(269 days)
Not Found
No
The device description and performance studies focus on a standard immunoassay technology and do not mention any AI or ML components.
No.
The device is an in-vitro diagnostic assay used for the quantitative measurement of erythropoietin to aid in the diagnosis of anemias and polycythemias; it does not directly treat or alleviate a medical condition.
Yes
Explanation: The "Intended Use / Indications for Use" section states that "Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias." This clearly indicates its role as a diagnostic aid.
No
The device is an in vitro diagnostic assay that utilizes chemical reagents and a physical system (ADVIA Centaur XP system) to perform measurements, indicating it is a hardware-based medical device with associated software, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
The Intended Use/Indications for Use explicitly states that the assay is for the "quantitative measurement of erythropoietin in pediatric and adult human serum or plasma... using the ADVIA Centaur XP system." It also states that the measurement is used "as an aid in the diagnosis of anemias and polycythemias." This clearly indicates that the device is intended to be used in vitro (outside the body) to examine specimens (serum or plasma) from the human body to provide information for diagnostic purposes.
N/A
Output:
Intended Use / Indications for Use
The ADVIA Centaur® Erythropoietin (EPO) assay is for in vitro diagnostic use in the quantitative measurement of erythropoietin in pediatric and adult human serum or plasma (K2-EDTA, lithium heparin, sodium heparin) using the ADVIA Centaur XP system. Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias.
Product codes
GGT
Device Description
The ADVIA Centaur EPO assay is a fully automated, one-step sandwich immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium-ester-labeled monoclonal mouse anti-EPO antibody in the Lite Reagent. The Solid Phase consists of mouse anti-EPO monoclonal antibody-coated paramagnetic microparticles.
The ADVIA Centaur EPO reagent kit contains the following:
ADVIA Centaur EPO ReadyPack® primary reagent pack;
Lite Reagent (10.0 mL/reagent pack): monoclonal mouse anti-EPO antibody (0.5 µg/mL) labeled with DMAE acridinium conjugate reagent in buffer with bovine serum albumin, surfactant, and sodium azide (10% change in EPO values.
Precision: Seven pooled serum samples were prepared with EPO concentrations spanning the measuring interval. Samples were tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample. One ADVIA Centaur XP system and 3 reagent lots were used.
Specimen Collection Comparison: The assay is designed to have a correlation coefficient (r) >= 0.95, a slope of 0.90-1.10, and an intercept +/- 1.00 mIU/mL for alternate tube types (y) versus human serum (x). A specimen collection study was performed with serum EPO values ranging from 4.39 - 707.81 mIU/mL. Passing-Bablok regression and a Pearson coefficient analysis were performed and no significant difference between tube types was observed.
Method Comparison:
- A total of 216 human serum samples in the range of 3.29 – 691.60 mIU/mL were tested on the Centaur XP system vs. the predicate following CLSI EP09-A3. ADVIA Centaur EPO (y) = 0.99 (x) + 0.81 mIU/mL (intercept), r = 0.99.
- A second method comparison was performed with a total of 100 human serum samples from US population in the range of 4.45 - 407.74 mIU/mL were tested on the Centaur EPO assay and a comparator EPO assay following CLSI EP09-A3. ADVIA Centaur EPO (y) = 1.07 (x) + 0.00 mIU/mL (intercept), r = 1.00.
- A third multi-site study was performed at 3 sites (2 within Europe and 1 within the US) tested a total of 327 human serum samples (>= 100 samples per site) in the range of 3.55 - 596.81 mIU/mL were tested on the Centaur EPO assay and a comparator EPO assay. ADVIA Centaur EPO (y) = 1.01 (x) + 0.36 mIU/mL (intercept), r = 0.99.
Expected Values:
Adults (>21yrs): Results obtained on 251 apparently healthy subjects (males=128, females=123). Combined Male and Female 95% Reference Range: 5.44 -26.25 mIU/mL.
Pediatric Ranges: Results obtained on 266 apparently healthy children (2 to
§ 864.7250 Erythropoietin assay.
(a)
Identification. A erythropoietin assay is a device that measures the concentration of erythropoietin (an enzyme that regulates the production of red blood cells) in serum or urine. This assay provides diagnostic information for the evaluation of erythrocytosis (increased total red cell mass) and anemia.(b)
Classification. Class II. The special control for this device is FDA's “Document for Special Controls for Erythropoietin Assay Premarket Notification (510(k)s).”
