(241 days)
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No
The document describes a standard automated clinical chemistry and immunoassay analyzer and the performance of specific assays. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis focuses on traditional analytical methods and statistical performance metrics.
No.
This device is an automated analyzer used for in vitro diagnostic testing, which provides information for diagnosis and treatment but does not directly provide therapy.
Yes
The text explicitly states that the device is "intended for running qualitative, semiguantitative and quantitative clinical chemistry and immunochemistry assays as well as ion selective measurements" and that "cobas pure integrated solutions is a fully automated, random-access, software controlled system intended for in vitro quantitative and qualitative analysis of analytes in body fluids." Furthermore, it details specific assays (e.g., Glucose, Sodium, TSH) whose measurements "are used in the diagnosis and treatment of" various medical conditions, directly indicating a diagnostic purpose.
No
The device description explicitly states that the cobas pure integrated solutions is a "fully automated, random-access, software controlled system" that "consists of a clinical chemistry analytical unit (cobas c 303) with an integrated ISE analytical unit, an immunoassay analytical unit (cobas e 402) and a core unit." This indicates the device includes significant hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states that the cobas pure integrated solutions is "intended for running qualitative, semiguantitative and quantitative clinical chemistry and immunochemistry assays as well as ion selective measurements." It also describes the intended use of specific assays (Glucose HK Gen.3, ISE analytical unit for Na+, Methadone II, Elecsys TSH) for the "in vitro" determination of analytes in human samples (serum, plasma, urine, CSF) for diagnostic purposes (diagnosis and treatment of various conditions).
- Device Description: The description details a system designed for "in vitro quantitative and qualitative analysis of analytes in body fluids."
- Assay Descriptions: The descriptions of the individual assays (Glucose HK Gen.3, ISE analytical unit for Na+, Methadone II, Elecsys TSH) all describe methods for analyzing components in vitro (outside the body) using biological samples.
- Performance Studies: The performance studies described (precision, linearity, limit of blank/detection/quantitation, interference, method comparison, matrix comparison, stability) are all typical studies conducted to validate the performance of in vitro diagnostic devices.
- Predicate Devices: The listed predicate devices (K191899 cobas pro integrated solutions, K191899 Glucose HK Gen.3, K191899 ISE indirect Na for Gen.2, K021505 ONLINE DAT Methadone II, K191899 Elecsys TSH) are all known IVD devices.
The core function of the device and its associated assays is to analyze biological samples in vitro to provide information for the diagnosis and treatment of medical conditions, which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
cobas pure integrated solutions is an automated analyzer, intended for running qualitative, semiguantitative and quantitative clinical chemistry and immunochemistry assays as well as ion selective measurements.
Glucose HK Gen.3 is an in vitro test for the quantitative determination of glucose in human serum, plasma, urine and CSF on Roche/Hitachi cobas c systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoqlycemia, idiopathic hypoglycemia and pancreatic islet cell tumors.
The ISE analytical unit of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.
Methadone II (MDN2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of methadone in human urine on Roche/Hitachi cobas c systems at a cutoff concentration of 300 ng/mL. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC-MS).
Elecsys TSH is an immunoassay for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Product codes (comma separated list FDA assigned to the subject device)
CFR, JGS, DJR, JLW, JJE
Device Description
cobas pure integrated solutions
The cobas pure integrated solutions is a fully automated, random-access, software controlled system intended for in vitro quantitative and qualitative analysis of analytes in body fluids. It will typically be used in low to mid throughput clinical laboratories. The system consolidates clinical chemistry, homogenous immunoassays as well as electrolyte testing within one workplace. The cobas pure integrated solutions consists of a clinical chemistry analytical unit (cobas c 303) with an integrated ISE analytical unit, an immunoassay analytical unit (cobas e 402) and a core unit.
