(455 days)
For the quantitative determination of creatine kinase activity in serum and plasma. Rx only.
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infaction and muscle disease, such as progressive Duchenne-type muscular dystrophy.
The Pointe Scientific Creatine Kinase (CK) Reagent Set consists of ready-to-use liguid reagents:
- . CK R1 (buffer) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L; NADP 2.0 mmol/L: HK (Baker's yeast) 2.5 KU/L: Glucose 20.0 mmol/L: Magnesium Acetate 10.0 mmol/L; EDTA 2.0 mmol/L and N-acetylcysteine (NAC) 20.0 mmol/L.
- . CK R2 (enzyme reagent) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L: ADP 2.0 mmol/L: AMP 5.0 mmol/L: Diadensosine pentaphosphate 10.0 mmol/L: Creatine phosphate 30.0 mmol/L; G6PDH (Baker's yeast) 1.5 KU/L and EDTA 2.0 mmol/L.
The kinetic procedure presented is a modification of Szasz of the Rosalki technique, which optimizes the reaction by reactivation of CK activity with N-actyl-L-cysteine (NAC).
Creatine Kinase specifically catalyzes the transphosphorylation of ADP to ATP. Through a series of coupled enzymatic reactions, NADPH is produced at a rate directly proportional to the CK activity. The method determines the NADPH absorbance increase per min at 340 nm.
The provided document describes the analytical performance studies for the Pointe Scientific Creatine Kinase (CK) Reagent Set, which supports its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance:
The document doesn't explicitly state "acceptance criteria" in a separate table for each test. Instead, it presents the study results and implies that these results were considered acceptable for demonstrating substantial equivalence. For some tests, like Linearity, an acceptable deviation is stated.
However, based on the provided performance data, we can infer the acceptance criteria that the manufacturer likely aimed for to support their claims.
| Performance Study | Implied Acceptance Criteria (Inferred from results/general practice) | Reported Device Performance (Pointe Scientific Creatine Kinase (CK) Reagent Set) |
|---|---|---|
| Method Comparison (Serum vs. Predicate) | High correlation (e.g., R > 0.975), acceptable bias | Correlation Coefficient: 0.9991, Regression: y = 1.041x - 5.2 |
| Method Comparison (Plasma vs. Predicate) | High correlation (e.g., R > 0.975), acceptable bias | Correlation Coefficient: 0.9946, Regression: y = 1.032x - 0.4 |
| Precision (Controls & Patient Samples - Serum/Plasma) | Low CV% for repeatability and total precision (typically <5-10% depending on analyte level) | Repeatability CV%: 0.5-1.7%, Total CV%: 1.5-3.8% across various levels |
| Linearity/Assay Range | % Recovery within a specified range (e.g., 90-110%) | % Recovery: 92-105% (Serum & Plasma) for the claimed range (9-1200 U/L) |
| Detection Capability (LoB) | LoB consistent with clinical need for low-level detection | LoB: 2 U/L (Serum & Plasma) |
| Detection Capability (LoD) | LoD consistent with clinical need for low-level detection | LoD: 4 U/L (Serum & Plasma) |
| Detection Capability (LoQ) | LoQ defined by a precision CV < 20% | LoQ: 8 U/L (Serum & Plasma) |
| Dilution Recovery | % recovery within a specified range (e.g., 90-110%) for diluted samples | % Recovery: 90-109% (Serum & Plasma) for samples diluted up to 1:12 |
| Analytical Specificity (Endogenous Substances) | No significant interference (defined as % difference > 10% from control) up to clinically relevant concentrations | Bilirubin, Ascorbic Acid, Hemoglobin, Intralipid showed no significant interference at high concentrations (e.g., Bilirubin 60 mg/dL, Hemoglobin 500 mg/dL) |
2. Sample size used for the test set and the data provenance:
- Method Comparison (Serum):
- Sample Size: 120 de-identified remnant serum samples. 4 samples were altered by mixing.
- Data Provenance: Obtained from a commercial repository. Retrospective. Country of origin not specified, but likely within the US given the FDA submission.
- Method Comparison (Plasma):
- Sample Size: 123 de-identified remnant plasma samples. 2 samples were altered by mixing.
- Data Provenance: Obtained from a commercial repository. Retrospective. Country of origin not specified.