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August 2, 2019
Axis-Shield Diagnostics Limited Claire Dora Regulatory Affairs Manager Luna Place, The Technology Park Dundee DD2 1XA, Scotland, UK
Re: K183088
Trade/Device Name: ADVIA Centaur Erythropoietin (EPO) assay Regulation Number: 21 CFR 864.7250 Regulation Name: Erythropoietin Assay Regulatory Class: Class II Product Code: GGT Dated: July 1, 2019 Received: July 3, 2019
Dear Claire Dora:
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
1
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,
Takeesha Taylor-Bell Chief Division of Immunology and Hematology 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)
Device Name ADVIA Centaur® Erythropoietin (EPO) assay
Indications for Use (Describe)
The ADVIA Centaur® Erythropoietin (EPO) assay is for in the quantitative measurement of exythropoitin in pediatric and adult human serum or plasma (K2-EDTA, lithium heparin) using the ADVIA Centaur XP system. Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias..
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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ADVIA Centaur Erythropoietin (EPO) Assay 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
A. 510(k) number is: K183088
B. Date of Preparation: 08-02-2019
C. Submission correspondent:
Dr. Claire Dora Regulatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee DD2 1XA, Scotland, UK
D. Device Name:
ADVIA Centaur® Erythropoietin (EPO) Assay
E. Regulatory Information:
Classification Name: Assay, Erythropoietin Trade Name: ADVIA Centaur® Erythropoietin (EPO) Assay Common Name: Erythropoietin Governing Regulation: 864.7250 Device Classification: Class II Classification Panel: Hematology Product Code: GGT
F. Legally marketed device to which equivalency is claimed:
Beckman Coulter Access EPO Assay (K052223)
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G. Intended Use of Device:
The ADVIA Centaur® Erythropoietin (EPO) assay is for in vitro diagnostic use in the quantitative measurement of erythropoietin in pediatric and adult human serum or plasma (K2-EDTA, lithium heparin, sodium heparin) using the ADVIA Centaur XP system. Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias.
H. Device Description:
Principles of the Device:
The ADVIA Centaur EPO assay is a fully automated, one-step sandwich immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium-ester-labeled monoclonal mouse anti-EPO antibody in the Lite Reagent. The Solid Phase consists of mouse anti-EPO monoclonal antibody-coated paramagnetic microparticles.
The ADVIA Centaur EPO reagent kit contains the following:
ADVIA Centaur EPO ReadyPack® primary reagent pack;
Lite Reagent (10.0 mL/reagent pack): monoclonal mouse anti-EPO antibody (0.5 µg/mL) labeled with DMAE acridinium conjugate reagent in buffer with bovine serum albumin, surfactant, and sodium azide (21yrs) | 5.44 – 26.25 mIU/mL | 2.59 – 18.50 mIU/mL |
| Expected Values –
Paediatrics (750 | N/A |
| | 250 mIU/mL | 72.35 | 27.13 |
| | 125 mIU/mL | 27.59 | 18.46 |
| | 65 mIU/mL | 18.28 | 21.17 |
| Dabepoetin alfa | 2075 mIU/mL (12.5 ng/mL) | 152.82 | 7.14 |
| | 518.75 mIU/mL (3.125 ng/mL) | 32.26 | 5.31 |
| | 259.29 mIU/mL (1.562 ng/mL) | 20.84 | 6.22 |
| | 129.65 mIU/mL (0.781 ng/mL) | 13.5 | 6.78 |
1 Conversion from ng/mL to mIU/mL used, ng/mL x 166, this was taken from Owen & Roberts Clinica Acta. 412 (2011) 480-482
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Interference
Potential interference in the ADVIA Centaur EPO assay from hemoglobin, bilirubin, and lipemia, is designed to be ≤ 10% at EPO concentrations of approximately 4 - 6 mIU/mL and 25 - 35 mIU/mL.
