K Number
K142021
Device Name
Elecsys Estradiol III CalSet
Manufacturer
Date Cleared
2014-08-12

(18 days)

Product Code
Regulation Number
862.1150
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
Estradiol III CalSet is used for calibrating the quantitative Elecsys Estradiol III assay on the Elecsys and cobas e immunoassay analyzers.
Device Description
The Elecsys Estradiol III CalSet is a lyophilized product consisting of synthetic Estradiol in a human serum matrix. It has been standardized against ID-GC/MS (isotope dilution gas chromatography mass spectrometry).
More Information

Not Found

No
The device is a calibration set for an immunoassay analyzer and the description focuses on chemical composition, standardization, and performance testing related to calibration accuracy and stability. There is no mention of AI or ML in the intended use, device description, or performance studies.

No.
The device is a calibrator for a diagnostic assay, not a therapeutic agent. It is used to calibrate an Elecsys Estradiol III assay, which is a quantitative test, meaning it measures the amount of Estradiol, contributing to diagnosis, not treatment.

No

This device is a calibrator used to ensure the accuracy of a quantitative assay, rather than directly diagnosing a condition.

No

The device description explicitly states it is a lyophilized product consisting of synthetic Estradiol in a human serum matrix, indicating it is a physical substance, not software.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The intended use explicitly states it is used for "calibrating the quantitative Elecsys Estradiol III assay on the Elecsys and cobas e immunoassay analyzers." This indicates it is a component used in a diagnostic test performed in vitro (outside the body) to measure a substance (Estradiol) in a biological sample (human serum matrix).
  • Device Description: The description mentions it is a "lyophilized product consisting of synthetic Estradiol in a human serum matrix." This further confirms it is a reagent or calibrator used in a laboratory setting for testing biological samples.
  • Calibration: The primary function is calibration, which is a crucial step in ensuring the accuracy and reliability of an in vitro diagnostic assay.
  • Predicate Device: The mention of a "Predicate Device(s)" with a K number (K992981) is a strong indicator that this device is regulated as a medical device, specifically an IVD, by regulatory bodies like the FDA. K numbers are associated with 510(k) submissions for medical devices, including IVDs.

Therefore, based on the intended use, device description, and regulatory context (implied by the predicate device), this device clearly falls under the definition of an In Vitro Diagnostic.

N/A

Intended Use / Indications for Use

Estradiol III CalSet is used for calibrating the quantitative Elecsys Estradiol III assay on the Elecsys and cobas e immunoassay analyzers.

Product codes (comma separated list FDA assigned to the subject device)

JIT

Device Description

The Elecsys Estradiol III CalSet is a lyophilized product consisting of synthetic Estradiol in a human serum matrix. It has been standardized against ID-GC/MS (isotope dilution gas chromatography mass spectrometry).

Mentions image processing

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Mentions AI, DNN, or ML

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Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

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Description of the training set, sample size, data source, and annotation protocol

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Description of the test set, sample size, data source, and annotation protocol

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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Stability Studies:
Three studies were performed to verify the stability claims for the Estradiol III CalSet. Stability studies after reconstitution and an accelerated stability study were completed on the cobas e 411. Additionally, a real-time stability study is planned.

Study 1. Stability at 2-8ºC, -20ºC, in open vial and freeze/thaw cycles (after reconstitution):
The on-test materials were reconstituted and stored closed for 73 hours at 2 to 8°C, and for 32 days at -20°C and for 7 hours at 20 to 25°C in open vial prior to testing. In addition, the stability of the Estradiol III CalSet for two (2) freeze/thaw cycles was evaluated.
The on-test and reference materials were tested in duplicate and the recovery was calculated as percent of the reference value.
The acceptance criterion was 95 to 105 % signal recovery of the reference material value. The reference material was a freshly reconstituted set of Estradiol III CalSet.

Study 2. Accelerated Stability:
The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a freshly reconstituted set of Estradiol III CalSet (stored at 2 to 8℃). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. One Estradiol III CalSet lot was evaluated in duplicate.
The acceptance criterion was 95 to 105 % recovery of the reference material value.

Study 3. Real-Time Stability:
In the on-going real-time stability study, the Estradiol III CalSet test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (19 months).
Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -20°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point).
The acceptance criterion for Estradiol III Calibrator 1 and 2 is recovery of 95-105 % of the reference value.
The testing will continue with this stability protocol until data to support a claim of 18 months are achieved.

