(201 days)
The O-Pad Test System is comprised of the O-Pad Kit and the O-Pad A1c Test.
The Q-Pad Kit is an in vitro diagnostic specimen collection and storage device intended for the collection of menstrual blood samples by individuals 18 years and older for subsequent analysis by an assay validated for use with the Q-Pad menstrual pad.
The Q-Pad A1c Test is an in vitro diagnostic device for the quantitative measurement of Hemoglobin A1C using menstrual whole blood collected onto filter paper using the Q-Pad A1c Test is for the measurement of HbA I c on whole menstrual blood which will be self-collected by lay users at home and shipped to the laboratory by mail. Measurements obtained through this method can be used for monitoring the long-term control of blood sugar (glucose) in women with diabetes.
This test is not to be used to diagnose or screen for diabetes.
The Q-Pad Test System consists of the Q-Pad Kit and the Q-Pad A1c Test. The Q-Pad Kit is an in vitro diagnostic specimen collection and storage device intended for the collection of menstrual blood samples. The Q-Pad A1c Test is an in vitro diagnostic device for the quantitative measurement of Hemoglobin A1C using menstrual whole blood collected onto filter paper using the Q-Pad Kit. The Q-Pad menstrual pad (also referred to as "Q-Pad") is a modified menstrual pad which looks, feels, and is used like a normal menstrual pad. The Q-Pad has an embedded blood collection strip (Q-Strip) which can easily be removed and shipped for analysis at a laboratory. Instructions for use and results are presented in a HIPAA compliant mobile application.
The provided text describes the acceptance criteria and study that proves the Q-Pad Test System meets the acceptance criteria. It focuses on the performance of a medical device designed for measuring Hemoglobin A1c (HbA1c) from menstrual blood samples.
Here's the breakdown of the information requested, based on the provided text:
Acceptance Criteria and Device Performance
A table summarizing the acceptance criteria and the reported device performance for several key studies:
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision (Venous Blood) | Overall imprecision no greater than 2.56% (acceptance criterion ≤ 4%) | Low A1c: Total %CV = 1.99% Elevated A1c: Total %CV = 1.82% High A1c: Total %CV = 1.91% Very High A1c: Total %CV = 2.44% (All met the ≤ 4% criterion, and the overall maximum was 2.56%) |
| Precision (Menstrual Blood) | Overall imprecision no greater than 3.59% (acceptance criterion ≤ 4%) | Low A1c: Total %CV = 3.59% Elevated A1c: Total %CV = 2.15% High A1c: Total %CV = 1.60% (All met the ≤ 4% criterion, and the overall maximum was 3.59%) |
| Intra-strip Precision | Bias < 10% between punches 2 and 3 compared to the first punch; Average imprecision < 3.9% between punches. | Maximum bias of 4.90% recorded. Maximum CV between punches of 2.92%. Low A1c: %CV (95% CI) = 1.15 (0.00, 2.36) Mid A1c: %CV (95% CI) = 1.75 (0.00, 4.26) High A1c: %CV (95% CI) = 1.08 (0.00, 2.30) (Met criteria) |
| Inter-strip Precision | Bias < 10%; Average imprecision < 3.9% between Q-Strip samples. | Maximum bias of 3.92%. Maximum %CV of 2.72%. Low A1c: %CV (95% CI) = 0.44 (0.00, 1.22) Mid A1c: %CV (95% CI) = 2.59 (2.06, 3.11) High A1c: %CV (95% CI) = 0.44 (0.00, 1.41) (Met criteria) |
| Linearity (Menstrual Blood) | Based on linear regression and polynomial fit analysis; to support a claimed measuring range of 4.0% to 15.0% HbA1c. | Polynomial fit analysis verified linearity. 2nd and 3rd order polynomials were statistically equivalent to zero, making the best fit polynomial a linear function. Linearity established from 4.4% to 14.5% HbA1c. This range supports the claimed measuring range (AMR) of 4.0% to 15.0%. |
| Interfering Substances | Significant interference defined as >10% bias between a spiked and an unspiked sample. | No incidence of interference detected with any of the 40 tested exogenous and endogenous substances (at four HbA1c levels for each substance). Exception: For Hemoglobin variant F, with variant concentration >10%, interference was observed. This resulted in a limitation in the product package insert. |
| Specimen Stability with Simulated Shipping | <10% deviation from T0 for measured values at various time points (Day-6, Day-10, Day-14, Day-28, Day-31). No significant drift. | All measured values were within the acceptable range (<10% deviation). No significant drift observed (95% CI of regression lines did not cross TEa bounds). Claimed sample stability period of 28 days. |
| Shelf-Life (Accelerated) | All measured values within acceptable range (<10% bias from reference). | All measured values were within the acceptable range. Supports 3-year shelf life. Real-time study running concurrently. |
| Open Pouch Shelf-Life | All measured values within acceptable range (<10% bias from reference). | All measured values were within the acceptable range. Mitigates risk of inaccurate results from opened but unused kits. |
| Reference Interval | Verification of equivalence to NACB recommended HbA1c reference range of 4.0% to 6.0% HbA1c. | All participant results were inside the expected reference range. Mean = 5.17% HbA1c, Central 95% interval = 4.54% to 5.77%. Standardized range found to be equivalent to the NACB recommended range. Claimed reference interval for healthy individuals: 4.0% - 6.0%. |
| Method Comparison (Clinical Study) | Slope between 0.93 and 1.07 with CI including 1; Intercept between -0.7 and 0.7 with CI including 0; R² of >0.95. No samples outside of total allowable error of 6%. | Slope = 1.003 (95% CI 0.987, 1.020); Intercept = -0.0461 (95% CI -0.170, 0.0669); R² = 0.99. All acceptance criteria met. Demonstrated clinical performance equivalent to the reference method (venous blood). 99% of participants successfully collected a sample. No samples outside of the stated total allowable error of 6%. |
| Usability Study | Users able to follow Instructions for Use (IFU) and successfully collect a sample leading to a valid HbA1c result. | 40 naive participants (self-reported diabetics) were able to follow IFU. 97.5% successfully collected a sample that led to a valid HbA1c result. (Met criteria) |
| Elution Stability | <10% bias between measured time point and initial measurement immediately after extraction for up to 4 hours. | For all time points and HbA1c levels, the maximum bias was 3.37%. Verified stability of eluted sample for up to 4 hours. |
Study Details
Here's a breakdown of the specific details regarding the studies:
2. Sample size used for the test set and the data provenance:
- Sample Matrix Equivalency Study: 40 paired (venous and menstrual blood) samples. Data provenance not explicitly stated, but implies clinical samples.
