(30 days)
The Atellica® IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum or plasma (EDTA or lithium heparin) using the Atellica® IM Analyzer.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
The Atellica® IM Total hCG (ThCG) Assay reagents come in the following configurations:
1 ReadyPack primary reagent pack containing Atellica IM ThCG Lite Reagent and Solid Phase Atellica IM ThCG master curve and test definition (90 Tests)
5 ReadyPack primary reagent packs containing Atellica IM ThCG Lite Reagent and Solid Phase Atellica IM ThCG master curve and test definition (450 Tests)
The ReadyPack consists of the following:
Atellica IM ThCG ReadyPack primary reagent pack Lite Reagent: 4.5 mL/reagent pack Goat polyclonal anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline; sodium azide (0.1%); preservatives
Solid Phase: 20.3 mL/reagent pack Mouse monoclonal anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline; sodium azide (0.1%); preservatives.
Atellica IM ThCG DIL ReadyPack ancillary reagent pack: 25.0 mL/pack Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives
Atellica IM ThCG DIL: 50.0 mL/vial Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives
Here's a breakdown of the acceptance criteria and study information for the Atellica® IM Total hCG (ThCG) device, based on the provided FDA 510(k) summary:
The purpose of this submission (K192790) is to add a plasma (EDTA and lithium heparin) sample claim for the Atellica® IM Total hCG (ThCG) assay, which was previously cleared for serum samples under K172322. Therefore, the acceptance criteria and supporting studies specifically address the performance of the device with these new sample types.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the new plasma sample types are implicitly derived from the established performance of the predicate device with serum and are demonstrated through equivalency studies. The key performance indicator for this submission is the agreement between plasma and serum samples.
| Acceptance Criteria Category | Specific Criteria (Implicit for equivalency to serum) | Reported Device Performance (Plasma vs. Serum) | Comments |
|---|---|---|---|
| Specimen Equivalence | Slope: 0.90 – 1.10 | Dipotassium EDTA plasma (y) vs. Serum (x): Slope = 1.02, Intercept = -1.4 mIU/mL | Meets the acceptance criteria for slope. |
| Intercept: Close to 0 | Intercept is low relative to the assay range. | ||
| Correlation Coefficient (r): Close to 1.00 | Correlation Coefficient (r) = 1.00 | Excellent correlation. | |
| Lithium heparin plasma (y) vs. Serum (x): Slope = 1.05, Intercept = 0.2 mIU/mL | Meets the acceptance criteria for slope. | ||
| Intercept is very low, indicating good agreement. | |||
| Correlation Coefficient (r) = 1.00 | Excellent correlation. | ||
| Interference | Bias %: No significant bias | Dipotassium EDTA (9.0 mg/mL): 1.5% (at 21.1 mIU/mL), 0.7% (at 626.4 mIU/mL) | Low bias, indicating no significant interference. |
| Heparin (75 U/mL): 1.8% (at 25.4 mIU/mL), 0.7% (at 668.9 mIU/mL) | Low bias, indicating no significant interference. |
2. Sample Size Used for the Test Set and Data Provenance
-
Sample Size for Specimen Equivalence (Test Set):
- Dipotassium EDTA plasma: 116 samples
- Lithium heparin plasma: 134 samples
-
Sample Interval: 3.8 - 959.2 mIU/mL (IU/L) for both plasma types.
-
Data Provenance: The document does not explicitly state the country of origin or whether the samples were retrospective or prospective.
-
Sample Size for Interference (Test Set): Not explicitly stated, however, the results show bias at two analyte concentrations for each interferent, suggesting a controlled experimental setup, likely with replicates for each condition.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
This type of immunoassay (quantitative determination of hCG) typically does not involve human experts establishing a subjective "ground truth" for individual test samples, as the analyte concentration is an objective biochemical measurement. The ground truth, in this context, is the measured hCG concentration in the serum samples, which essentially serves as the reference for comparison against plasma samples. The accuracy of these serum measurements would be ensured by laboratory quality controls and standardization against international reference materials (WHO 4th IS 75/589 reference material), as mentioned in the "Standardization" section. Therefore, no "experts" in the sense of clinical reviewers are used to establish ground truth for this type of quantitative assay performance study.
4. Adjudication Method for the Test Set
Not applicable. For a quantitative assay comparing different sample matrices, adjudication methods like N+1 consensus are not used. The comparison is statistical, based on linear regression and bias analysis between the results from the plasma samples and the reference serum samples.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay that quantitatively measures a biomarker (hCG). MRMC studies are typically performed for imaging devices or other diagnostic tools where human interpretation plays a role, to assess the impact of AI assistance on human reader performance. This submission focuses on the analytical performance of the assay itself with different sample types.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was done
Yes, the performance studies described are standalone. The "device" in question is the Atellica® IM Total hCG (ThCG) assay, which is an automated in vitro diagnostic system. The performance data presented (specimen equivalence and interference) directly reflects the analytical performance of the assay when run on the Atellica® IM Analyzer, without human intervention in the measurement process itself, beyond standard laboratory procedures for sample handling and instrument operation.
