(59 days)
Intended Use: For the quantitative determination of α-Amylase activity in human serum or plasma.
Indications for Use: Levels of serum and plasma α-amylase in patients have provided needed evidence for the diagnosis of acute pancreatitis. For In Vitro Diagnostic Use.
The Genzyme Direct Amylase Reagent is a quantitative method for the detection of a-amylase activity in serum and plasma.
Here's an analysis of the provided text regarding the Genzyme Direct Amylase Reagent, focusing on acceptance criteria and supporting studies:
Product Name: Genzyme Direct α-Amylase Test Reagent
Common Name: Reagent for α-Amylase Test
Intended Use: For the quantitative determination of α-Amylase activity in human serum or plasma for the diagnosis of Pancreatitis.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for each metric (e.g., "The slope must be between X and Y"). Instead, it presents the results of the performance studies and then concludes that these results are "acceptable" or "excellent," implying that the observed performance met their internal criteria. Based on the provided text, the acceptance criteria are inferred from these conclusions.
| Acceptance Criterion (Inferred) | Reported Device Performance | Study Conclusion |
|---|---|---|
| Comparative Performance | ||
| Correlation Coefficient (r) | 0.9985 | Acceptable correlation with predicate method. |
| Slope | 0.90 | |
| Intercept (U/L) | -2.50 | |
| Linearity | Linearity up to 2000 U/L | Demonstrated linearity. |
| Precision | ||
| Within-Run CV | ≤ 2.0% | Excellent within-run precision. |
| Between-Run CV | ≤ 2.0% | Excellent between-run precision. |
| Interference | No interference found at tested concentrations. | |
| Liposyn | 3000 mg/dL (1%) | |
| Triglyceride | 3000 mg/dL | |
| Ascorbic Acid | 50 mg/dL | |
| Bilirubin (unconjugated) | 50 mg/dL | |
| Bilirubin (conjugated) | 50 mg/dL | |
| Hemoglobin | 500 mg/dL | |
| Glucose | 2000 mg/dL |
2. Sample Size Used for the Test Set and Data Provenance
-
Sample Size (Test Set):
- Comparative Performance Study: 50 samples
- Linearity Study: Not specified, but data points would typically cover the range up to 2000 U/L.
- Precision Studies (Within-Run & Between-Run):
- Within-Run: Each of 3 serum pools tested 20 times. (3 pools * 20 tests = 60 measurements)
- Between-Run: Each of 3 serum pools tested in duplicate, twice per day, for at least five days, totaling 40 determinations per pool. (3 pools * 40 measurements = 120 measurements)
- Interference Studies: "a specimen pool" was used, with varying levels of interferents added. Specific number of test samples per interferent not specified beyond "a specimen pool."
-
Data Provenance: The document does not specify the country of origin of the data. Given it's a 510(k) submission to the FDA, it's typically for the US market, but the sample origin is not stated. The studies are prospective in nature, as they are specifically conducted to evaluate the performance of the Genzyme Direct Amylase Reagent.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This type of in-vitro diagnostic (IVD) device for quantitative biochemical measurement does not typically involve human expert readers for establishing "ground truth" in the same way imaging devices do.
- For the Comparative Performance Study, the "ground truth" is defined by the results obtained from the predicate method (Roche Boehringer Mannheim α-Amylase/EPS) using the same 50 samples. This is a comparison against a legally marketed and accepted method, not expert consensus on qualitative interpretation.
- For Linearity, Precision, and Interference Studies, the "ground truth" is established by the inherent properties of the samples themselves (known concentrations, spiked interferents, etc.) as measured by the device and the reference methods used to prepare or characterize those samples (e.g., gravimetric for spiking, reference methods for initial concentrations). There are no "experts" establishing image interpretations or diagnoses.
4. Adjudication Method for the Test Set
Not applicable for this type of quantitative IVD performance study. Adjudication methods (e.g., 2+1, 3+1) are typically used when subjective review or interpretation by multiple human experts is involved, such as in clinical trials evaluating diagnostic accuracy of imaging or pathology results. The performance is assessed through statistical comparisons to a reference method or known values.