- Precision (Venous Blood) Study: 320 samples (80 per HbA1c level from 4 participants). Implies lab-controlled testing.
- Precision (Menstrual Blood) Study: 20 samples per HbA1c level (from 3 participants). Implies self-collected samples from lay users.
- Intra-strip Precision Study: Samples from 9 participants.
- Inter-strip Precision Study: Samples from 9 participants.
- Linearity (Menstrual Blood) Study: Not explicitly stated, but involved serially diluted samples to create a nine-member known interval menstrual blood panel. Lab-based.
- Interfering Substances Study: 40 substances evaluated, each tested at four HbA1c levels. Lab-based.
- Hemoglobin Variants Study: Hemoglobin variants C, -D, -E, -F, and -S from an NGSP reference laboratory, tested at three HbA1c levels each. Lab-based.
- Specimen Stability with Simulated Shipping Study: Samples from 8 participants. Implies self-collected.
- Reference Interval Study: 128 healthy participants. Implies clinical samples.
- Method Comparison (Clinical Validation) Study: 396 specimens from 198 participants.
- Data Provenance: Not explicitly stated regarding country of origin, but implies multi-site or broader collection for the clinical validation study as samples were collected via "Instructions for Use (IFU) and were returned to the laboratory using USPS First-class Return Service." This suggests a US-based, prospective, at-home collection study.
- Usability Study: 40 naive participants (self-reported diabetics). Implies US-based, prospective, at-home collection.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number or qualifications of experts used to establish ground truth.
- For HbA1c measurements, the "ground truth" or reference method is typically the results from a highly accurate, standardized laboratory analyzer using a reference method (e.g., Beckman Coulter AU480 for the subject device, Beckman Coulter AU640e for the predicate) and traceable to the National Glycohemoglobin Standardization Program (NGSP) and IFCC reference calibrators. The Method Comparison study used a "venous blood reference method" performed by a phlebotomist and analyzed at a CLIA-certified clinical laboratory (Qvin Labs) on the Beckman Coulter Hemoglobin A1c Test on an AU480 chemistry analyzer.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The document does not describe an adjudication method for the test set data. For quantitative measurements like HbA1c, adjudication by multiple readers is generally not applicable in the same way it would be for qualitative assessments (e.g., image interpretation). Instead, the reference method's accuracy and traceability are key.
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:
- This device is an in vitro diagnostic for quantitative measurement, not an AI-assisted diagnostic imaging or qualitative interpretation device. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance is not applicable and was not performed. The focus is on the accuracy and precision of the device's measurement compared to a reference method.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The device performs a quantitative measurement of HbA1c. The "standalone" performance here refers to the device itself (the Q-Pad Test System, which includes the collection kit and the A1c test performed in a lab) providing a numeric result. All the performance studies (precision, linearity, interference, stability, method comparison) are essentially standalone performance evaluations of the device system. Human involvement is primarily in sample collection, not in interpreting the final quantitative output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The primary ground truth for the HbA1c measurements was reference methodology using a venous blood sample analyzed by an FDA-cleared laboratory reagent and analysis system (Beckman Coulter AU480 clinical chemistry device), traceable to NGSP and IFCC reference calibrators.
- For the Interfering Substances and Hemoglobin Variants studies, reference values or known concentrations were used.
- For the Reference Interval study, samples from healthy participants were used to establish a range and compare to national recommendations (NACB).
8. The sample size for the training set:
- The document describes performance studies for a medical device (Q-Pad Test System) which is an in vitro diagnostic for measuring HbA1c. This device does not appear to rely on a "training set" in the context of machine learning. The studies described are validation studies for the analytical and clinical performance of the test system itself, not for an algorithm that learns from data.