- Precision Studies:
- Sample Size: 2 commercial quality controls, 3 serum pools, and 3 plasma pools. Each pool/control was tested in duplicate twice per day for 20 days (n=80 per sample type).
- Data Provenance: Not explicitly stated, but common practice is for manufacturers to prepare pools or use commercially available controls.
- Linearity/Assay Range Study:
- Sample Size: A set of 12 serum samples and 12 plasma samples (prepared by admixture of high-level and low-level pools).
- Data Provenance: Not explicitly stated, likely prepared in-house or from common available resources.
- Detection Capability (LoB, LoD, LoQ):
- LoB: Saline (1 sample * 20 repetitions * 3 days).
- LoD: 20 low-level depleted serum samples and 20 depleted plasma samples.
- LoQ: 5 low activity samples (each run in 8 duplicates over 5 days).
- Data Provenance: Not explicitly stated, likely prepared in-house or from common available resources.
- Dilution Recovery Studies:
- Sample Size: Three contrived high-level samples for both serum and plasma.
- Data Provenance: Not explicitly stated, likely prepared in-house.
- Analytical Specificity (Endogenous Substances):
- Sample Size: Not explicitly stated, but interference testing was conducted using "randomly selected serum and plasma samples ranging from 43 U/L to 268 U/L."
- Data Provenance: Not explicitly stated.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is a diagnostic reagent for quantitative determination of an analyte (Creatine Kinase), not an imaging or qualitative diagnostic device requiring expert interpretation of results to establish ground truth.
- Ground Truth for Method Comparison: The predicate device's results (Beckman Coulter Creatine Kinase (CK-Nac) on the Beckman Coulter Olympus AU400 Clinical Chemistry Analyzer) serve as the "reference" or "ground truth" for comparison. This is a common method for demonstrating substantial equivalence for in vitro diagnostic (IVD) devices. No human experts are used to establish ground truth in this context; rather, the established method of the predicate device is the reference.
- Ground Truth for other studies (Precision, Linearity, Detection, Dilution Recovery, Specificity): The "ground truth" is typically established by the analytical method itself, or by preparing samples with known concentrations/characteristics, without the need for human expert consensus.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
No adjudication method is relevant or mentioned as this device measures an objective biochemical marker. The 'ground truth' is the quantitative measurement itself or the reference method's result.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
No. This is not applicable. The device is a diagnostic reagent for quantitative measurement of creatine kinase, not an AI-powered diagnostic system for image interpretation or a device requiring human readers/scorers. Therefore, MRMC studies are not relevant.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device is a reagent set used on an automated chemistry analyzer (Shenzhen Mindray BA-800M Chemistry Analyzer). The performance studies presented are for the "algorithm only" in the sense that they demonstrate the analytical performance of the reagent on the analyzer without human interpretation of the raw data to generate the numerical result. The "human-in-the-loop" would be a lab technician performing the test and reviewing the results, but the analytical performance itself is standalone.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Method Comparison: The results obtained from the legally marketed predicate device (Beckman Coulter Creatine Kinase (CK-Nac) on the Beckman Coulter Olympus AU400 Clinical Chemistry Analyzer) served as the reference for comparison.
- Precision, Linearity, Detection, Dilution Recovery, Analytical Specificity: Ground truth is based on the inherent analytical properties of the method/reagent including samples with known concentrations (e.g., prepared standards, spiked samples, qualified controls, or established reference material). Linearity was assessed against expected values based on known admixtures. Detection limits were determined using statistical methods on low-level and blank samples.
8. The sample size for the training set:
There is no "training set" in the context of this 510(k) submission for a diagnostic reagent. This device is not an AI/machine learning algorithm that requires training data. The studies performed are analytical validation studies.
9. How the ground truth for the training set was established:
Not applicable, as there is no training set for this type of medical device.
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August 11, 2020
MedTest Dx William Cripps Director, R&D, QA/RA 5449 Research Drive Canton, MI 48188
Re: K191296
Trade/Device Name: Pointe Scientific Creatine Kinase (CK) Reagent Set Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: CGS Dated: July 8, 2020 Received: July 10, 2020
Dear William Cripps:
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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.
510(k) Number (if known) K191296
Device Name
Pointe Scientific Creatine Kinase (CK) Reagent Set
Indications for Use (Describe)
For the quantitative determination of creatine kinase activity in serum and plasma. Rx only.
