(29 days)
The ST AIA-PACK hsE2 Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK hsE2 assay.
- 2 x 1 mL ST AIA-PACK hsE2 Calibrator (1) 0 pg/mL Human serum containing no detectable concentration of estradiol with sodium azide as a preservative.
- 2 x 1 mL ST AIA-PACK hsE2 Calibrator (2) 25 pg/mL (approx.)
- ST AIA-PACK hsE2 Calibrator (3) 50 pg/mL (approx.)
- ST AIA-PACK hsE2 Calibrator (4) 100 pg/mL (approx.)
- ST AIA-PACK hsE2 Calibrator (5) 500 pg/mL (approx.)
- ST AIA-PACK hsE2 Calibrator (6) 1,100 pg/mL (approx.)
Human serum containing the assigned concentration of estradiol (described on each vial) with sodium azide as a preservative.
ST AIA-PACK hsE2 Calibrator Set P/N # 025325
The ST AIA-PACK hsE2 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 hsE2 Calibrator Set is designed for use with ST AIA-PACK hsE2 and ST AIA-PACK hsE2 Sample Diluting Solution.
The provided document describes the ST AIA-PACK hsE2 Calibrator Set and its performance.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance:
The document details two types of stability studies, each with its own acceptance criteria and results for recovery and reproducibility (CV%).
| Test Type | Acceptance Criteria (Recovery) | Reported Device Performance (Recovery) | Acceptance Criteria (Reproducibility - CV%) | Reported Device Performance (Reproducibility - CV%) |
|---|---|---|---|---|
| Real Time Testing | 100% +/- 10% | Not explicitly stated; "Current Real Time Studies support a 12 month Shelf life at 2-8°C" implies criteria were met | <= 10% | Not explicitly stated; "Current Real Time Studies support a 12 month Shelf life at 2-8°C" implies criteria were met |
| Open Vial Stability | 100% +/- 10% | Not explicitly stated; "Current open vial studies support a reconstituted claim of 1 day when stored at 2-8°C" implies criteria were met | <= 10% | Not explicitly stated; "Current open vial studies support a reconstituted claim of 1 day when stored at 2-8°C" implies criteria were met |
Regarding Value Assignment, separate acceptance criteria are also provided:
| Test Type | Calibrator Levels | N | Acceptance Criteria (Grand Mean CV%) | Reported Device Performance (Grand Mean CV%) |
|---|---|---|---|---|
| Value Assignment (referencing 200 Standard) | Not applicable | Not applicable | < 10% | Not explicitly stated; "The grand mean value is the assigned value if this criteria is met" implies criteria were met |
| Value Assignment (ST-AIA PACK hsE2 Calibrator) | Cal (2) | 5 | < 10% | 6.3 % |
| Cal (3) | 5 | < 10% | 2.5 % | |
| Cal (4) | 5 | < 10% | 1.9 % | |
| Cal (5) | 5 | < 10% | 2.1 % | |
| Cal (6) | 5 | < 10% | 1.5 % |
2. Sample size used for the test set and the data provenance:
- Real Time Testing: The calibrator sets were tested at 6, 12, and 13 months. The exact number of calibrator sets (samples) used for each time point is not specified, but it refers to "ST AIA-PACK hsE2 Calibrator Set" in plural.
- Open Vial Stability: Samples were reconstituted and stored for 0, 7, and 8 days. The exact number of samples tested for each time point is not specified.
- Value Assignment (200 Standard): 5 replicates on each of 2 analyzers and 3 lots of reagent were used. This means 5 * 2 * 3 = 30 measurements for the 200 Standard assignment.
- Value Assignment (ST-AIA PACK hsE2 Calibrator): 5 replicates of each calibrator level on 2 analyzers and 3 lots of reagent were used. For each calibrator level shown in the table (Cal 2-6), this means 5 * 2 * 3 = 30 measurements.
- Data Provenance: The document does not specify the country of origin but implies data was generated internally by Tosoh Bioscience, Inc. The studies appear to be prospective as they involve specific testing protocols to assess stability and value assignment.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This device is a calibrator set for an in vitro diagnostic assay. The "ground truth" here is the assigned concentration of estradiol, which is established through a metrological traceability chain rather than expert consensus on medical images or diagnoses.
- The calibrators are referenced to the IRMM (Institute for Reference Materials and Measurements) CRM577 (Traceability section).
- The 17β-estradiol chemical compound used is from SIGMA, derived from a plant source.
