(876 days)
The FINDER G6PD test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood specimens collected in lithium heparin tubes, for the identification of G6PD deficient samples. The FINDER G6PD test is intended to be used with the FINDER Instrument in point of care or clinical laboratory settings.
The FINDER G6PD test system measures G6PD quantitatively from a 50uL venous whole blood specimen. The blood specimen should be collected in lithium heparin anticoagulant. The G6PD test system is suitable for use in both a point-of-care setting and a clinical laboratory. The time to result is around 16 minutes from sample introduction. The FINDER G6PD test system consists of the FINDER G6PD Test Cartridge and the FINDER Instrument. The cartridge uses electrowetting-based digital microfluidics to integrate and automate all the sample and reagent handling steps. The instrument contains all the hardware and software required to operate the cartridge, providing electrowetting control, thermal control and detection capability, a touch-screen user interface and software necessary to perform the test and report results.
FINDER G6PD Test: Acceptance Criteria and Performance Study
The FINDER G6PD Test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood to identify G6PD deficient samples. The device is used with the FINDER Instrument in point-of-care or clinical laboratory settings.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate section with specific numerical targets. However, the performance data presented from precision, linearity, interference, sensitivity, and method comparison studies collectively demonstrate the device's acceptable performance in comparison to the predicate device and established guidelines. For the purpose of this analysis, key performance metrics from the non-clinical and clinical studies will be presented as the "reported device performance."
| Category | Specific Metric | Reported Device Performance |
|---|---|---|
| Precision | Single Site Precision (CV%) | |
| (Hemolysate Controls) | Low (1.4 U/gHb) | Repeatability: 4.1%, Reproducibility: 6.5% |
| Intermediate (7.0 U/gHb) | Repeatability: 3.6%, Reproducibility: 5.3% | |
| High (17.4 U/gHb) | Repeatability: 2.4%, Reproducibility: 5.2% | |
| Reproducibility Precision (CV%) | ||
| (Fresh Whole Blood) | Low (1.1 U/gHb) | Repeatability: 5.9%, Reproducibility: 6.0% |
| Intermediate (3.5 U/gHb) | Repeatability: 3.4%, Reproducibility: 4.4% | |
| High (11.2 U/gHb) | Repeatability: 6.6%, Reproducibility: 7.0% | |
| Linearity | Linear Range | 0.8 to 19.7 U/g Hb |
| Interference | Endogenous Substances | Non-interfering at maximum tested concentrations (e.g., Bilirubin 50 mg/dL, Hemoglobin 5 g/L) |
| Common Drugs | Non-interfering at maximum tested concentrations (e.g., Ampicillin 0.16 mM, Ibuprofen 2.5 mM) | |
| Hematocrit | Bias of -15.3% at 29% Hct (normal sample), -11.1% at 30% Hct (MDL sample) compared to 50% Hct. | |
| Sensitivity | Limit of Blank (LoB) | 0.2 U/g Hb |
| Limit of Detection (LoD) | 0.4 U/g Hb | |
| Limit of Quantitation (LoQ) | 1.1 U/g Hb | |
| Method Comparison | Slope (95% CI) | 0.92 (0.89, 0.95) |
| Intercept (95% CI) | 0.28 (0.12, 0.44) | |
| Correlation Coefficient | 0.9 | |
| Bias at 3.1 U/gHb (30% AMM) | 0.0 U/gHb (-0.1, 0.2) or 1.4% (-2.5%, 5.4%) | |
| Bias at 8.4 U/gHb (80% AMM) | -0.4 U/gHb (-0.5, 0.2) or -4.3% (-6.5%, -2.0%) | |
| Categorical Agreement (<30% AMM vs ≥30% AMM) | Agreement: 98.8% (95% CI: 95.7%, 99.7%) | |
| Categorical Agreement (<70% AMM vs ≥70% AMM) | Agreement: 94.0% (95% CI: 89.3%, 96.7%) | |
| Categorical Agreement (<80% AMM vs ≥80% AMM) | Agreement: 90.4% (95% CI: 85.0%, 94.0%) |
2. Sample Size Used for the Test Set and Data Provenance
For the Clinical Method Comparison Study (test set):
- Sample Size: 200 subjects. The results of 167 samples were used in the concordance analysis after the first 36 normal male samples were used to calculate the adjusted male median.
