(47 days)
The CEDIA® DAU Multi-Drug Calibrators are intended for the calibration of qualitative and semiquantitative CEDIA® DAU Assays on automated clinical chemistry andy zers.
The CEDIA ® DAU Multi-Drug Calibrators are manufactured using drug free human urine, various drugs of abuse and a preservative. At this time, the drugs of abuse are d-methamphetamine, secobarbital, nitrazepam, morphine, benzoylecgonine, phencyclidine, and EDDP. The drug raw materials are obtained from a commercially available source and are spiked appropriately into the calibrator matrix to obtain the correct calibrator concentration levels. The calibrators are in-process checked and quality controlled against in-house reference calibrators (prepared using a similar procedure) which have had values confirmed using GC/MS by 3 laboratories.
Here's an analysis of the provided text regarding the acceptance criteria and study for the CEDIA® DAU Multi-Drug Calibrators:
The provided 510(k) summary focuses on demonstrating substantial equivalence to a predicate device, specifically regarding EDDP (Methadone Metabolite) concentration. It does not contain a comprehensive "acceptance criteria" table as would typically be presented for a new or significantly modified device, nor does it detail a study that proves the device meets broad performance acceptance criteria beyond the specific EDDP concentration verification.
However, based on the information provided, we can extract the relevant performance data and study details for the EDDP component.
1. Table of Acceptance Criteria and Reported Device Performance
For the specific aspect of EDDP concentration within the CEDIA® DAU Multi-Drug Calibrators:
| Calibrator Type | Acceptance Criteria (Target EDDP ng/mL) | Reported Device Performance (Mean EDDP ng/mL) |
|---|---|---|
| Primary Cutoffs | 100 | 103.1 |
| Secondary Cutoffs | 100 | 101.0 |
| Intermediate | 500 | 496.3 |
| High | 2000 | 2033 |
Note: The document implies that meeting these target concentrations demonstrates satisfactory performance for the EDDP component, thus serving as an implicit acceptance criterion for this specific performance characteristic in the context of substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: Not explicitly stated how many individual calibrator samples were tested for each concentration level (Primary Cutoffs, Secondary Cutoffs, Intermediate, High). The results are presented as "Mean [EDDP] ng/mL," suggesting multiple replicates were tested to arrive at these means.
- Data Provenance: The calibrators were manufactured by Boehringer Mannheim Corporation (USA-based company). The testing was for an in-house product. The document does not specify the country of origin of the raw human urine used in the calibrators. The study is retrospective in the sense that it's a verification of a manufactured product designed to meet established concentration levels.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts/Laboratories: The "ground truth" for the calibrators with the addition of EDDP was established by 2 separate laboratories using GC/MS (Gas Chromatography/Mass Spectrometry).
- Qualifications of Experts: Not explicitly stated, but GC/MS is a highly precise analytical technique, implying the laboratories and their personnel would be qualified analytical chemists/scientists experienced in such methods.
4. Adjudication Method for the Test Set
- Adjudication Method: Not explicitly described. The text states "The CEDIA® DAU Multi-Drug Calibrators were analyzed for EDDP by GC/MS in 2 separate laboratories. The results of the study were as follows:". This suggests that the results from the two laboratories were combined or compared, but the specific method of reconciliation if there were discrepancies (e.g., averaging, independent verification by a third party, or requiring agreement within a certain tolerance) is not detailed. The reported "Mean [EDDP] ng/mL" for each calibrator implies an averaging or consensus of results between the two labs.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not reported. This type of study is typically for diagnostic imaging devices where human readers interpret results with and without AI assistance. The CEDIA® DAU Multi-Drug Calibrators are in-vitro diagnostic products (calibrators for assays), and their performance evaluation methods differ.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- This question is not applicable in the traditional sense of an "algorithm" or "AI" device. The device is a set of chemical calibrators. The "standalone" performance here refers to the analytical accuracy of the calibrator itself, which was tested by GC/MS. The results in the table ("Mean [EDDP] ng/mL") represent this standalone performance, where the calibrators' concentrations were measured independently.
7. The Type of Ground Truth Used
- Type of Ground Truth: The ground truth for the EDDP concentrations was established using GC/MS (Gas Chromatography/Mass Spectrometry), which is considered a definitive analytical method, often referred to as a "gold standard" for quantifying specific compounds in complex matrices. This method provides objective, quantitative measurement data.
8. The Sample Size for the Training Set
- Sample Size for Training Set: The document describes the CEDIA® DAU Multi-Drug Calibrators as being "in-process checked and quality controlled against in-house reference calibrators (prepared using a similar procedure) which have had values confirmed using GC/MS by 3 laboratories."
- This refers to the preparation and quality control of the calibrators themselves, rather than a "training set" for an algorithm. The reference calibrators could be considered analogous to a "training/development set" in that they are used to establish and verify the manufacturing process. However, a specific sample size for this "training" aspect is not provided.
- For the drug raw materials, it mentions they are "obtained from a commercially available source and are spiked appropriately into the calibrator matrix to obtain the correct calibrator concentration levels." This process itself relies on prior knowledge and standards.
