(29 days)
Progesterone III CalSet is used for calibrating the quantitative Elecsys Progesterone III assay on the Elecsys and cobas e immunoassay analyzers.
The Elecsys Progesterone III CalSet is a lyophilized product consisting of plant-derived progesterone in a human serum matrix. It is traceable via ID-GC/MS (isotope dilution gas chromatography/mass spectrometry) to highly purified progesterone by weight analogous to BCR-348R and ERM-DA347.
Here's a breakdown of the acceptance criteria and the study details for the Elecsys Progesterone III CalSet, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes three stability studies with a consistent acceptance criterion.
| Acceptance Criteria Category | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| CalSet Value Assignment | Passed pre-defined acceptance criteria (specific values not detailed but stated as met). PreciControl Universal (Level 1 & 2) acceptance criteria must be met. | Passed. Assigned values are the median value over at least six runs on at least three analyzers. PreciControl Universal acceptance criteria met. |
| Stability (Reconstituted) | 95 to 105% signal recovery of reference value | All tested conditions (2-8°C for 25 hours, -20°C for 32 days, 20-25°C open vial for 3 hours, 2 freeze/thaw cycles) met the acceptance criterion. |
| Accelerated Stability (Lyophilized) | 95 to 105% recovery of reference value | One lot evaluated in duplicate met the acceptance criterion. |
| Real-Time Stability (Lyophilized) | 95-105% recovery of the reference value | Ongoing study, but the testing will continue until data supports an 18-month claim. Implied to be meeting acceptance criteria during the evaluation period to support the claim. |
2. Sample Size Used for the Test Set and Data Provenance
- CalSet Value Assignment: Tested on "at least three (3) cobas e 411 analyzers and at least three (3) cobas e 601/MODULAR ANALYTICS E170 analyzers with all Progesterone III reagent lots available." The assigned value is the median of at least six runs of the respective calibrator. The testing also involved PreciControl Universal levels 1 & 2.
- Stability Studies (Reconstitution, Accelerated, Real-Time): Specific sample sizes for each test condition (e.g., number of vials, number of runs per vial) are not explicitly stated as a single number. However, for recombinant stability and accelerated stability, it mentions "on-test materials" and "one Progesterone III CalSet lot was evaluated in duplicate" for accelerated stability. The real-time study is ongoing with "Progesterone III CalSet test material" tested in duplicate.
- Data Provenance: The studies were conducted at Roche Diagnostics GmbH in Mannheim, Germany, and Penzberg, Germany, and Roche Diagnostics United States. The data appears to be prospective as it's part of the premarket notification for a new device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This device is a calibrator for an immunoassay. The concept of "experts establishing ground truth" in the diagnostic imaging/CAD sense does not directly apply here. Instead, the ground truth for the analyte concentration in the calibrator is established through traceability to highly purified progesterone by weight analogous to BCR-348R and ERM-DA347 using ID-GC/MS (isotope dilution gas chromatography/mass spectrometry). This is a metrological approach to establishing a reference value, rather than expert interpretation of a clinical finding.
4. Adjudication Method for the Test Set
Not applicable in the context of a calibrator's analytical performance.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not performed. This type of study is designed for diagnostic tools that assist human readers (e.g., CAD systems for mammography), whereas the Elecsys Progesterone III CalSet is a calibrator for an automated immunoassay system.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance studies described (value assignment and stability) are standalone evaluations of the calibrator's analytical characteristics. The calibrator itself is a component used by an automated immunoassay system (Elecsys and cobas e immunoassay analyzers) and does not involve human interpretation in its direct function.
7. The Type of Ground Truth Used
The ground truth for the Elecsys Progesterone III CalSet is established through traceability via ID-GC/MS (isotope dilution gas chromatography/mass spectrometry) to highly purified progesterone by weight analogous to certified reference materials (BCR-348R and ERM-DA347). This provides a highly accurate, metrologically sound reference for the concentration of progesterone in the calibrator.
8. The Sample Size for the Training Set
The concept of a "training set" is not directly applicable in the documentation for this calibrator. Calibrators are manufactured to specific specifications and then undergo verification and validation testing, not a machine learning training process. The value assignment process involves running calibrators on multiple instruments and reagent lots to determine assigned values, which is more akin to a robust validation process than machine learning training.
9. How the Ground Truth for the Training Set was Established
As noted above, a "training set" in the machine learning sense is not used. The reference values (ground truth) for the calibrator were established through the metrological traceability mentioned in point 7.
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October 2, 2015
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
ROCHE DIAGNOSTICS PATTY BATES REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD INDIANAPOLIS IN 46250
Re: K152526
Trade/Device Name: Elecsvs Progesterone III Calset Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: September 2, 2015 Received: September 3, 2015
Dear Ms. Bates:
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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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 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) K152526
Device Name Elecsys Progesterone III CalSet
Indications for Use (Describe)
Progesterone III CalSet is used for calibrating the quantitative Elecsys Progesterone 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)
Over-The-Counter Use (21 CFR 801 Subpart C)
Form Approved: OMB No. 0910-0120
Expiration Date: January 31, 2017
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510(k) Summary, Elecsys Progesterone 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.
| Submitter Name, Address, Contact Information | Roche Diagnostics Corporation9115 Hague Road, P.O. Box 50416Indianapolis, IN 46250-0416Contact Person: Patty Bates, BS, MT (ASCP)Phone: 317-521-4572Fax: 317-521-2324Email: patty.bates@roche.comSecondary Contact Person: Adam Clark, MBAPhone: 317-521-4371Fax: 317-521-2324Email: adam.clark@roche.comDate Prepared: September 2, 2015 |
|---|---|
| Device Name | |
| Proprietary name: Elecsys Progesterone III CalSet | |
| Common name: Progesterone III CalSet | |
| Classification: 21 CFR 862.1150, Calibrator, Secondary | |
| Product Code: JIT |
Establishment For the Progesterone III CalSet, the establishment registration number for 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.