- Data Provenance: Venous whole blood samples were collected from 6 sites, including one biorepository. The samples were collected in lithium heparin tubes. The study design was based on CLSI EP09-c – Measurement Procedure Comparison and Bias Estimation Using Patient Samples. The subjects included 89 males and 92 females with ages ranging from 20 to 72 years. 19 contrived samples were also included in the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their qualifications used to establish the ground truth for the test set. Instead, the "ground truth" for the method comparison study was established by a comparator method: the Pointe Scientific Glucose-6-Phosphate Dehydrogenase Reagent Set (K024006), run on a Cobas Mira instrument. This predicate device served as the reference method.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method involving human experts for the test set. The comparison was made directly between the FINDER G6PD Test results and the results obtained from the predicate device (Pointe Scientific G6PD Reagent Set on Cobas Mira).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no indication of a multi-reader multi-case (MRMC) comparative effectiveness study being performed in this document. The study focuses on the performance of the device (FINDER G6PD Test) compared to a predicate device, not on human readers' improvement with or without AI assistance. The FINDER G6PD Test is an in vitro diagnostic device, not an imaging AI diagnostic tool for human readers.
6. Standalone Performance Study
Yes, a standalone performance study was conducted for the FINDER G6PD Test. All the non-clinical and clinical performance data presented (precision, linearity, interference, sensitivity, and method comparison) reflect the performance of the FINDER G6PD Test system (FINDER G6PD Test Cartridge + FINDER Instrument) operating by itself, without human interpretation of the primary result. The results are reported directly by the instrument in U/gHb and as a % of the site-specific Adjusted Male Median (AMM).
7. Type of Ground Truth Used
The ground truth for the clinical method comparison study was established using a comparator method, specifically the Pointe Scientific Glucose-6-Phosphate Dehydrogenase (G6PD) Reagent Set (K024006) run on a Cobas Mira instrument. This serves as a reference standard for measuring G6PD activity.
8. Sample Size for the Training Set
The document does not specify a distinct "training set" sample size for developing the FINDER G6PD Test. This is typical for IVD devices that measure an analyte directly, where the underlying principle is biochemical and validated through analytical and clinical performance studies, rather than a machine learning model that requires a labeled training dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" described in the context of a machine learning model for this IVD device, the concept of establishing ground truth for a training set does not directly apply. The "training" for the device's underlying measurement methodology would involve established biochemical principles and extensive internal analytical validation prior to the formal performance studies presented in the 510(k) submission.
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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 and 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 14, 2022
Baebies, Inc. Candice Prowse Regulatory Affairs Specialist 615 Davis Drive Suite 800 Morrisville, North Carolina 27560
Re: K201049
Trade/Device Name: FINDER G6PD Test Regulation Number: 21 CFR 864.7360 Regulation Name: Erythrocytic Glucose-6-Phosphate Dehydrogenase Assay Regulatory Class: Class II Product Code: JBF Dated: September 14, 2022 Received: June 17, 2022
Dear Candice Prowse:
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.
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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 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.
Min Wu Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K201049
Device Name FINDER G6PD
Indications for Use (Describe)
The FINDER G6PD test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood specimens collected in lithium heparin tubes, for the identification of G6PD deficient samples. The FINDER G6PD test is intended to be used with the FINDER Instrument in point of care or clinical laboratory settings.
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) | ☐ |
Prescription Use (Part 21 CFR 801 Subpart D)
__ Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary
[In accordance with 21 CFR 807.92]
Baebies, Inc.