Interfering substances at the levels indicated in the table below were tested as described in CLSI Document EP07-A227 using the ADVIA Centaur EPO assay.
| Serum specimens that are... | Have an insignificant effect on the assay up to... |
|---|---|
| hemolyzed | 500 mg/dL (0.31 mmol/L) of haemoglobin |
| icteric | 60 mg/dL (1026 $ \mu $ mol/L) of unconjugated bilirubin |
| icteric | 40 mg/dL (475 $ \mu $ mol/L) of conjugated bilirubin |
| lipemic | 3000 mg/dL (34.0 mmol/L) of lipemia (Intralipid) |
Two levels of EPO were tested with each of the following substances at the levels indicated, and caused no significant interference in the ADVIA Centaur EPO assay at EPO concentrations of approximately 4 - 6 mIU/mL and 25 - 35 mIU/mL.
| Substances | Concentrations |
|---|---|
| Acetaminophen | 14 mg/dL (927 $\mu$ mol/L) a |
| Acetylsalicyclic acid | 50 mg/dL (2.8 mmol/L) |
| Biotin | 100 mg/dL (4.1 mmol/L) |
| Cholesterol | 500 mg/dL (12.95 mmol/L) |
| EPO Soluble Receptor | 15 ng/mLa |
| Heparin | 8000 U/dL |
| Human Gamma Globulins | 4.9 g/dLb |
| Ibuprofen | 40 mg/dL (1942 $\mu$ mol/L) |
| Multivitamin | 0.2% (therapeutic level) |
| Protein Albumin (human) | 6 g/dL (60 g/L)a |
| Rheumatoid Factor | 200 IU/mL |
| Silwet L720 | 0.2 mg/dL |
| Total Protein | 12 g/dL (120 g/L) |
| Triglycerides | 1000 mg/dL (11.3 mmol/L) |
4 concentration-response curve performed to determine non-interfering levels (See detailed study below) bconcentration determined by spiking and recovery method
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When targeted concentrations of interfering substances caused >10% change in EPO values, further investigation was performed.
| Substances | EPO
Concentrations
Tested | Level ≤10% change was
observed | Level >10% change was
observed |
|--------------------------------|---------------------------------|-----------------------------------|-----------------------------------|
| Acetaminophen | 4-6 mIU/mL | 18 mg/dL (1192µmol/L) |
| | 25 - 35 mIU/mL | 20 mg/dL (1324 µmol/L) | -- |
| Albumin (human) | 4-6 mIU/mL | 6.8 g/dL (68 g/L) |
| | 25 – 35 mIU/mL | 65.2 mg/mL | -- |
| EPO soluble receptor | 4-6 mIU/mL | 31.25 ng/dL |
| | 25 - 35 mIU/mL | 18.75 ng/mL |
| Human gamma
globulins (IgG) | 4-6 mIU/mL | 7.2 g/dL | -- |
| | 25 – 35 mIU/mL | 4.9 g/dL | 6.7 g/dL |
Assay results obtained at individual laboratories may vary from the data presented.
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Precision
Seven pooled serum samples were prepared with EPO concentrations spanning the measuring interval. Samples were tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample. One ADVIA Centaur XP system and 3 reagent lots were used.
| Repeatability (Within-Run) | Within-Lab (Total) | ||||||
|---|---|---|---|---|---|---|---|
| Specimen | N | Mean (mIU/mL) | SD (mIU/mL) | CV (%) | SD (mIU/mL) | CV (%) | |
| Sample 1 | 80 | 1.69 | 0.08 | 4.8 | 0.14 | 8.4 | |
| Sample 2 | 80 | 4.51 | 0.13 | 2.9 | 0.23 | 5.0 | |
| Sample 3 | 80 | 9.30 | 0.25 | 2.6 | 0.33 | 3.6 | |
| Sample 4 | 80 | 25.16 | 0.54 | 2.2 | 1.00 | 4.0 | |
| Sample 5 | 80 | 94.30 | 1.82 | 1.9 | 3.22 | 3.4 | |
| Sample 6 | 80 | 220.25 | 3.69 | 1.7 | 7.03 | 3.2 | |
| Sample 7 | 80 | 579.41 | 9.20 | 1.6 | 15.17 | 2.6 |
Representative data from the study is shown in the following table:
Specimen Collection Comparison
The ADVIA Centaur EPO assay was evaluated using different human serum and plasma matrices. The assay is designed to have a correlation coefficient (r) ≥ 0.95, a slope of 0.90-1.10, and an intercept ± 1.00 mIU/mL for alternate tube types (y) versus human serum (x). A specimen collection study was performed with serum EPO values ranging from 4.39 - 707.81 mIU/mL.