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infaction and muscle disease, such as progressive Duchenne-type muscular dystrophy.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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FORM FDA 3881 (7/17)
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5. 510(k) SUMMARY (K191296)
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
a. Device Information
| Category | Comments |
|---|---|
| Sponsor | MedTest Dx5449 Research DriveCanton, MI 48188Phone: 734-487-8300Fax: 734-483-1592 |
| CorrespondentContact Information | William CrippsDirector, R&D/RA/QAEmail: wcripps@medtestdx.comPhone: 734-487-8300 ext. 120Fax: 734-483-1592 |
| Device CommonName | Creatine Kinase (CK) |
| Trade or ProprietaryName | Pointe Scientific Creatine Kinase (CK) Reagent Set |
| Candidate DeviceProduct Code,Classification,Classification Name& Panel | CGS, Class II, 21 CFR 862.1215 - Nad Reduction/NadhOxidation, Cpk Or Isoenzymes, 75 – Clinical Chemistry |
Predicate Device Information
| Predicate Device | Olympus Creatine KinaseReagent |
|---|---|
| Predicate DeviceManufacturer | Beckman Coulter, Inc. |
| Predicate DevicePremarketNotification #: | K043202 |
b. Date Summary Prepared
May 10, 2019 Updated on: October 4, 2019 Updated on: November 8, 2019 Updated on: July 8, 2020 Updated on: August 4, 2020
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c. Description of Device
The Pointe Scientific Creatine Kinase (CK) Reagent Set consists of ready-to-use liguid reagents:
- . CK R1 (buffer) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L; NADP 2.0 mmol/L: HK (Baker's yeast) 2.5 KU/L: Glucose 20.0 mmol/L: Magnesium Acetate 10.0 mmol/L; EDTA 2.0 mmol/L and N-acetylcysteine (NAC) 20.0 mmol/L.
- . CK R2 (enzyme reagent) contains: Imidazole buffer (pH 6.7) 100.0 mmol/L: ADP 2.0 mmol/L: AMP 5.0 mmol/L: Diadensosine pentaphosphate 10.0 mmol/L: Creatine phosphate 30.0 mmol/L; G6PDH (Baker's yeast) 1.5 KU/L and EDTA 2.0 mmol/L.
The kinetic procedure presented is a modification of Szasz of the Rosalki technique, which optimizes the reaction by reactivation of CK activity with N-actyl-L-cysteine (NAC).
Creatine Kinase specifically catalyzes the transphosphorylation of ADP to ATP. Through a series of coupled enzymatic reactions, NADPH is produced at a rate directly proportional to the CK activity. The method determines the NADPH absorbance increase per min at 340 nm.
d. Intended Use
For the quantitative determination of creatine kinase activity in serum and plasma. Rx Only.
Measurements of Creatine Kinase are used in the diagnosis and treatment of myocardial infarction and muscle disease, such as progressive Duchenne-type muscular dystrophy.
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e. Comparison to Predicate Device
The chart below illustrates the similarities between the Pointe Scientific Creatine Kinase (CK) Reagent Set and the predicate, Beckman Coulter Creatine Kinase.