9. How the ground truth for the training set was established:
- As the device is an in vitro diagnostic measurement system and not an AI/ML algorithm that requires a training set, the concept of "ground truth for the training set" is not applicable here.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
December 6, 2023
Qurasense % Richard Lewis, Senior Regulatory Device and Biologics Expert Hyman, Phelps & McNamara P.C. 700 13th Street NW, Suite 1200 Washington, District of Columbia 20005
Re: K231465
Trade/Device Name: Q-Pad Test System Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, QZG Dated: May 19, 2023 Received: May 19, 2023
Dear Richard Lewis:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,
Joshua Balsam -S
Joshua M. Balsam, Ph.D. Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K231465
Device Name Q-Pad Test System
Indications for Use (Describe)
The O-Pad Test System is comprised of the O-Pad Kit and the O-Pad A1c Test.
The Q-Pad Kit is an in vitro diagnostic specimen collection and storage device intended for the collection of menstrual blood samples by individuals 18 years and older for subsequent analysis by an assay validated for use with the Q-Pad menstrual pad.
The Q-Pad A1c Test is an in vitro diagnostic device for the quantitative measurement of Hemoglobin A1C using menstrual whole blood collected onto filter paper using the Q-Pad A1c Test is for the measurement of HbA I c on whole menstrual blood which will be self-collected by lay users at home and shipped to the laboratory by mail. Measurements obtained through this method can be used for monitoring the long-term control of blood sugar (glucose) in women with diabetes.
This test is not to be used to diagnose or screen for diabetes.
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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510(k) Summary for K231465
| Date of Summary: | December 6th, 2023 |
|---|---|
| Product Name: | Q-Pad Test System |
| Sponsor: | Qurasense3517 Edison Way, Ste. DMenlo Park, CA 94025United States |
| Correspondent: | Richard A. LewisSenior Regulatory Device and Biologics ExpertHyman, Phelps & McNamara, P.C.700 13th Street, N.W., Suite 1200Washington, D.C. 20005Office: (202) 737-4280RLewis@hpm.comwww.hpm.com |
The Q-Pad Test System consists of the following:
| Proprietary Name: | Q-Pad A1c Test |
|---|---|
| Common Name: | Glycosylated hemoglobin assay |
| Classification Name: | Assay, glycosylated hemoglobin |
| Regulation Number: | 21 CFR §864.7470 |
| Product Code: | LCP |
| Proprietary Name: | Q-Pad Kit |
| Common Name: | Blood specimen collection device |
| Classification Name: | Menstrual Blood Collection Device |
| Regulation Number: | 21 CFR §862.1675 |
| Product Code: | QZG |
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Substantial Equivalency
Qurasense's Q-Pad Test System has technological characteristics that are substantially equivalent to the predicate device identified in the table below. Both the proposed device and the predicate device provide the patient a method to collect a sample at home, mail the sample to the clinical laboratory, and later receive a report showing the measured Hemoglobin A1c.
Among the components included with the Q-Pad Test System is the collection device, Q-Pad, a menstrual pad that contains filter paper. Once the Q-Pad is received in the clinical laboratory, the dried blood sample is punched, eluted, and tested using FDA-cleared laboratory reagent and analysis systems, specifically the Beckman Coulter AU480 clinical chemistry device. The technological characteristics and intended use are substantially equivalent to the predicate device as summarized in the following table:
| Description | Subject DeviceQ-Pad Test System | Predicate DeviceHome Access A1c TestK141944 |
|---|---|---|
| Intended Use | Whole blood quantitativemeasurement of Hemoglobin A1c. | Whole blood quantitativemeasurement of Hemoglobin A1c. |
| Indications for use | The Q-Pad Test System is comprised ofthe Q-Pad Kit and the Q-Pad A1c Test.The Q-Pad Kit is an in vitro diagnosticspecimen collection and storagedevice intended for the collection ofmenstrual blood samples byindividuals 18 years and older forsubsequent analysis by an assayvalidated for use with the Q-Padmenstrual pad. The Q-Pad A1c Test isan in vitro diagnostic device for thequantitative measurement ofHemoglobin A1c using menstrualwhole blood collected onto filterpaper using the Q-Pad Kit. The Q-PadA1c Test is for the measurement ofHbA1c on whole menstrual bloodwhich will be self-collected by layusers at home and shipped to thelaboratory by mail. Measurementsobtained through this method can beused for monitoring the long-term | The Home Access® A1C Test is an invitro test method for thequantitative measurement ofHemoglobin A1c using capillaryblood collected from the fingertip,collected onto filter paper via theHome Access collection cassette.The Home Access A1C Test is formeasurement of HbA1c on bloodspecimens which can be collected atthe patient's home or in a healthcareprofessional setting and delivered tothe laboratory by mail. Measurementsobtainedthrough this method can be usedfor monitoring the long-termcontrol of blood sugar (glucose) inpeople with diabetes.This test is not to be used todiagnose or screen for diabetes.Not for use on neonates. |
| Description | Subject DeviceQ-Pad Test System | Predicate DeviceHome Access A1c TestK141944 |
| control of blood sugar (glucose) inwomen with diabetes. | ||
| This test is not to be used to diagnoseor screen for diabetes. | ||
| Prescription/ Over-the-counter use | Over the counter | Prescription and Over the counter |
| Usage | Single Use | Single Use |
| Collect Sample AtHome | Yes | Yes |
| Whole BloodSample | Yes | Yes |
| Collection KitComponents | (2) Q-PadsSample ContainerInstructions for UsePrepaid return MailerOuter PackagingPatient Information Card | Blood sample collection CassetteSample PouchSterile Safety LancetsGauze PadBandageInstructions for UsePrepaid return MailerPatient Info CardOuter Packaging |
| Send Samples toCLIA certified lab | Yes. Samples can only be sent andanalyzed at Qurasense's CLIA-certifiedlaboratory (Qvin Labs). | Yes. Samples sent to Home AccessHealth Corporation laboratory facility. |
| Analysis | Beckman Coulter A1c reagentsBeckman Coulter device AU480 | Beckman Coulter A1c reagentsBeckman Coulter device AU640e(formerly Olympus) |
| Return Results | Yes, via mobile app or email. | Yes, mailed to the user. |
| Description | Subject DeviceQ-Pad Test System | Predicate DeviceHome Access A1c TestK141944 |
| Precision | % CV < 2.44 % | % CV ≤ 3.9% |
| Measuring Range | 4.0% to 15.0% HbA1c | 4.5 – 14.5% HbA1c |
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Indication for Use
The Q-Pad Test System is comprised of the Q-Pad Kit and the Q-Pad A1c Test.