7. The Type of Ground Truth Used
For the specimen equivalence study, the ground truth for comparison was the hCG concentration determined in human serum samples using the Atellica® IM Total hCG (ThCG) assay (the predicate device). The new sample types (EDTA plasma and lithium heparin plasma) were then tested on the same device and compared against these serum results.
For interference testing, the "ground truth" would be the expected hCG concentration in the samples without the interferent, or a known spiked concentration.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of this 510(k) submission. This is typical for in vitro diagnostic assays based on established immunoassay principles, where the assay design, calibration, and optimization (which can be analogous to "training" in AI/ML) would have been performed during the initial development and clearance of the predicate device (K172322). This submission is an extension of that device for new sample types, relying on the already established assay method.
9. How the Ground Truth for the Training Set was Established
As noted above, a distinct "training set" in the AI/ML sense is not directly applicable here. The "ground truth" for the development and establishment of the assay's performance would have involved:
- Standardization: Against the World Health Organization (WHO) 4th IS 75/589 reference material for hCG. This provides the fundamental "ground truth" reference for hCG concentration.
- Calibration: Assigned values for calibrators are traceable to this WHO standard.
- Analytical Performance Studies: Initial studies (precision, linearity, detection capability) performed for the predicate device (K172322) would have established the assay's performance characteristics against these standardized references and known concentrations.
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October 30, 2019
Siemens Healthcare Diagnostics Inc. Mey Lyn Vasquez Regulatory Clinical Affairs Specialist 511 Benedict Ave. Tarrytown, NY 10591
Re: K192790
Trade/Device Name: Atellica® IM Total hCG (ThCG) Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: Class II Product Code: DHA Dated: September 27, 2019 Received: September 30, 2019
Dear Mey Lyn Vasquez:
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.
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
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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 (OS) 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 mediation-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,
For: Kellie B. Kelm, Ph.D. Acting 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) K192790
Device Name Atellica® IM Total hCG (ThCG)
Indications for Use (Describe)
The Atellica® IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum or plasma (EDTA or lithium heparin) using the Atellica® IM Analyzer.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
| 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 of Safety and Effectiveness
Introduction: According to the requirements of SMDA 1990 and 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number: k192790___________________________________________________________________________________________________________________________________
1. APPLICANT
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue, Tarrytown, NY 10591 USA
| Contact: | Mey Lyn VasquezRegulatory Clinical Affairs Specialist |
|---|---|
| Phone: | (914) 524-2458 |
| Fax: | (914) 524-3579 |
| E-mail: | mey.vasquez@siemens-healthineers.com |
Date Prepared: October 30, 2019
Regulatory Information 2.
Assay
| Trade Name | Atellica® IM Total hCG (ThCG) |
|---|---|
| Device | System, Test, Human Chorionic Gonadotropin |
| Regulation Description | Human chorionic gonadotropin (HCG) test system |
| FDA Classification | Class II |
| Review Panel | Clinical Chemistry |
| Product Code | DHA |
| Regulation Number | 21 CFR 862.1155 |
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3. PREDICATE DEVICE
Assay
Name of Device: Atellica® IM Total hCG (ThCG) 510 (k): K172322
DEVICE DESCRIPTION 4.
The Atellica® IM Total hCG (ThCG) Assay reagents come in the following configurations:
| Contents | Numberof Tests |
|---|---|
| 1 ReadyPack primary reagent pack containing Atellica IM ThCGLite Reagent and Solid PhaseAtellica IM ThCG master curve and test definition | 90 |
| 5 ReadyPack primary reagent packs containing Atellica IM ThCGLite Reagent and Solid PhaseAtellica IM ThCG master curve and test definition | 450 |
The ReadyPack consists of the following:
Atellica IM ThCG ReadyPack primary reagent pack Lite Reagent
4.5 mL/reagent pack Goat polyclonal anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline; sodium azide (0.1%); preservatives
Solid Phase
20.3 mL/reagent pack Mouse monoclonal anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline; sodium azide (0.1%); preservatives.
Atellica IM ThCG DIL ReadyPack ancillary reagent pack
25.0 mL/pack Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives
Atellica IM ThCG DIL
50.0 mL/vial Buffered heat-treated equine serum; EDTA; sodium azide (< 0.1%); preservatives
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5. INDICATIONS FOR USE
The Atellica® IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum or plasma (EDTA or lithium heparin) using the Atellica® IM Analyzer.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
6. INTENDED USE
Same as Indications for Use
7. Purpose of the Submission
The purpose of this submission is for the addition of plasma (EDTA and lithium heparin) sample claim for the Atellica® IM Total hCG (ThCG) assay.
