2 x 1 mL ST AIA-PACK PROG II Calibrator (1) 0 ng/mL Protein matrix containing no detectable concentration of PROG with sodium azide as a preservative (Liquid).
2 x 1 mL ST AIA-PACK PROG II Calibrator (2) 0.5 ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (3) 1.5 ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (4) 5.0 ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (5) 15 ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (6) 45 ng/mL (approx.)
Human serum containing the assigned concentration of progesterone (described on each vial) with sodium azide as a preservative.

The ST AIA-PACK PROG II Calibrator Set is designed specifically for use on the Tosoh AIA System 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 PROG II Calibrator Set is designed for use with ST AIA-PACK PROG II and ST AIA-PACK PROG II Sample Diluting Solution.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the ST AIA-PACK PROG II Calibrator Set, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion (Stability)	Requirement	Reported Performance (ST AIA-PACK PROG II Calibrator Set)
Real-Time Stability	Recovery within 100 ± 10%	Met (supports 6-month shelf life)
Real-Time Stability	Reproducibility (CV%) ≤ 10%	Met (supports 6-month shelf life)
Open Vial Stability	Recovery within 100 ± 10%	Met (supports 1-day reconstituted claim)
Open Vial Stability	Reproducibility (CV%) ≤ 10%	Met (supports 1-day reconstituted claim)
Value Assignment Precision	Precision (CV%) ≤ 10%	Met (all calibrator levels were ≤ 5.8%)

Acceptance Criterion (Value Assignment - Precision)	Test for Calibrator levels (Mean CV%)
CV% ≤ 10% (for 5 replicates)	Cal (2): 5.8%
	Cal (3): 3.5%
	Cal (4): 1.9%
	Cal (5): 2.2%
	Cal (6): 1.8%

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

Sample Size:
- For stability studies (Real-Time and Open Vial): The exact number of individual samples tested isn't explicitly stated, but it mentions "AIA-PACK Progesterone Calibrator Set were stored..." and "Samples were reconstituted..." implying multiple sets or vials.
- For value assignment: 5 replicates for each of the 5 calibrator levels (Cal 2-6) were analyzed.
Data Provenance: The document does not specify the country of origin for the data. The data appears to be prospective as it involves the testing of the newly formulated ST AIA-PACK PROG II Calibrator Set under defined conditions (stability studies, value assignment protocol).

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

The document does not mention the use of experts to establish the ground truth for the test set.
The ground truth for the calibrators is established through a chain of traceability:
- Primary reference material uses USP (United States Pharmacopeia) Standard as calibrator.
- Secondary reference material is assigned against the primary reference material.
- Product calibrators are assigned against the secondary reference material.
The "experts" are the "Tosoh AIA-2000" instruments and the established calibration process rooted in the USP Standard.

4. Adjudication Method for the Test Set

No human adjudication method (e.g., 2+1, 3+1) is mentioned or implied for the test set.
The determination of acceptance is based on quantitative measurements against predefined criteria (recovery % and CV%).

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 vs Without AI Assistance

No, an MRMC comparative effectiveness study was not done.
This device is a calibrator set for an in vitro diagnostic assay, not an AI-powered diagnostic tool that assists human readers. Therefore, this type of study is not applicable.

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

This device is a calibrator set, not an algorithm. Therefore, "standalone algorithm performance" is not applicable in the context of AI.
However, the performance of the calibrator itself is tested in a "standalone" fashion in that its stability and assigned values are determined within the analytical system (Tosoh AIA-2000 with the specified assay) without human interpretation being part of the performance measurement itself. The results are quantitative and objective based on instrument readings.

7. The Type of Ground Truth Used

The ground truth for the calibrator values is established based on a reference standard and hierarchical assignment process:
- The highest level of truth is the USP (United States Pharmacopeia) Standard for progesterone.
- Subsequent calibrator lots and levels are then assigned values through a traceable process against this primary reference and internal secondary standards.

