(55 days)
ELITech Clinical Systems ALP IFCC SL is intended for the quantitative in vitro diagnostic determination of alkaline phosphatase in human serum and plasma on ELITech Clinical Systems Selectra analyzers.
It is not intended for use In Point of Care settings.
Alkaline phosphatase or its isoenzymes measurements are used in the diagnosis and treatment of liver, bone, parathyroid and intestinal diseases.
The device for this submission is available as kit only. It consists of 2 reagents R1 & reagent R2.
Reagent R1 contains: 2-Amino-2-methyl-1-propanol (AMP) buffer (pH 10.45), Magnesium ions, Zinc ions.
Reagent R2 contains: p-Nitrophenylphosphate (p-NPP), sodium azide.
The provided text describes a 510(k) premarket notification for the ELITech Clinical Systems ALP IFCC SL device, which is an in vitro diagnostic for measuring alkaline phosphatase. The document focuses on establishing substantial equivalence to a predicate device (Roche Diagnostics ALP2S).
Here's an analysis of the acceptance criteria and the study data, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets. Instead, the document presents a comparison of performance characteristics between the new device (ELITech Clinical Systems ALP IFCC SL) and the predicate device (Roche Diagnostics ALP2S). The "acceptance criteria" are implicitly demonstrated by showing comparable or superior performance to the predicate.
| Performance Metric | ELITech Clinical Systems ALP IFCC SL | Predicate Device (Roche Diagnostics ALP2S) | Implied Acceptance Criteria (relative to Predicate) |
|---|---|---|---|
| Measuring Range | 20 - 1023 U/L | 3 - 1200 U/L | Comparable range |
| Limit of Detection (LoD) | 6 U/L | 3 U/L | Comparable LoD |
| Limit of Quantification (LoQ) | 20 U/L | Not explicitly stated (implied by LoD and range) | Comparable LoQ |
| Precision (Within Run) | Level 57 U/L: CV=1.3%Level 144 U/L: CV=0.9%Level 262 U/L: CV=0.6% | Level 87.5 U/L: CV=0.5%Level 229 U/L: CV=0.7%Level 43.1 U/L: CV=0.6%Level 190 U/L: CV=1.2% | Comparable or better CV |
| Precision (Total) | Level 57 U/L: CV=4.4%Level 144 U/L: CV=3.8%Level 262 U/L: CV=2.9% | Level 90.0 U/L: CV=1.0%Level 229 U/L: CV=0.8%Level 53.2 U/L: CV=0.8%Level 195 U/L: CV=0.9% | Comparable or better CV |
| Method Comparison | y= 1.025 x - 1 U/Lr= 0.998Range: 18 to 1005 U/L | y= 1.008 x - 2.207 U/Lr= 1.000Range: 32 to 828 U/L | Strong correlation (r>0.99) and similar regression equation slope/intercept |
| Interferences (Hemoglobin) | No significant interference up to 500 mg/dL | No significant interference up to 250 mg/dL | Comparable or better interference tolerance |
| Interferences (Triglycerides/Lipemia) | No significant interference up to 3141 mg/dL | No significant influence up to an L index of 2000 (poor correlation to triglycerides) | Comparable or better interference tolerance |
| Interferences (Bilirubin) | Unconjugated: No significant interference up to 30.0 mg/dLConjugated: No significant interference up to 29.5 mg/dL | No significant influence up to I Index of 60 (approx. 60 mg/dL total bilirubin) | Comparable or better interference tolerance |
| Interferences (Ascorbic Acid) | No significant interference up to 20.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Interferences (Acetaminophen) | No significant interference up to 30.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Interferences (Acetylsalicylic Acid) | No significant interference up to 200.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Calibration Frequency | 1 day | 5 days | Acceptable calibration frequency (new device is more frequent, implying sufficient stability for daily calibration) |
| On Board Stability | 1 day | 10 days | Acceptable stability (new device has shorter stability, but within acceptable limits for IVD use) |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size for the test set used for performance validation studies (e.g., precision, method comparison, interference). It only provides the results (CVs, regression equations, interference limits).
