(127 days)
The CEDIA® DAU AmphAssure Assay is a homogeneous enzyme immunoassay for the in vitro qualitative determination of amphetamines in human urine on automated clinical chemistry analyzers. This device is used as an accessory to immunoassay screening tests to reduce the number of false positive results needing confirmation testing. Measurements are used as an aid in the diagnosis and treatment of amphetamine use or overdose.
The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. GCMS is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result particularly when preliminary positive test results are used.
The CEDIA® DAU AmphAssure assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. This assay is based on the bacterial enzyme B-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. The CEDIA DAU AmphAssure assay is a unique test for identification of amphetamines in urine and for the elimination of false positive results due to other cross-reactant substances. Most cross-reactive substances must be present in high concentrations compared to amphetamines in order to give a false-positive result in immunoassay based methods that detect amphetamines. AmphAssure employs the addition of a limited amount of a neutralizing antibody to amphetamine and methamphetamine to neutralize the signal in a true positive sample, without any effect on the signal from a sample containing a high concentration of cross-reactive substance. The neutralizing antibody does not bind the labeled conjugate in the assay, so that its primary effect is to reduce the signal resulting from amphetamines in the sample. Samples containing amphetamines can be distinguished from false-positive samples by the difference in signal before and after addition of the neutralizing antibody. Two analyzer channels are programmed with identical test parameters for the CEDIA AmphAssure assay; reagents without neutralization antibodies are assigned to the first channel, and the reagents with neutralization antibodies are assigned to the second channel. A calculated test (channel three) is programmed to give the difference in results between the first and second channel. Calibrators, controls and patient samples are tested on both channels. The device consists of following: AmphAssure Reagents, AmphAssure Calibrator, Standard, and Control Set.
The provided text does not contain detailed acceptance criteria and supporting study data for the CEDIA® DAU AmphAssure Assay. The document is a 510(k) summary for regulatory clearance, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a comprehensive study report with quantitative acceptance criteria and performance data.
Here's what can be inferred and what is missing based on your request:
1. A table of acceptance criteria and the reported device performance
- Acceptance Criteria: Not explicitly stated in the document. For an immunoassay like this, acceptance criteria would typically involve sensitivity, specificity, accuracy (e.g., concordance with GC-MS), precision (intra-assay and inter-assay variability), linearity, and cross-reactivity profiles. The document mentions the intended use of reducing false positives, implying that high specificity is a key performance characteristic.
- Reported Device Performance: No specific quantitative performance data is provided in this summary directly comparing the device to acceptance criteria. The document states that the AmphAssure assay is a "unique test for identification of amphetamines in urine and for the elimination of false positive results due to other cross-reactant substances." It also mentions that "Samples containing amphetamines can be distinguished from false-positive samples by the difference in signal before and after addition of the neutralizing antibody." This describes the mechanism intended to improve performance but doesn't present the numerical results of that improvement against a specific criterion.
2. Sample size used for the test set and the data provenance
- Sample Size: Not mentioned.
- Data Provenance: Not mentioned (e.g., country of origin, retrospective or prospective).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Number of Experts: Not mentioned.
- Qualifications of Experts: Not mentioned.
4. Adjudication method for the test set
- Adjudication Method: Not mentioned.
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
- MRMC Study: This is a diagnostic immunoassay device, not an imaging device typically associated with "human readers" or "AI assistance" in the context of MRMC studies. Therefore, this type of study is not applicable and not mentioned.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Standalone Performance: The device itself is an automated immunoassay. Its performance is standalone in the sense that it provides a qualitative result (presence or absence of amphetamines) based on the enzymatic reaction and spectrophotometric measurement, without direct human interpretation of complex images or data to generate that initial result. However, the result is "only a preliminary analytical result" and requires "a more specific alternative chemical method... to obtain a confirmed analytical result," usually GC-MS. So, while the assay performs standalone to produce a preliminary result, it's not the definitive standalone diagnostic.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- Ground Truth: The document explicitly states: "A more specific alternative chemical method must be used to obtain a confirmed analytical result. GCMS is the preferred confirmatory method." This indicates that Gas Chromatography-Mass Spectrometry (GC-MS) is used as the gold standard or ground truth for confirming the presence of amphetamines.
