(931 days)
The Nova Allegro HbA1c Assay is intended for in vitro diagnostic use on the Nova Allegro Analyzer for the quantitative determination of the glycated Hemoglobin A1c) in capillary whole blood obtained from the fingertip. The results from this assay are intended to be used for the monitoring of long-term blood glucose/metabolic control in individuals with diabetes mellitus.
The Nova Allegro Analyzer is intended for in vitro diagnostic use in clinical laboratory and near-patient testing (point-of-care) settings for the quantitative determination of Nova Allegro Assays using Nova Allegro Test Cartridges.
Nova Allegro Analyzer: The Nova Allegro Analyzer is a compact, point-of-care analyzer that features a clinically important menu of measured and calculated tests. All tests are measured with disposable, ready-to-use cartridges, and are easily performed by non-technical personnel. The analyzer supports multiple wavelengths that are used to measure the assay of interest. The analyzer consists of the following key systems/components that the user interacts with: Two analytical bays where the single use test cartridges are analyzed, Color Touchscreen Display, Barcode Scanner, Printer, Data Export Options, Ethernet Connection, USB Port.
Nova Allegro HbA1c Assay: The Allegro HbA1c Assay is a completely automated assay for the HbA1c in human whole blood and the calculation of estimated average glucose (eAG). Nova Allegro HbA1c Test Cartridges are the key element a user interacts with to obtain the HbA1c concentration in a Capillary finger-stick whole blood sample. The main components of the Test Cartridge are the Capillary that is used to obtain the Capillary finger-stick whole blood specimen and present it to the Test Cartridge and the reaction chamber. The Test Cartridge has a barcode label with lot specific information.
The provided text describes the performance testing of the Nova Allegro HbA1c Assay and Nova Allegro Analyzer for the quantitative determination of glycated Hemoglobin A1c (HbA1c) in capillary whole blood.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes various performance tests and their outcomes, implying that meeting these outcomes constitutes the acceptance criteria. Explicit, numerical acceptance criteria are not always stated as "acceptance criteria," but rather as the successful outcome of the test.
| Test Category | Acceptance Criteria (Implied by successful results) | Reported Device Performance |
|---|---|---|
| Linearity | Met across the reportable range (4.0-14.0 % HbA1c) compared to a reference method. | The resulting linearity data met the acceptance criteria when compared to the reference method across the reportable range of 4.0-14.0 % HbA1c. |
| Interference Testing | Absolute difference between mean test value and mean control value for interfering substances < 10%. | All potential interfering substances (Acetylsalicyclic Acid, Ibuprofen, Glyburide, Cholesterol, Acetaminophen, Non-conjugated Bilirubin, Conjugated bilirubin, Ascorbic Acid, Metformin, Glucose, Glipizide, Chlorpropamide, Tolbutamide, Acarbose, Captopril, Rheumatoid Factor, Ampicillin, Cyclosporine, Heparin, Levodopa, Metronidazole, Phenylbutazone, Rifampicin, Theophylline, vitamin B12, Furosemide, Gemfibrozil, Losartan, Nicotinic Acid, Urea, y-Tocopherol, Atorvastatin, Intralipid, Propanolol, Uric Acid, Acetylcysteine, Cefoxitin, Doxycyclin, Immunoglobulin, Methyldopa, Ozempic (semaglutide), Protein (Total), Salicylic acid, Triglycerides) tested met the acceptance criteria. No significant interference (<10%) was observed up to the reported concentration levels. |
| Total Hemoglobin Interference | Difference between mean HbA1c measured at tested HGB level and neat HbA1c sample < 10%. | All tested HGB levels (between 6 and 20 g/dL) met the Acceptance Criteria; no significant clinical interference was identified. |