Glucose HK Gen. 3
Glucose is phosphorylated by hexokinase (HK) in the presence of adenosine triphosphate (ATP) and magnesium ions to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase (G-6-PDH) specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide reduced (NADH). One micromole of NADH is produced for each micromole of glucose consumed. The NADH produced absorbs light at 340 nm and can be detected spectrophotometrically as an increased absorbance.
ISE indirect Na for Gen. 2
The ISE analytical unit for Na+ employs ion-selective membrane to develop an electrical potential (electromotive force, EMF) for the measurements of ions in solution. Selective membrane is in contact with both the test solution and an internal filling solution. Due to the selectivity of the membrane, only the ions to be EMF. The membrane EMF is determined by the difference in concentration of the test ion in the test solution and the internal filling solution.
The ISE analytical unit of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium is the major extracellular cation and functions to maintain fluid distribution and osmotic pressure. Some causes of decreased levels of sodium include prolonged vomiting or diarrhed reabsorption in the kidney and excessive fluid retention. Common causes of include excessive fluid loss, high salt intake and increased kidney reabsorption.
ONLINE DAT Methadone II
The Methadone assay is based on the kinetic interaction of microparticles in a solution (KIMS) as measured by changes in light transmission. In the absence of sample drug conjugates bind to antibody-bound microparticles, causing the formation of particle aggregates. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.
When a urine sample contains the drug in question, this drug derivative conjugate for microparticle-bound antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.
Elecsys TSH
The Elecsys TSH immunoassay makes use of a sandwich test principle using monoclonal antibodies specifically directed against human TSH. The antibodies labeled with ruthenium complex) construct from human and mouse specific components. Elecsys TSH immunoassay is intended for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. It is intended for use on the cobas e immunoassay analyzers.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Glucose HK Gen.3
Precision experiments were performed in accordance with CLSI quideline EP05-A3. Two aliquots per run, two runs per day for ≥ 21 days were performed on the same cobas c 303 analytical unit using 1 lot of reagent. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated.
The linearity study was performed according to CLSI quideline EP06-A on one cobas c 303 analyzer.
The Limit of Blank (LoB) of the Glucose HK Gen.3 assay on the cobas c 303 analytical unit assay was determined according to CLS EP 17-A2.
The Limit of Detection (LoD) of the Glucose HK Gen.3 assay on the cobas c 303 analytical unit was determined according to CLSI EP 17-A.
The Limit of Quantitation (LoQ) of the Glucose HK Gen.3 assay was determined according to CLSI EP 17-A2.
Endogenous Interference studies were conducted to determine the effects of interference by hemoglobin, lipemia (Intralipid), albumin, Immunoglobulin (lgG) and bilirubin on the Glucose HK Gen.3 were determined on the cobas c 303.
Drug Interference studies were conducted to evaluate drugs for potential interference with Glucose Gen.3 HK assay measured on the cobas c 303 analytical unit.
Method Comparison experiments were performed for all sample types using the Gen.3 assay on the cobas c 303 versus the Glucose HK Gen.3 assay on the cobas c 503.
Matrix Comparison studies were performed to support the use of several different anticoagulant tube types.
On-board reagent stability was verified on the cobas c 303 for the specified time frame: 26 weeks on board.
Post Dilution Check experiments were run across the measuring range to verify the automatic rerun function of the analytical unit.
Recovery in Controls on cobas c 303 were tested.
ISE indirect Na for Gen.2
Precision experiments were performed in accordance with CLSI guideline EP05-A3. One run per day for ≥ 21 days with two parts, two aliquots per part were performed on the same cobas c 303 ISE analytical unit using one reagent lot. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated.
The linearity study was conducted to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI quideline EP06-A.
The Limit of Blank (LoB) of the ISE indirect Na for Gen. 2 assay on the cobas c 303 ISE analytical unit was determined according to CLSI EP 17-A2.
The Limit of Detection (LoD) of the ISE indirect Na for Gen. 2 assay on the cobas c 303 ISE analytical unit was determined according to CLSI EP17-A2.