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Classification FDA has classified the product as a Class II device.
| ProductName | Panel | ProductCode | ClassificationName | RegulationCitation |
|---|---|---|---|---|
| ProgesteroneIII CalSet | ClinicalChemistry | JIT | Calibrator,Secondary | 21 CFR 862.1150 |
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| DeviceDescription | Elecsys Progesterone III CalSet:• The Elecsys Progesterone III CalSet is a lyophilized product consisting ofplant-derived progesterone in a human serum matrix. It is traceable viaID-GC/MS (isotope dilution gas chromatography/mass spectrometry) tohighly purified progesterone by weight analogous to BCR-348R andERM-DA347. |
|---|---|
| Intended use | Elecsys Progesterone III CalSet:• The Progesterone III CalSet is used for calibrating the quantitativeElecsys Progesterone III assay on the Elecsys and cobas e immunoassayanalyzers. |
| Predicatedevice | The Elecsys Progesterone III CalSet is substantially equivalent to thepredicate device, Elecsys Progesterone II CalSet (K964841). |
| SubstantialEquivalenceComparison | The following table compare the Elecsys Progesterone III CalSet with thepredicate device. |
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The table below compares Elecsys Progesterone III CalSet with the predicate Comparison device, Elecsys Progesterone II CalSet (K964841). Table
The change in the new product is the addition of calibrator stability at -20°C.
Table
| Characteristic | Elecsys Progesterone IIICalSet(Candidate) | Elecsys Progesterone IICalSet(Predicate) (K964841) |
|---|---|---|
| Intended Use | Progesterone III CalSet is usedfor calibrating the quantitativeElecsys Progesterone III assayon the Elecsys and cobas eimmunoassay analyzers. | Progesterone II CalSet is usedfor calibrating the quantitativeElecsys Progesterone assay onthe Elecsys and cobas eimmunoassay analyzers. |
| Analyte | Progesterone (plant-derived) | Same |
| Matrix | Human serum matrix | Same |
| Levels | Two | Same |
| Target Values | Cal 1: 0.080 ng/mLCal 2: 53 ng/mL | Same |
| Format | Lyophilized | Same |
| Handling | Carefully dissolve the contentsof one bottle by adding exactly1.0 mL of distilled or deionizedwater and allow to stand closedfor 15 minutes to reconstitute.Mix carefully, avoiding thefoam formation.Transfer aliquots of thereconstituted calibrators intoempty labeled snap-cap bottles(CalSet Vials). Attach thesupplied labels to the additionalbottles. Store the aliquotsimmediately at -20°C.Perform only one calibrationprocedure per aliquot. | Carefully dissolve the contentsof one bottle by adding exactly1.0 mL of distilled or deionizedwater and allow to stand closedfor 15 minutes to reconstitute.Mix carefully, avoiding thefoam formation.Transfer aliquots of thereconstituted calibrators intoempty labeled snap-cap bottles(CalSet Vials). Attach thesupplied labels to the additionalbottles. Store the aliquots at2-8°C for later use.Perform only one calibrationprocedure per aliquot. |
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| Table continued | ||
|---|---|---|
| Characteristic | Elecsys Progesterone IIICalSet(Candidate) | Elecsys Progesterone IICalSet(Predicate) (K9648441) |
| Stability | Unopened:• Store at 2-8°C until expiration dateOpened:• 2-8°C: 24 hours• 20-25°C on the analyzer: use only once• -20°C: 31 days (freeze only once) | Unopened:• Store at 2-8°C until expiration dateOpened:• 2-8°C: 12 weeks• 20-25°C on the analyzer: use only once |
Table continued
| Traceability | The Elecsys Progesterone III CalSet is traceable via ID-GC/MS (isotope dilution gas chromatography/mass spectrometry) to highly purified progesterone by weight analogous to BCR-348R and ERM-DA347. |
|---|---|
| Evaluations Summary | The Elecsys Progesterone 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 Progesterone 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 Progesterone III CalSet lot manufactured, the calibrators are run in duplicate on at least three (3) cobas e 411 analyzers and at least three (3) cobas e 601/MODULAR ANALYTICS E170 analyzers with all Progesterone III reagent lots available. The assigned value of each calibrator is defined as the median 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) are read off from the calibration curves generated. The PreciControl Universal is a multi-analyte control recommended for use with specified analytes. The controls are used for monitoring accuracy and precision of the specified assays. The pre-defined acceptance criteria for PreciControl Universal have to be met to release the Assigned Values for Progesterone III CalSet.
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Stability Three studies were performed in order to verify the stability claims for the Studies Progesterone 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 2-8°C, -20°C, in open vial and freeze/thaw cycles (after reconstitution):
The on-test materials were reconstituted and stored closed for 25 hours at 2 to 8°C, and for 32 days at -20°C and for 3 hours at 20 to 25°C in open vial prior to testing. In addition, the stability of the Progesterone III CalSet for two (2) freeze/thaw cvcles 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 Progesterone 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 Progesterone III CalSet (stored at 2 to 8°C). 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 Progesterone III CalSet lot was evaluated in duplicate.
The acceptance criterion was 95 to 105 % recovery of the reference material value.
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| Stability Studies, continued | Study 3. Real-Time Stability: In addition, real-time stability is being evaluated as follows: In the on-going real-time stability study, the Progesterone 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 Progesterone 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 is achieved. |
|---|---|
| ------------------------------ | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Conclusion | We trust that the information provided in this Premarket Notification (510(k)) will support a determination of substantial equivalence for the Elecsys Progesterone III CalSet. |
|---|---|
| ------------ | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
§ 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.