The Q-Pad Kit is an in vitro diagnostic specimen collection and storage device intended for the collection of menstrual blood samples by individuals 18 years and older for subsequent analysis by an assay validated for use with the Q-Pad menstrual pad.
The Q-Pad A1c Test is an in vitro diagnostic device for the quantitative measurement of Hemoglobin A1C using menstrual whole blood collected onto filter paper using the Q-Pad Kit. The Q-Pad A1c Test is for the measurement of HbA1c on whole menstrual blood which will be self-collected by lay users at home and shipped to the laboratory by mail. Measurements obtained through this method can be used for monitoring the long-term control of blood sugar (glucose) in women with diabetes.
This test is not to be used to diagnose or screen for diabetes.
Methodology
The Q-Pad menstrual pad (also referred to as "Q-Pad") is a modified menstrual pad which looks, feels, and is used like a normal menstrual pad. The Q-Pad has an embedded blood collection strip (Q-Strip) which can easily be removed and shipped for analysis at a laboratory. Instructions for use and results are presented in a HIPAA compliant mobile application.
Performance Data
Sample Matrix Equivalency
A CLSI EP35 based study was conducted to assess the sample matrix equivalency between venous blood and menstrual blood collected on the Q-Pad. Forty (40) paired (venous and menstrual blood) samples, that span the Analytical Measurement Range (AMR) of the assay, were tested. The regression analysis between venous and menstrual blood resulted in a slope of 0.969 (95% Cl 0.944-0.994), an intercept of 0.181 (95% CI -0.017 to 0.380) and a R² of 0.997. The systematic difference between specimens at the 6.5 %HbA1c predetermined medical decision point (MDP) was 0.3% (the absolute systemic difference
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between the specimens being 0.02) and the 95% confidence interval was 6.42 to 6.54 %HbA1c. The study results demonstrated that venous blood and menstrual DBS are equivalent sample types for measurement of HbA1c.
Precision using venous blood
A venous blood precision study was performed according to CLSI EPO5-A3. Whole blood from four participants with known A1c levels of around 5%, 6.5%, 8% and 12% was obtained. A total of 320 samples were run. Each HbA1c level was tested in duplicate, twice a day for a total of 20 days (N = 80 per level). Overall, within-run, and within-day precision results were evaluated in the presence of multiple lots of reagents. Operator precision was also assessed (Tables 1-3). Overall, the studies show an imprecision of no greater than 2.56% (acceptance criterion ≤ 4%).