FINDER® G6PD Test
1. Submitter / 510(k) Holder
Baebies Inc., 25 Alexandria Way, Durham, NC 27703, USA Main phone number: (919) 891-0432 Main fax number: (919) 328-8402
Contact Person: Candice Prowse, Director of Regulatory Affairs and Clinical Affairs
Date Prepared: September 12, 2022
2. Device
| Proprietary Name: | FINDER G6PD Test |
|---|---|
| 510(k) Number | K201049 |
| Classification Name: | Glucose-6-Phosphate Dehydrogenase(Erythrocytic), Quantitative |
| Classification Panel: | Hematology |
| Classification: | Class II |
| Classification Regulation: | 21 CFR 864.7360 |
| Product Code: | JBF |
3. Predicate Device
| Class | Manufacturer | 510(k)Number | Device Name/Description |
|---|---|---|---|
| II | Pointe Scientific, Inc. | K024006 | Glucose-6-PhosphateDehydrogenase (G6PD) ReagentSet |
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4. Device Description
The FINDER G6PD test system measures G6PD quantitatively from a 50uL venous whole blood specimen. The blood specimen should be collected in lithium heparin anticoagulant. The G6PD test system is suitable for use in both a point-of-care setting and a clinical laboratory. The time to result is around 16 minutes from sample introduction.
The FINDER G6PD test system consists of the following main components.
-
FINDER G6PD Test Cartridge – The FINDER Cartridge uses electrowetting-based digital microfluidics to integrate and automate all the sample and reagent handling steps required to perform the G6PD test. The cartridge is sinqle-use and contains all the reagents necessary to perform the test.
-
FINDER Instrument – The FINDER Instrument contains all the hardware and software required to operate the FINDER Cartridge. The instrument provides electrowetting control, thermal control and detection capability, required to perform the G6PD test. The instrument also provides a touch-screen user interface and software necessary to perform the test and report results.
4.1. Accessories
The following accessories have not received prior 510(k) clearance.
The FINDER System includes a 50µL fixed-volume micropipette used to transfer specimens from the specimen collection device to the FINDER Cartridge for testing.
The FINDER system includes an optional thermal printer that is connected to the instrument via USB.
4.2. Test Principle
G6PD activity is measured from a whole blood sample input. Red blood cells are lysed osmotically in the cartridge by combining whole blood with water. The lysed blood cells are then incubated with ß-nicotinamide adenine dinucleotide phosphate (NADP) and glucose-6phosphate (G6P), resulting in the production of NADPH. Kinetic fluorescence measurements are used to quantify the rate of NADPH production, which is proportional to G6PD enzymatic activity. The reaction occurs in the presence of maleimide, which is used to improve the specificity of the test by inhibiting the production of NADPH from 6-phosphogluconate dehydrogenase. Hemoglobin present in the lysed sample is measured by absorbance and used to normalize G6PD enzymatic activity, resulting in a final reported unit of U/gHb.
$$G\text{"}6P + NADP^{+} \xrightarrow{G\text{"}6PD} 6-PG + NADPH + H^{+} $$
The FINDER G6PD Test reports the hemoglobin normalized G6PD activity in U/gHb and as a % of the site-specific Adjusted Male Median (AMM). The site-specific AMM is calculated using a minimum of 36 normal male samples and can be set by the user.
Baebies, Inc.
FINDER G6PD Test
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5. Indications for Use
The FINDER G6PD test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood specimens collected in lithium heparin tubes, for the identification of G6PD deficient samples.
The FINDER G6PD test is intended to be used with the FINDER Instrument in point of care or clinical laboratory settings.
The Indications for Use statement of the predicate is substantially the same as the candidate device. Any differences do not alter the intended use of the device, nor do they affect the safety and effectiveness of the device relative to the predicate.
6. Comparison of Technological Characteristics with Predicate
The FINDER G6PD test is intended for use on the FINDER Instrument. The similarities and differences between the FINDER G6PD Test and its predicate are presented in the following Table 1.