The Limit of Quantitation (LoQ) of the ISE indirect Na for Gen. 2 assay was determined according to CLSI EP 17-A2.
The effects of interference by endogenous substances bilirubin, hemolysis and lipemia (htralipid) on the ISE Na test system were determined on the cobas c 303 ISE analyzer using pooled human plasma and serum samples spiked with varying levels of interferent.
A Drug Interference study was conducted to evaluate drugs for potential interference with ISE indirect Na for Gen.2 assay measured on the cobas c 303 ISE analytical unit.
Method Comparison experiments were performed for all sample types using ISE indirect Na for Gen2. on the cobas c 303 ISE versus ISE indirect Na for Gen2. on cobas pro ISE and flame photometry to assess the bias.
The effect of the presence of anticoagulants on analyte recovery was determined by matrix comparison on one cobas c 303 15E, obtained from samples drawn into Li-Heparin Plasma and Serum collection tubes.
A study verifying calibration frequency was performed.
Post Dilution Check experiments were run across the measuring range to verify the automatic rerun function of the cobas c 303 SE analytical unit.
Recovery in controls were measured on the cobas c 303 ISE analytical unit.
ONLINE DAT Methadone II
Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days).
To test endogenous interference, interfering substances were added to urine containing methadone at - 25 % of the cutoff level at specified concentrations. Samples were tested on the cobas c 303 analytical unit with the ONLINE DAT Methadone II assay.
The effects of drug interference were conducted on one cobas c 303.
Cross Reactivity studies were conducted by generating inhibition curves and determining the approximate quantity of each compound that is equivalent in assay reactivity to a 300 ng/mL assay cutoff.
Method Comparison studies were conducted with the Methadone II assay on the cobas c 303 and relative to GC-MS and relative to cobas c 503.
Recovery in Controls on cobas c 303 were tested.
Elecsys TSH
Precision measurements were conducted to evaluate repeatability (within-run precision) and the intermediate precision (withinlaboratory precision) according the CLSI guideline EP05-A3.
Linearity of the Elecsys TSH assay was assessed on the cobas e 402 Immunoassay analyzer according to CLSJ EP06-A.
LoB of the Elecsys TSH on the cobas e 402 analyzer was determined according to CLSJ EP17-A2.
LoD of the Elecsys TSH assay on the cobas e 402 Immunoassay analyzer has been determined according to CLSI EP17-A2.
The LoQ of the Elecsys TSH was determined on the cobas e 402 analyzer according to CLSI Guideline EP17-A2.
The effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys TSH was determined on the cobas e 402 immunoassay analyzer using human serum samples (native serum pools).
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with commonly and specially used pharmaceutical compounds with the reference sample (unspiked).
The effect on quantitation of analyte in the presence of potential cross-reacting compounds using the Elecsys TSH was determined on the cobas e 402 immunoassay analyzer using a native human serum sample pool.
On-board reagent stability for the Elecsys TSH assay was tested on one cobas e 402 immunoassay analyzer.
A method comparison was performed using the Elecsys TSH updated assay (candidate device, cobas e 402 in cobas pure integrated solution, Y) and the Elecsys TSH current assay (predicate device, cobas e 801 in cobas pro integrated solution, X) to assess the bias between the two assays.
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys TSH Immunoassay was determined by comparing values obtained from samples (native human serum samples, single donors as well as pools) drawn into Serum, Li-Heparin, K2-EDTA, K3-EDTA plasma tubes.
The high-dose hook effect of the Elecsys TSH assay was assessed on the cobas e 402 analyzer.
Key results: The analytical performance data for all representative assays meet specifications and support the substantial equivalence of Glucose HK Gen.3, ISE indirect Na for Gen.2, ONLINE DAT Methadone II, Elecsys TSH, and cobas pure integrated solutions to the predicate devices.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.