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 specifically designed for evaluating the impact of an AI-assisted tool on human reader performance, common in radiology or pathology. The Genzyme Direct Amylase Reagent is a standalone in-vitro diagnostic assay; it does not involve human readers interpreting results in a subjective or diagnostic manner that would be "assisted" by the device in the context of an MRMC study. Its performance is measured directly (e.g., U/L) and compared to another quantitative method.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the entire series of studies described (Comparative Performance, Linearity, Precision, Interference) are essentially standalone performance studies for the Genzyme Direct Amylase Reagent. The device itself is the algorithm/method being evaluated, and its performance is measured directly from the assay results without human interpretative input in the loop for the performance metrics.
7. The Type of Ground Truth Used
- Comparative Performance Study: The ground truth was the measurements obtained from the predicate method (Roche Boehringer Mannheim α-Amylase/EPS). This is a reference method comparison.
- Linearity Study: The ground truth was based on the known dilution series or spiked concentrations of α-amylase, demonstrating the device's ability to accurately measure over a range.
- Precision Study: The ground truth was the mean concentration of α-amylase within the serum pools, with the study assessing the device's variability around that mean.
- Interference Study: The ground truth was the known concentrations of purified interfering substances (e.g., Liposyn, Triglyceride, etc.) added to a specimen pool. The goal was to show that these known interferents did not affect the amylase measurement.
8. The Sample Size for the Training Set
The document does not mention a training set or any machine learning/AI algorithms that would require one. The Genzyme Direct Amylase Reagent appears to be a traditional biochemical reagent-based assay, not an AI/ML powered device. Its "learning" comes from its chemical formulation and calibration, not from data-driven training.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or implied for this type of traditional IVD device, this question is not applicable.
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510(k) PREMARKET NOTIFICATION
Genzyme Corporation One Kendall Square Cambridge, MA 02139 Direct Amylase Reagent
June 11, 2001
AUG 1 0 2001
ATTACHMENT 1
510(k) Summary Of Safety and Effectiveness Information Upon Which An Equivalence Determination Could be Made
| Trade or Proprietary Name: | Genzyme Direct α-Amylase Test Reagent |
|---|---|
| Common or Usual Name: | Reagent for α-Amylase Test |
| Classification Name: | Amylase Test System |
| Establishment Name and Address | Genzyme CorporationOne Kendall SquareCambridge, MA 02139-1562 |
| Contact Person: | Barbara Pizza, Manager, Regulatory Affairs(617) 252-7953 |
The use of the Genzyme Direct Amylase Reagent assay in the clinical laboratory setting is substantially equivalent to a currently marketed method for Roche Boehringer Mannheim α-Amylase/EPS for the diagnosis of Pancreatitis.
The Genzyme Direct Amylase Reagent is a quantitative method for the detection of a-amylase activity in serum and plasma.
PERFORMANCE STUDIES
Comparative Performance Studies
A Comparative performance study was conducted using the Genzyme Direct Amylase Reagent, and predicate method (Roche Boehringer Mannheim x-Amylase/EPS).
The slope, intercept, correlation coefficient, and sample range for this comparison is provided below.
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Koi/8743
510(k) PREMARKET NOTIFICATION
Genzyme Corporation One Kendall Square Cambridge, MA 02139 Direct Amylase Reagent
June 11, 2001
| Direct Amylase vs. RocheSerum | |
|---|---|
| Number of samples | 50 |
| Slope | 0.90 |
| Intercept (U/L) | -2.50 |
| Correlation Coefficient (r) | 0.9985 |
| Sample Range (U/L) | 28 - 304 (EPS) |
| Sample Range (U/L) | 22 - 278 (Genzyme) |
The Genzyme method yielded acceptable correlation with the predicate method for samples across the usable range of the product.
Linearity
Linearity studies demonstrated that the Direct Amylase assay is linear up to 2000 U/L.
Precision
Both within-run and between-run studies were performed. Testing was done using frozen serum pools at three target levels of x-amylase activity for within-run precision and between-run.