| Characteristic | PredicatePointe Scientific Glucose-6-Phosphate Dehydrogenase(G6PD) Reagent Set K024006) | FINDER G6PD Test |
|---|---|---|
| Regulation | 21 CFR 864.7360 | Same |
| Regulation Name | Erythrocytic glucose-6-phosphatedehydrogenase assay | Same |
| Procode | JBF | Same |
| Intended Use | For the quantitative determinationof glucose-6-phosphatedehydrogenase (G6PD) in bloodat 340 nm. For in vitro diagnosticuse only. | The FINDER G6PD test isintended for semi-quantitativemeasurement of glucose-6-phosphate dehydrogenase invenous whole blood specimenscollected in lithium heparin tubes,for the identification of G6PDdeficient samples.The FINDER G6PD test isintended to be used with theFINDER Instrument in point of careor clinical laboratory settings |
| Characteristic | PredicatePointe Scientific Glucose-6-Phosphate Dehydrogenase(G6PD) Reagent Set K024006) | FINDER G6PD Test |
| Class | II | Same |
| Device Panel | Hematology | Same |
| Analyzer | Cobas Mira | FINDER Instrument |
| Assay Manufacturer | Pointe Scientific | Baebies, Inc. |
| Analytes | G6PD | Same |
| Linear Range | 2.78 to 20.69 U/g Hb | 0.8 to 19.7 U/g Hb |
| Limit of Blank | Not specified | 0.2 U/g Hb |
| Sensitivity(Limit of Detection) | 0.4 U/g Hb | 0.4 U/g Hb |
| Limit ofQuantitation | Not specified | 1.1 U/g Hb |
| Specimen | Whole blood | Same |
| Method | NADPH kineticspectrophotometric method | NADPH kinetic fluorometricmethod |
| ComponentReagent matrices | G6P, Buffer, NADP andMaleimide | G6P, Buffer, NADP and Maleimide |
| Reagent Format | Dry and liquid, ready to usereagents; manual reconstitution | Dry test-specific reagents andliquid diluent and filler fluid;reconstitution performed byinstrument |
| Detection ofanalyte, Measurand | Spectrophotometric, quantitativeat 340nm | Fluorimetric, semi-quantitative370nm Excitation/460nm Emission |
| Characteristic | PredicatePointe Scientific Glucose-6-Phosphate Dehydrogenase(G6PD) Reagent Set K024006) | FINDER G6PD Test |
| The FINDER G6PD Test reportsthe hemoglobin normalized G6PDactivity in U/gHb and as a % of thesite-specific Adjusted Male Median(AMM). | ||
| Hemoglobin | Reaction with potassium cyanide | Absorbance at 524nm |
| Controls | Hemolysate | Same |
| CalibrationTraceability | Absorptivity of NADPH | NADPH extinction coefficient of$6.3mM^{-1}cm^{-1}$ |
Table 1 - FINDER G6PD versus Pointe Scientific G6PD Reagent Set
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baebies
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7. Performance Testing Summary
7.1. Nonclinical Performance
7.1.1. Precision
Two precision studies (internal and external) were performed to evaluate the repeatability and reproducibility precision of the FINDER G6PD test. Precision was evaluated in accordance with the CLSI EP05-A3 guideline.
The single site precision study was conducted at one site over a period of 21 non-consecutive days with 2 sessions per day and 2 runs per session. A session was defined as a batch of multiple runs where each session was separated by at least two hours. A run was defined as a single instance of a sample being tested. Results were determined using three levels of hemolysate control samples (low = 1.4 U/gHb, medium = 7.0 U/gHb, high = 17.4 U/gHb) resulting in 84 replicates per level. The study was conducted on 3 instruments using 3 cartridge lots.
The reproducibility study was conducted at 3 sites using fresh whole blood samples that were prepared each of 5 days by appropriate dilution to obtain 3 target G6PD levels (low = < 2.0 U/g Hb, medium = 3.0 – 5.0 U/g Hb, and high = > 8.0 U/g Hb) per day. Each day aliquots at the three sample levels were delivered to each testing site, where they were subdivided into 8 samples that were evaluated on 2 instruments by 2 operators, with 2 replications each. A total of 15 samples (3 G6PD levels, prepared on each of 5 days) were evaluated, and each sample was measured by the FINDER Instrument 24 times (across 3 sites, 2 instruments, 2 operators per site, 2 replicates), resulting in a total of 360 measurements for analysis.
