(35 days)
For in vitro diagnostic use with the CARESIDE Analyzer™ to measure amylase from whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with disease of the pancreas, salivary gland, and kidney.
CARESIDE™ Amylase cartridges are used with the CARESIDE Analyzer™ to measure amylase activity in whole blood, serum or plasma specimens. The CARESIDE™ Amylase cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of amylase activity. The film cartridge (patent pending) contains all reagents necessary to measure amylase activity.
Each CARESIDE™ Amylase cartridge consists of an amylase-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge Sample Well, closes the lid and inserts the cartridge into the CARESIDE Analyzer™.
Once loaded, the CARESIDE Analyzer™ scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers. 8.5 microliters of sample remains in the metering passage. Any excess sample flows into an overflow well.
The 8.5 microliters of sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the specimen uniformly. Amylase converts p-nitrophenyl-α-D-maltopentaoside (PNP-Gm) to p-nitrophenyl-oligosaccharides and free oligosaccharides (Gn). The sample mixture diffuses into the underlying detection layer where PNP-Gm is converted by a-glucosidase to generate Gm and p-nitrophenol which converts to a vellow dye. The color intensity of the resulting yellow dye, as measured by the amount of reflected light at 425 nanometers, directly relates to the amylase activity of the specimen.
As the cartridges spin. a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate amylase activity.
Here's an analysis of the provided text regarding the CARESIDE™ Amylase device, structured to answer your questions:
Acceptance Criteria and Device Performance Study for CARESIDE™ Amylase
This document describes the 510(k) submission (K990025) for the CARESIDE™ Amylase device, seeking substantial equivalence to a predicate device. The information focuses on the device's technical characteristics and comparative performance.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state "acceptance criteria" in a numerical or target format. Instead, it presents Comparative Performance Characteristics with the predicate device, Vitros AMYL DT Slides. The implied acceptance criteria are that the CARESIDE™ Amylase performs "as well as or better than" the predicate device in these areas, demonstrating "substantial equivalence."
| Characteristic | Implied Acceptance Criteria (relative to Predicate) | CARESIDE™ Amylase Performance | Vitros AMYL DT Slides Performance |
|---|---|---|---|
| Detection Limit | As good as or better than predicate | 15 U/L | 5 U/L |
| Reportable Range | Overlap and sufficient range | 15 to 600 U/L | 5 to 900 U/L |
| Accuracy | Acceptable, ideally similar to or better than predicate | Mean recovery 95% | Not provided |
| Precision | As good as or better than predicate | Total CV, 75 U/L, 13% | Total CV, 51 U/L, 13% |
| Method Comparison | Good correlation to predicate and other methods | CARESIDE™ = 0.94 (Trace Sci. Amylase DST) + 11.5 U/L, r = 0.97CARESIDE™ = 0.76 (Vitros AMYL DT) + 14.6 U/L, r = 0.95 | N/A (this is the predicate) |
| Interference | No significant interference | No significant interference observed at tested concentrations (Ascorbic Acid, Hemoglobin, Triglycerides) | No reported interference |
| Linearity | Acceptable slope and correlation coefficient | Linearity yielded slope and correlation coefficient within acceptable limits. | Not provided |
Note: The document explicitly states: "The nonclinical and clinical data provided demonstrate that the CARESIDE™ Amylase product is as safe, effective, and performs as well as or better than the legally marketed predicate device." This general statement serves as the overarching acceptance criterion for the 510(k) submission.
2. Sample Size for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the test set in the comparative performance characteristics section.
The data provenance (country of origin, retrospective/prospective) is also not explicitly stated. However, given the context of a 510(k) submission to the FDA, it is highly probable that the studies were conducted under controlled laboratory conditions, likely in the US or in a manner compliant with US regulatory standards.
3. Number of Experts and their Qualifications for Establishing Ground Truth for the Test Set
The document does not mention the use of experts to establish ground truth for the test set. In the context of in vitro diagnostic (IVD) devices like this amylase test, ground truth is typically established by reference laboratory methods, other commercially available and validated diagnostic tests, or clinical outcomes, rather than expert consensus on images or interpretations.
4. Adjudication Method for the Test Set
Given that the ground truth is established through laboratory methods and comparative studies with established devices, an "adjudication method" as typically understood in qualitative or image-based diagnostic studies (e.g., 2+1, 3+1) is not applicable and not mentioned in this document.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is more relevant for diagnostic imaging devices where human readers interpret patient scans. The CARESIDE™ Amylase is an in vitro diagnostic (IVD) device that provides a quantitative measurement, not an interpretation by a human reader.
Therefore, the effect size of human readers improving with or without AI assistance is not applicable here.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was Done
The performance characteristics presented (detection limit, reportable range, accuracy, precision, method comparison, linearity, interference) describe the standalone performance of the CARESIDE™ Amylase device. The device itself is an automated system (cartridge with analyzer) measuring amylase activity. There isn't a human-in-the-loop component for interpretation of the measurement itself; rather, a human uses the analyzer and interprets the numerical result it provides.
