(289 days)
Elecsys HCG STAT (K002148)
Elecsys HCG STAT (K002148)
No
The summary describes a standard immunoassay using electrochemiluminescence technology and monoclonal antibodies for quantitative determination of hCG. There is no mention of AI, ML, image processing, or any other technology typically associated with AI/ML applications in medical devices. The performance studies and metrics are standard for an immunoassay.
No
This device is for in vitro diagnostic (IVD) use to quantify hCG, which is used for the "early detection of pregnancy," not for therapeutic purposes.
Yes
The device is described as an immunoassay for the quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma, intended for use in the early detection of pregnancy. This process of identifying and measuring a specific substance in the body for the purpose of detecting a condition (pregnancy) falls under the definition of a diagnostic device.
No
The device is an immunoassay kit intended for use on a specific immunoassay analyzer, indicating it is a hardware-based in vitro diagnostic device, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma." The phrase "in vitro" is a key indicator of an IVD, meaning it is used outside of the living body.
- Device Description: The description reinforces the in vitro nature by stating it "is used for the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma."
- Sample Type: The device analyzes "human serum and plasma," which are biological samples taken from the body for testing.
- Assay Principle: The use of an "electrochemiluminescence immunoassay (ECLIA)" is a common technique used in IVD tests to detect and quantify specific substances in biological samples.
- Performance Studies: The description of performance studies like "Detection Limit," "Linearity," "Interferences," and "Analytical Specificity" are typical evaluations performed on IVD devices to ensure their accuracy and reliability for diagnostic purposes.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.
Product codes
DHA
Device Description
The Elecsys HCG STAT immunoassay makes use of a sandwich test principle using monoclonal antibodies specifically directed against Human Chorionic Gonadotropin (HCG). The antibodies labeled with ruthenium complex consist of a chimeric construct from human and mouse specific components. The Elecsys HCG STAT immunoassay is used for the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. It is intended for use on the cobas e 601immunoassay analyzer.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Non-clinical performance studies were conducted for the Elecsys HCG STAT, including:
- Precision: Evaluated through 5-Day and 21-Day studies according to CLSI guideline EP05-A3.
- 21-Day Precision: Tested on one cobas e 601 analyzer with 2 replicates of each control (PreciControl Universal level 1 and 2) and human serum samples (HS1-HS5) per run, 2 runs per day for 21 days with 1 lot.
- 5-Day Precision: Tested on one cobas e 601 analyzer with 5 aliquots of each control (PreciControl Universal level 1 and 2) and human serum samples (HS1-HS5) per run, 1 run per day for 5 days with 3 lots.
- Reproducibility: Evaluated at three sites (1 internal, 2 external) on cobas e 601 using one lot of updated assay. 1 run per day with 5 replicates of human sera (HSP 1-6) and controls (CTR 1-2) per run.
- Analytical Sensitivity (Detection Limit): LoB, LoD, and LoQ determined according to CLSI EP17-A2.
- LoB: Determined using five analyte-free samples measured in two-fold determinations in 6 runs over ≥3 days, with 2 different lots on one cobas e 601 analyzer.
- LoD: Determined using five samples with low-analyte concentration measured in 2-fold determinations in 6 runs over ≥3 days, with 2 different lots on one cobas e 601 analyzer.
- LoQ: Determined using 2 lots, each with 5 human serum samples across the range of LoB to 2x LoQ, measured in 5 replicates, one run per day for 5 days on one cobas e 601 analyzer.
- Linearity/Assay Reportable Range: Assessed on one cobas e 601 with one run, using a high-analyte human serum sample diluted to the lower end of the measuring range. Dilution series contained 21 steps, assayed in 3-fold determinations. Data analysis according to CLSI EP6-A.
- High Dose Hook Effect: Assessed with one reagent lot on one cobas e 601 analyzer in one-fold determination, using three human serum samples spiked with high HCG concentrations.
- Endogenous Interferences: Evaluated for hemoglobin, intralipid, bilirubin, and rheumatoid factor on one cobas e 601 analyzer, using three HCG concentrations (low, medium, high) spiked with interfering substances. Recovery calculated compared to reference.
