(153 days)
HbA1C Enzymatic Assay is intended for the in vitro quantitative determination of stable HbA1c (glycated hemoglobin A1c; A1c) in human whole blood samples. Measurement of hemoglobin A1C is a valuable indicator for long-term diabetic control.
The Diazyme's HbA1C assay kit is a clinical test kit, intended for quantitative determination of HbA1C to monitor long-term glucose control in individuals with diabetes mellitus. The Diazyme's HbA1C assay kit is comprised of a Reagent 1, Reagent 2, Lysis Buffer, THb Reagent, and calibrators. Measurement of hemoglobin A1C is determined enzymaticly by subjecting lyseted samples to extensive protease digestion. This process releases amino acids including glycated valines from the hemoglobin octa peptide. Fructosyl valine oxidase (FVO) then serves as a substrate for fructosyl valine oxidase (FVO) which releases N-terminal valines and produces hydrogen peroxide. The hydrogen peroxide is measured using a peroxidase catalyzed reaction. Total hemoglobin is determined separately by conversion of all hemoglobin derivatives of the samples into hematin using an alkaline method. HbA1C concentration is expressed as a concentration ratio of glycated hemoglobin to total hemoglobin.
The provided text describes the Diazyme HbA1C Enzymatic Assay. Here's an analysis of its acceptance criteria and the study proving it meets those criteria:
1. Table of Acceptance Criteria and the Reported Device Performance:
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | CV% to be low/acceptable | Intra-Assay Precision: |
| 5.3% Alc: CV%= 3.5% | ||
| 12% Alc: CV%= 1.6% | ||
| Inter-Assay Precision: | ||
| 5.3% Alc: CV%= 5.0% | ||
| 12% Alc: CV%= 7.2% | ||
| Correlation with Predicate Device | High correlation coefficient (close to 1) | Correlation coefficient of 0.92 with Tosoh's Automated HPLC Analyzer. |
| Interference | Minimal or no significant interference from common substances at specified concentrations | No significant interference observed from: Triglyceride (2000 mg/dl) Bilirubin (10 mg/dl) Ascorbic Acid (4 mg/dl) Uric Acid (5 mg/dl) Glucose (2400 mg/dl) |
| Accuracy / Equivalence | "Excellent accuracy" and "substantially similar" to the predicate device, with "no significant deviation" in results from clinical patient samples. | The precision, correlation, and interference studies are presented as evidence for excellent accuracy and substantial equivalence. The document explicitly states: "There is no significant deviation between the results obtained by Diazyme's and [predicate device] actively testing clinical patient samples." |
| Safety and Effectiveness | To be safe and effective for its intended use | Concluded to be safe and effective based on the presented studies. |
Study that Proves the Device Meets Acceptance Criteria:
The study presented to prove the device meets the acceptance criteria is a comparison study against a legally marketed predicate device (Tosoh Medics, Inc. Automated HPLC Analyzer: HbA1c Variant Analysis Mode, K011434), along with internal performance evaluations for precision and interference.
- Comparison Study: Diazyme's HbA1C Enzymatic Assay showed a correlation coefficient of 0.92 with the predicate device. This high correlation is presented as evidence of substantial equivalence.
- Precision (Reproducibility) Study: Both Intra-Assay and Inter-Assay precision were evaluated at two HbA1c levels (5.3% and 12%). The CV% values are reported as shown in the table above.
- Interference Study: The assay was tested for interference from common substances (Triglyceride, Bilirubin, Ascorbic Acid, Uric Acid, Glucose) at clinically relevant concentrations. No significant interference was found.
2. Sample size used for the test set and the data provenance:
- Sample Size for Test Set: The document mentions "actively testing clinical patient samples" for the comparison study, but does not specify the exact number of samples used for the correlation study or the precision/interference studies.
- Data Provenance: Not explicitly stated, but the mention of "clinical patient samples" implies retrospective or prospective clinical samples. The country of origin is not provided.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. For an HbA1C assay, the "ground truth" for the comparison study would typically be the results generated by the predicate device and for internal studies, carefully prepared reference materials or controls. The document does not describe an expert panel establishing ground truth in the way it might for an imaging AI device.
4. Adjudication method for the test set:
Not applicable in the context of an HbA1C enzymatic assay. Adjudication methods like 2+1 or 3+1 are typically used for subjective clinical assessments where multiple experts independently rate cases, and discrepancies are resolved. For a quantitative assay like this, the "ground truth" is established by the reference method (predicate device) and analytical measurements.
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:
Not applicable. This is an in vitro diagnostic device for quantitative determination of HbA1C, not an AI-assisted diagnostic imaging or classification tool that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the device is inherently a standalone (algorithm/assay only) system. Its performance is evaluated purely on its analytical capabilities (precision, accuracy, correlation to a reference method, interference). It does not involve human interpretation in its primary function.
7. The type of ground truth used:
- For the comparison study, the results from the predicate device (Tosoh Medics, Inc. Automated HPLC Analyzer: HbA1c Variant Analysis Mode) served as the ground truth/reference method.
- For precision studies, presumably calibrated control materials with known HbA1C concentrations were used.
- For interference studies, spiked control materials with known concentrations of interfering substances were used.
8. The sample size for the training set:
Not applicable. This is a traditional in vitro diagnostic (IVD) assay based on enzymatic reactions, not a machine learning or AI algorithm that requires a "training set" in the computational sense. The development of the assay would involve various R&D experiments, but not a formally defined "training set" like for AI models.