| Mean | Repeatability(within run) | Between run | Repeatability (withinday) | Between day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | %HbA1c | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV |
| Low A1c | 5.21 % | 0.05 | 0.87(0.58,1.15) | 0.04 | 0.84(0.82,1.24) | 0.06 | 1.13(0.74, 1.53) | 0.08 | 1.61(1.21, 2.01) | 0.10 | 1.99 |
| Elevated A1c | 6.70% | 0.06 | 0.88(0.57, 1.19) | 0.06 | 0.87(0.84, 1.28) | 0.08 | 1.21(0.91, 1.51) | 0.09 | 1.41(1.11, 1.71) | 0.12 | 1.82 |
| High A1c | 8.30% | 0.08 | 0.93(0.75, 1.11) | 0.07 | 0.82(0.78, 1.20) | 0.10 | 1.15(0.92, 1.38) | 0.13 | 1.61(1.37, 1.84) | 0.16 | 1.91 |
| Very High A1c | 12.74% | 0.13 | 1.03(0.77, 1.29) | 0.10 | 0.81(0.76,1.19) | 0.16 | 1.22(0.86, 1.57) | 0.27 | 2.14(1.78, 2.49) | 0.31 | 2.44 |
Table 1. Precision/Reproducibility Data Summary - venous blood
Table 2. Precision summary for samples run with different lots of each reagent - venous blood
| Different HbA1c reagent kit lots | Different hemolysis reagent lots | ||||||
|---|---|---|---|---|---|---|---|
| %HbA1cmean | Total imprecision | %HbA1cmean | Total imprecision | ||||
| Sample | %HbA1c | SD | %CV (95%CI) | SD | %CV (95%CI) | ||
| Low A1c | 5.21 | 5.21 | 0.07 | 1.26 (1.10, 1.43) | 5.21 | 0.01 | 0.20 (0.18, 0.23) |
| Elevated A1c | 6.70 | 6.71 | 0.08 | 1.24 (1.03, 1.44) | 6.70 | 0.04 | 0.57 (0.47, 0.66) |
| High A1c | 8.30 | 8.30 | 0.10 | 1.20 (0.95, 1.45) | 8.28 | 0.09 | 1.06 (0.84, 1.28) |
| Very High A1c | 12.74 | 12.75 | 0.18 | 1.43 (0.97, 1.89) | 12.72 | 0.10 | 0.79 (0.54, 1.04) |
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| Sample | Operator 1 | Operator 2 | Operator 1 | Operator 2 | Operator 1 | Operator 2 | Operator toOperator |
|---|---|---|---|---|---|---|---|
| %HbA1c mean | %HbA1c mean | SD | SD | %CV (95%CI) | %CV (95%CI) | %CV (95%CI) | |
| Low A1c | 5.19 | 5.25 | 0.08 | 0.08 | 2.04 (2.01, 2.07) | 1.54 (1.50, 1.58) | 1.88 (1.85, 1.92) |
| Elevated A1c | 6.69 | 6.73 | 0.12 | 0.11 | 1.86 (1.83, 1.89) | 1.66 (1.60, 1.72) | 1.98 (1.94, 2.02) |
| High A1c | 8.28 | 8.38 | 0.15 | 0.17 | 1.81 (1.78, 1.85) | 1.98 (1.90, 2.07) | 1.96 (1.91, 2.02) |
| Very High A1c | 12.71 | 12.83 | 0.33 | 0.24 | 2.56 (2.48, 2.64) | 1.83 (1.72, 1.95) | 1.80 (1.72, 1.87) |
Table 3. Precision summary for samples run with different operators - venous blood
Precision using menstrual blood
A precision study using Q-Pad collected menstrual DBS samples was performed according to CLSI EPO5-A3. Three participants with a low, mid and high HbA1c level collected samples using the Q-Pad Kit. Samples were collected, shipped and processed according to the IFU. The samples were tested in duplicate, two times a day, over five days (N = 20 per level). Within-day-run, and between day-run precision results were evaluated (Table 4). Overall, the study shows an imprecision of no greater than 3.59% (acceptance criterion ≤ 4%).
| Mean | Repeatability(within run) | Between run | Repeatability(within day) | Between day | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | %HbA1c | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV(95%CI) | SD | %CV |
| Low A1c | 5.28% | 0.07 | 1.33(0.41, 2.24) | 0.04 | 0.79(0.72, 1.02) | 0.11 | 2.01(0.87, 3.15) | 0.17 | 3.21(1.59, 4.82) | 0.19 | 3.59 |
| Elevated A1c | 7.63% | 0.10 | 1.32(0.76, 1.87) | 0.00 | 0.05(0.04, 0.06) | 0.11 | 1.43(0.97, 1.89) | 0.14 | 1.83(1.18, 2.48) | 0.16 | 2.15 |
| High A1c | 12.35% | 0.09 | 0.72(0.08, 1.36) | 0.06 | 0.47(0.40, 0.63) | 0.14 | 1.11(0.40, 1.75) | 0.15 | 1.22(0.32, 2.12) | 0.20 | 1.60 |
Table 4. Precision/Reproducibility Data Summary - menstrual blood
Lot-to-Lot Precision
Lot-to-lot accuracy and precision were evaluated as part of the method comparison study and shelf-life studies. During the method comparison study, three lots were distributed randomly to study participants. Table 5 compares the accuracy between the multiple lots of the Q-Pad Kit across 4 HbA1c levels.
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| Slope (95%CI) | Intercept (95%CI) | |
|---|---|---|
| Lot 1 | 1.000 (0.975, 1.032) | -0.020 (-0.228, 0.182) |
| Lot 2 | 0.983 (0.957, 1.010) | 0.072 (-0.097, 0.239) |
| Lot 3 | 1.027 (0.989, 1.066) | -0.212 (-0.471, 0.063) |
Table 5. Passing-Bablok Estimates per Lot (method comparison study)
Multiple lots of the Q-Pad Kit were used during shelf-life studies. A summary of the precision data from the shelf-life studies is presented in Table 6.
| Accelerated Shelf Life | Open-Pouch Shelf Life | |
|---|---|---|
| HbA1c Level | Average %CV (95%CI) | Average %CV (95%CI) |
| Low A1c | 1.03 (0.06, 2.00) | 0.44 (0.00, 1.58) |
| Elevated A1c | 1.50 (0.00, 3.68) | 0.90 (0.00, 1.97) |
| High A1c | 1.40 (0.37, 2.42) | 0.31 (0.17, 0.45) |
| Very High A1c | 0.84 (0.00, 2.75) | 1.45 (0.09, 2.81) |
Table 6. Accelerated and Open-pouch Shelf Life lot precision data
The lot-to-lot analysis in the method comparison, combined with the analysis from two controlled shelflife studies demonstrated negligible risk of imprecision due to different lots.