CalSet Value Assignment:
Value assignment testing was conducted and passed pre-defined acceptance criteria. The target values for the two levels of the Estradiol III CalSet kit are chosen to obtain the best fit with the Master Calibration Curve, together with the Rodbard curve parameters encoded in the reagent barcode. For each Elecsys Estradiol III CalSet lot manufactured, the calibrators are run in duplicate on at least three (3) Elecsys 2010/cobas e 411 analyzers and at least three (3) cobas e 601/MODULAR ANALYTICS E170 analyzers with all Estradiol III reagent lots available. The assigned value of each calibrator is defined as the mean value obtained over at least six (6) runs on at least three (3) analyzers) of the respective calibrator.
Measurement values for PreciControl Universal (Level 1 & 2), a multi-analyte control recommended for use to monitor accuracy and precision of specified analytes, are read from the calibration curves generated. The pre-defined acceptance criteria for PreciControl Universal have to be met to release the Assigned Values for Estradiol III CalSet.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Acceptance criterion for stability studies: 95 to 105 % signal recovery of the reference material value.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K992981

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

§ 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.

0

510(k) Summary, Elecsys Estradiol III CalSet

Introduction 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 NameProprietary name:Elecsys Estradiol III CalSet
Common name:Estradiol III CalSet
Classification:21 CFR 862.1150, Calibrator, Secondary
Product Code:JIT

For the Estradiol III CalSet, the establishment registration number for Establishment Roche Diagnostics GmbH in Mannheim, Germany, is 9610126 and for Registration Penzberg, Germany, is 9610529. The establishment registration number for Roche Diagnostics United States is 1823260.

Classification FDA has classified the product as a Class II device.

Product NamePanelProduct CodeClassification NameRegulation Citation
Estradiol III
CalSetClinical
ChemistryJITCalibrator,
Secondary21 CFR 862.1150

1

| Device
Description | Elecsys Estradiol III CalSet:
• The Elecsys Estradiol III CalSet is a lyophilized product consisting of
synthetic Estradiol in a human serum matrix. It has been standardized
against ID-GC/MS (isotope dilution gas chromatography mass
spectrometry). |
|------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | Elecsys Estradiol III CalSet:
• Estradiol III CalSet is used for calibrating the quantitative Elecsys
Estradiol III assay on the Elecsys and cobas e immunoassay analyzers. |
| Predicate
device | The Elecsys Estradiol III CalSet is substantially equivalent to the predicate
device, Elecsys Estradiol II CalSet II (K992981). |
| Substantial
Equivalence
Comparison | The following tables compare the Elecsys Estradiol III CalSet with the
predicate device. |

2

Comparison The table below compares Elecsys Estradiol III CalSet with the predicate device, Table Elecsys Estradiol II CalSet II (K992981).

The change in the new product was a shift in the Cal 2 target value.