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Results of the precision studies are shown below are shown in Table 2 and Table 3.
| Sample | N | Mean(U/gHb) | BetweenRun(%CV) | BetweenDay(%CV) | BetweenOperator(%CV) | BetweenLot (%CV) | BetweenInstrument(%CV) | Repeatability(%CV) | Reproducibility(%CV) |
|---|---|---|---|---|---|---|---|---|---|
| Low | 84 | 1.4 | 3.2% | 0.7% | 0.0% | 0.0% | 3.8% | 4.1% | 6.5% |
| Inter. | 84 | 7.0 | 2.2% | 1.1% | 0.0% | 1.8% | 2.4% | 3.6% | 5.3% |
| High | 84 | 17.4 | 2.6% | 0.0% | 0.0% | 0.0% | 3.9% | 2.4% | 5.2% |
Table 2 – Summary of Single Site Precision Study
| Sample | N | Mean (U/gHb) | Between Site(%CV) | BetweenInstrument(%CV) | BetweenOperator(%CV) | Repeatability(%CV) | Reproducibility(%CV) |
|---|---|---|---|---|---|---|---|
| Low | 120 | 1.1 | 0.0% | 0.9% | 0.0% | 5.9% | 6.0% |
| Inter. | 120 | 3.5 | 0.7% | 2.5% | 1.0% | 3.4% | 4.4% |
| High | 120 | 11.2 | 0.5% | 0.6% | 2.2% | 6.6% | 7.0% |
Table 3 – Summary of Reproducibility Precision Study
7.1.2. Linearity
Linearity was evaluated in accordance with CLSI EP06-A. Two separate studies were conducted to evaluate linearity. The first study was a full range linearity study that used contrived samples of recombinant G6PD enzyme spiked into whole blood to achieve activity levels that cover the intended linear range of the test. Nine samples were generated with increasing levels of G6PD activity from 2.0 to 19.7 U/gHb.
The second study was a native linearity study that used whole blood from a normal and G6PDdeficient donor. The native linearity study was performed to ensure that linearity demonstrated in the full range linearity study with contrived samples is not an artifact associated with usage of recombinant G6PD. Nine samples were generated with increasing levels of G6PD activity from 0.8 to 13.9 U/gHb.
The linear range for the FINDER G6PD test is given by the full range of both linearity studies. The FINDER G6PD test was demonstrated to be linear from 0.8 to 19.7 U/g Hb.
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7.1.3. Interference
Interference was evaluated in accordance with CLSI EP07 3rd edition quidelines. Whole blood test samples were spiked with possible interfering substances at concentrations equal to or greater than the quidelines. Each whole blood sample was tested at two G6PD enzymatic activity levels: normal G6PD activity (>7 U/qHb) and near the medical decision level (MDL near 2 – 4 U/gHb). Spiked samples (test pools) were compared to control pool without the interfering substances.
Hematocrit values greater than 40% did not interfere with the G6PD test result. A bias of -15.3% was observed for a normal sample at 29% hematocrit (8.9 g/dL hemoqlobin on FINDER) as compared to the control pool of 50% hematocrit (15.3 g/dL hemoglobin on FINDER). A bias of -11.1% was observed for a sample near the medical decision level at 30% hematocrit (11.3 g/dL hemoqlobin on FINDER). as compared to the control pool of 50% hematocrit (15.3 g/dL hemoglobin on FINDER).
The following endogenous substances were found to be non-interfering at the maximum tested concentrations.
| Substance | Maximum TestedConcentration |
|---|---|
| Bilirubin | 50 mg/dL |
| Hemoglobin | 5 g/L |
| Intralipid | 1000 mg/dL |
| Glucose | 55 mM |
| Galactose | 1 mM |
| Copper | 0.150 mg/dL |
| Lactate | 90 mg/dL |
| Lactatedehydrogenase | 6000 U/L |
Endogenous Substances:
The following common drugs were found to be non-interfering at the maximum tested concentrations.
Common Drugs
| Substance | Maximum TestedConcentration |
|---|---|
| Ampicillin | 0.16 mM |
| Ibuprofen | 2.5 mM |
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7.1.4. Sensitivity
The Limit of Blank (LoB), Limit of Detection (LoD), and the Limit of Quantitation (LoQ) for the FINDER G6PD test were evaluated in accordance with CLSI EP17-A2.
The LoB was evaluated using whole blood altered to a blank G6PD activity; the LoD was evaluated using whole blood at low G6PD activity; the LoQ was evaluated using four whole blood samples with increasing levels of G6PD activity prepared by spiking a blank pool with increasing concentrations of a normal pool.