- Biotin Interference: Assessed on a cobas e 601 analyzer using three serum samples (low, medium, high) of HCG concentration, spiked with biotin up to 3600 ng/mL according to CLSI EP07-A3.
- Common Drug Interferences: Evaluated for 17 common pharmaceutical compounds on one cobas e 601, using one human serum sample with HCG concentrations near 5 mIU/mL and 50 mIU/mL.
- Analytical Specificity/Cross-Reactivity: Determined with one reagent lot on one cobas e 601 mixer using a human serum matrix with one HCG level (5 mIU/mL), spiked with LH, FSH, and TSH.
- Sample Matrix Comparison: Compared serum samples (reference) to Li-Heparin, K2-EDTA, and K3-EDTA plasma using at least 40 serum/plasma pairs, assessed by Passing/Bablok regression analysis.
- Method Comparison to Predicate: A method comparison study was conducted against the predicate device (Elecsys HCG STAT current assay, K002148) on the cobas e 601 analyzer according to CLSI Guideline EP09-A3. 131 samples spanning the measuring range were tested. Passing-Bablok analysis performed.
- Stability: Stability studies and acceptance criteria found acceptable, supporting claims in package labeling.
Key results: All performance specifications were met. The updated Elecsys HCG STAT immunoassay was found substantially equivalent to the predicate device.
Key Metrics
- Measuring Range: 1.0-10000 mIU/mL (defined by the Limit of Detection and the maximum of the master curve)
- LoB: 0.5 mlU/mL
- LoD: 1.0 mIU/mL
- LoQ: 1.0 mlU/mL
- Analytical Specificity: FSH 0.007 %, TSH 0.001 %
- Biotin Interference: No biotin interference up to 1200 ng/mL.
- Hook Effect: No Hook Effect up to ≥ 500,000 mIU/mL
- Method Comparison (Updated Biotin assay (y) vs. current Elecsys HCG STAT assay (x)):
- Passing/Bablok: y= 1.012x-0.970, T = 0.996
- Linear regression: y = 1.011x + 4.81, r = 1.000
Predicate Device(s)
Elecsys HCG STAT (K002148)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 18, 2021
Roche Diagnostics Adennis Cora Regulatory Affairs Consultant 9115 Hague Road PO Box 50416 Indianapolis, IN 46250
Re: K203227
Trade/Device Name: Elecsys HCG STAT Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: Class II Product Code: DHA Dated: October 31, 2020 Received: November 2, 2020
Dear Adennis Cora:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
1
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez- Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K203227
Device Name
Elecsys HCG STAT
Indications for Use (Describe)
For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy. The electrochemiluminescence immunoassay "ECLIA" is intended for use
on the cobas e 601 immunoassay analyzer.
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) |
|---|---|
| -------------------------------------------------------------------- | ------------------------------------------------------------------- |
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Elecsys HCG STAT K203227 Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Elecsys HCG STAT on the cobas e 601.
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| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Adennis Cora |
| Phone: (317) 521-3915 | |
| FAX: (317) 521-2324 | |
| Email: adennis.cora_gress@roche.com |
Tammy Dean
Phone: (317) 450-5193
FAX: (317) 521-2324
Email: tammy.dean@roche.com |
| Date Prepared | March 17, 2021 |
| Proprietary Name | Elecsys HCG STAT |
| Common Name | Beta HCG STAT Test |
| Classification Name | System, Test, Human Chorionic Gonadotropin |
| Product Codes,
Regulation Numbers | DHA
21 CFR 862.1155 |
| Predicate Devices | Elecsys HCG STAT (K002148) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126
Roche Diagnostics GmBH Penzberg, Germany: 9610529
Roche Diagnostics Indianapolis, IN United States: 1823260. |
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1. DEVICE DESCRIPTION
The Elecsys HCG STAT immunoassay makes use of a sandwich test principle using monoclonal antibodies specifically directed against Human Chorionic Gonadotropin (HCG). The antibodies labeled with ruthenium complex consist of a chimeric construct from human and mouse specific components. The Elecsys HCG STAT immunoassay is used for the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. It is intended for use on the cobas e 601immunoassay analyzer.