8. The Sample Size for the Training Set

This document describes a calibrator set and its performance validation, not a machine learning or AI model. Therefore, there is no training set in the context of AI. The "training" for this device would be analogous to the manufacturing and value assignment process itself, ensuring each lot meets specifications.

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

N/A, as there is no training set in the AI context. The ground truth for the calibrator's assigned values is established through traceability to the USP Standard as described in point 7.

Summary

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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of three human profiles facing right, arranged in a stacked formation. The profiles are connected and form a single, abstract shape. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the image.

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

December 3, 2014

TOSOH BIOSCIENCE, INC. c/o ROBERT WICK REGULATORY SPECIALIST 6000 SHORELINE COURT, STE. 101 SOUTH SAN FRANCISCO CA 94080

Re: K143144

Trade/Device Name: ST AIA-PACK PROG II Calibrator Set Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: October 31, 2014 Received: November 3, 2014

Dear Mr. Robert 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. Wick

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/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 Industry and Consumer Education 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.

Sincerely yours,

Katherine Serrano -S

For : 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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Indications for Use

510(k) Number (if known) K143144

Device Name ST AIA-PACK PROG II Calibrator Set

Indications for Use (Describe) The ST AIA-PACK PROG II Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK PROG II assay.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) Summary (k)143144 ST AIA-PACK PROG II Calibrator Set

SAFETY AND EFFECTIVENESS AS REQUIRED BY 1. 21 CFR 807.92

This Summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirement 21 CFR 807.92.

SUBMITTER NAME AND ADDRESS 2.

Date of Summary Preparation: Submitter:

November 20, 2014 Tosoh Bioscience, Inc 3600 Gantz Road Grove City, OH 43123

Contact Person:

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

510K NUMBER, DEVICE PROPRIETARY NAME, 3. COMMON NAME, PURPOSE FOR THE SUBMISSION, REGULATORY CLASSIFICATION, PANEL, PRODUCT CODE, AND 21 CFR NUMBER.

510k No.:	K143144
Device Proprietary Name:	ST AIA-PACK PROG II Calibrator Set
Purpose of Submission:	Labeling Change
Regulatory Classification	Calibrator, Secondary
Common Name:	Progesterone Test System
Classification:	Class II
Product Code:	JIT
Panel:	Clinical Chemistry
21 CFR Number:	21 CFR 862.1150

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PREDICATE DEVICE PROPRIETARY NAMES AND 4. 510 (K) NUMBERS

Predicate Device Number: Predicate: Manufacturer:

K933269 ST AIA-PACK PROG (Calibrator Set) Tosoh Bioscience, Inc. (previously known as Tosoh Medics, Inc.)

INTENDED USE 5.

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

DEVICE DESCRIPTION 6.

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 PROG II Calibrator (1)	0	ng/mL
Protein matrix containing no detectable concentration of PROG with sodiumazide as a preservative (Liquid).
2 x 1 mL ST AIA-PACK PROG II Calibrator (2)	0.5	ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (3)	1.5	ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (4)	5.0	ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (5)	15	ng/mL (approx.)
ST AIA-PACK PROG II Calibrator (6)	45	ng/mL (approx.)

Human serum containing the assigned concentration of progesterone (described on each vial) with sodium azide as a preservative.

ST AIA-PACK PROG II Calibrator Set

P/N # 025339

The ST AIA-PACK PROG II Calibrator Set is designed for use with ST AIA-PACK PROG II and ST AIA-PACK PROG II Sample Diluting Solution.

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Tosoh Bioscience, Inc.

PREDICATE COMPARISON TABLE 7.