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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.
September 16, 2022
Roche Diagnostics Noel Mencias Program Manager, Regulatory Affairs 9115 Hague Road Indianapolis, IN 46250
Re: K220134
Trade/Device Name: Glucose HK Gen.3, ISE indirect Na for Gen.2, Elecsys TSH, ONLINE DAT Methadone II, cobas pure integrated solutions Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CFR, JGS, JLW, DJR, JJE Dated: July 1, 2022 Received: July 5, 2022
Dear Noel Mencias:
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,
Paula V. Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
Submission Number (if known)
K220134 Device Name
cobas pure integrated solutions; Glucose HK Gen.3; ISE indirect Na for Gen.2; ONLINE DAT Methadone II; Elecsys TSH ndications for Use (Describe)
Indications for Use (Describe)
cobas pure integrated solutions is an automated analyzer, intended for running qualitative, semiguantitative and quantitative clinical chemistry and immunochemistry assays as well as ion selective measurements.
Glucose HK Gen.3 is an in vitro test for the quantitative determination of glucose in human serum, plasma, urine and CSF on Roche/Hitachi cobas c systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoqlycemia, idiopathic hypoglycemia and pancreatic islet cell tumors.
The ISE analytical unit of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.
Methadone II (MDN2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of methadone in human urine on Roche/Hitachi cobas c systems at a cutoff concentration of 300 ng/mL. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC-MS).
Elecsys TSH is an immunoassay for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
e-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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| 510(k) #: K220134 | 510(k) Summary | Prepared on: 2022-09-09 |
|---|---|---|
| Contact Details | 21 CFR 807.92(a)(1) | |
| Applicant Name | Roche Diagnostics | |
| Applicant Address | 9115 Hague Road Indianapolis IN 46250 United States | |
| Applicant Contact Telephone | 463-336-2546 | |
| Applicant Contact | Mr. Noel Mencias | |
| Applicant Contact Email | noel.mencias@roche.com | |
| Device Name | 21 CFR 807.92(a)(2) | |
| Device Trade Name | Glucose HK Gen.3; | |
| ISE indirect Na for Gen.2; | ||
| ONLINE DAT Methadone II; | ||
| Elecsys TSH; | ||
| cobas pure integrated solutions | ||
| Common Name | GLUC3; ISE Na; MDN2; TSH; cobas pure integrated solutions | |
| Classification Name | Hexokinase, glucose; Electrode, ion specific, sodium; enzyme immunoass | |
| Regulation Number | 862.1345; 862.1665; 862.3620; 862.1690; 862.2160 | |
| Product Code | CFR; JGS; DJR; JLW; JJE | |
| Legally Marketed Predicate Devices 21 CFR 807.92(a)(3) | ||
| Predicate # | Predicate Trade Name (Primary Predicate is listed first) | Product Code |
| K191899 | cobas pro integrated solutions | JJE |
| K191899 | Glucose HK Gen.3 | CFR |
| K191899 | ISE indirect Na for Gen.2 | JGS |
| K021505 | ONLINE DAT Methadone II | DJR |
| K191899 | Elecsys TSH | JLW |
| Device Description Summary 21 CFR 807.92(a)(4) | ||
| cobas pure integrated solutions | ||
| The cobas pure integrated solutions is a fully automated, random-access, software controlled system intended for in vitro quantitative |
and qualitative analysis of analytes in body fluids. It will typically be used in low to mid throughput clinical laboratories. The system consolidates clinical chemistry, homogenous immunoassays as well as electrolyte testing within one workplace. The cobas pure integrated solutions consists of a clinical chemistry analytical unit (cobas c 303) with an integrated ISE analytical unit, an immunoassay analytical unit (cobas e 402) and a core unit.