Intra- and Inter-Strip Precision Flex studies
Additional flex studies were performed to assess imprecision from various locations on a Q-Strip (intrastrip) and between two Q-Strips (inter-strip).
Intra-strip Precision
The purpose of this study was to evaluate intra-strip (punch-to-punch) imprecision. Nine (9) participants were enrolled based on anticipated A1c levels. For each sample, three punches were selected by the operator and analyzed. Punches 2 and 3 were compared to the measured value of the first punch. Bias and %CV were calculated. Acceptance criteria was <10% bias of punches 2 and 3 when compared to the first punch and an average imprecision of <3.9% between the punches.
A maximum bias of 4.90% was recorded with a maximum CV between punches of 2.92% (Table 7).
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| Sample | Participant 1%CV | Participant 2%CV | Participant 3%CV | SD (%) | %CV (95% CI) |
|---|---|---|---|---|---|
| Low A1c | 0.94 | 0.81 | 1.71 | 0.49 | 1.15 (0.00, 2.36) |
| Mid A1c | 1.17 | 2.92 | 1.18 | 1.01 | 1.75 (0.00, 4.26) |
| High A1c | 1.72 | 0.90 | 0.62 | 0.49 | 1.08 (0.00, 2.30) |
Table 7. Intra-Strip Precision
Inter-strip Precision
Inter-strip precision was evaluated by comparing results from two Q-Pads, both used during the same collection event. Nine (9) participants were enrolled based on anticipated A1c levels. Each Q-Strips was punched once and the resulting values were compared. Acceptance criteria was <10% bias and an average imprecision of <3.9% between Q-Strip samples.
A maximum bias of 3.92% and a maximum %CV of 2.72 was measured (Table 8).
| Sample | Participant 1 %CV | Participant 2 %CV | Participant 3 %CV | SD(%CV) | %CV (95% CI) |
|---|---|---|---|---|---|
| Low A1c | 0.76 | 0.41 | 0.14 | 0.31 | 0.44 (0.00, 1.22) |
| Mid Alc | 2.72 | 2.70 | 2.34 | 0.21 | 2.59 (2.06, 3.11) |
| High A1c | 0.87 | 0.35 | 0.10 | 0.39 | 0.44 (0.00, 1.41) |
Table 8. Inter-Strip Precision
Linearity menstrual blood
A CLSI EPOG-A based linearity study was performed on the Q-Pad Test System using known interval methodology. High and low %HbA1c menstrual DBS samples were extracted and then serially diluted to create a nine-member known interval menstrual blood panel that ranged from 4.47 to 14.5 %HbA1c. Data was analyzed using linear regression and polynomial fit analysis. A linear regression graph of the resulting data is presented in Figure 1, and results of a polynomial fit analysis are shown in Table 9.
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Image /page/11/Figure/0 description: This image is a scatter plot that shows the relationship between two variables, "Result %HbA1c" and "Reference %HbA1c". The data points are clustered around a straight line, indicating a strong positive correlation between the two variables. The equation of the line is y = 0.988*x + 0.013, and the R-squared value is 0.998, which indicates that the line fits the data very well. The x and y axis range from 4 to 15.
Figure 1. Plot of %HbA1c results vs. reference %HbA1c values.
Table 9. Polynomial Fit Analysis (*statistically equivalent to zero)
| Polynomia1 | Constant(T statistic) | X(T statistic) | X2(T statistic) | X3(T statistic) | Std Error ofEstimate (%) | "Best"Polynomial |
|---|---|---|---|---|---|---|
| Line | 3.074 (42.5) | 1.254 (97.5) | 0.1726 | Best Fit | ||
| 2nd Order | 3.132 (24.4) | 1.223 (20.7) | 0.00316 (0.5*) | 0.1751 | ||
| 3rd Order | 3.035 (13.7) | 1.316 (7.2) | -0.01898 (0.5*) | 0.001476 (0.5*) | 0.1777 |
Polynomial fit analysis verified linearity of the Q-Pad Test System. The 2nd and 3rd order polynomials were determined to be "statistically equivalent to zero" making the best fit polynomial a linear function. The linearity of the Q-Pad Test System has been established from 4.4 to 14.5 %HbA1c. This range along with the totality of device performance supports a claimed measuring range (AMR) of the Q-Pad Test System of 4.0 to 15.0%.
Interfering Substances
Interference was assessed using methodologies described in CLSI EP07-Ed3. Studies were conducted to assess the Q-Pad Test System's performance in the presence of common exogenous and endogenous substances known or suspected to interfere with HbA1c measurements. Forty (40) substances were evaluated, each tested at four HbA1c levels. CLSI EP37 and similar references were used to determine the test concentrations for exogenous and endogenous substances. Test concentrations for bodily fluids were determined empirically using the analyzer. Topical products were tested by simulating normal use.