- The "experts" in this context are the analytical chemists and laboratory personnel conducting the value assignment studies, and ultimately, the established reference materials and their certification bodies (like IRMM). The document does not specify the number or qualifications of the personnel performing these lab tests.
4. Adjudication method for the test set:
Not applicable in the traditional sense of clinical interpretations. The "adjudication" for value assignment is based on meeting the predefined statistical acceptance criteria (<10% CV for grand mean).
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:
This is not applicable. The device is an in vitro diagnostic calibrator set, not an AI-assisted diagnostic tool that involves human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
This is not applicable. The device is a calibrator set, not an algorithm. Its performance is evaluated through analytical stability and accuracy against reference materials.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The ground truth for the assigned values of estradiol in the calibrator set is established through:
- Reference Materials: Specifically, the IRMM CRM577.
- Chemical Purity and Dilution: 17β-estradiol purchased from SIGMA and diluted in a base matrix.
- Analytical Measurement: Rigorous analytical testing using multiple replicates, analyzers, and reagent lots, with statistical criteria to assign values.
8. The sample size for the training set:
This is not applicable. As a calibrator set, it does not involve machine learning or a "training set" in the conventional sense of AI development. Its purpose is to calibrate a measurement system.
9. How the ground truth for the training set was established:
This is not applicable as there is no training set.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
February 17, 2016
TOSOH BIOSCIENCES, INC. ROBERT L. WICK REGULATORY SPECIALIST 6000 SHORELINE COURT, STE. 101 SOUTH SAN FRANCISCO, CA, 94080, US
Re: K160113
Trade/Device Name: ST AIA-PACK hsE2 Calibrator Set Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator, Secondary Regulatory Class: Class II Product Code: JIT Dated: January 18, 2016 Received: January 19, 2016
Dear 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
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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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (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/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) K160113
Device Name ST AIA-PACK hsE2 Calibrator Set
Indications for Use (Describe)
The ST AIA-PACK hsE2 Calibrator Set is intended for In Vitro Diagnostic Use Only for the calbration of the ST AIA-PACK hsE2 assay.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary ST AIA-PACK hsE2 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.
2. SUBMITTER NAME AND ADDRESS
Date of Summary Preparation: Submitter:
January 18, 2016 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.: Device Proprietary Name: Purpose of Submission: Regulatory Classification Common Name: Classification: Product Code: Panel: 21 CFR Number:
ST AIA-PACK hsE2 Calibrator Set New Product Calibrator, Secondary Estradiol Test System Class II JIT Clinical Chemistry 21 CFR 862.1260
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PREDICATE DEVICE PROPRIETARY NAMES AND 4. 510 (K) NUMBERS
Predicate Device Number: Predicate: Manufacturer:
K932084 ST AIA-PACK E2 (Calibrator Set) Tosoh Bioscience, Inc. (previously known as Tosoh Medics, Inc.)
INTENDED USE 5.
The ST AIA-PACK hsE2 Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK hsE2 assay.
6. DEVICE DESCRIPTION
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 hsE2 Calibrator (1) 0 pg/mL
Human serum containing no detectable concentration of estradiol with sodium azide as a preservative.
| 2 x 1 mL ST AIA-PACK hsE2 Calibrator (2) | 25 pg/mL (approx.) |
|---|---|
| ST AIA-PACK hsE2 Calibrator (3) | 50 pg/mL (approx.) |
| ST AIA-PACK hsE2 Calibrator (4) | 100 pg/mL (approx.) |
| ST AIA-PACK hsE2 Calibrator (5) | 500 pg/mL (approx.) |
| ST AIA-PACK hsE2 Calibrator (6) | 1,100 pg/mL (approx.) |
Human serum containing the assigned concentration of estradiol (described on each vial) with sodium azide as a preservative.
ST AIA-PACK hsE2 Calibrator Set
P/N # 025325
The ST AIA-PACK hsE2 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 hsE2 Calibrator Set is designed for use with ST AIA-PACK hsE2 and ST AIA-PACK hsE2 Sample Diluting Solution.
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Tosoh Bioscience, Inc.
PREDICATE COMPARISON TABLE 7.