2. INDICATIONS FOR USE
For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.
TECHNOLOGICAL CHARACTERISTICS 3.
The reagent working solutions include:
Rack Pack (kit placed on the analyzer).
- M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL: Streptavidin-. coated microparticles 0.72 mg/mL; preservative.
- R1 Anti-hCG-Ab~biotin (gray cap), 1 bottle, 9 mL: Biotinylated monoclonal anti-hCG . antibody (mouse) 2.3 mg/L; phosphate buffer 40 mmol/L, pH 7.5; preservative.
- R2 Anti-hCG-Ab~Ru(bpy)=+ (black cap), 1 bottle, 10 mL:Monoclonal anti-hCG antibody (mouse) labeled with ruthenium complex 6.0 mg/L; phosphate buffer 40 mmol/L, pH 6.5; preservative.
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The following table compares the updated Elecsys HCG STAT with its predicate device, the current Elecsys HCG STAT (K002148).
| Feature | Candidate Device
Updated Elecsys HCG STAT | Predicate Device
Elecsys HCG STAT (K002148) |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For the in vitro quantitative
determination of human chorionic
gonadotropin (hCG) in human serum
and plasma. The Elecsys HCG STAT
immunoassay is intended for use in
the early detection of pregnancy.
The electrochemiluminescence
immunoassay "ECLIA" is intended
for use on the cobas e 601
immunoassay analyzer. | Same |
| Assay Method | Sandwich Principle | Same |
| Detection Method | Electrochemiluminescence | Same |
| Applications/Test Time | 9 minutes | Same |
| Instrument Platform | cobas e 601 | cobas e 411, cobas e 601,
cobas e 602, and cobas e 801 |
| Sample Type/Matrix | Human serum, plasma | Same |
| Sample Anticoagulants | Li-heparin, K2-EDTA and
K3-EDTA plasma. | Same |
| Calibrator | HCG STAT CalSet | Same |
| Calibration Method | Traceability: This method has been
standardized against the 4th
International Standard for Chorionic
Gonadotropin from the National
Institute for Biological Standards and
Control (NIBSC) code 75/589.
Every Elecsys reagent set has a
barcoded label containing specific
information for calibration of the
particular reagent lot. The predefined
master curve is adapted to the
analyzer using the relevant CalSet. | Same |
| Feature | Candidate Device
Updated Elecsys HCG STAT | Predicate Device
Elecsys HCG STAT (K002148) |
| Calibration Interval | Calibration must be performed once
per reagent lot using fresh reagent
(i.e. not more than 24 hours since the
reagent kit was registered on the
analyzer).
Calibration interval may be extended
based on acceptable verification of
calibration by the laboratory.
Renewed calibration is
recommended as follows:
■ after 1 month (28 days) when using
the same reagent lot
■ after 7 days (when using the same
reagent kit on the analyzer) | Same |
| Controls | Controls for the various
concentration ranges should be run
individually at least once every 24
hours when the test is in use, once
per reagent kit, and following each
calibration.
The control intervals and limits
should be adapted to each
laboratory's individual requirements.
Values obtained should fall within
the defined limits. Each laboratory
should establish corrective measures
to be taken if values fall outside the
defined limits. | Same |
| Traceability/Standardization | This method has been standardized
against the 4th International Standard
for Chorionic Gonadotropin from the
National Institute for Biological
Standards and Control (NIBSC) code
75/589 | Same |
| Reagent Stability | unopened at 2-8 °C up to the stated
expiration date
after opening at 2-8 °C 12 weeks
on the analyzer 4 weeks | Same |
| Measuring Range | 1.0-10000 mIU/mL (defined by the
Limit of Detection and the maximum
of the master curve) | 0.500-10000 mIU/mL (defined by the
lower detection limit and the
maximum of the master curve). |
| Feature | Candidate Device
Updated Elecsys HCG STAT | Predicate Device
Elecsys HCG STAT (K002148) |
| Precision | Precision was evaluated on one
cobas e 601 analyzer according to
CLSI guideline EP05-A3. The
protocol consisted of testing 5
Aliquots of each control
(PreciControl Universal level 1 and
PreciControl Universal level 2) and
human serum samples (HS1-HS5)
per run, 1 run per day for 5 days with
3 lots. Repeatability and intermediate
precision (SD and CV values) were
calculated according to CLSI EP05-
A3.