Glucose HK Gen. 3
Glucose is phosphorylated by hexokinase (HK) in the presence of adenosine triphosphate (ATP) and magnesium ions to produce
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glucose-6-phosphate (G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase (G-6-PDH) specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide reduced (NADH). One micromole of NADH is produced for each micromole of glucose consumed. The NADH produced absorbs light at 340 nm and can be detected spectrophotometrically as an increased absorbance.
ISE indirect Na for Gen. 2
The ISE analytical unit for Na+ employs ion-selective membrane to develop an electrical potential (electromotive force, EMF) for the measurements of ions in solution. Selective membrane is in contact with both the test solution and an internal filling solution. Due to the selectivity of the membrane, only the ions to be EMF. The membrane EMF is determined by the difference in concentration of the test ion in the test solution and the internal filling solution.
The ISE analytical unit of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium is the major extracellular cation and functions to maintain fluid distribution and osmotic pressure. Some causes of decreased levels of sodium include prolonged vomiting or diarrhed reabsorption in the kidney and excessive fluid retention. Common causes of include excessive fluid loss, high salt intake and increased kidney reabsorption.
ONLINE DAT Methadone II
The Methadone assay is based on the kinetic interaction of microparticles in a solution (KIMS) as measured by changes in light transmission. In the absence of sample drug conjugates bind to antibody-bound microparticles, causing the formation of particle aggregates. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.
When a urine sample contains the drug in question, this drug derivative conjugate for microparticle-bound antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.
Elecsys TSH
The Elecsys TSH immunoassay makes use of a sandwich test principle using monoclonal antibodies specifically directed against human TSH. The antibodies labeled with ruthenium complex) construct from human and mouse specific components. Elecsys TSH immunoassay is intended for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. It is intended for use on the cobas e immunoassay analyzers.
Intended Use/Indications for Use
21 CFR 807.92(a)(5)
cobas pure integrated solutions is an automated analyzer, intended for running qualitative and quantitative clinical chemistry and immunochemistry assays as well as ion selective measurements.
Glucose HK Gen.3 is an in vitro test for the quantitative determination of glucose in human serum, plasma, urine and CSF on Roche/ Hitachi cobas c systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and pancreatic islet cell tumors.
The ISE analytical unit of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipids (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.
Methadone II (MDN2) is an in vitro diagnostic test for the qualitative detection of methadone in human urine on Roche/Hitachi cobas c systems at a cutoff concentration of 300 ng/mL. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmatory method such as gas chromatography/mass spectrometry (GC-MS).
Elecsys TSH is an immunoassay for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Indications for Use Comparison
21 CFR 807.92(a)(5)
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Indications for use are the same as the predicate device.
Technological Comparison
21 CFR 807.92(a)(6)
21 CFR 807.92(b)
The cobas pure integrated solutions is a next generation of the cobas 6000 analyzer series (cobas 6000) which was cleared under K060373. The cobas pro integrated solutions, cleared in K191899, is the first of the next generation platforms and the predicate of cobas pure integrated solution. The cobas pure integrated solutions consists of a clinical chemistry analytical unit (cobas c 303) with an integrated ISE analytical unit, an immunoassay analytical unit (cobas e 402) and a core unit. The clinical chemistry (CC) and the ISE analytical units are part of the existing Roche/Hitachi/cobas c family of analyzers and the immunoassay (IM) analyzer are part of the existing Elecsys family of analyzers. These share technological characteristics with the predicate solutions, modified for lower throughput. The reagents and calibrators/controls to be applied on cobas pure integrated solutions will be existing devices already cleared on existing Roche/Hitachi cobas c or Elecsys instrumentation.
The representative reagents Glucose HK Gen.3, ISE indirect Na for Gen.2, ONLINE DAT Methadone II, and Elecsys TSH share the technological characteristics of their predicate devices.
Non-Clinical and/or Clinical Tests Summary & Conclusions
Glucose HK Gen.3
Precision experiments were performed in accordance with CLSI quideline EP05-A3. Two aliquots per run, two runs per day for ≥ 21 days were performed on the same cobas c 303 analytical unit using 1 lot of reagent. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated.