The studies were conducted using 3 lots of FINDER G6PD Cartridges on 6 FINDER Instruments.
| Detection Capability | G6PD (U/g Hb) |
|---|---|
| Limit of Blank (LoB) | 0.2 |
| Limit of Detection (LoD) | 0.4 |
| Limit of Quantitation (LoQ) | 1.1 |
Table 6 - Sensitivity (LoB, LoD, LoQ)
Clinical Performance 8.
8.1. Method Comparison with Predicate Method
A clinical method comparison study was performed to demonstrate and compare the clinical performance of the FINDER Instrument and the FINDER G6PD Cartridge test to a comparator method using venous whole blood sample collected in lithium heparin tubes. The study design for this method comparison study was based on CLSI EP09-c – Measurement Procedure Comparison and Bias Estimation Using Patient Samples.
Lithium heparinized whole blood samples from 200 subjects were analyzed on the FINDER Instrument across 6 collection sites. Whole blood samples were shipped to a central laboratory under refrigerated conditions to analyze using the comparator method.
The samples tested were collected from 6 sites including one biorepository. Subjects included 89 males and 92 females with ages ranging from 20 to 72 years. 19 contrived samples were included in the study
G6PD activity results were compared using a Deming Regression linear fit yielding an estimated slope of 0.92, an intercept of 0.28, and a correlation coefficient of 0.9. The slope, intercept, and correlation coefficient are shown in the table below.
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| Measurand | N | Range | Slope (95% CI) | Intercept (95% CI) | CorrelationCoefficient |
|---|---|---|---|---|---|
| G6PD | 200 | 1.1 - 16.6 U/gHb | 0.92 (0.89, 0.95) | 0.28 (0.12, 0.44) | 0.9 |
The bias and percentage bias at the medical decision levels are shown in the table below
| MDLs | Bias (95% CI) | %Bias (95% CI) |
|---|---|---|
| 3.1 U/gHb (30% of AMM) | 0.0 U/gHb (-0.1, 0.2) | 1.4% (-2.5%, 5.4%) |
| 8.4 U/gHb (80% of AMM) | -0.4 U/gHb (-0.5, 0.2) | -4.3% (-6.5%, -2.0%) |
A concordance analysis was performed where the first 36 normal male samples were used to calculate the adjusted male median. The remaining 167 samples were used in the data analysis. The adjusted male median for the FINDER G6PD Test was 10.45 U/gHb. The adjusted male median for the Pointe Scientific G6PD test run on Cobas Mira was 10.88 U/gHb.
The following tables summarize the agreement between the FINDER G6PD Test and the Pointe Scientific Glucose-6-Phosphate Dehydrogenase Reagent Set on Cobas Mira) using different cutoffs. The results are presented as a percentage of the Adjusted Male Medium and include male, female, and contrived samples.
| Pointe Scientific Glucose-6-Phosphate DehydrogenaseReagent Set on Cobas Mira | Total | Agreement | Wilson Score 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| <30% | 30 to 70% | > 70% | ||||||
| FINDERG6PDTest | <30% | 28 | 2 | 0 | 30 | 100.0% | 87.9% | 100.0% |
| 30 to 70% | 0 | 22 | 2 | 24 | 68.8% | 51.4% | 82.1% | |
| > 70% | 0 | 8 | 105 | 113 | 98.1% | 93.4% | 99.5% | |
| Total | 28 | 32 | 107 | 167 | 92.8% | 87.9% | 95.8% |
3 x 3 Contingency Table: <30% AMM, 30 to 70% AMM, ≥70% AMM
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3 x 3 Contingency Table <30% AMM, 30 to 80% AMM, ≥80% AMM
| Pointe Scientific Glucose-6-Phosphate DehydrogenaseReagent Set on Cobas Mira | Total | Agreement | Wilson Score 95% CI | |||||
|---|---|---|---|---|---|---|---|---|
| <30% | 30 to 80% | > 80% | ||||||
| FINDERG6PDTest | <30% | 28 | 2 | 0 | 30 | 100.0% | 87.9% | 100.0% |
| 30 to 80% | 0 | 31 | 6 | 37 | 70.5% | 55.8% | 81.8% | |
| > 80% | 0 | 11 | 89 | 100 | 93.7% | 86.9% | 97.1% | |