| Method Comparison | Substantial equivalence to comparator method when using fingerstick whole blood samples. | Passing-Bablok regression results: Overall N=526, Slope = 0.972, Intercept = 0.217, r = 0.993. The data indicates substantial equivalence. |
| Precision (20-Day Imprecision - Controls) | Clinically acceptable precision for HbA1c (specific values not explicitly stated as criteria, but demonstrated excellence). | Control 1 (Mean 5.67%): Reproducibility SD 0.113, %CV 2.00%. Control 2 (Mean 9.47%): Reproducibility SD 0.242, %CV 2.55%. |
| Precision (Repeatability - Capillary Fingerstick Blood) | Clinically acceptable precision for HbA1c (specific values not explicitly stated as criteria, but demonstrated excellence). | For 4.0-6.0% range (N=200): Mean 5.50%, SD 0.083, %CV 1.50%. For 6.1-8.0% range (N=169): Mean 6.83%, SD 0.103, %CV 1.51%. For 8.1-10.0% range (N=106): Mean 8.94%, SD 0.171, %CV 1.92%. For 10.1-14.0% range (N=49): Mean 11.32%, SD 0.270, %CV 2.38%. Data met acceptance criteria. |
| Hemoglobin Derivative and Fractions | Absolute difference between mean test value and mean control value for interfering substances < 10%. | All tested substances (Glycated Albumin, Acetylated Hemoglobin, Labile Hemoglobin, Carbamylated Hemoglobin, HbA0, HbA1a, HbA1b) met acceptance criteria; no clinical interference up to reported concentrations. |
| Hemoglobin Variants | Absolute difference between mean test value and mean control value for interfering substances < 10%. | No significant interference for Hemoglobin C (≤ 38.2%), Hemoglobin D (≤41.1%), Hemoglobin E (≤27.9%), Hemoglobin S (≤ 38.6%), and Hemoglobin A2 (≤ 6.5%). Significant interference with fetal hemoglobin (HbF) at > 5.4%. |
2. Sample Size Used for the Test Set and Data Provenance
- Linearity Testing: Eleven (11) linearity specimens.
- Interference Testing: Ten (10) replicate HbA1c tests per substance on prepared hemolysate specimens. Specific number of substances tested is indicated in Table 1 (40 substances).
- Total Hemoglobin Interference Testing: Not explicitly stated, but implies multiple HGB levels were tested.
- Method Comparison: A total of 526 subjects/specimens across four clinical sites.
- Site 1: 156 samples
- Site 2: 154 samples
- Site 3: 102 samples
- Site 4: 114 samples
- Precision (20-Day Imprecision - Controls): Two control solutions, each analyzed 80 times (20 days * 2 times/day * 2 duplicates) at each of four sites.
- Repeatability (Capillary Fingerstick Blood): 524 subjects from the Method Comparison study had a second fingerstick specimen collected and measured.
- Hemoglobin Derivative and Fractions, Hemoglobin Variants: Specific sample sizes for these tests are not provided, but imply testing of prepared specimens with varying concentrations.
Data Provenance:
- Country of Origin: Not explicitly stated, but "four (4) clinical sites" and "physician's offices" for point-of-care clinical performance studies indicate real-world clinical settings. The FDA submission suggests a US-centric regulatory and approval process.
- Retrospective or Prospective: The "Method Comparison" and "Precision" studies involved collecting and measuring samples, suggesting a prospective design for these clinical performance studies. The "Bench testing" for linearity and interference would be laboratory-based and controlled.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not mention "experts" in the context of establishing ground truth in the way one would for image-based AI studies (e.g., radiologists reviewing images).
For this device, the "ground truth" is established by a reference method or a "NGSP Certified central laboratory reference method" for HbA1c measurements, which are analytical instruments and laboratory processes, not human experts making subjective assessments.
- Method Comparison: Compared to an "NGSP Certified central laboratory reference method." NGSP (National Glycohemoglobin Standardization Program) certification implies a high standard of analytical accuracy and traceability to a primary reference method, essentially serving as a highly precise chemical/metrological "ground truth."