The linearity study was performed according to CLSI quideline EP06-A on one cobas c 303 analyzer.
The Limit of Blank (LoB) of the Glucose HK Gen.3 assay on the cobas c 303 analytical unit assay was determined according to CLS EP 17-A2. The LoB is the highest observed measurement value for an analyte-free sample. The Limit of Blank was determined as the 95th percentile of measurements of blank samples.
The Limit of Detection (LoD) of the Glucose HK Gen.3 assay on the cobas c 303 analytical unit was determined according to CLSI EP 17-A. The LoD determines the lower limit for samples with analyte. The lowest amount of analyte in a sample that can be detected with a 95% probability.
The Limit of Quantitation (LoQ) of the Glucose HK Gen.3 assay was determined according to CLSI EP 17-A2. LoQ determines the lowest amount of analyte that can be quantitatively determined with stated experimental conditions. The LoQ was determined as the lowest concentration of analyte which can be quantified with a total error of no more than 20%.
Endogenous Interference studies were conducted to determine the effects of interference by hemoglobin, lipemia (Intralipid), albumin, Immunoglobulin (lgG) and bilirubin on the Glucose HK Gen.3 were determined on the cobas c 303.
Drug Interference studies were conducted to evaluate drugs for potential interference with Glucose Gen.3 HK assay measured on the cobas c 303 analytical unit.
Method Comparison experiments were performed for all sample types using the Gen.3 assay on the cobas c 303 versus the Glucose HK Gen.3 assay on the cobas c 503.
Matrix Comparison studies were performed to support the use of several different anticoagulant tube types.
On-board reagent stability was verified on the cobas c 303 for the specified time frame: 26 weeks on board.
Post Dilution Check experiments were run across the measuring range to verify the automatic rerun function of the analytical unit.
Recovery in Controls on cobas c 303 were tested.
ISE indirect Na for Gen.2
Precision experiments were performed in accordance with CLSI guideline EP05-A3. One run per day for ≥ 21 days with two parts, two aliquots per part were performed on the same cobas c 303 ISE analytical unit using one reagent lot. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated.
The linearity study was conducted to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI quideline EP06-A.
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The Limit of Blank (LoB) of the ISE indirect Na for Gen. 2 assay on the cobas c 303 ISE analytical unit was determined according to CLSI EP 17-A2. The LoB is the highest observed measurement value for an analyte-free sample. The Limit of Blank was determined as the 95th percentile of measurements of blank samples.
The Limit of Detection (LoD) of the ISE indirect Na for Gen. 2 assay on the cobas c 303 ISE analytical unit was determined according to CLSI EP17-A2. The LoD determines the lower limit for samples with analyte. The lowest amount of analyte in a sample that can be detected with a 95% probability.
The Limit of Quantitation (LoQ) of the ISE indirect Na for Gen. 2 assay was determined according to CLSI EP 17-A2.
LoQ determines the lowest amount of analyte that can be quantitatively determined with stated experimental conditions. The LoQ was determined as the lowest concentration of analyte which a total error of no more than 30%.
The effects of interference by endogenous substances bilirubin, hemolysis and lipemia (htralipid) on the ISE Na test system were determined on the cobas c 303 ISE analyzer using pooled human plasma and serum samples spiked with varying levels of interferent.
A Drug Interference study was conducted to evaluate drugs for potential interference with ISE indirect Na for Gen.2 assay measured on the cobas c 303 ISE analytical unit.
Method Comparison experiments were performed for all sample types using ISE indirect Na for Gen2. on the cobas c 303 ISE versus ISE indirect Na for Gen2. on cobas pro ISE and flame photometry to assess the bias.
The effect of the presence of anticoagulants on analyte recovery was determined by matrix comparison on one cobas c 303 15E, obtained from samples drawn into Li-Heparin Plasma and Serum collection tubes.