Substantial Equivalence:

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

Similarities

Characteristic	Predicate
	Tosoh AIA-PACK PROG IICalibrator Set	Tosoh AIA-PACK PROGCalibrator Set (K933269)
Intended Use	The ST AIA-PACK PROG IICalibrator Set is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKPROG II assay.	The AIA-PACK PROG CalibratorSet is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKPROG Assays.
Indications for Use (sameas Intended Use)	The ST AIA-PACK PROG IICalibrator Set is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKPROG II assay.	The AIA-PACK PROG CalibratorSet is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKPROG Assays.
Analyte	Progesterone	Same
Format	LiquidSix bottles, one foreach of the six calibratorlevels.	Same
Matrix	Serum and heparinized plasma	Same
Storage	Store upright and refrigerate at 2 to8°C.	Same
Stability(unopened vial)	Stable until the expiration datestated on the label when stored at 2- 8°C.	Same
Calibration Stability	Stable up to 90 days	Same
Stability(opened vial)	24 hours (1 day)	Same

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Characteristic	Tosoh AIA-PACK PROG IICalibrator Set	PredicateTosoh AIA-PACK PROGCalibrator Set (K951848)
Shelf-life	6 months when stored unopenedand refrigerated at 2-8°C	12 months when stored unopenedand refrigerated at 2-8°C
Traceability	The calibrators for use with the STAIA-PACK PROG II were referred toUSP (United States Pharmacopeia)Standard.	The calibrators in this set areprepared gravimetrically and arecompared to internal referencestandards.
Levels	Six(0, 0.5, 1.5, 5.0, 15, 45ng/mL approximately)	Six(0, 0.5, 1.5, 5.0, 20, 60ng/mL approximately)
Analyzer	Tosoh AIA-2000	Tosoh AIA-1200

Differences

SUMMARY OF STABILITY STUDIES 8.

Summary of Stability Studies

Real Time Testing

AIA-PACK Progesterone Calibrator Set were stored at refrigerated temperatures and assayed at 1, 2, 3, 4 and 6 months after the day of the first assay.

The acceptance criteria for recovery was within 100 +/- 10%.

The criterion for reproducibility (CV %) was </= 10%.

Current Real Time Studies support a 6 month Shelf life at 2-8°C.

Open Vial Stability

Open vial stability of the AIA-PACK Progesterone Calibrator Set was assessed by reconstituting the material according to the package insert. Samples were reconstituted and stored at refrigerated temperatures for 2 days and tested for progesterone.

The criterion for recovery was within 100 +/-10%.

The criterion for reproducibility (CV %) was </= 10%.

Current open vial studies support a reconstituted claim of 1 day when stored at 2-8°C.

SUMMARY OF VALUE ASSIGNMENT 9.

The ST AIA-PACK PROG II Calibrator Set contains assigned concentrations of progesterone. The assigned value is determined on a lot-by-lot basis and is designed to provide an assay calibration range of 0.1 to 40 ng/mL of progesterone. The calibrators for use with the ST AIA-PACK PROG II were referred to through the USP (United States Pharmacopeia) Standard.

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The primary reference material was using the Tosoh AIA-2000 with the USP Reference as calibrator. The values were verified by comparing measured results with those obtained with the previous lot for control materials.

The value of the secondary reference material was assigned using the Tosoh AIA-2000 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-2000 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.

The value assignment was determined by analyzing 5 replicates of the test calibrator on two Tosoh AIA-2000 instruments and the mean, SD and CV calculated for each lot before release to the user. The acceptance criteria states the precision measured by the CV should be within 10%.

Progesterone(Calibrator Levels)	N	ReferenceValue(ng/mL)	Mean(ng/mL)	CV %
Cal (2)	5	0.5	.447	5.8
Cal (3)	5	1.5	1.34	3.5
Cal (4)	5	5.0	5.16	1.9
Cal (5)	5	15	15.1	2.2
Cal (6)	5	45	46.3	1.8

TRACEABILITY 10.

ANALYTE	SUPPLIER	PRODUCTNUMBER	ORIGIN	SOURCE
Progesterone	Sigma	I1J239	Steroid strippedand lipidstripped humanserum	ChemicalCompound

11. CONCLUSION

Testing results indicate that the proposed device is substantially equivalent to the predicate device.

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.