4. Adjudication Method for the Test Set
Not applicable. This is a quantitative diagnostic test where the "ground truth" is established by a reference laboratory method, not by human interpretation or consensus that would require adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging diagnostics or other subjective interpretation tasks where human readers' performance with and without AI assistance is evaluated. This device is a quantitative assay, with performance evaluated against a reference laboratory method and through precision studies, not human reader performance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance data presented (Linearity, Interference, Total Hemoglobin Interference, Method Comparison against a reference lab, Precision, Hemoglobin Derivative/Fractions, and Hemoglobin Variants) represents the standalone performance of the Nova Allegro HbA1c Assay and Analyzer. The results are generated directly by the device and compared to established analytical standards or reference methods. There is no human-in-the-loop component in the device's measurement process that is being evaluated in these tests.
7. The Type of Ground Truth Used
- Reference Method/NGSP Certified Central Laboratory Reference Method: For Linearity and Method Comparison studies, the device's measurements were compared against a "reference method" and an "NGSP Certified central laboratory reference method." This is an analytical ground truth based on established, highly accurate laboratory techniques.
- Prepared Samples with Known Concentrations: For Interference testing, Hemoglobin Derivative and Fractions, and Hemoglobin Variants, prepared hemolysate specimens with known concentrations of interfering substances or variants were used. This constitutes a controlled, analytical ground truth where the expected outcome is known based on the sample preparation.
- Control Solutions: For 20-Day Imprecision testing, "Nova Allegro HbA1c Control Solutions" were used, which are materials with known, stable HbA1c values, serving as an analytical ground truth for precision assessment.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an AI/algorithm. This device is a diagnostic assay and analyzer, not an AI algorithm that undergoes machine learning training. The "development" of such a device involves chemical and engineering optimization, and analytical validation. Therefore, the concept of a "training set" as understood in machine learning is not applicable here.
9. How the Ground Truth for the Training Set was Established
As noted above, the concept of a training set and its ground truth is not applicable to this type of medical device (a quantitative diagnostic assay). The device's operational range and internal calibration would be established through a process of characterization and calibration using traceable standards and reference materials, which is standard for analytical instruments.
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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 22, 2024
Nova Biomedical Corporation Cesidio Tempesta Regulatory Affairs Manager 200 Prospect St. Waltham, Massachusetts 02454
Re: K221326
Trade/Device Name: Nova Allegro HbA1c Assay, Nova Allegro Analyzer Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated Hemoglobin Assay Regulatory Class: Class II Product Code: LCP, JQT Dated: April 25, 2024 Received: April 26, 2024
Dear Cesidio Tempesta:
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.
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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).
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.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
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 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-regulatory
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assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D. Deputy Division Director Division of Chemistry and Toxicology 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) K221326
Device Name
Nova Allegro HbA1c Assay, Nova Allegro Analyzer
Indications for Use (Describe)
The Nova Allegro HbA1c Assay is intended for in vitro diagnostic use on the Nova Allegro Analyzer for the quantitative determination of the glycated Hemoglobin A1c) in capillary whole blood obtained from the fingerty. The results from this assay are intended to be used for the monitoring of long-term blood glucose/metabolic control in individuals with diabetes mellitus.
The Nova Allegro Analyzer is intended for in vitro diagnostic use in clinical laboratory and near-patient testing (point-ofcare) settings for the quantitative determination of Nova Allegro Assays using Nova Allegro Test Cartridges.
| 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
510(K): K221326/CW220003
510(K) Owner: Nova Biomedical Corporation Registration Number: 1219029 Address: 200 Prospect St. Waltham, MA 02454 Phone: 781-894-0800 Fax Number: 784-891-4806 Contact Person: Cesidio Tempesta
| Contact Person: | Cesidio Tempesta | ||||
|---|---|---|---|---|---|
| Date Prepared: | November 22, 2024 |
Proprietary Name:
Nova Allegro Analyzer Nova Allegro HbA1c Assay
Common or Usual Name: Analyzer HbA1c Test
Classification Name
| Classification Name | Regulation # | Class | Product Code |
|---|---|---|---|
| Glycosylated Hemoglobin Assay | 864.7470 | II | LCP |
| Analyzer | 862.2400 | I | JQT |
Predicate Device:
K171650 - Alere Afinion HbA1c Assay on the Afinion 2 Analyzer
Device Description:
Nova Allegro Analyzer
The Nova Allegro Analyzer is a compact, point-of-care analyzer that features a clinically important menu of measured and calculated tests. All tests are measured with disposable, ready-to-use cartridges, and are easily performed by non-technical personnel. The analyzer supports multiple wavelengths that are used to measure the assay of interest. The analyzer consists of the following key systems/components that the user interacts with:
- Two analytical bays where the single use test cartridges are analyzed ●
- Color Touchscreen Display
- Barcode Scanner
- . Printer
- Data Export Options
- Ethernet Connection ●
- USB Port .