7. The Type of Ground Truth Used
The ground truth for the performance evaluations (accuracy, precision, method comparison) appears to be established by:
- Reference laboratory methods: "Rate determination using ethylidene-pNP-G7 substrate, spectrophotometric detection, 37 °C" is listed as a "Reference Method."
- Predicate device measurements: Comparisons were made against the Vitros AMYL DT (predicate device).
- Other commercially available methods: The method comparison also references "Trace Sci. Amylase DST."
Therefore, the ground truth is based on established, conventional, and predicate quantitative measurement methods for amylase.
8. The Sample Size for the Training Set
The document does not provide information on the sample size used for the training set. This information is typically proprietary to the manufacturer and not usually detailed in a 510(k) summary for an IVD device unless it's a novel AI/ML algorithm requiring extensive training data disclosure.
9. How the Ground Truth for the Training Set was Established
Similar to the training set sample size, the document does not describe how ground truth for a training set was established. Since this is a chemical assay, rather than an AI/ML system that "learns" from data, the concept of a "training set" in the machine learning sense of establishing ground truth isn't directly applicable in the same way. Performance characteristics are validated through testing the chemical reactions and reflectance photometry against known concentrations and reference methods. If there was internal calibration or optimization, it would involve reference solutions or materials with known amylase concentrations.
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CARESIDE, Inc. Page 10
510(K) SUMMARY: CARESIDE™ AMYLASE SAFETY V. AND EFFECTIVENESS
I. Applicant Information
- Applicant Name A.
- Applicant/Manufacturer Address B.
- ட் Telephone Number
- Contact Person D.
- FAX Number E.
- F. e-Mail Address
- G. Date 510(k) Summary prepared
II. Device Information
- Device Name (Trade) A.
- B. Device Name (Classification)
- C. Device Classification
CARESIDE, Inc.
6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 AsarchK@CARESIDE.com December 30, 1998
CARESIDE™ Amylase
Amylase test system Clinical chemistry panel Amylase test system Regulation Number: 21 CFR 862.1070 Regulatory Class 2 Classification Number: 75JFJ None applicable
D. Special controls and performance standards
III. Substantial Equivalence Claim
- A. General equivalency claim
The ability to monitor analyte-specific biochemical reactions in dry film and other formats is widely recognized and has gained widespread acceptance for use in chemistry assays.
Amylase in vitro diagnostic products, in both dry film and other formats, are already on Amylase products include those that use amyloclastic methods the U.S. market. (measure the disappearance of substrate and include the iodine-starch method), saccharogenic methods (measure the production of sugars such as maltose and glucose), and chromogenic methods (measure a colored product).
B. Specific equivalency claim
This CARESIDE™ Amylase test is substantially equivalent in intended use and clinical performance to the currently marketed Vitros slides for the quantitative measurement of amylase on the Vitros DT 60 II system with the DTSC II module. Both are based on the principle of dry film and are read by reflectance photometry; however, the Vitros method is based upon the conversion of dyed starch to dyed saccharides while the CARESIDE method is based upon the conversion of a synthetic substrate to a colored product.
Name of Predicate Device: Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros AMYL Slides for Johnson and Johnson's Vitros DT 60 II system with the DTSC II module (formerly Eastman Kodak's DT 60 II). Predicate Device 510K number: K912844/A Product Code: 75CIW
FEB
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IV. Device Description
CARESIDE™ Amylase cartridges are used with the CARESIDE Analyzer™ to measure amylase activity in whole blood, serum or plasma specimens. The CARESIDE™ Amylase cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of amylase activity. The film cartridge (patent pending) contains all reagents necessary to measure amylase activity.
Explanation of Device Function A.
Each CARESIDE™ Amylase cartridge consists of an amylase-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge Sample Well, closes the lid and inserts the cartridge into the CARESIDE Analyzer™.
Once loaded, the CARESIDE Analyzer™ scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers. 8.5 microliters of sample remains in the metering passage. Any excess sample flows into an overflow well.
The 8.5 microliters of sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the specimen uniformly. Amylase p-nitrophenyl-α-D-maltopentaoside to p-nitrophenyl-oligosaccharides converts (PNP-Gm) and free oligosaccharides (Gn). The sample mixture diffuses into the underlying detection layer where PNP-Gm is converted by a-glucosidase to generate Gm and p-nitrophenol which converts to a vellow dye. The color intensity of the resulting yellow dye, as measured by the amount of reflected light at 425 nanometers, directly relates to the amylase activity of the specimen.
Test Reaction Sequence:
amylase > PNP-Gm + Gn (m+n=5) PNP-Gs a-glucosidase > PNP + Gm PNP-Gm -
As the cartridges spin. a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate amylase activity.