8. The sample size for the training set
- Training Set Sample Size: Not mentioned. The document describes the technology and mechanism of the assay but does not detail the development or validation studies, which would typically include training set information.
9. How the ground truth for the training set was established
- Ground Truth for Training Set: Since the training set size is not mentioned, the method for establishing its ground truth is also not mentioned. However, it's highly probable that GC-MS would have been used for establishing ground truth for any training or development samples, consistent with its role as the preferred confirmatory method.
In summary, the provided 510(k) summary lacks the detailed study information regarding acceptance criteria, sample sizes, expert involvement, and specific performance metrics that would typically be found in a full study report. It focuses on the device description, intended use, and comparison to a predicate device to demonstrate substantial equivalence, which is the primary goal of a 510(k) submission.
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MAY - 2 2000
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 | Microgenics Corporation46360 Fremont BoulevardFremont, CA 94538(510) 979-5029Fax: (510) 979-5229 |
| Contact Person: Neal BelletDate Prepared: April 20, 2000 | |
| 2) Device name | Proprietary name: CEDIA® DAU AmphAssure AssayCommon name: Homogeneous enzyme immunoassay for the determination of amphetamines in urine.Classification name: Amphetamine test system |
| 3) Predicate device | We claim substantial equivalence to the TDx/TDxFLxAmphetamine/Methamphetamine II Immunoassay (K883707) manufactured by Abbott Laboratories Inc.Continued on next page |
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510(k) Summary, Continued
| 4) Device Description | The CEDIA® DAU AmphAssure assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. This assay is based on the bacterial enzyme B-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. The CEDIA DAU AmphAssure assay is a unique test for identification of amphetamines in urine and for the elimination of false positive results due to other cross-reactant substances. Most cross-reactive substances must be present in high concentrations compared to amphetamines in order to give a false-positive result in immunoassay based methods that detect amphetamines. AmphAssure employs the addition of a limited amount of a neutralizing antibody to amphetamine and methamphetamine to neutralize the signal in a true positive sample, without any effect on the signal from a sample containing a high concentration of cross-reactive substance. The neutralizing antibody does not bind the labeled conjugate in the assay, so that its primary effect is to reduce the signal resulting from amphetamines in the sample. Samples containing amphetamines can be distinguished from false- positive samples by the difference in signal before and after addition of the neutralizing antibody. Two analyzer channels are programmed with identical test parameters for the CEDIA AmphAssure assay; reagents without neutralization antibodies are assigned to the first channel, and the reagents with neutralization antibodies are assigned to the second channel. A calculated test (channel three) is programmed to give the difference in results between the first and second channel. Calibrators, controls and patient samples are tested on both channels.The device consists of following: |
|---|---|
| ----------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| AmphAssure Reagents | |
|---|---|
| 1 | EA Reconstitution Buffer |
- EA Reconstitution Buffer l Piperazine-N, N-bis [2-ethanesulfonic acid] buffer, buffer salts, stabilizer, and preservative la
- EA Reagent 0.16 g/l Enzyme Acceptor (microbial), 7 mg/l mouse monoclonal antibodies reactive to d-amphetamine and 7 mg/l mouse monoclonal antibodies reactive to d-methamphetamine, buffer salts, detergent, and preservative
- 2 ED Reconstitution Buffer Piperazine-N, N-bis [2-ethanesulfonic acid] buffer; buffer salts, and preservative
Continued on next page
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510(K) Summary, Continued
| DeviceDescriptioncontinued | 2a | ED Reagent7.1 µg/l Enzyme Donor (microbial) conjugated to d-amphetamineand 11.3 µg/l Enzyme Donor (microbial) conjugated to d-methamphetamine, 1.7g/l chlorophenol red-b-D-galactopyranoside,stabilizer, and preservative |
|---|---|---|
| 3 | EA Reconstitution Buffer350 mg/l mouse monoclonal antibodies reactive to d-amphetamineand d-methamphetamine, Piperazine-N, N-bis [2-ethanesulfonic acid]buffer, buffer salts, stabilizer, and preservative | |