Substantial Equivalence:
Comparison between the Tosoh ST AIA-PACK hsE2 Calibrator Set and the Tosoh ST AIA-PACK E2 Calibrator Set
Similarities
| Characteristic | Tosoh ST AIA-PACK hsE2Calibrator Set | Predicate | Tosoh AIA-PACK E2 CalibratorSet (K932084) |
|---|---|---|---|
| Intended Use | The ST AIA-PACK hsE2 CalibratorSet is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKhsE2 assay. | The AIA-PACK E2 Calibrator Set isintended for In Vitro Diagnostic UseOnly for the calibration of the STAIA-PACK E2 Assays. | |
| Indications for Use (sameas Intended Use) | The ST AIA-PACK hsE2 CalibratorSet is intended for In VitroDiagnostic Use Only for thecalibration of the ST AIA-PACKhsE2 assay. | The AIA-PACK E2 Calibrator Set isintended for In Vitro Diagnostic UseOnly for the calibration of the STAIA-PACK E2 Assay. | |
| Analyte | Estradiol | 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 | |
| Shelf-life | 12 months when stored unopenedand refrigerated at 2-8°C | 12 months when stored unopenedand refrigerated at 2-8°C | |
| Base | Human Serum | Human serum |
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| Characteristic | Predicate | |
|---|---|---|
| Tosoh AIA-PACK hsE2 Calibrator Set | Tosoh AIA-PACK E2 Calibrator Set (K932084) | |
| Traceability | IRMM (Institute for ReferenceMaterials and Measurements)CRM577 | Internal reference standards. |
| Levels | Six(Approximately 0, 25, 50, 100, 500and 1100 pg/mL - lot specific) | Six(Approximately 0, 40, 100, 500,1000 and 3250 – lot specific) |
Differences
8. SUMMARY OF STABILITY STUDIES
Summary of Stability Studies
Real Time Testing
ST AIA-PACK hsE2 Calibrator Set were stored at refrigerated temperatures and assayed at 6, 12 and 13 months after the day of the first assay.
The acceptance criteria for recovery was 100% +/- 10%.
The criterion for reproducibility (CV %) was </= 10%.
Current Real Time Studies support a 12 month Shelf life at 2-8°C.
Open Vial Stability
Open vial stability of the ST AIA-PACK hsE2 Calibrator Set was assessed by reconstituting the material according to the package insert. Samples were reconstituted and stored at refrigerated temperatures for 0, 7 and 8 days and tested for estradiol.
The criterion for recovery was 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 hsE2 Calibrator Set contains assigned concentrations of estradiol. The assigned value is determined on a lot-by-lot basis and is designed to provide an assay calibration ranqe of 7 to 1,000 pg/mL of estradiol. The calibrators in this set are referenced to the IRMM (Institute for Reference Materials and Measurements) CRM577.
The Tosoh AIA-PACK hsE2 Calibrator, 1st Standard Series of (2) to (6) was prepared by diluting the 17β -estradiol (purchased from SIGMA) with the calibrator base matrix free of estradiol. Calibrators (2) through (6) were value assigned according to the dilution ratio. The base matrix was used as the zero (0) calibrator.
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The value of the Tosoh AIA-PACK hs E2 Calibrator 200 Standard was assigned using the primary reference material as calibrator. The mean value of 5 replicates on each of 2 analyzers and 3 lots of reagent was calculated. The grand mean, SD and CV (%) was calculated from the mean values. The acceptance criteria of the grand mean is <10% CV. The grand mean value is the assigned value if this criteria is met.
The value assignment for the Tosoh ST-AIA PACK hsE2 Calibrator was determined by analyzing 5 replicates of the calibrator on 2 analyzers and 3 lots of reagent using the 200 Standard as the calibrator. The mean value from the 5 replicates on each analyzer and each lot was calculated as above. The grand mean, SD and CV (%) was calculated from the mean values. The acceptance criteria of the grand mean is <10% CV. The grand mean value is the assigned value if this criteria is met.
| hsE2(Calibrator Levels) | N | ReferenceValue(pg/mL) | Grand Mean(pg/mL) | CV % |
|---|---|---|---|---|
| Cal (2) | 5 | 25 | 26.8 | 6.3 |
| Cal (3) | 5 | 50 | 52.6 | 2.5 |
| Cal (4) | 5 | 100 | 102 | 1.9 |
| Cal (5) | 5 | 500 | 519 | 2.1 |
| Cal (6) | 5 | 1100 | 1120 | 1.5 |
10. TRACEABILITY
| ANALYTE | SUPPLIER | PRODUCTNUMBER | ORIGIN | SOURCE |
|---|---|---|---|---|
| Estradiol | Sigma | E8875 | Derived from aplant source | ChemicalCompound |
11. CONCLUSION
Testing results indicate that the proposed device is substantially equivalent to the predicate device.
§ 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.