9. How the Ground Truth for the Training Set Was Established
- Ground Truth for Training Set (Reference Calibrators): The ground truth for the "in-house reference calibrators" (which can be seen as the basis for developing and controlling the manufacturing process) was established using GC/MS by 3 laboratories. This indicates a high level of analytical rigor for these internal reference standards.
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| APR 21 1998 | 510(k) Summary |
|---|---|
| ------------- | ---------------- |
Introduction
According to the requirements of 21 CFR 807.92, the following information
provides sufficient detail to understand the basis for a determination of
substantial equivalence.
| 1) Submitter name, address, contact | Boehringer Mannheim Corporation4300 Hacienda DrivePleasanton, CA 94588-2722(510) 730-8240Fax: (510) 225-0654 |
|---|---|
| Contact Person: Betsy Soares-Maddox | |
| Date Prepared: March 2, 1998 |
| 2) Device name | Proprietary name: CEDIA ® DAU Multi-Drug Calibrators |
|---|---|
| Common name: Drug of Abuse calibrators for use in the calibration ofCEDIA ® DAU Assays | |
| Classification name: Calibrators, Drug Mixture |
| 3) Predicate device | We claim substantial equivalence to the Methadone Metabolite UrineCalibrators manufactured by Diagnostic Reagents, Inc. |
|---|---|
| --------------------- | ----------------------------------------------------------------------------------------------------------------------------- |
Continued on next page
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510(k) Summary, Continued
| 4) Device Description | The CEDIA ® DAU Multi-Drug Calibrators are manufactured using drug free human urine, various drugs of abuse and a preservative. At this time, the drugs of abuse are d-methamphetamine, secobarbital, nitrazepam, morphine, benzoylecgonine, phencyclidine, and EDDP. The drug raw materials are obtained from a commercially available source and are spiked appropriately into the calibrator matrix to obtain the correct calibrator concentration levels. The calibrators are in-process checked and quality controlled against in-house reference calibrators (prepared using a similar procedure) which have had values confirmed using GC/MS by 3 laboratories. |
|---|---|
| 5) Intended use | The CEDIA ® DAU Multi-Drug Calibrators are used for the calibration of qualitative and semiquantitative CEDIA ® DAU assays in human urine on automated clinical chemistry analyzers. |
Continued on next page
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510(k) Summary, Continued
6) Comparison to predicate device
The Boehringer Mannheim Modified CEDIA® DAU Multi-Drug Calibrators are substantially equivalent to other products in commercial distribution (8) DAU Multiintended for similar use. Most notably, the Modified CEDIA Drug Calibrators with the addition of EDDP are substantially equivalent to the Methadone Metabolite Urine Calibrators manufactured by Diagnostic Reagents Inc. (DRI).
| Feature | DRI EDDP UrineCalibrators | Modified CEDIA®DAU Multi-DrugCalibrators |
|---|---|---|
| Matrix | Human Urine | Human Urine |
| Preservative | Sodium Azide | Sodium Azide |
| Storage conditions | 2-8 ° C | 2-8 ° C |
| Ease of use | Ready to use | Ready to use |
| EDDP concentration: | ||
| Cutoff calibrator | 300 ng/ml | 100 ng/ml |
| Intermediate Calibrator | 1000 ng/ml | 500 ng/ml |
| High Calibrator | 2000 ng/ml | 2000 ng/ml |
| Calibrator composition | Single analyte | Multiple analytes |
| Intended Use | For in vitro diagnosticuse for the calibration ofenzyme immunoassayfor detection ofmethadone metabolitesin human urine. | For use as calibrators inthe CEDIA DAUqualitative andsemiquantitativedetermination of drugsof abuse in human urineon automated clinicalchemistry analyzers. |
Continued on next page
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510(k) Summary, Continued
Performance Characteristics:
- Comparison to predicate device, (cont.)
The CEDIA® DAU Multi-Drug Calibrators were analyzed for EDDP by GC/MS in 2 separate laboratories. The results of the study were as follows:
| Calibrator | Target [EDDP]ng/mL | Mean [EDDP]ng/mL |
|---|---|---|
| Primary Cutoffs | 100 | 103.1 |
| Secondary Cutoffs | 100 | 101.0 |
| Intermediate | 500 | 496.3 |
| High | 2000 | 2033 |
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Image /page/4/Picture/11 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
APR 21 1998
Betsy Soares-Maddox . Manager, Regulatory Affairs and Quality Assurance Boehringer Mannheim Coporation 4300 Hacienda Drive P.O. Box 9002 Pleasanton, California 94566-0900
Re : K980853 CEDIA® DAU Multi-Drug Calibrators Requlatory Class: II Product Code: DKB Dated: March 2, 1998 Received: March 5, 1998
Dear Ms. Soares-Maddox:
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 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 Requlations, 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 Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory In addition, FDA may publish further announcements action. 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 beqin 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/dsmamain.html".
Sincerely yours,
Steven Sitman
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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510(k) Number (if known): N/A
Device Name: CEDIA® DAU Multi-Drug Calibrators
Indications For Use:
The CEDIA® DAU Multi-Drug Calibrators are intended for the calibration of qualitative and semiquantitative CEDIA® DAU Assays on automated clinical chemistry andy zers.
| 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)
(Division Sign-Off)
Division of Clinical, Laboratory Devices
510(k) Number 980853
§ 862.3200 Clinical toxicology calibrator.
(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.