A study verifying calibration frequency was performed.
Post Dilution Check experiments were run across the measuring range to verify the automatic rerun function of the cobas c 303 SE analytical unit.
Recovery in controls were measured on the cobas c 303 ISE analytical unit.
ONLINE DAT Methadone II
Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days).
To test endogenous interference, interfering substances were added to urine containing methadone at - 25 % of the cutoff level at specified concentrations. Samples were tested on the cobas c 303 analytical unit with the ONLINE DAT Methadone II assay.
The effects of drug interference were conducted on one cobas c 303. Aliguots of the drug in a human urine containing methadone at the control level concentrations were prepared. The compounds were added at the specified concentrations to pooled human urine containing methadone at a concentration of 225 ng/mL (negative control level) or 375 ng/mL (positive control level). For each compound, negative results relative to the 300 ng/mL cutoff were obtained for the samples containing methadone at a concentration of 225 ng/ml (negative control level) and positive results were obtaining methadone at a concentration of 375 ng/mL (positive control level), with the Methadone II assay.
Cross Reactivity studies were conducted by generating inhibition curves and determining the approximate quantity of each compound that is equivalent in assay reactivity to a 300 ng/mL assay cutoff.
Method Comparison studies were conducted with the Methadone II assay on the cobas c 303 and relative to GC-MS and relative to cobas c 503.
Recovery in Controls on cobas c 303 were tested.
Elecsys TSH
Precision measurements were conducted to evaluate repeatability (within-run precision) and the intermediate precision (withinlaboratory precision) according the CLSI guideline EP05-A3.
Linearity of the Elecsys TSH assay was assessed on the cobas e 402 Immunoassay analyzer according to CLSJ EP06-A.
LoB of the Elecsys TSH on the cobas e 402 analyzer was determined according to CLSJ EP17-A2. Limit of Blank determines the highest
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observed measurement values for samples The Limit of Blank was determined as the 95th percentile of measurements of blank samples.
LoD of the Elecsys TSH assay on the cobas e 402 Immunoassay analyzer has been determined according to CLSI EP17-A2. The LoD was determined as the lowest amount of analyte in a sample that can be detected with 95% probability.
The LoQ of the Elecsys TSH was determined on the cobas e 402 analyzer according to CLSI Guideline EP17-A2. LoQ determines the lowest amount of analyte that an be quantitatively determined with stated experimental conditions. The LoO was determined as the lowest concentration of analyte which can be quantified with a total error of no more than 20%.
The effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys TSH was determined on the cobas e 402 immunoassay analyzer using human serum samples (native serum pools).
The effect on quantitation of analyte in the presence of drugs was determined by comparing values obtained from samples spiked with commonly and specially used pharmaceutical compounds with the reference sample (unspiked).
The effect on quantitation of analyte in the presence of potential cross-reacting compounds using the Elecsys TSH was determined on the cobas e 402 immunoassay analyzer using a native human serum sample pool.
On-board reagent stability for the Elecsys TSH assay was tested on one cobas e 402 immunoassay analyzer.
A method comparison was performed using the Elecsys TSH updated assay (candidate device, cobas e 402 in cobas pure integrated solution, Y) and the Elecsys TSH current assay (predicate device, cobas e 801 in cobas pro integrated solution, X) to assess the bias between the two assays.
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys TSH Immunoassay was determined by comparing values obtained from samples (native human serum samples, single donors as well as pools) drawn into Serum, Li-Heparin, K2-EDTA, K3-EDTA plasma tubes.
The high-dose hook effect of the Elecsys TSH assay was assessed on the cobas e 402 analyzer.
The analytical performance data for all representative assays meet specifications and support the substantial equivalence of Glucose HK Gen.3, ISE indirect Na for Gen.2, ONLINE DAT Methadone II, Elecsys TSH, and cobas pure integrated solutions to the predicate devices.