| Total | 28 | 44 | 95 | 167 | 88.6% | 82.9% | 92.6% |
2 x 2 Agreement Table <30% AMM, ≥30% AMM
| Pointe Scientific Glucose-6-Phosphate DehydrogenaseReagent Set on Cobas Mira | Total | Agreement | Wilson Score 95% CI | ||||
|---|---|---|---|---|---|---|---|
| <30% | ≥30% | ||||||
| FINDERG6PDTest | <30% | 28 | 2 | 30 | 100.0% | 87.9% | 100.0% |
| ≥30% | 0 | 137 | 137 | 98.6% | 94.9% | 99.6% | |
| Total | 28 | 139 | 167 | 98.8% | 95.7% | 99.7% |
2 x 2 Agreement Table <70% AMM, ≥70% AMM
| Pointe Scientific Glucose-6-Phosphate DehydrogenaseReagent Set on Cobas Mira | Total | Agreement | Wilson Score 95%CI | ||||
|---|---|---|---|---|---|---|---|
| <70% | ≥70% | ||||||
| FINDERG6PD Test | <70% | 52 | 2 | 54 | 86.7% | 75.8% | 93.1% |
| ≥70% | 8 | 105 | 113 | 98.1% | 93.4% | 99.5% | |
| Total | 60 | 107 | 167 | 94.0% | 89.3% | 96.7% |
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2 x 2 Agreement Table <80% AMM, ≥80% AMM
| Pointe Scientific Glucose-6-Phosphate DehydrogenaseReagent Set on Cobas Mira | Total | Agreement | Wilson Score 95% CI | ||||
|---|---|---|---|---|---|---|---|
| <80% | ≥80% | ||||||
| FINDERG6PDTest | <80% | 61 | 6 | 67 | 85.9% | 76.0% | 92.2% |
| ≥80% | 10 | 90 | 100 | 93.8% | 87.0% | 97.1% | |
| Total | 71 | 96 | 167 | 90.4% | 85.0% | 94.0% |
9. Calibration Traceability
There is no international conventional reference measurement procedure or international conventional calibrator for G6PD. The G6PD assay on the Finder G6PD Cartridge is traceable to NADPH extinction coefficient of 6.3mM-1cm-1.
10. Quality Control
Performance of the FINDER system can be verified by analyzing hemolysate controls. Other controls may not be compatible.
11. Stability
The FINDER G6PD Test Cartridges are provided in sealed foil pouches. The expiration date of the unopened cartridge is stated on the outer label and is encoded in the barcode printed on the cartridge label. The current assigned shelf life is 77 weeks at 2-8°C from date of manufacturing.
12. Limitations of the Procedure
The FINDER G6PD test is indicated for lithium heparin venous whole blood samples.
G6PD levels may appear falsely elevated during or right after a severe hemolytic crisis because of higher G6PD levels in the new red cells'
Samples with low hemoglobin (<10.0 g/dL) on FINDER may result in clinically significant negative bias
Samples with high hemoglobin (>20.0 q/dL) on the FINDER can generate inaccurate results when a sample is not adequately mixed. Samples suspected of improper mixing should be retested using a new sample.
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13. Conclusion
The results drawn from the non-clinical tests presented in these 510(k) submissions demonstrate that the FINDER G6PD test is safe, effective, and performs as well as the legally marketed predicate device identified in this 510(k) summary.
1 E. Beutler, "G6PD Deficiency," Blood, vol. 84, no. 11, pp. 3613-3636, 1994.
§ 864.7360 Erythrocytic glucose-6-phosphate dehydrogenase assay.
(a)
Identification. An erythrocytic glucose-6-phosphate dehydrogenase assay is a device used to measure the activity of the enzyme glucose-6-phosphate dehydrogenase or of glucose-6-phosphate dehydrogenase isoenzymes. The results of this assay are used in the diagnosis and treatment of nonspherocytic congenital hemolytic anemia or drug-induced hemolytic anemia associated with a glucose-6-phosphate dehydrogenase deficiency. This generic device includes assays based on fluorescence, electrophoresis, methemoglobin reduction, catalase inhibition, and ultraviolet kinetics.(b)
Classification. Class II (performance standards).