Within-Run
Each serum pool was tested 20 times in one batch using the Direct Amylase assay. The mean, standard deviation (SD) and coefficient of variation (%CV) were calculated for each serum pool.
| --------Sample | ||||
|---|---|---|---|---|
| C | -------- | |||
| --------11 1 18 1162 C | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | 0701 | 000ﺮ | 200 |
| -------------------CARACTA | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------61 | 0.62 |
The Direct Amylase assay yielded excellent within-run precision with CVs of ≤ 2.0%.
Between-Run
Each serum pool was tested in duplicate, twice per day, for at least five days using the Direct Amylase assay for a total of 40 determinations. The mean, SD and %CV were calculated for each pool as follows:
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The Direct Amylase assay yielded excellent between-run precision with CVs ≤ 2.0%.
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Koll 843
510(k) PREMARKET NOTIFICATION
Direct Amylase Reagent
June 11, 2001
Interference Studies
The effects of interfering substances was evaluated by adding varying levels of potential interferents to a specimen pool. These determined that lipemia, triglyceride, ascorbic acid, bilirubin, hemoglobin and glucose did not interfere with the performance of the Genzyme Direct Amylase assay at the levels up to and including those indicated below.
| Interfering Substance | Concentration |
|---|---|
| Liposyn | 3000 mg/dL (1%) |
| Triglyceride | 3000 mg/dL |
| Ascorbic Acid | 50 mg/dL |
| Bilirubin (unconjugated) | 50 mg/dL |
| Bilirubin (conjugated) | 50 mg/dL |
| Hemoglobin | 500 mg/dL |
| Glucose | 2000 mg/dL |
Conclusion
Based on the results of the studies described above, the Genzyme Direct Amylase Reagent assay is substantially equivalent in performance to the predicate method for quantifying a-amylase activity in serum and plasma.
In lieu of a 510(k) statement under 513(i) of the Act, this information is provided as a 510(k) summary for disclosure to any other persons/companies without the specific written authorization from Genzyme Corporation.
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three curved lines representing its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 1 0 2001
Ms. Barbara Pizza Manager, Regulatory Affairs Genzyme Corporation One Kendall Square Cambridge, MA 02139-1562
510(k) Number: K011843 Re: Trade/Device Name: Direct Amylase Reagent Regulation Number: 862.1070 Regulatory Class: Class II Product Code: JFJ Dated: June 11, 2001 Received: June 12, 2001
Dear Ms. Pizza:
We have reviewed your Section 510(k) notification of intent to market the device referenced we have leviewed your boomer of substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device interslate commerce pror to that have been reclassified in accordance with the provisions of the Ameliuments, of to devices and in . C (Act). You may, therefore, market the device, subject to rederal rood, Drug, and Cooment Fron et. The general controls provisions of the Act include the general controls pro risens of as 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations (Fremarks) Approval), it they of bacyeer Code of Federal Regulations, Title 21, Parts 800 to 895. allecting your device can of rounder assumes compliance with the Good Manufacturing A Substantally oquiratelly assisteneral (GMP) regulation (21 CFR Part 820) and that, through I ractive for Meansal bons, the Food and Drug Administration (FDA) will verify such perious offirmspoolis, are room the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal adultion, I DA may puonshilation and over premarket notification submission does not affect Register. Thease note: this respense to your 542 of the Act for devices under the ally oongation you inight in Control provisions, or other Federal laws or regulations.
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Page 2 -
This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and i additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INTENDED USE 3.0
Page _ 1_of __ 1
Kolli843 510(k) Number (if known): __
Device Name: __ Direct Amylase Reagent
Intended Use:
For the quantitative determination of α-Amylase activity in human serum or plasma.
NOTE: This is not changed from the original Premarket submission K933397.
Indications for Use:
Levels of serum and plasma α-amylase in patients have provided needed evidence for the diagnosis of acute pancreatitis.
For In Vitro Diagnostic Use.
NOTE: This is not changed from the original Premarket submission K933397.
Cun Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K011843
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED.)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109) OR
Over-The-Counter-Use (Optional Format 1-2-96)
§ 862.1070 Amylase test system.
(a)
Identification. An amylase test system is a device intended to measure the activity of the enzyme amylase in serum and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas).(b)
Classification. Class II.