| 3a | EA Reagent0.16 g/l Enzyme Acceptor (microbial), 7 mg/l mouse monoclonalantibodies reactive to d-amphetamine and 7 mg/l mousemonoclonal antibodies reactive to d-methamphetamine, buffer salts,detergent, and preservative | |
| 4 | ED Reconstitution BufferPiperazine-N, N-bis [2-ethanesulfonic acid] buffer; buffer salts, andpreservative | |
| 4a | ED Reagent7.1 µg/l Enzyme Donor (microbial) conjugated to d-amphetamineand 11.3 µg/l Enzyme Donor (microbial) conjugated tod-methamphetamine,1.7 g/l chlorophenol red-b-D-galactopyranoside, stabilizer, andpreservative | |
| AmphAssure Calibrator, Standard, and Control Set | ||
| • | Upper Limit Standard15,000 ng/ml d-methamphetamine in normal urine with preservative | |
| • | Cut-off Calibrator375 ng/ml d-methamphetamine and 225K ng/ml pseudoephedrine innormal urine with preservative | |
| False Positive Control500K ng/ml pseudoephedrine in normal urine with preservative | ||
| AmphAssure Calibrator, Standard and Control Kit is designed for use withthe AmphAssure assay only and will be packaged separately. |
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- Intended use The CEDIA® DAU AmphAssure Assay is a homogeneous enzyme immunoassay for the in vitro qualitative determination of amphetamines in human urine on automated clinical chemistry analyzers. This device is used as an accessory to immunoassay screening tests to reduce the number of false positive results needing confirmation testing. Measurements are used as an aid in the diagnosis and treatment of amphetamine use or overdose.
The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. GCMS is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result particularly when preliminary positive test results are used.
6) Comparison to predicate device
The Microgenics Corporation CEDIA® DAU AmphAssure Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to TDx/TDx FLx Amphetamine /Methamphetamine II (K883707) manufactured by Abbott Laboratory Inc.
The following table compares the CEDIA® DAU AmphAssure Assay with the predicate device, TDx/TDx FLx Amphetamine /Methamphetamine II.
| Similarities | Differences |
|---|---|
| Both assays utilize a monoclonal antibody. | The two assays have different monitoring systems:AmphAssure (β-galactosidase hydrolysis of CPRG)TDX (Fluorescein tracer) |
| Both assays yield negative results to ephedrine, pseudoephedrine, and phenylpropanolamine at concentrations of 1 mg/mL. | TDx uses periodate |
| Both assays are used to detect the presence of amphetamines in human urine | AmphAssure assay is a two-channel system that generate a difference in rate when amphetamines are present. |
| Both assays are run on automated clinical analyzers | TDx is semi-quantitative, whereas AmphAssure Assay is qualitative. |
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Image /page/4/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services USA. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the circumference. Inside the circle is a stylized symbol that resembles three overlapping profiles of human heads, with flowing lines suggesting movement or connection.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY - 2 2000
Mr. Andrew Morozovsky VP of Regulatory and Compliance Systems Microgenics Corporation 46360 Fremont Boulevard Fremont, California 94538
Re: K994380 Trade Name: CEDIA DAU AMPHASSURE Assay Regulatory Class: II Product Code: DKZ, DKB Dated: March 28, 2000 Received: March 29, 2000
Dear Mr. Morozovsky:
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
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" (21CFR 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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510(k) Number (if known): N/A
(R) Device Name: CEDIA DAU AmphAssure Assay
Indications For Use:
The CEDIA® DAU AmphAssure Assay is a homogeneous enzyme immunoassay for the in vitro qualitative determination of amphetamines in human urine on automated clinical chemistry analyzers. This device is used as an accessory to immunoassay screening tests to reduce the number of false positive results needing confirmation testing. Measurements are used as an aid in the diagnosis and treatment of amphetamine use or overdose.
The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. GCMS is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result particularly when preliminary positive test results are used.
(Division Sign-Off) Division of Clinical Labora 129945 510(k) Number_
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)
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. 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, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).