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Nova Allegro HbA1c Assay
The Allegro HbA1c Assay is a completely automated assay for the HbA1c in human whole blood and the calculation of estimated average glucose (eAG). Nova Allegro HbA1c Test Cartridges are the key element a user interacts with to obtain the HbA1c concentration in a Capillary finger-stick whole blood sample. The main components of the Test Cartridge are the Capillary that is used to obtain the Capillary finger-stick whole blood specimen and present it to the Test Cartridge and the reaction chamber. The Test Cartridge has a barcode label with lot specific information.
Sample Types:
Capillary whole blood (from finger stick)
Intended Use:
The Nova Allegro HbA1c Assay is intended for in vitro diagnostic use on the Nova Allegro Analyzer for the quantitative determination of the glycated Hemoglobin A1c) in capillary whole blood obtained from the fingertip. The results from this assay are intended to be used for the monitoring of longterm blood glucose/metabolic control in individuals with diabetes mellitus.
The Nova Allegro Analyzer is intended for in vitro diagnostic use in clinical laboratory and near-patient testing (point-of-care) settings for the quantitative determination of Nova Allegro Assays using Nova Allegro Test Cartridges.
Principle of Measurement:
A whole blood sample containing Hemoglobin A1c and Total Hemoglobin are nonspecifically absorbed to latex particles. The anti-human mouse HbA1c antibody reacts with this forming a complex. Agglutination occurs when polyclonal antibody specifically reacts with the mouse antibody bound to the Hemoglobin A1c on the surface of the latex particles. The amount of agglutination is measured as absorbance. The HbA1c value is obtained from a stored calibration curve and displayed on the Nova Allegro Analyzer.
Summary of Performance Testing:
Bench testing and point-of-care clinical performance studies were completed in physician's offices to demonstrate that the Nova Allegro HbA1c Assay achieves its intended performance during normal conditions of use in its intended environment and in its intended use population. Testing is summarized as follows:
Linearity Testing
Testing was performed to validate the Nova Allegro HbA1c Assay (Test Method) linearity when compared to a reference method. Eleven (11) linearity specimens were tested randomly on the Nova Allegro Analyzer. The same eleven linearity specimens were then analyzed on the reference method.
The resulting linearity data met the acceptance criteria when compared to the reference method across the reportable range of 4.0-14.0 % HbA1c.
Interference Testing
Testing was performed to test for specific interfering substances with the Allegro HbA1c Assay.
Ten (10) replicate HbA1c tests were performed on prepared hemolysate specimens containing potential interfering substances as well as control specimens without the interfering substance.
The test substance was considered to exhibit interference if the absolute difference between the mean test value and the mean control value was greater than 10%.