The data provenance (country of origin, retrospective/prospective) is not explicitly stated. However, given the manufacturer (SEPPIM S.A.S. in FRANCE) and the submission to the FDA, it's highly probable the studies were conducted by the manufacturer, likely in Europe, with data collected prospectively for the purpose of regulatory submission. The samples used would typically be human serum and plasma, as per the intended use.
3. Number of Experts and Qualifications for Ground Truth
This device is an in vitro diagnostic for measuring a biochemical analyte (alkaline phosphatase). The concept of "ground truth" for such a device is typically established through:
- Reference Methods: Highly accurate and precise laboratory methods.
- Certified Reference Materials: Solutions with known concentrations of the analyte.
- Clinical Samples with Established Values: Values determined by existing, validated diagnostic methods.
The document does not mention the use of human experts (like radiologists) for establishing ground truth, as this is not a device that relies on human interpretation of images or other qualitative data. The ground truth for chemical analytes is quantitative and typically relies on analytical methods.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used for qualitative assessments, especially in image interpretation tasks, where multiple experts review cases and resolve discrepancies. Since this is an in vitro diagnostic for a quantitative measurement, such adjudication methods are not applicable and thus not mentioned.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
An MRMC study was not done. MRMC studies are relevant for devices that involve human readers (e.g., radiologists, pathologists) interpreting data, potentially with AI assistance. This device is an automated biochemical analyzer, and therefore, human-in-the-loop performance or comparison is not relevant to its validation.
6. Standalone (Algorithm Only) Performance
This device is a standalone algorithm/device in the context of its function. It is a reagent kit used on an automated analyzer (ELITech Clinical Systems Selectra analyzers) to quantitatively determine alkaline phosphatase. Its performance metrics (precision, linearity, interference, method comparison) are inherently "standalone" in that they describe the performance of the device itself (reagent + analyzer) in measuring the analyte without human interpretation as part of the primary measurement.
7. Type of Ground Truth Used
The ground truth used for validating this type of device would typically be:
- Reference Standards/Calibrators: Solutions with precisely known concentrations of alkaline phosphatase.
- Comparison to a Predicate Device/Established Method: The "Method comparison" section (y= 1.025 x - 1 U/L, r= 0.998) explicitly indicates that the new device's results were compared against those obtained from an existing, validated method (likely the predicate device or a reference method for the x-axis values). The high correlation coefficient (r=0.998) demonstrates agreement with this established truth.
- Internal Quality Control Materials: Often assayed with known target ranges.
8. Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI. This device is a traditional chemical assay kit. As such, there isn't a "training set" in the sense it's used for AI models. The development and optimization of the assay would involve various experiments, but not a formally defined "training set" as in AI.
9. How Ground Truth for the Training Set Was Established
Since there is no "training set" in the AI sense, this question is not applicable. The assay's chemical principles, reagent concentrations, and reaction conditions are established through chemical and biological experimentation, aiming to accurately reflect the activity of alkaline phosphatase. Performance characteristics, like those listed in the comparison table, are then verified through rigorous testing with known standards and clinical samples.