Table

| Characteristic | Elecsys Estradiol III CalSet
(Candidate) | Elecsys Estradiol II CalSet II
(K992981) |
|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Estradiol III CalSet is used for
calibrating the quantitative
Elecsys Estradiol III assay on
the Elecsys and cobas e
immunoassay analyzers. | Estradiol II CalSet II is used for
calibrating the quantitative
Elecsys Estradiol II assay on the
Elecsys and cobas e
immunoassay analyzers. |
| Analyte | Estradiol (synthetic) | Same |
| Matrix | Human serum matrix | Same |
| Levels | Two | Same |
| Target Ranges | Cal 1: 20 pg/mL
Cal 2: 2000 pg/mL | Cal 1: 20 pg/mL
Cal 2: 3000 pg/mL |
| Format | Lyophilized | Same |
| Handling | Carefully dissolve the contents
of one bottle by adding exactly
1.0 mL of distilled or deionized
water and allow to stand closed
for 15 minutes to reconstitute.
Mix carefully, avoiding the
foam formation.
Transfer aliquots of the
reconstituted calibrators into
empty labeled snap-cap bottles
(CalSet Vials). Attach the
supplied labels to the additional
bottles. Store the aliquots
immediately at -20°C.
Perform only one calibration
procedure per aliquot. | Same. |
| Table continued | | |
| Characteristic | Elecsys Estradiol III CalSet
(Candidate) | Elecsys Estradiol II CalSet II
(K992981) |
| Stability | Unopened:
• Store at 2-8°C until expiration
date
Opened:
• 2-8°C: 24 hours
• 20-25°C: 5 hours on Elecsys
2010/cobas e 411; use only
once on MODULAR
ANALYTICS E170, cobas e
601 and cobas e 602
analyzers
• -20°C: 31 days (freeze only
once) | Unopened:
• Store at 2-8°C until expiration
date
Opened:
• 2-8°C: 24 hours
• 20-25°C: use only once
• -20°C: 3 month |
| Traceability | The Elecsys Estradiol III CalSet was standardized against ID-GC/MS
(isotope dilution gas chromatography mass spectrometry). | |
| Evaluations
Summary | The Elecsys Estradiol III CalSet was evaluated for value assignment,
reconstitution and stability. | |
| CalSet Value
Assignment | Value assignment testing was conducted and passed pre-defined acceptance
criteria. The target values for the two levels of the Estradiol III CalSet kit are
chosen to obtain the best fit with the Master Calibration Curve, together with
the Rodbard curve parameters encoded in the reagent barcode. For each
Elecsys Estradiol III CalSet lot manufactured, the calibrators are run in
duplicate on at least three (3) Elecsys 2010/cobas e 411 analyzers and at least
three (3) cobas e 601/MODULAR ANALYTICS E170 analyzers with all
Estradiol III reagent lots available. The assigned value of each calibrator is
defined as the mean value obtained over at least six (6) runs on at least three (3)
analyzers) of the respective calibrator.
Measurement values for PreciControl Universal (Level 1 & 2), a multi-analyte
control recommended for use to monitor accuracy and precision of specified
analytes, are read from the calibration curves generated. The pre-defined
acceptance criteria for PreciControl Universal have to be met to release the
Assigned Values for Estradiol III CalSet. | |

3

4

Stability Three studies were performed in order to verify the stability claims for the Studies Estradiol III CalSet. Stability studies after reconstitution and an accelerated stability study were completed on the cobas e 411. Additionally, a real-time stability study is planned.

Study 1. Stability at 2-8ºC, -20ºC, in open vial and freeze/thaw cycles (after reconstitution):

The on-test materials were reconstituted and stored closed for 73 hours at 2 to 8°C, and for 32 days at -20°C and for 7 hours at 20 to 25°C in open vial prior to testing. In addition, the stability of the Estradiol III CalSet for two (2) freeze/thaw cycles was evaluated.

The on-test and reference materials were tested in duplicate and the recovery was calculated as percent of the reference value.

The acceptance criterion was 95 to 105 % signal recovery of the reference material value. The reference material was a freshly reconstituted set of Estradiol III CalSet.

Study 2. Accelerated Stability:

The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a freshly reconstituted set of Estradiol III CalSet (stored at 2 to 8℃). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. One Estradiol III CalSet lot was evaluated in duplicate.

The acceptance criterion was 95 to 105 % recovery of the reference material value.

5


Stability Studies, continuedStudy 3. Real-Time Stability: In addition, real-time stability is being evaluated as follows: In the on-going real-time stability study, the Estradiol III CalSet test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (19 months). Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -20°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point). The acceptance criterion for Estradiol III Calibrator 1 and 2 is recovery of 95-105 % of the reference value. The testing will continue with this stability protocol until data to support a claim of 18 months are achieved.
ConclusionWe trust that the information provided in this Premarket Notification (510(k)) will support a determination of substantial equivalence for the Elecsys Estradiol III CalSet.

6

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Public Health Service

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

August 29, 2014

ROCHE DIAGNOSTICS KELLI TURNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD INDIANAPOLIS IN 46250-0416

Re: K142021

Trade/Device Name: Elecsys Estradiol III CalSet Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: July 24, 2014 Received: July 25, 2014

Dear Ms. Kelli Turner:

This letter corrects our substantially equivalent letter of August 12, 2014. 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

7

Page 2 - Ms. Kelli Turner

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 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/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/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

8

Indications for Use

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

510(k) Number (if known) k 142021

Device Name Elecsys Estradiol III CalSet

Indications for Use (Describe)

Estradiol III CalSet is used for calibrating the quantitative Elecsys Estradiol III assay on the Elecsys and cobas e immunoassay analyzers.

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

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

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

FOR FDA USE ONLY

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

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