Based upon the results, all potential interfering substances tested met the acceptance criteria and were demonstrated not to have a clinical interference on HbA1c test results. No significant interference (<10%) was observed up to the following concentration levels:
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| Test Substance | Concentration | Test Substance | Concentration |
|---|---|---|---|
| Acetylsalicyclic Acid | 65.2 mg/dL | Rifampicin | 6.4 mg/dL |
| Ibuprofen | 50.0 mg/dL | Theophylline | 10.0 mg/dL |
| Glyburide | 200 mg/dL | vitamin B12 | 1.2 mg/dL |
| Cholesterol | 1055 mg/dL | Furosemide | 7 mg/dL |
| Acetaminophen | 20.0 mg/dL | Gemfibrozil | 8 mg/dL |
| Non-conjugated Bilirubin | 60.0 mg/dL | Losartan | 6 mg/dL |
| Conjugated bilirubin | 30.0 mg/dL | Nicotinic Acid | 70 mg/dL |
| Ascorbic Acid | 6.0 mg/dL | Urea | 700 mg/dL |
| Metformin | 4.0 mg/dL | y-Tocopherol | 10 mg/dL |
| Glucose | 1000 mg/dL | Atorvastatin | 5 mg/dL |
| Glipizide | 0.2 mg/dL | Intralipid | 1000 mg/dL |
| Chlorpropamide | 74.8 mg/dL | Propanolol | 0.3 mg/dL |
| Tolbutamide | 64 mg/dL | Uric Acid | 30.0 mg/dL |
| Acarbose | 60 mg/dL | Acetylcysteine | 166 mg/dL |
| Captopril | 0.6 mg/dL | Cefoxitin | 650 mg/dL |
| Rheumatoid Factor | 572 IU/ml | Doxycyclin | 5.0 mg/dL |
| Ampicillin | 100 mg/dL | Immunoglobulin | 2.0 g/dL |
| Cyclosporine | 0.5 mg/dL | Methyldopa | 2.25 mg/dL |
| Heparin | 5 U/mL | Ozempic (semaglutide) | 0.192 mg/dL |
| Levodopa | 2.0 mg/dL | Protein (Total) | 21000 mg/dL |
| Metronidazole | 20.0 mg/dL | Salicylic acid | 59 mg/dL |
| Phenylbutazone | 40.0 mg/dL | Triglycerides | 1520 mg/dL |
Table 1: Tested Concentration Levels
Total Hemoglobin Interference Testing
Testing was performed to test for Total Hemoglobin (HGB) Interference on the Allegro HbA1c Assay.
The tested Total Hemoglobin (HGB) was considered non-interfering if the difference between the mean of the HbA1c measured at the tested HGB level and that of the neat HbA1c sample is less than 10%. All tested HGB levels met the Acceptance Criteria and were demonstrated to have no significant clinical interference on the measured A1c test results. No clinical interference was identified for total hemoglobin (HGB) levels between 6 and 20 g/dL.
Method Comparison
Method Comparison studies on capillary fingerstick whole blood specimens were conducted. A total of four (4) clinical sites, eight (8) Allearo Analyzers (2 per site) and three (3) lots of Allearo HbA1c Test Cartridges were used in the study. At each site, a minimum of three (3) CLIA-Waived operators conducted the HbA1c capillary testing by running a minimum of 90 specimens.
Samples were tested over a minimum of twenty (20) days to ensure system day-to-day variability was considered. Samples run on the Allegro Analyzers using the Allegro HbA1c assay were compared to a NGSP Certified central laboratory reference method.
The Passing-Bablok regression results are shown in Table 2:
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| Site | N | Sample RangeAllegro(%) | Slope | Intercept | r |
|---|---|---|---|---|---|
| 1 | 156 | 4.7 - 12.9 | 0.968 | 0.261 | 0.993 |
| 2 | 154 | 4.6 - 13.2 | 0.974 | 0.204 | 0.993 |
| 3 | 102 | 5.0 - 13.1 | 0.983 | 0.180 | 0.994 |
| 4 | 114 | 4.4 - 13.8 | 0.968 | 0.203 | 0.994 |
| Combined | 526 | 4.4 - 13.8 | 0.972 | 0.217 | 0.993 |
Table 2: Passing-Bablok Regression Results
The data indicates that the Nova Allegro System reports substantially equivalent HbA1c test results when using fingerstick whole blood samples when compared to the comparator method.
Precision
Total Imprecision of the Allegro HbA1c Assay in the hands of CLIA Waived professionals was assessed using methods described in CLSI "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guidelines - Second Edition", CLSI EP5-A3 as guidance.