Precision was determined using
Elecsys reagents, pooled human sera
and controls in a protocol (EP05-A3)
of the CLSI (Clinical and Laboratory
Standards Institute): 2 runs per day
in duplicate each for 21 days (n =
84). | Precision was determined using
Elecsys reagents, pooled human sera
and controls in a modified protocol
(EP5-A) of the CLSI (Clinical and
Laboratory Standards Institute): 6
times daily for 10 days (n = 60).
Different Performance Data.
Precision was determined using
Elecsys reagents, pooled human sera
and controls in a separate study
according to protocol (EP5-A2) of the
CLSI (Clinical and Laboratory
Standards Institute): 2 runs per day in
duplicate each for 21 days (n = 84). |
| LoB | 0.5 mlU/mL | Lower detection limit: 0.500 mIU/mL |
| LoD | 1.0 mIU/mL | Lower detection limit: 0.500 mIU/mL |
| LoQ | 1.0 mlU/mL | Lower detection limit: 0.500 mIU/mL |
| Analytical Specificity | FSH 0.007 %, TSH 0.001 % | FSH 0.09 %, TSH: no
cross-reactivity |
| Biotin | This assay has no biotin interference
in serum concentrations up to
1200 ng/mL. | ≤ 164 nmol/L or ≤ 40 ng/mL |
| Hook Effect | No Hook Effect up to
≥ 500,000 mIU/mL | Same |
| | Updated Biotin assay (y) compared to
current Elecsys HCG STAT assay (x) | Elecsys HCG STAT assay (y) with
the Elecsys HCG+ẞ assay (x) |
| Method Comparison | Passing/Bablok
y= 1.012x-0.970
T = 0.996
Linear regression
y = 1.011x + 4.81
r = 1.000 | Passing/Bablok
y = 1.0x - 7.38
T = 0.986
Linear regression
y = 1.05x - 5.26
r = 0.999 |
Technical Characteristics Comparison Table between updated Table 1: Elecsys HCG STAT and current Elecsys HCG STAT
7
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NON-CLINICAL PERFORMANCE EVALUATION 4.
The non-clinical performance studies for the Elecsys HCG STAT are summarized below. The following performance data are provided in support of the substantial equivalence determination:
- Precision (5-Day and 21-Day) according to CLSI EP5-A3 .
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- Detection Limit: LoB, LoD and LoO according to CLSI EP17-A2
- Linearity according to CLSI EP6-A .
- High Dose Hook Effect .
- Interferences Hemoglobin, Intralipid, Bilirubin, and Rheumatoid Factors .
- Biotin Interference (CLSI EP07-A3) .
- Common Drug Interferences .
- Analytical Specificity/ Cross Reactivity (CLSI EP17-A2) .
- Matrix Comparison Anticoagulants .
- Method Comparison to Predicate .
- Reagent Stability (CLSI EP25-A) .
- Lot Calibration Stability (CLSI EP25-A) .
All performance specifications were met.
4.1. Precision
21 Day Precision (1 lot on 3 sites) 4.1.1. -
Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing 2 replicates of each control (PreciControl Universal level 1 and PreciControl Universal level 2) and human serum samples (HS1-HS5) per run, 2 runs per day for 21 days with 1 lot. Repeatability and intermediate precision (SD and CV values) were calculated according to CLSI EP05-A3. Assay calibration was done as specified in the package insert.
