lot-by-lot basis and is designed to provide an assay calibration range of 0.02 to 30 ng/mL of C-peptide. The calibrators in this set have been standardized against WHO 1ª IRP 84/510.

Summary of Stability Studies

Three different lots of ST AIA-PACK C-Peptide II Calibrator Set were used as samples for the shelf life stability study. Each specimen was assaved in 5 replicates and the mean and CV % were calculated. The study was initiated within one month from manufacture the evaluated reagents, then assayed at 3, 6, 9, 12 and 13 months after the day of the first assay. The criterion for recovery was within 100 +/- 10%. The criterion for reproducibility (CV %) was </= 10%. The recovery was within 100 +/- 10% and the reproducibility (CV %) was </=10% at 13 months, the shelf life of the ST AIA-PACK C-Peptide II Calibrator Set was set at 12 months at 2-8° C from the date of manufacturing.

The in use stability study for the ST AIA-PACK C-Peptide II Calibrator Set was conducted at one site using one AIA-2000 analyzer and a single lot of calibrator. Three sets of calibrator material were opened and reconstituted at day 0, day 1 and day 2 before the measurement. The reconstituted calibrator vials were sealed and refrigerated for 1 day and 2 days. Urine, serum and EDTA plasma specimens were chosen for this study. Specimen aliquots were stored at less than - 70° C. Each specimen was assayed in 5 replicates. The criterion for recovery was 100 +/- 10%. The criterion for reproducibility (% CV) was </= 10%. Since the recovery and the reproducibility meet the acceptance criteria for 2 days at refrigerator temperature, the in use stability of the ST AIA-PACK C-Peptide II Calibrator Set after reconstitution, was set as 1 day (24 hours).

When stored unopened and refrigerated at 2-8 °C, the Calibrator Set is stable until the expiration date on the label. The calibrators should be used within 1 day of opening or reconstituting, provided the vials are kept tightly sealed and refrigerated at 2-8 °C.

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Summary of Value Assignment

The primary reference material was prepared by diluting the C-peptide with calibrator base and its value of C-peptide as reference material was assigned based on C-Peptide of Human Insulin, International Reference Reagent using ST AIA-PACK C-Peptide II. The value of the secondary reference material was assigned using the AIA instruments with the primary reference material as calibrator. The value was verified by comparing measured results with those obtained with the previous lot for patient samples. The values of the product calibrator were assigned using the Tosoh AIA instruments with the secondary reference material as calibrator. The values were verified by comparing measured results with those obtained with the previous lot for control materials.

Conclusion:

The Tosoh Bioscience, Inc. ST AIA-PACK C-Peptide II Calibrator Set is substantially equivalent to the Tosoh Bioscience, Inc. ST AIA-PACK C-Peptide Calibrator Set K951848 for In Vitro Diagnostic Use Only for the calibration of the ST AJA-PACK C-Peptide II assay.

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Image /page/5/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" in bold, black font. The text is horizontally oriented and centered. To the left of the text is a logo with a stylized design.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 April 10, 2014

TOSOH BIOSCIENCE, INC. C/O ROBERT L. WICK 6000 SHORELINE COURT SUITE 101 SOUTH SAN FRANCISCO CA 94080

Re: K140648

Trade/Device Name: ST AIA-PACK C-Peptide II Calibrator Set Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: March 11, 2014 Received: March 13, 2014

Dear Mr. Wick:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Mr. Robert L. Wick

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803). please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers. International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincercly yours,

Courtney H. Lias -S

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

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known) K140648

Device Name

�

ST AIA-PACK C-Peptide II CALIBRATOR SET

Indications for Use (Describe)

The ST AIA-PACK C-Peptide II Calibrator Set is intended for In Vitro Diagnostic Use Only for the CT AIA-PACK C-Peptide II assay.

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

[ ] Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Yung W. Chan -S

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Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.