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Significant interference was defined as a >10% bias between a spiked and an unspiked sample. The list of the substances tested is shown in Table 10, no incidence of interference was detected with any substance
| Endogenous and ExogenousSubstances Tested | TestConcentration | Topical Products Tested |
|---|---|---|
| Acetaminophen | 20.0 mg/dL | Lube Life Water-Based Personal Lubricant |
| Acetylsalicylic Acid | 65.0 mg/dL | Good Clean Love Restore Moisturizing Vaginal Gel |
| Azo-Standard | 0.0195 mg/dL | Replens Long Lasting Vaginal Moisturizer |
| Clindamycin | 5.10 mg/dL | Bonafide Revaree Vaginal Moisturizer |
| Conjugated Bilirubin | 40 mg/dL | Medicine Mama's Apothecary Vulva Balm |
| Glyburide | 0.2 mg/dL | VCF Contraceptive Gel |
| Ibuprofen | 50.0 mg/dL | Monistat 3 Yeast Infection Treatment |
| L-Ascorbic Acid | 5.25 mg/dL | Monistat 1 Yeast Infection Treatment |
| Liraglutide | 0.0168 mg/dL | Clotrimazole 3 Day Antifungal Cream |
| Metformin | 4.0 mg/dL | Monistat Anti-itch Relief Cream |
| Metronidazole | 12.3 mg/dL | Vagisil Maximum Strength Feminine Anti-Itch Cream |
| Rheumatoid Factor | 600 IU/mL | Summer's Eve Freshening Spray |
| Semen | 25%* | Summer's Eve Refresher Mist, Feminine Spray |
| Sitagliptin | 0.115 mg/dL | Summer's Eve Island Splash Body Powder |
| Sweat | 50%* | Monistat Chafing Relief Powder Gel |
| Tinidazole | 15.3 mg/dL | BORASOL Powder |
| Triglyceride-rich Lipoproteins | 1640 mg/mL | Summer's Eve Feminine Wipes |
| Unconjugated Bilirubin | 40 mg/dL | Vagisil Anti-Itch Medicated Feminine Intimate Wipes |
| Urine | 40%* | Summer's Eve Douche Island Splash |
| Vaginal Fluid | 50%* | Summer's Eve Vinegar & Water Douche |
Table 10. List of substances evaluated for interference and the highest concentrations tested with no measured interference (when applicable)
*highest test concentration that resulted in valid results for all four HbA1c levels.
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Hemoglobin variants
Interference from Hemoglobin Variants, sourced from a NGSP reference laboratory, was evaluated following CLSI EP07-Ed3. Hemoglobin C, -D, -E, -F, and -S were tested at three HbA1c levels each. Samples were dosed onto a Q-strip, dried and run according to standard laboratory procedures. Measured values were compared to reference %HbA1c values supplied by NGSP. Significant interference was defined as a bias of >10% from the reference value.
No interference was detected for hemoglobin variants C, -D, -E, and -S. For Hemoglobin variant F, with variant concentration above 10%, interference was observed. The sponsor will include the following limitation in the product package insert, listed in the warnings and limitations section:
"This device has significant negative interference with fetal hemoglobin (HbF). HbA1c results are invalid for patients with abnormal amounts of HbF including those with known Hereditary Persistence of Fetal Hemoglobin.".
Traceability
The Q-Pad Test System is certified with the National Glycohemoglobin Standardization Program (NGSP). See NGSP website for current certification at http://www.ngsp.org. The Q-Pad A1c Test is traceable to IFCC reference calibrators.
Specimen Stability with Simulated Shipping
A sample stability with simulated shipping study, based on CLSI EP-25A, was performed on Q-Pad Kit collected menstrual blood samples. Eight (8) participants with known A1c levels, spanning the range of the assay used the Q-Pad Kit. Samples were exposed to 13 days of simulated summer/spring and winter temperature profiles. A reference measurement was taken at the following time points: Day-6, Day-10, Day-14, Day-28, and Day-31. At each time point, samples were punched once and run in triplicate. The acceptance criteria for each time point was <10% deviation from T0.
All measured values were within this acceptable range. In addition, no significant drift was observed, meaning none of the 95% confidence intervals of the regression lines crossed the TEa bounds. Based on these results, the Q-Pad Test System will have a claimed sample stability period of 28 days.
Shelf-Life
An Accelerated Shelf-life study was performed to establish initial shelf stability for the Q-Pad Kit. Q-Pad Kits were stored at constant elevated temperature (55°C, 50%RH) for up to 3 simulated years (120 days). After aging, the kits were subjected to 7 days in an environmental chamber (Desert, Tropical, Frozen, and Room Conditions). Performance was evaluated using four HbA1c levels of bio-banked blood samples. A
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set of Q-Pad Kits was run at the following time-points: 0 year, 3 year, and 3 year + 1 month, where a year corresponds to 40 days in the environmental chamber. HbA1c results from aged kits were compared to the reference value captured at the initiation of the study.
All measured values were within the acceptable range (<10% bias from reference). Based on the initial accelerated study results, Q-Pad Kits will be labeled with a 3 year shelf life. The outer pouch will include symbology to represent acceptable storage conditions as room temperature (15-30 ºC). A real-time study is running concurrently to verify the results from the accelerated study.