Passing-Bablok regression and a Pearson coefficient analysis were performed and no significant difference between tube types was observed. The following results were obtained:
| Human Serum (x) Vs | n | Slope | Intercept (mIU/mL) | r |
|---|---|---|---|---|
| K2-EDTA (y) | 65 | 0.97 | -0.30 | 1.00 |
| Lithium Heparin (y) | 65 | 1.00 | -0.27 | 0.99 |
| Sodium Heparin | 65 | 0.98 | -0.33 | 0.99 |
| Plasma Separator Tube | 65 | 0.99 | -0.33 | 1.00 |
| Serum Separator Tube | 65 | 1.02 | -0.20 | 0.99 |
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K. Summary of Clinical Performance:
The ADVIA Centaur EPO assay demonstrated substantially equivalent performance to the predicate as indicated by reference intervals (expected values) and a method comparison.
Method Comparison
A total of 216 human serum samples in the range of 3.29 – 691.60 mIU/mL were tested on the Centaur XP system vs. the predicate following CLSI EP09-A3.
The relationship of the ADVIA Centaur EPO assay (y) and a comparator EPO assay (x) is described using Passing-Bablok regression and a Pearson coefficient using the ADVIA Centaur XP system. Data from the study is shown below:
ADVIA Centaur EPO (y) = 0.99 (x) + 0.81 mIU/mL (intercept), r = 0.99.
A second method comparison was performed with a total of 100 human serum samples from US population in the range of 4.45 - 407.74 mIU/mL were tested on the Centaur EPO assay and a comparator EPO assay following CLSI EP09-A3.
The relationship of the ADVIA Centaur EPO assay (y) and the comparator EPO assay (x) is described using Passing-Bablok regression and a Pearson coefficient using the ADVIA Centaur XP system. Data from the study is shown below:
ADVIA Centaur EPO (y) = 1.07 (x) + 0.00 mIU/mL (intercept), r = 1.00.
A third mutli-site study was performed 3 sites, 2 within Europe and 1 within the US tested a total of 327 human serum samples (≥ 100 samples per site) in the range of 3.55 - 596.81 mIU/mL were tested on the Centaur EPO assay and a comparator EPO assay.
The relationship of the ADVIA Centaur EPO assay (y) and the comparator EPO assay (x) is described using Passing-Bablok regression and a Pearson coefficient using the ADVIA Centaur XP system. Data from the study is shown below:
ADVIA Centaur EPO (y) = 1.01 (x) + 0.36 mIU/mL (intercept), r = 0.99.
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Expected Values
The ADVIA Centaur EPO assay results were obtained on 251 apparently healthy subjects, males (n=128) and females (n=123), older than 21 years of age using the ADVIA Centaur XP system. Samples were collected between 7:30 am and 12 noon from individuals with normal hematocrit and hemoglobin levels. Smokers, pregnant women, people living at high altitude or having donated blood within 60 days were excluded.
The reference intervals in the following table were calculated non-parametrically according to EP28-A3.
| Gender | N | Mean
(mIU/mL) | Median
(mIU/mL) | 95% CI of Median
(mIU/mL) | 95% Reference Range
(mIU/mL) |
|-----------------------------|-----|------------------|--------------------|------------------------------|---------------------------------|
| Combined
Male and Female | 251 | 11.20 | 10.08 | 9.43 - 10.52 | 5.44 -26.25 |
ADVIA Centaur EPO Reference Ranges
ADVIA Centaur EPO Pediatric Ranges
The ADVIA Centaur EPO assay results were obtained on 266 apparently healthy children (2 to 2 Horn P, Pesce A. Reference Intervals – A User's Guide. Washington DC: AACC Press; 2005
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L. Standardization:
The ADVIA Centaur EPO assay is traceable to the World Health Organization (WHO) 2ªª International Reference Preparation for Erythropoietin (Human, urinary derived); NIBSC code: 67/343. Assigned values for calibrators are traceable to this standard. The ADVIA Centaur EPO assay is also traceable to the 3rd World Health Organization (WHO) International Standard for Erythropoietin, recombinant, for bioassay; NIBSC code: 11/170
M. Conclusion:
Based on the performance characteristics the ADVIA Centaur EPO assay is substantially equivalent to the predicate device.