9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" in the AI/machine learning sense. The ground truth for developing and validating the assay relies on established biochemical principles, analytical chemistry techniques, and comparison to recognized reference methods.
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Diazyme Laboratories Division, General Atomics
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JUN 2 8 2005
Summary
Submitter's name:
Submitter's address:
Phone: Fax:
Name of Contact Person:
Huan Tran Diazyme Laboratories Division General Atomics 3550 General Atomics Court San Diego, CA 92121 Phone: 858-455-4761 Fax: 858-455-4750
3550 General Atomics Court
San Diego, CA 92121
858-455-4754
858-455-4750
Date the summary was prepared:
December 25, 2004
HbA1C Enzymatic Assay Name of the device: HbA1C Enzymatic Assay Trade Name: Enzymatic Assay, HbA1C Common/Usual Name: Glycosylated Hemoglobin Assay (Per 21CFR section 864.7470) Classification Name: Device Class: II
Predicate Device:
The legally marketed device to which we are claiming equivalence [807.92(4)(3)]: G7 I he regally marketed device to willon we are canning of I
Automated HPLC Analyzer: HbA1c Variant Analysis Mode (K011434) manufactured by Tosoh Medics, Inc., San Francisco, CA, 94080.
Description of the device
The Diazyme's HbA1C assay kit is a clinical test kit, intended for quantitative determination of The Diazynie's TibATC assay ar is a chailed to monitor long-term glucose control in individuals with diabetes mellitus.
The Diazyme's HbA1C assay kit is comprised of a Reagent 1, Reagent 2, Lysis Buffer, THb Reagent, and calibrators.
Measurement of hemoglobin A1C is determined enzymaticly by subjecting lyseted samples to extensive protease digestion. This process releases amino acids including glycated samples to extensive process digestion: This process sines then serve as a substrate for fructosyl valines from the nemogrom octa enainer - Ery - Leaves N-terminal valines and produces valife oxidase (1' V O) chiz milen special is measured using a peroxidase catalyzed reaction nydrogen peroxiac. The fryarogen personalism is determined separately by conversion of all
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hemoglobin derivatives of the samples into hematin using an alkaline method as of scribed in nemogram delivatives of the samples mosterialism sed as a concentration ratio of glycated hemoglobin to total hemoglobin.
Intended Use of the Device:
HbA1C Enzymatic Assay is intended for the in vitro quantitative determination of stable HbA1C (glycated hemoglobin A1c; A1c) in human whole blood samples. Measurement of hemoglobin A1C is a valuable indicator for long-term diabetic control.
HbAIC Enzymatic Assay Kit contains an A1C calibrator and a THb calibrator. The calibrators HDATC Entzymanc Assay for the quantitative determination of HbA1C in blood.
HbAIC Enzymatic Assay has controls design to be used with the assay for the quantitative determination of HbA1C in blood.
Performance Characteristics
Diazyme's HbA1C Enzymatic Assay is a two reagents based kinetic assay system. The assay offers excellent precision as shown in the table below:
| 5.3% Alc | 12% Alc | |
|---|---|---|
| Intra-Assay Precision | CV%= 3.5% | CV%= 1.6% |
| Inter-Assay Precision | CV%= 5.0% | CV%= 7.2% |
Diazyme's HbA1C Enzymatic Assay has a good correlation with Tosoh's with arthershap Diazyine S TIOATC Litzynatic Tissay has a good - See a good by spiking the substances correlation coefinelen of 0.22. We have connected at the indicated concentrations:
| Interference | Concentration |
|---|---|
| Triglyceride | 2000 mg/dl |
| Bilirubin | 10 mg/dl |
| Ascorbic Acid | 4 mg/dl |
| Uric Acid | 5 mg/dl |
| Glucose | 2400 mg/dl |
Conclusion: Comparison analysis presented in the 510K submission for this device in the comparison section, together with linearity, precision and interference study presented demonstrated that the Diazyme's HBAIC Enzymatic Assay has excellent accuray and is safe and effective. There is no significant deviation between the results obtained by Diazyme's and enective. There is no significant actively come testing clinical patient samples.
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Therefore, Diazyme's HbA1C Enzymatic Assay is substantially similar to the commercially Therefore, Diazyme's HDATC Entzymane Assay is Sabstannally Ships of Same Shole blood samples.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Public Health Service
JUN 2 8 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Huan Tran Quality Assurance Manager Diazyme Laboratories Division General Atomics 3550 General Atomics Court San Diego, CA 92121
K050178 Re:
Trade/Device Name: HbA1C Enzymatic Assay Kit Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, JIS; JJX Dated: June 1, 2005 Received: June 3, 2005
Dear Mr. Tran:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Carol C. Benam
Carol C. Benson, M.A. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K050178
Device Name: HbA1C Enzymatic Assay Kit
Indications for Use:
HbA1C Enzymatic Assay is intended for the in vitro quantitative determination of stable HbA1C Enzymatic Assay is intented for the in human whole blood samples. Measurement
HbA1c (glycated hemoglobin A1c; A1c) in human whole blootis control HDATC (glycated nemogrobin ATC, ATC) in management diabetic control.
of hemoglobin A1C is a valuable indicator for long-term diabetic control.
Prescription Use (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Keeleff
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
210(k)_KOSO178
§ 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).