4.1.2. 5 Day Precision
Precision was evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. The protocol consisted of testing 5 Aliguots of each control (PreciControl Universal level 1 and PreciControl Universal level 2) and human serum samples (HS1-HS5) per run, 1 run per day for
10
5 days with 3 lots. Repeatability and intermediate precision (SD and CV values) were calculated according to CLSI EP05-A3. Assay calibration was done as specified in the package insert.
4.1.3. Reproducibility
Reproducibility of the Elecsys HCG STAT assay was evaluated at three sites (1 internal and 2 external) on the cobas e 601 immunoassay analyzer using one lot of updated assay. The Reproducibility study was performed for a total of 1 run per day with 5 replicates of each human sera (HSP 1-6) and each control (CTR 1-2) per run, 1 run per day. The samples were run in randomized order on the analyzers. Human serum pools (HSP 1-4) and diluted single donor samples (HSP 5-6) were used to calculate Repeatability and Intermediate precision according to EP05-A3.
Analytical Sensitivity 4.2.
4.2.1. Limit of Blank (LoB)
LoB of the Elecsys HCG STAT on the cobas e 601 analyzer was determined according to CLSI EP17-A2. Limit of Blank determines the highest observed measurement values for samples free of analyte. The Limit of Blank was determined as the 95th percentile of measurements of blank samples. For determination of LoB five analyte free samples were measured in two-fold determinations in 6 runs, distributed over ≥ 3 days, with 2 different lots on one cobas e 601 analyzer. In total 60 measured values of analyte free samples were obtained per lot. As the analyzers do not report negative sample concentrations the data set is truncated and the data were evaluated according to EP17-A2, chapter 5.3.3.1 as the linear interpolation of the 57th and 58th ranked observation.
Limit of Detection (LoD) 4.2.2.
The LoD determines the lower limit for samples with analyte. The LoD was determined as the lowest amount of analyte in a sample that can be detected with a 95% probability. For determination of LoD five samples with low-analyte concentration (from LoB up to approx. 4 times the LoB) were measured in 2-fold determination in 6 runs, distributed over ≥ 3 days, with 2 different lots on one cobas e 601 analyzer. In total 60 measured values of samples with low
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analyte concentrations were obtained per lot. Data analysis was based on determination of the 60 measured values of the 5 low analyte samples (according to CLSI EP17-A2, chapter 5.3.3.2).
Limit of Quantitation (LoQ) 4.2.3.
For the determination of LoO. 2 lots were evaluated, each with 5 human serum samples covering the range between LoB and 2x LoQ. Each sample was measured in 5 replicates (single determination of each replicate) with one run per day over 5 days on one cobas e 601 analyzer. Assay calibration was performed as specified in the package insert. Analyte-low samples or sample pools were used for the determination of LoQ.
The mean value and the intermediate precision as coefficient of variation (CV) and standard deviation (SD) were calculated for each LoQ sample. Data Analysis was determined according to CLSI EP17-A2.
4.3. Linearity/Assay Reportable Range
For linearity, one lot was tested on one cobas e 601 with one run. One human serum sample with high analyte content above the measuring range was diluted to the lower end of the measuring range with various amounts of human serum sample without analyte content. The dilution series contained 21 steps. Samples were assayed in 3-fold determinations. Data Analysis was determined according to CLSI EP6-A.
4.4. High Dose Hook Effect
The high-dose hook effect of the Elecsys HCG STAT assay was assessed with one reagent lot on one cobas e 601 analyzer in one-fold determination. Three human serum samples were spiked with analyte (HCG) to achieve high HCG concentrations. For each sample, a dilution series was performed using serum. The hook concentration reported corresponds to the highest analyte concentration that generates a signal ≥ 10% above the upper limit of the measuring range.
Endogenous Interferences 4.5.
Hemoglobin/Intralipid/Bilirubin/Rheumatoid Factor 4.5.1. -
The effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys HCG immunoassay was determined on one cobas e 601 analyzer for the following
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four interfering substances: hemoglobin, intralipid, bilirubin and rheumatoid factor. The effect on quantitation of analyte in the presence of endogenous interfering substances was determined for HCG concentrations and a dilution set of the added interfering substances. For the sample with highest HCG concentration, spiked samples were used. One reagent lot was tested on 3 samples of each interfering substance.