COMPARISION OF TECHNOLOGICAL CHARACTERISTICS WITH THE 8. PREDICATE DEVICE
The following table demonstrates substantial equivalence between the Atellica® IM Total hCG (ThCG) assay (Candidate Device) that has modified Instructions for Use (Package Inserts) with the addition of the plasma (EDTA and lithium) sample claim and the currently marketed Atellica® IM Total hCG (ThCG) assay (Predicate Device) that was cleared under 510(k) K172322.
| Assay | ||
|---|---|---|
| Item | Predicate Device | Candidate Device |
| Atellica® IM Total hCG (ThCG) | Atellica® IM Total hCG (ThCG) | |
| Intended Use | The Atellica® IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum using the Atellica® IM Analyzer.The Atellica IM ThCG assay is intended for use as an aid in the early detection of pregnancy. | The Atellica® IM Total hCG (ThCG) assay is for in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in human serum or plasma (EDTA or lithium heparin) using the Atellica® IM Analyzer.Human chorionic |
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| gonadotropinmeasurements areintended for use as an aidin the early detection ofpregnancy. | ||||
|---|---|---|---|---|
| Measurement | Quantitative | Same | ||
| Assay Range | 2.6–1000 mIU/mL (IU/L) | Same | ||
| Assay Principle | Sandwich immunoassay | Same | ||
| Technology | Direct chemiluminescent | Same | ||
| Sample Type | Serum | serum or plasma (EDTA orlithium heparin) | ||
| Sample Volume | 25 µL | Same | ||
| ReagentVolume | 45 µL of Lite Reagent and 203 µL of SolidPhase | Same | ||
| IncubationTime | 8 minutes at 37°C | Same | ||
| Standardization | Standardized against the World HealthOrganization (WHO) 4th IS 75/589 referencematerial. Assigned values for calibrators aretraceable to thisstandardization. | Same | ||
| Calibration | 2-point | Same | ||
| Calibrators | Atellica IM CAL B | Same | ||
| Number ofCalibratorLevels | Two levels | Same | ||
| Controls | Commercial Controls | Same | ||
| Number ofControl Levels | 2 | Same | ||
| DetectionAntibody | Goat polyclonal anti-hCG antibody labeledwith acridinium ester | Same | ||
| CaptureAntibody | Mouse monoclonal anti-hCG antibodycovalently coupled to paramagnetic particles | Same | ||
| ExpectedValues | Data were obtained on 366 serum samplesfrom 192 apparently healthy non-pregnantfemales and 174 apparently healthypostmenopausal females. The expectedvalue range of non-pregnant females was1.5–4.2 mIU/mL (IU/L) and thepostmenopausal female populationwas 1.8–10.1 mIU/mL (IU/L), as shown inthe table below. | Same | ||
| Sample Category | N° | MedianmIU/mL (IU/L) | Reference IntervalmIU/mL (IU/L)2.5-97.5 Percentile | |
| Non-Pregnant Females(Age: 17-54) | 192 | 2.0 | 1.5-4.2 | |
| Postmenopausal FemalesAge: ≥ 41 | 174 | 3.9 | 1.8-10.1 |
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PERFORMANCE CHARACTERISTICS DATA 9.
Detection Capability
Cleared under premarket submission K172322
Precision
Cleared under premarket submission K172322
Method Comparison
Cleared under premarket submission K172322
Specimen Equivalence
Specimen equivalency was determined using the Deming linear regression model in accordance with CLSI Document EP09-A3. The following results were obtained:
| Tube (y) vs. Serum (x) | Na | Sample Interval | Slope | Intercept | rb |
|---|---|---|---|---|---|
| Dipotassium EDTA plasma | 116 | 3.8-959.2 mIU/mL (IU/L) | 1.02 | -1.4 mIU/mL(IU/L) | 1.00 |
| Lithium heparin plasma | 134 | 3.8-959.2 mIU/mL (IU/L) | 1.05 | 0.2 mIU/mL(IU/L) | 1.00 |
a Number of samples tested.
b Correlation coefficient.
The assay is designed to have a slope of 0.90–1.10 for alternate tube types versus serum. Agreement of the specimen types may vary depending on the study design and sample population used. Assay results obtained at individual laboratories may vary from the data presented.
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Interferences
l
Interference testing was performed in accordance with CLSI Document EP07-ed3.12 The following results were obtained:
| Substance | Substance Test Concentration | Analyte ConcentrationmIU/mL (IU/L) | Bias (%) |
|---|---|---|---|
| Dipotassium EDTA | 9.0 mg/mL | 21.1 | 1.5 |
| 626.4 | 0.7 | ||
| Heparin | 75 U/mL | 25.4 | 1.8 |
| 668.9 | 0.7 |
Assay results obtained at individual laboratories may vary from the data presented.
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Expected Values
Cleared under premarket submission K172322
X. CONCLUSION
Comparative testing of the Atellica IM ThCG Assay is substantially equivalent in principle and performance to the Predicate Device – Atellica IM Total hCG (ThCG) assay cleared under 510(k) K172322.
§ 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.