An Open Pouch Shelf-Life study was performed to test the stability of a Q-Pad Kit after the main packaging Q-Pad kits were first subjected to 7 days in an environmental chamber (Desert, Tropical, is opened. Frozen, and Room Conditions). After stressing, the Q-Pad Kits were opened and then stored at room temperature for up to 67 days. Performance was evaluated using four HbA1c levels of bio-banked blood samples. A set of Q-Pad Kits was run at the following time-points: Day-0, Day-30, and Day-67. HbA1c results from aged kits were compared to the reference value captured at the initiation of the study.
All measured values were within the acceptable range (<10% bias from reference . The Open Pouch study adequately mitigates the risk that a kit opened but not used immediately would result in an inaccurate result.
Reference Interval
A reference interval study was performed according to CLSI EP28-A3c. Samples from 128 healthy participants were collected to establish a reference range for the Q-Pad Test System and to verify its equivalence to the The National Academy of Clinical Biochemistry (NACB) recommended HbA1c reference range of 4.0 to 6.0 %HbA1c.
All participant results were inside the expected reference range. The samples had a mean of 5.17 %HbA1c and a central 95% interval of 4.54% to 5.77%. The standard deviation of the dataset was 0.33%, and the CV was 6.34%. These results verify that the calculated reference interval for Q-Pad collected menstrual DBS samples falls within the standardized range recommended by NACB. Therefore, it is claimed that the reference interval for samples collected from healthy individuals using the Q-Pad Test System have a reference interval of 4.0% - 6.0%, equivalent to the range accepted for whole blood.
Clinical Studies
Method Comparison
A clinical validation study was performed to test the performance of the Q-Pad Test System. The study design followed CLSI EP09-A2 and CLSI EP21-A guidelines. IRB approval was obtained for participant enrollment and 396 specimens from 198 participants were utilized in the study. Samples were collected
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using the Q-Pad kit according to the Instructions for Use (IFU) and were returned to the laboratory using USPS First-class Return Service. A venous blood draw was performed by a phlebotomist to provide the reference sample. Both samples were received and processed at Qvin Labs (CLIA certified clinical laboratory) using the Beckman Coulter Hemoglobin A1c Test on an AU480 chemistry analyzer.
The acceptance criteria for the comparative linear regression was a slope between 0.93 and 1.07 with a confidence interval that includes 1, an intercept between -0.7 and 0.7 whose confidence interval includes 0, and an R² of >0.95.
Participant HbA1c values ranged from 4.6% to 14.2%. 99% of participants successfully collected a sample. Linear regression analysis was performed to compare the results from the Q-Pad to the venous blood reference method using Passing-Bablok analysis, see Table 11.
| Method | Slope | 95% Cl | y-Intercept | 95% Cl |
|---|---|---|---|---|
| Passing-Bablok | 1.003 | 0.987 - 1.02 | -0.046 | -0.170 - 0.067 |
Table 11. Summary of the clinical validation data
99% of study subjects successfully collected and returned samples to the laboratory for analysis verifying the effectiveness of the Instructions for Use. The comparative methods exhibited strong correlation. No samples were outside of the stated total allowable error of 6%. The overall linear regression showed a slope of 1.003 (95% Cl 0.987, 1.020), intercept of -0.0461 (95% Cl -0.170, 0.0669) and R² of 0.99. The study met all acceptance criteria and demonstrated that the clinical performance of the Q-pad Test system is equivalent to the reference method using venous blood.
Usability Study
A dedicated usability study was conducted following the FDA Human Factors guideline. 40 naive participants, who were self-reported diabetics, received the Q-Pad kit. Users followed the provided Instructions for Use to collect their sample and returned it to Qvin Labs via USPS First-Class Return Service. Each participant provided answers to a questionnaire regarding the use of the Q-Pad kit, the Qvin app and the mock results provided to them. The usability study showed that all 40 women were able to follow the Instruction for Use for the Q-Pad Kit, with 97.5% successfully collecting a sample that led to a valid HbA1c result.
Flex Studies
Elution Stability
The purpose of this study was to verify the stability of eluted menstrual blood samples collected using the Q-Pad Kit for up to 4 hours after extraction. Samples from four (4) participants were used. Samples were
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extracted, aliquoted, and run immediately on the Beckman AU480. Additional aliquots were run at the following time points after extraction: 1, 1.5, 2, 3, and 4 hours. All samples were run in triplicate and the results from each timepoint were compared to the initial timepoint for each sample. Acceptance criteria was <10% bias between the measured time point and the initial measurement immediately after extraction.
For all time points and HbA1c levels, the maximum bias was 3.37%. The elution stability study verified the stability of the eluted sample for up to 4 hours.
Conclusion Drawn
Based on the comparison of technological features and intended use, and as a result of the non-clinical and clinical performance testing completed on Qurasense's Q-Pad Test System, the proposed device devices does not raise new questions of safety and effectiveness and supports the conclusion that the proposed device is substantially equivalent to the predicate device. The non-clinical and clinical testing demonstrate the device is as safe, as effective and performs as well as or better than the predicate device.
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).