| Characteristics | Pointe Scientific CreatineKinase (CK) Reagent Set(Proposed Device) | Beckman Coulter K043202(Predicate Device) |
|---|---|---|
| Intended Use | For the quantitativedetermination of creatine kinaseactivity in serum and plasma. RxOnly.Measurements of CreatineKinase are used in the diagnosisand treatment of myocardialinfarction and muscle disease,such as progressive Duchenne-type muscular dystrophy. | For use in the Olympusautomated clinical chemistryanalyzers for the quantitativedetermination of creatinekinase activity in humanserum and plasmaMeasurements of CreatineKinase are used in thediagnosis and treatment ofmyocardial infarction andmuscle disease, such asprogressive Duchenne-typemuscular dystrophy. |
| Contents | • CK R1 (buffer) contains:Imidazole buffer (pH 6.7) 100.0mmol/L; NADP 2.0 mmol/L; HK(Baker's yeast) 2.5 KU/L;Glucose 20.0 mmol/L;Magnesium Acetate 10.0mmol/L; EDTA 2.0 mmol/L andN-acetylcysteine (NAC) 20.0mmol/L.• CK R2 (enzyme reagent)contains: Imidazole buffer (pH6.7) 100.0 mmol/L; ADP 2.0mmol/L; AMP 5.0 mmol/L;Diadensosine pentaphosphate10.0 mmol/L;Creatinephosphate 30.0 mmol/L;G6PDH (Baker's yeast) 1.5KU/L and EDTA 2.0 mmol/L. | • Final concentration ofreactive ingredients:• Imidazole (pH 6.5) 100mmol/L• HK (Yeast) ≥ 4.0 kU/L (66.7µkat/L)• NADP 2 mmol/L• G6P-DH (Leuconostocmesenteroides) ≥ 2.8 kU/L(46.7 µkat/L)• ADP 2 mmol/L• Mg2+ 20 mmol/L• AMP 5 mmol/L• Diadenosinepentaphosphate 10 µmol/L• EDTA 2 mmol/L• Glucose 20 mmol/L• Creatine Phosphate 30mmol/L• N-Acetylcysteine 0.2 mmol/L• Stabilizers• Also contains preservatives |
| Principle | The kinetic procedure presentedis a modification of Szasz of theRosalki technique, whichoptimizes the reaction byreactivation of CK activity withN-actyl-L-cysteine (NAC).CK specifically catalyzes thetransphosphorylation of ADP toATP. Through a series ofcoupled enzymatic reactions,NADPH is produced at a ratedirectly proportional to the CKactivity. The method determinesthe NADPH absorbanceincrease per min at 340 nm. | This CK procedure is amodification of the IFCCmethod. CK reversiblycatalyzes the transfer of aphosphate group fromcreatine phosphate toadenosine diphosphate (ADP)to give creatine andadenosine triphosphate (ATP)as products. The ATP formedis used to produce glucose-6-phosphate and ADP fromglucose. This reaction iscatalyzed by hexokinase (HK)which requires magnesiumions for maximum activity.The glucose6-phosphate isoxidized by the action of theenzyme glucose-6-phosphatedehydrogenase (G6P-DH)with simultaneous reductionof the coenzymenicotinamide adeninedinucleotide (NADP) to giveNADPH and 6-phosphogluconate. The rateof increase of absorbance at340/660 nm due to theformation of NADPH isdirectly proportional to theactivity of CK in the sample |
| Sample Type | Serum and lithium heparinplasma | Serum and heparinizedplasma |
| MeasurementRange | 9-1200 U/L | 10-2000 U/L |
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Performance Data
All analytical performance studies presented below were performed on the Shenzhen Mindrav BA-800M Chemistry Analyzer. All studies were performed using either serum samples collected in serum separator tubes (SST) or plasma collected in lithium heparin tubes.
Method Comparison Study
Two separate split-sample method comparison studies between the Pointe Scientific Creatine Kinase (CK) Reagent Set on the Shenzhen Mindray BA-800M Chemistry Analyzer versus the predicate Beckman Coulter Creatine Kinase (CK-Nac) on the Beckman Coulter Olympus AU400 Clinical Chemistry Analyzer were performed on either serum or plasma samples following CLSI EP09-A2 guidelines using one lot of each of the manufacturer's reagents and a single BA-800M Chemistry analyzer and a single AU400 Clinical Chemistry Analyzer.
a. Method Comparison with serum:
A total of 120 deidentified remnant serum samples were obtained from a commercial repository and tested in duplicate across the assay range of 9-1188 U/L. Of these samples, 4 were altered by mixing of two samples together to obtain an analyte level within the measurement range. Samples were analyzed in singlicate. Results using a Deming regression were obtained with EP Evaluator Software. Results from single representative data set are summarized below:
| Serum-Serum | |
|---|---|
| Method | Creatine Kinase |
| N | 120 |
| Range (U/L) | 9-1188 |
| Standard Deviation | 249.5 |
| Regression Analysis | y = 1.041x - 5.2 |
| Correlation Coefficient | 0.9991 |
b. Method Comparison with plasma:
A total of 123 deidentified remnant Plasma samples were obtained from a commercial repository and tested in duplicate across the assay range of 9-1119 U/L. Of these samples, 2 were altered by mixing of two samples together to obtain an analyte level within the measurement range. Samples were analyzed in singlicate. Results using a Deming regression were obtained with EP Evaluator Software. Results from single representative data set are summarized below:
| Plasma-Plasma | |
|---|---|
| Method | Creatine Kinase |
| N | 123 |
| Range (U/L) | 9-1119 |
| Standard Deviation | 255.4 |
| Regression Analysis | $y = 1.032x - 0.4$ |
| Correlation Coefficient | 0.9946 |
Plasma-Plasma
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Precision Studies
Precision studies were conducted in accordance with CLSI EP05-A3. Samples consisted of two commercial quality controls, three serum pools and three plasma pools. Analyte levels of the tested pools approximated Westgard medical decision points for normal and elevated creatine kinase levels. A third level for each matrix was included above the mid-point of the measurable range for each matrix.