One aliquot of each HCG sample (low, medium, high) was spiked with the interfering endogenous substance and used as "interference pool". Another aliquot of the sample was spiked with the same volume of the solvent of the interfering endogenous substance (without interfering substance) and used as the related "dilution pool". A series of at least 9 dilution steps were prepared by mixing the interference pools and the related dilution pools in 10 % increments.
The recovery (absolute deviation or % recovery) was calculated for each sample compared to the reference (unspiked) sample.
4.6. Biotin
The effect on quantitation of analyte in the presence of biotin using the Elecsys HCG STAT assay was determined on a cobas e 601 analyzer using three serum samples (low, medium, and high) concentration of HCG according to CLSI EP07-A3. One aliquot of each sample (low, medium, high) was spiked with biotin up to 3600 ng/mL and used as "interference pool". Another aliquot of the sample was spiked with the same volume of the interfering endogenous substance (without interfering substance) and used as the related "dilution pool". A series of 11 dilution steps were prepared by mixing the interference pools and the related dilution pools. The recovery (absolute deviation or % recovery) were calculated for each sample compared to the reference (unspiked) sample. For the sample with highest HCG concentration, spiked samples were used.
Common druq Interferences 4.7.
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with 17 common pharmaceutical compounds with the reference sample. One human serum sample was used and tested on the cobas e 601 immunoassay analyzer. Samples (with HCG concentrations near 5 mIU/mL
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and near 50 mIU/mL) were divided into aliquots and spiked with the common drug interferents. The reference sample without drug was spiked with the respective amount of solvent.
Analytical Specificity/Cross-Reactivity 4.8.
The analytical specificity of the Elecsys HCG STAT assay was determined with one reagent lot on one cobas e 601 analyzer using a human serum matrix with one HCG level (5 mIU/mL). The sample was spiked with the following potential cross-reactants: LH, FSH, and TSH. The sample was measured in presence and absence of the potential cross-reactants and cross reactivity was calculated using the following % Cross-reactivity formula:
mean analyte conc. of spiked sample — mean analyte conc. of unspiked sample x 100% = spiked concentration of cross — reactant
4.9. Sample Matrix Comparison
The effect on quantitation of analyte in the presence of anticoagulants on the Elecsys HCG STAT assay. Values obtained from serum samples drawn into serum primary tubes (reference) were compared to Li-Heparin, K2-EDTA and K3-EDTA plasma. At least 40 serum/plasma pairs were tested in one run on one cobas e 601 analyzer. Data was assessed by Passing/Bablok regression analysis. Spiked samples were used when necessary for reaching high HCG concentrations but allotted for less than 10 % of all samples.
4.10. Method Comparison to Predicate
A method comparison (MC) study of the updated Elecsys HCG STAT assay (candidate device, Y) versus the predicate device, Elecsys HCG STAT current assay (X) was conducted on the cobas e 601 analyzer according to CLSI Guideline EP09-A3. Serum samples were measured internally using both the current and updated reagent formulations. One hundred thirty one (131) samples that span the measuring range were tested with 1 run per sample (no replicates). To sufficiently cover the measuring range, samples were spiked with recombinant HCG to cover the upper end of the measuring range, or diluted to cover the lower end of the measuring range.
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Equivalence of the current Elecsys HCG STAT (K002148) assay and the updated Elecsys HCG STAT assay were evaluated as described below.
· Samples without further clinical or demographic information were used. Samples were distributed to span the reportable range.
• Calculation: Scatter-plot of numerical values of the current assay (x-axis) versus the updated assay (y-axis).
• Passing-Bablok analysis for slope and intercept was performed for the updated lot against the current lot.
4.11. Stability
The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports Roche Diagnostic's claims as reported in the package labeling.
4.12. Substantial Equivalence
The Elecsys HCG STAT immunoassay (updated assay, Mat. No. 08890587190) is substantially equivalent to the Elecsys HCG STAT immunoassay (current assay, Mat. No. 03300811190).