B. Test Summary
Amylase is an enzyme produced by the pancreas and parotid glands that occurs in blood. Amylase catalyzes the hydrolysis of starch and related polysaccharide to yield maltose and other oligosaccharides. Amylase activity in the blood is elevated in inflammation and hemorrhage of the pancreas and is decreased in pancreatic insufficiency. Amylase measurement is useful in the differential diagnosis of the digestive system. Various other causes of hyperamylasemia include salivary lesions, biliary tract disorders, trauma, neoplastic diseases, ruptured ectopic pregnancy, pulmonary disease, and alcoholic intoxication. Certain drugs can also increase amylase activity in the blood in vivo.
V. Intended Use
A. Intended Use
The CARESIDE™ Amylase cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure amylase activity in whole blood, serum or plasma.
- B. Indications for Use
This product is indicated for use in the diagnosis and treatment of patients with disease of the pancreas, salivary gland, and kidney.
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VI. Technological Characteristics
- A. Similarities
| CARESIDE™ Amylase | Vitros AMYL DT Slides | |
|---|---|---|
| Intended Use | Primarily to aid in the diagnosis and treatment of patients with disease of the pancreas, salivary gland, and kidney.For in vitro diagnostic use. | Primarily to aid in the diagnosis of diseases of the pancreasFor in vitro diagnostic use |
| Indications | For professional laboratory:not for point of care or physician office laboratory use. | |
| Measurement | Quantitative | Same |
| Method Principle | Dry film, p-nitrophenyl-α-D-maltopentaoside substrate reaction coupled with α-glucosidase | Dry film conversion by amylase of high molecular weight dyed starch into low molecular weight dyed saccharides |
| Specimen dilution | Not required | Same |
| Materials | p-nitrophenyl-α-D-maltopentaoside,α-glucosidase | Dyed amylopectin |
| Detector | Reflectance (425 nm) | Reflectance (555 nm) |
| Test time | Approx. 4 minute warm-up (on-board) plus approximately 6 minute test time. | 15 minutes slide warm-up (off-line) plus 5 minutes test time. |
| Reference Method | Rate determination using ethylidene-pNP-G7 substrate, spectrophotometric detection, 37 °C | PNP Maltopentaoside Method, 37 °C |
| Sample Type | Anti-coagulated whole blood, serum, or heparinized plasma. | Serum or heparinized plasma |
| Specimen volume | 8.5 µl test volume(85 ± 15 µl applied volume) | 10 µl |
| Calibration | Calibration information bar-coded on each cartridge.Calibration information may change with each lot. | Run Vitros DT II calibrators whenever a new slide lot is used or when necessary. |
| Quality Control | 2 levels | Same |
| Reporting Units | U/L | Same |
| Reaction Temp. | 37 °C | Same |
B. Differences
| CARESIDE™ Amylase | Vitros AMYL DT Slides | |
|---|---|---|
| SpecimenProcessing | Not required | Required |
| Accuratepipetting | Not required | Required |
| Reagent pre-warming | Not required | Required |
.
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Comparative Performance Characteristics C.
| CARESIDE™ Amylase | Vitros AMYL DT Slides | |
|---|---|---|
| Detection limit | 15 U/L | 5 U/L |
| Reportable range | 15 to 600 U/L | 5 to 900 U/L |
| Accuracy | Mean recovery 95% | Not provided |
| Precision | Total CV, 75 U/L, 13% | Total CV, 51 U/L, 13% |
| Methodcomparison | CARESIDE™ = 0.94 (Trace Sci. Amylase DST) + 11.5 U/L, r = 0.97CARESIDE™ = 0.76 (Vitros AMYL DT) + 14.6 U/L, r = 0.95 | |
| Linearity | Linearity yielded slope andcorrelation coefficient withinacceptable limits. | Not provided |
| Interference | No significant interference observed at tested concentration of interferent:Ascorbic Acid,........20 mg/dLHemoglobin,......... 100 mg/dLTriglycerides ..... 1500 mg/dL | No reported interference |
D. Conclusion
The nonclinical and clinical data provided demonstrate that the CARESIDE™ Amylase product is as safe, effective, and performs as well as or better than the legally marketed predicate device
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FEB 8 1999
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Kenneth B. Asarch, Pharm. D., Ph.D. Vice President, Quality Systems/ Regulatory Affairs Careside Inc. 6100 Bristol Parkway Culver City, California 90230
Re: K990025 Trade Name: CARESIDE™ Amylase Regulatory Class: II Product Code: JFJ Dated: December 30, 1998 Received: January 5, 1999
Dear Dr. Asarch:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
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 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"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Autman
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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CARESIDE, Inc. Page 15
VII. INDICATIONS FOR USE
510(k) Number:
K 990025
Device Name:
CARESIDE™ Amylase
Indications for use:
For in vitro diagnostic use with the CARESIDE Analyzer™ to measure amylase from whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with disease of the pancreas, salivary gland, and kidney.
Alan Cooper
orv Devices
(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.