Testing was performed utilizing two lots of the Pointe Scientific Creatine Kinase (CK) Reagent Set on the same Shenzhen Mindray BA-800M Chemistry Analyzer. Pools were tested in duplicate twice per day for a total of 20 days (final n per sample = 80). Results from a single representative lot are summarized below.
| Matrix | Sample | N | Mean CK | Repeatability | Total | ||
|---|---|---|---|---|---|---|---|
| (U/L) | SD | %CV | SD | %CV | |||
| Controls | Control 1 | 80 | 134.37 | 1.22 | 0.9 | 1.97 | 1.5 |
| Controls | Control 2 | 80 | 265.18 | 1.35 | 0.5 | 4.39 | 1.7 |
| Serum | Level 1 | 80 | 88.19 | 1.50 | 1.7 | 3.16 | 3.6 |
| Serum | Level 2 | 80 | 288.02 | 1.79 | 0.8 | 8.71 | 3.8 |
| Serum | Level 3 | 80 | 691.63 | 3.20 | 0.5 | 10.40 | 1.5 |
| Plasma | Level 1 | 80 | 109.18 | 1.12 | 1.0 | 3.83 | 3.5 |
| Plasma | Level 2 | 80 | 219.33 | 1.36 | 0.6 | 5.05 | 2.3 |
| Plasma | Level 3 | 80 | 686.11 | 5.79 | 0.8 | 13.86 | 2.0 |
Linearity/Assay Range Study
A linearity study was conducted according to CLSI EP06-A. A set of 12 serum samples ranging from 9 to 1700 U/L or 12 plasma samples ranging from 8 to 1595 U/L were prepared by admixture of high-level and low-level sample pools. Each admixture was analyzed in duplicate using two lots of reagent on the same Shenzhen Mindray BA-800M Chemistry Analyzer.
The results from one representative lot run are summarized below. Acceptable deviation from expected value was set at less than or equal to 10%. The linearity study data supports the claimed range of 9 to 1200 U/L.
| Matrix: Serum | Matrix: Plasma | ||||||
|---|---|---|---|---|---|---|---|
| Sample | MeanResult | ExpectedResult | %Recovery | Sample | MeanResult | ExpectedResult | %Recovery |
| Low | 9 | 9 | 100% | Low | 8 | 8 | 100% |
| Dil 1 | 96 | 94 | 102% | Dil 1 | 88 | 87 | 102% |
| Dil 2 | 145 | 145 | 100% | Dil 2 | 133 | 135 | 99% |
| Dil 3 | 222 | 221 | 100% | Dil 3 | 196 | 206 | 95% |
| Dil 4 | 252 | 263 | 96% | Dil 4 | 227 | 246 | 93% |
| Dil 5 | 423 | 432 | 98% | Dil 5 | 372 | 404 | 92% |
| Dil 6 | 645 | 643 | 100% | Dil 6 | 595 | 603 | 99% |
| Dil 7 | 855 | 855 | 100% | Dil 7 | 801 | 801 | 100% |
| Dil 8 | 1060 | 1066 | 99% | Dil 8 | 1024 | 999 | 102% |
| Dil 9 | 1254 | 1277 | 98% | Dil 9 | 1206 | 1198 | 101% |
| Dil 10 | 1448 | 1489 | 97% | Dil 10 | 1455 | 1396 | 104% |
| High | 1637 | 1700 | 96% | High | 1669 | 1595 | 105% |
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Detection Capability
The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined for both serum and plasma in accordance to CLSI EP17-A2 suggested quidelines on two lots of Pointe Creatine Kinase (CK) Reagent Sets and a single BA-800M Chemistry Analyzer.
