(55 days)
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay intended for use in the quantitative analysis of caffeine levels in human serum in subjects undergoing therapy with caffeine, especially in cases of neonatal apnea.
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in biological fluids. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate deyhdrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH. resulting in an absorbance change that can be measured spectrophotometrically.
This document describes the Emit® Caffeine Assay, a homogeneous enzyme immunoassay for the quantitative analysis of caffeine levels in human serum.
Here's an analysis of the provided information regarding acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., a specific correlation coefficient or accuracy range that the device needed to meet to be deemed acceptable). Instead, it presents the results of a method comparison study as evidence of equivalence.
| Performance Metric | Reported Device Performance | Acceptance Criteria (Explicitly Stated) |
|---|---|---|
| Correlation with HPLC (Caffeine levels) | Excellent correlation with HPLC (correlation coefficient = 0.99) | Not explicitly stated |
Note: The phrase "excellent correlation" implies a qualitative acceptance, but a specific quantitative threshold for the correlation coefficient is not provided. The study's purpose was to demonstrate "substantial equivalence" to a predicate device for a broader intended use, rather than meeting novel performance criteria.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 110 neonate samples.
- Data Provenance: Retrospective, as all samples were collected from patients who had already received Theophylline or Caffeine. The country of origin is not specified but can be inferred to be the USA given the FDA submission.
- 31 samples were from patients who had received Theophylline.
- 79 samples were from patients who had received Caffeine.
- The values of these samples "spanned the assay range."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This type of information is generally not applicable to a diagnostic assay for a chemical compound like caffeine. The ground truth (reference method) was established using High-Performance Liquid Chromatography (HPLC). HPLC is a well-established analytical technique and does not require "experts" in the sense of human readers for interpretation, but rather skilled laboratory personnel to operate the equipment and interpret chromatograms.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by an objective analytical method (HPLC), not by human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is more relevant for imaging devices or other diagnostics where human interpretation plays a significant role. The Emit® Caffeine Assay is an in-vitro diagnostic (IVD) assay that produces a quantitative result, not an image or subjective interpretation.
6. Standalone Performance Study
Yes, a standalone study was implicitly performed. The method comparison study directly evaluated the Emit® Caffeine Assay's performance against HPLC without human intervention in the assay's execution or result generation. The "correlation coefficient = 0.99" refers to the algorithm's (assay's) performance.
7. Type of Ground Truth Used
The type of ground truth used was High-Performance Liquid Chromatography (HPLC). HPLC is a recognized gold standard analytical method for quantifying various substances, including caffeine, in biological samples.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its sample size. This type of terminology (training set/test set) is more commonly used in machine learning or AI-based device development. For this immunoassay, the "development" or "validation" of the assay's performance characteristics (like linearity, precision, etc.) would have been established during the initial clearance (K853872), and the current submission is focused on demonstrating equivalence for an expanded intended use. The 110 samples mentioned were used for a method comparison study, which serves as a validation (or test) of the device against a gold standard for its expanded indication rather than for training.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is mentioned in the context of this device and study, the method for establishing its ground truth is not applicable. The assay's fundamental characteristics (e.g., dose-response curve, calibration) would have been established using known concentrations of caffeine in a laboratory setting during its initial development, but this is not generally referred to as establishing "ground truth for a training set" in this context.
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510(k) Summary Emit® Caffeine Assay
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
The assigned 510(k) number is: K042407
Manufacturer's Name, Address, Telephone, and Contact Person, Date of 1. Preparation
| Manufacturer: | Dade Behring Inc.20400 Mariani Ave.Cupertino, CA 95014 |
|---|---|
| Contact Information: | Dade Behring Inc.P.O. Box 6101Newark, DE 19714Attn: Yuk-Ting LewisTel: 302-631-7626 |
| Date of Preparation: | October 18, 2004 |
Device Name / Classification 2.
Emit® Caffeine Assay / Enzyme immunoassay, Theophylline
Product code: 91 KLS
3. Identification of the Legally Marketed Device
Emit® Caffeine Assay - K853872
4. Device Description
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in biological fluids. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate deyhdrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH. resulting in an absorbance change that can be measured spectrophotometrically.
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Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.
5. Device Intended Use
The Emit® Caffeine Assay is a homoqeneous enzyme immunoassay intended for use in the quantitative analysis of caffeine levels in human serum in subjects underqoing therapy with caffeine, especially in cases of neonatal apnea.
6. Medical device to which equivalence is claimed and comparison information
The modified Emit® Caffeine Assay has a broader intended use than the currently cleared Emit® Caffeine Assay to include measurement of caffeine as a parent drug.
The use of the current Emit® Caffeine Assav is limited to measurement of caffeine as a metabolite of Theophylline.
To support the broader intended use, a method comparison study was performed using 110 neonate samples with values spanning the assay range. Of these samples, thirty-one (31) were from patients who had received Theophylline and 79 were from patients who had received with Caffeine. The Assay results were compared to HPLC. The Emit® Caffeine Assay had excellent correlation with HPLC (correlation coefficient=0.99).
Other performance characteristics of the Emit® Caffeine Assay were previously established under K853872.
The Emit® Caffeine Assay, with broader intended use, is substantially equivalent to the current Emit® Caffeine Assay.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus, which is a symbol often associated with medicine and healthcare. The caduceus is depicted with three wavy lines representing snakes intertwined around a staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the caduceus.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
OCT 2 8 2004
Ms. Yuk-Ting Lewis Regulatory Affairs and Compliance Manager Dade Behring, Inc PO Box 6101 M/S 514 Newark, DE 19714
Re: K042407
Trade/Device Name: Emit® Caffeine Assay Regulation Number: 21 CFR 862.3880 Regulation Name: Theophylline test system Regulatory Class: Class II Product Code: KLS Dated: September 1, 2004 Received: September 3, 2004
Dear Ms. 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 (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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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 (301) 594-3084. 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/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, US. DVM.
Jean M. Cooper, MS. D.V.M. 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):
Emit® Caffeine Assay Device Name:
Indications For Use:
The Emit® Caffeine Assay is a homogeneous enzyme immunoassay intended for use in the quantitative analysis of caffeine levels in human serum in subjects undergoing therapy with caffeine, especially in cases of neonatal apnea.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Robert Cates
Division Sign-Off
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Office of In Vitro Diagnostia Device Evaluation an
510(k) K042407
§ 862.3880 Theophylline test system.
(a)
Identification. A theophylline test system is a device intended to measure theophylline (a drug used for stimulation of the muscles in the cardiovascular, respiratory, and central nervous systems) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of theophylline overdose or in monitoring levels of theophylline to ensure appropriate therapy.(b)
Classification. Class II.