20-Day Imprecision (Controls)
Two Nova Allegro HbA1c Control Solutions were analyzed for twenty days in duplicate twice a day (total of eighty measurements per sample) at each of the four POC CLIA waived sites, using three HbA1c test cartridge lots and three different untrained operators at each site. Analyses were performed for each individual site and for all sites combined.
| Repeatability | Between-Run/Operator | Between-Day/Lot | Between-Site | Reproducibility | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Control1 | 5.67 | 0.091 | 1.61% | 0.037 | 0.65% | 0.034 | 0.60% | 0.045 | 0.79% | 0.113 | 2.00% |
| Control2 | 9.47 | 0.175 | 1.85% | 0.035 | 0.37% | 0.118 | 1.25% | 0.112 | 1.18% | 0.242 | 2.55% |
Repeatability (Capillary Fingerstick Blood)
For evaluation of fingerstick precision/repeatability, a second fingerstick specimen was collected and measured for HbA1c on 524 subjects enrolled in the Method Comparison study. Three lots of HbA1c test cartridges, eight analyzers (two at each of four sites) and three different untrained operators were used for the fingerstick precision measurements. Estimates of repeatability are shown below.
| Repeatability | ||||
|---|---|---|---|---|
| HbA1C range | N | Mean | SD | %CV |
| 4.0 - 6.0 | 200 | 5.50 | 0.083 | 1.50% |
| 6.1 - 8.0 | 169 | 6.83 | 0.103 | 1.51% |
| 8.1 - 10.0 | 106 | 8.94 | 0.171 | 1.92% |
| 10.1 - 14.0 | 49 | 11.32 | 0.270 | 2.38% |
The data met the acceptance criteria for repeatability and indicates that the Allegro Analyzer System reports clinically acceptable HbA1c precision when testing capillary whole blood samples.
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Hemoglobin Derivative and Fractions
Testing was performed to test for specific interfering Hemoglobin Derivatives and cross-reactivity of hemoglobin fractions including HbA0, HbA1a, and HbA1b with the Nova Allegro HbA1c.
The test substance will not be considered an interfering substance if the absolute difference between the mean test value and the mean control value is less than 10%. All substances met the Acceptance Criteria and were demonstrated not to have a clinical interference on the measured HbA1c test results. No clinical interference was identified up to the test concentrations reported.
Hemoglobin Derivatives
Testing was performed to assess any possible interference effects of Glycated Albumin, Acetylated Hemoglobin, Labile Hemoglobin, and Carbamylated Hemoglobin on the measured HbA1c test results.
The test substance will not be considered an interfering substance if the absolute difference between the mean test value and the mean control value is less than 10%. All substances met the Acceptance Criteria and were demonstrated not to have a clinical interference on the measured HbA1c test results. No clinical interference was identified with the Allegro HbA1c Assay up to the following test concentrations: 50 mg/mL glycated albumin, 50 mg/mL acetylated hemoglobin, 0.5 mg/mL carbamylated hemoglobin, 20 mg/mL labile hemoglobin
Hemoglobin Fractions
Testing was preformed to assess the cross-reactivity from HbA0, HbA1b components on the Allegro HbA1c assay.
The test substance was considered an interfering substance if the absolute difference between the mean test value and the mean control value was greater than 10%.
All substances met the Acceptance Criteria and HbA0, HbA1a, and HbA1b were demonstrated not to have a clinical interference on the measured HbA1c test results. No clinical interference was identified up to the test concentrations reported.
| Potentialinterferent | Highest Level Tested with NoSignificant Interference |
|---|---|
| HbA0 | Up to 93.5% |
| HbA1a | Up to 1.6% |
| HbA1b | Up to 1.7% |
Hemoglobin Variants
Testing was performed to determine specific Hemoglobin Variant (HbA2, HbC, HbD, HbE, HbS, and HbF) interference on the Allegro HbA1c assay.
The test substance was considered to be an interfering substance if the absolute difference between the mean test value and the mean control value is greater than 10%.
The test results show that there is significant interference due to the presence of fetal hemoglobin at a HbF concentration of > 5.4%. The results from the Nova Allegro HbA1c Assay show that there is no significant interference for samples containing Hemoglobin C (≤ 38.2%), Hemoglobin D (≤41.1%), Hemoglobin E (≤27.9%), Hemoglobin S (≤ 38.6%), and Hemoglobin A2 (≤ 6.5%).