Saline was used as the blank sample for the determination of LoB. Sixty measurements (1 sample X 20 repetitions x 3 days each) were analyzed across two lots of reagent to determine the LoB of the system. Using a non-parametric distribution calculation of LoB, as detailed in CLSI EP17-A2, the limit of blank was determined to be 2 U/L.
For LoD determination, twenty low-level depleted serum samples and twenty depleted plasma samples were analyzed in duplicate across two lots of reagent within a single day. Results were used in conjunction with Limit of Blank results to determine LoD using the equation LoD=LoB +1.625(SDLow Level Samples), per CLSI 17-A2 quidance. Results from one representative lot are presented below.
The LoQ is the lowest amount of creatine kinase that can be determined quantitatively within a defined precision (<20% CV). A series of 5 low activity samples were each run in 8 duplicates over a range of 5 days. Data analysis was performed by EP Evaluator statistical software. The LoQ value was derived from the lowest sample results exhibiting a precision CV of less than 20%.
| Creatine Kinase (U/L) | |||
|---|---|---|---|
| Plasma | Serum | ||
| Limit of Blank | 2 | 2 | |
| Limit of Detection | ব | ব | |
| Limit of Quantitation | ರ | ರ |
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Dilution Recovery Studies
Studies were performed to provide evidence that values of highly concentrated samples of creatine kinase outside of the claimed measurement range (9-1200 U/L) can be accurately determined through a 10-fold dilution of the sample (as prescribed in the instruction for use). A dilution recovery study was undertaken utilizing suggested methods from CLSI EP34-E1. Three contrived high-level samples greater than the Pointe Creatine Kinase (CK) Reagent Set's measurement range for both serum and plasma were diluted in physiological saline at dilutions of 1:2; 1:4; 1;10 and 1:12 then subsequently analyzed using two lots of the Pointe Creatine Kinase (CK) Reagent set on the same Shenzhen Mindray BA-800M Chemistry. Results from one representative reagent lot for each matrix type are presented below.
| Dilution Factor | Mean(U/L, dilute) | TheoreticalResult (U/L) | Calculated Result(U/L) | % recovery |
|---|---|---|---|---|
| Matrix: Serum | ||||
| 1:2 | 1664.5 | 3686 | 3329 | 90 |
| 1:4 | 903 | 3686 | 3612 | 98 |
| 1:10 | 380 | 3686 | 3800 | 103 |
| 1:12 | 322.5 | 3686 | 3870 | 105 |
| Matrix: Plasma | ||||
| 1:2 | 1608 | 3064 | 3216 | 105 |
| 1:4 | 832 | 3064 | 3328 | 109 |
| 1:10 | 328.5 | 3064 | 3285 | 107 |
| 1:12 | 266 | 3064 | 3192 | 104 |
Analytical Specificity (Endogenous Substances)
Interference studies were performed following the recommendation of CLSI EP07-A3. Interference testing was conducted using one lot of reagent and one Mindray BA-800M analyzer. All interferents were evaluated in randomly selected serum and plasma samples ranging from 43 U/L to 268 U/L. Interferents were tested across an evenly spaced range of concentrations. The range of interferent concentrations were derived through admixtures of high and low interferent concentration pools. Significant interference was defined by the sponsor as a percent difference greater than 10% from control.
| Interferent | Highest Concentration at which nosignificant interference was observed |
|---|---|
| Bilirubin (Conjugated andUnconjugated) | 60 mg/dL |
| Ascorbic Acid | 500 mg/dL |
| Hemoglobin | 500 mg/dL |
| Intralipid | 1382 mg/dL |
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Traceability, Stability, Expected values
Traceability: The Pointe Scientific Creatine Kinase (CK) Assay is traceable to the IFCC reference method.
Stability: The reagent shelf life stability claim is 24 months at 2-8°C. The reagent onboard (in use and refrigerated) stability claim is 29 days.
Expected Values: This information is the same as for the predicate device (K043202). The expected values in an adult population (from 200 blood donors in North Texas) are 30-223 U/L creatine kinase.
Conclusion: Based on the results of the testing conducted, the Pointe Scientific Creatine Kinase (CK) Reagent Set is substantially equivalent to the predicate device, the Olympus Creatine Kinase Reagent (K043202).
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.