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SECTION 5 - 510(k) Summary
/ / /
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination of sub-stantial equivalence. | ||||
|---|---|---|---|---|---|
| The assigned 510(k) number is: K 113269 | |||||
| SubmitterAddressPhone numberFax number | SEPPIM S.A.S.Zone Industrielle, 61500 SEES, FRANCE+ 33 (0)2 33 81 21 00+ 33 (0)2 33 28 77 51 | ||||
| Contact | Valérie GOURDON (Email: v.gourdon@elitechgroup.com) | ||||
| Date of Preparation | November 2nd, 2011 | ||||
| Device names | |||||
| REAGENTTrade/proprietary Name:Common or Usual Name:Device ClassClassification nameProduct code | ELITech Clinical Systems ALP IFCC SLAlkaline phosphatase, "ALP IFCC SL"Class IIAlkaline phosphatase or isoenzymes test system (Sec.862.1050)CJE- Nitrophenylphosphate, alkaline phosphatase or isoenzymes | ||||
| Predicate device | Roche Diagnostics ALP2S (Alkaline phosphatase acc. to IFCC Gen.2) (K033185) | ||||
| Device description | The device for this submission is available as kit only. It consists of 2reagents R1 & reagent R2.Reagent R1 contains: 2-Amino-2-methyl-1-propanol (AMP) buffer (pH10.45), Magnesium ions, Zinc ions.Reagent R2 contains: p-Nitrophenylphosphate (p-NPP), sodium azide. | ||||
| Intended Use | ELITech Clinical Systems ALP IFCC SL is intended for the quantitative invitro diagnostic determination of alkaline phosphatase in human serum andplasma on ELITech Clinical Systems Selectra analyzers.It is not intended for use In Point of Care settings. | ||||
| Indication for use | Alkaline phosphatase or its isoenzymes measurements are used in thediagnosis and treatment of liver, bone, parathyroid and intestinal diseases. |
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Comparison to Predicate device
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| ELITech Clinical Systems Device(ALP IFCC SL) | Predicate device(Roche Diagnostics ALP2S (K033185) | |
|---|---|---|
| Intended use | Intended for the quantitative in vitrodiagnostic determination of alkalinephosphatase in human serum andplasma on ELITech Clinical SystemsSelectra analyzers.It is not intended for use in Point ofCare settings. | In vitro test for the quantitative deter-mination of alkaline phosphatase inhuman serum and plasma on the co-bas c 111 system. |
| Indication for Use | Alkaline phosphatase or its isoen-zymes measurements are used in thediagnosis and treatment of liver,bone, parathyroid and intestinal di-seases. | Alkaline phosphatase or its isoen-zymes measurements are used in thediagnosis and treatment of liver, bone,parathyroid and intestinal diseases. |
| Assay protocol | Colorimetric. Kinetic.Measurement of the rate of productionof p-nitrophenol at 405 nm.Based on IFCC recommendations. | Colorimetric. KineticMeasurement of the rate of productionof p-nitrophenol at 409 nm.Based on IFCC recommendations. |
| Composition | Reagent R1:AMP buffer (pH 10.45)Magnesium ions2.4 mmol/LZinc ions1.2 mmol/L | Reagent R1:AMP buffer (pH 10.5) 1.724 mol/LMagnesium acetate 3.83 mmol/LZinc sulfate 0.766 mmol/LN-(2-hydroxyethyl)-ethylenediamine triace-tic acid: 3.83 mmol/L |
| Reagent R2:p-NPP 80 mmol/LSodium azide < 0.1% | Reagent R2:p-NPP 132.8 mmol/LPreservatives | |
| Appearance of reagents | Liquid form, ready to use | Liquid form, ready to use |
| Sample type | SerumPlasma | SerumPlasma |
| Reagent storage | Store at 2-8 °C and protect from light.The reagent is stable until the expirydate stated on the label. | Store at 2-8 °C the reagent is stableuntil the expiry date stated on reagent. |
| Expected values | Serum/plasma:Men:20-50 years old: 53-128 U/L≥ 60 years old: 56-119 U/LWomen:20-50 years old: 42-98 U/L≥ 60 years old: 53-141 U/L | Serum/plasma:AdultsMales (n = 221) 40-129 U/LFemales (n = 229) 35-104 U/LConsensus valuesMales 40-130 U/LFemales 35-105 U/LChildrenaged 1 day <250 U/Laged 2-5 days <231 U/Laged 6 days-6 months <449 U/Laged 7 months-1 year <462 U/Laged 1-3 years <281 U/Laged 4-6 years <269 U/Laged 7-12 years <300 U/Laged 13-17 years (f) <187 U/Laged 13-17 years (m) <390 U/L |