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| Table 3: Comparison of Predicate and Proposed Devices | ||||
|---|---|---|---|---|
| Characteristic | Predicate: | Proposed: |
|---|---|---|
| Analyzer | K171650 - Alere Afinion™ 2 Analyzer | K221326 - Nova Allegro Nova AllegroAnalyzer |
| Intended Use | Afinion 2 analyzer is a compact multi-assayanalyzer for point-of-care testing, designed toanalyze the Alere AfinionTM test cartridges. Afinion2 system, consisting of Afinion 2 analyzer andAlere Afinion test cartridges is for in vitrodiagnostic use only. | The Nova Allegro Analyzer is intended for invitro diagnostic use in clinical laboratory andnear-patient testing (point-of-care) settings forthe quantitative determination of Nova AllegroAssays using Nova Allegro Test Cartridges. |
| AnalyzerFunction | Assay cartridge processing including pumping,heating, image processing | Same |
| CartridgeInterface | Physical processing of cartridge (locking, docking,splitting, foil penetration, merging) | Physical processing of cartridge (locking,docking, foil penetration, mixing assay) |
| User Interface | User display and operating instructions in labeling | Same |
| Peripheral units | A barcode reader and printer can be connected | Barcode reader and printer integrated intoanalyzer |
| Components | Components in metal and injection moldedplastics | Same |
| Dimensions | 200 mm W x 186 mm H x 328 mm D 3.4 kg | 203 mm W x 356 mm H x 381 mm D 9.1 kg |
| Connectivity | Ethernet plug incorporated into the analyzer andconnectivity software incorporated in the software. | Same |
| HbA1c Assay | K171650 - Alere Afinion HbA1c OnAfinion 2 Analyzer | K221326 - Nova Allegro HbA1c Assay onNova Allegro Analyzer |
| Intended Use | Alere AfinionTM HbA1c is an in-vitro diagnostictest for quantitative determination of glycatedhemoglobin (% hemoglobin A1c, % HbA1c) inhuman whole blood. The measurement of %HbA1c is recommended as a marker of long-termmetabolic control in persons with diabetes mellitus | The Nova Allegro HbA1c Assay is intended forin vitro diagnostic use on the Nova AllegroAnalyzer for the quantitative determination ofthe glycated Hemoglobin (% hemoglobin A1c)in capillary whole blood obtained from thefingertip. The results from this assay areintended to be used for the monitoring of long-term blood glucose/metabolic control inindividuals with diabetes mellitus. |
| MeasurementRange | 4.0-15.0 % | 4.0-14.0% |
| Test Principle | Automated boronate affinity assay. | Latex enhanced turbidimetric immunoassay. |
| Type of Test | Quantitative in-vitro diagnostic test | Same |
| Intended Users | Prescription use. Waived users. | Same |
| Blood Sampling | Standard phlebotomy techniques for obtainingvenous blood samples. Fingerstick by use oflancet. | For use only with capillary Fingerstick wholeblood |
| Procedure forFilling ofSamplingDevice | Touch the surface or bring the tip of the capillaryjust beneath the surface of the blood drop/sample.Do not wipe off the capillary after filling | Same |
| Sample Volume | 1.5 µL | Same |
| CapillaryMaterial | Plastic | Glass |
| CartridgeBarcode | For analyzer identification of HbA1c test withcapillary sampling device | Same |
| Package InsertandQuick Guide | Illustrations of cartridge and sampling device withplastic capillary. | Illustrations of cartridge and sampling devicewith glass capillary |
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Substantial Equivalence
The results obtained from the nonclinical and clinical evaluations confirmed the accuracy of the Nova Allegro Analyzer and Nova Allegro HbA1c Assay when used in the health care settings outlined in its intended use.
The Nova Allegro Analyzer and Nova Allegro HbA1c Assay displayed substantial equivalence to the legally marketed predicate device, Alere Afinion HbA1c Assay on the Afinion 2 Analyzer (K171650).
§ 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).