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| ELITech Clinical Systems Device(ALP IFCC SL) | Predicate device(Roche Diagnostics ALP2S (K033185) | |||
|---|---|---|---|---|
| Instrument | Selectra ProM Analyzer | Cobas c111 | ||
| Measuring range | 20 - 1023 U/L | 3 - 1200 U/L | ||
| Limit of detection(LoD) | 6 U/L | 3 U/L | ||
| Limit of quantification(LoQ) | 20 U/L | |||
| Precision | Within runLevel 57 U/LLevel 144 U/LLevel 262 U/L | CV= 1.3%CV= 0.9%CV= 0.6% | Within runLevel 87.5 U/LLevel 229 U/LLevel 43.1 U/LLevel 190 U/L | CV= 0.5%CV= 0.7%CV= 0.6%CV= 1.2% |
| TotalLevel 57 U/LLevel 144 U/LLevel 262 U/L | CV= 4.4%CV= 3.8%CV= 2.9% | TotalLevel 90.0 U/LLevel 229 U/LLevel 53.2 U/LLevel 195 U/L | CV= 1.0%CV= 0.8%CV= 0.8%CV= 0.9% | |
| Method comparison | y= 1.025 x - 1 U/Lr= 0.998range: 18 to 1005 U/L | y= 1.008 x - 2.207 U/Lr= 1.000range: 32 to 828 U/L | ||
| Limitations | Hemoglobin: No significant interfer-ence up to 500 mg/dL.Triglycerides: No significant interfer-ence up to 3141 mg/dLUnconjugated bilirubin: No signifi-cant interference up to 30.0 mg/dL(513 µmol/L).Conjugated bilirubin: No significantinterference up to 29.5 mg/dL (504µmol/L).Ascorbic acid: No significant interfer-ence up to 20.0 mg/dL.Acetaminophen: No significant inter-ference up to 30.0 mg/dL.Acetylsalicylic acid: No significantinterference up to 200.0 mg/dL. | Hemoglobin: No significant interfer-ence up to an H Index of 250 (ap-proximate 250 mg/dL).Lipemia (Intralipid): No significantinfluence up to an L index of 2000.There is poor correlation between theL index (corresponds to turbidity) andtriglycerides concentration.Icterus: No significant influence up toI Index of 60 (approximate conju-gated and unconjugated bilirubin con-centration of 60 mg/dL (1026 µmol/L)). | ||
| Calibration Frequency | 1 day | 5 days | ||
| On board stability | 1 day | 10 days | ||
| Calibrator | Recommended calibration material(not included):ELITech Clinical Systems ELICAL 2 | Recommended calibration material(not included):Roche Calibrator f.a.s. | ||
| Controls | Recommended quality control material(not included):ELITech Clinical Systems ELITROL I(Normal control)ELITech Clinical Systems ELITROL II(Pathologic control) | Recommended quality control material(not included):Roche Precinorm URoche Precipath U |
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10903 New Hampshire Avenue Silver Spring, MD 20993
ELITechGroup Epoch Biosciences c/o Debra K. Hutson 21720 23rd Dr., SE Suite 150 Bothell, WA 98021 USA
DEC 2 9 2011
Re: K113269
Trade Name: ELITech Clinical Systems ALP IFCC SL Regulation Number: 21 CFR §862.1050 Regulation Name: Alkaline Phosphatase or Isoenzymes Test System Regulatory Class: Class II Product Codes: CJE Dated: December 13, 2011 Received: December 22, 2011
Dear Ms. Hutson:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm
Sincerely yours,
signature
Couriney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Form
510(k) Number (if known): _ L 32 (36 ELITech Clinical Systems ALP IFCC SL Device Name:
Indications for Use:
ELITech Clinical Systems ALP IFCC SL is intended for the quantitative in vitro diagnostic determination of alkaline phosphatase in human serum and plasma on ELITech Clinical Systems Selectra analyzers.
It is not intended for use in Point of Care settings.
Alkaline phosphatase or its isoenzymes measurements are used in the diagnosis and treatment of liver, bone, parathyroid and intestinal diseases.
Prescription Use × (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Hvanth
Division Sign Off
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K113264
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§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.