(8 days)
AC/AD Linearity Verifiers are intended to be used to verify the calibration, linear operating range and reportable range (linearity) of methods used to determine the concentration of therapeutic drugs.
AC/AD Linearity Verifiers should be used any time it is necessary to confirm the proper callbration and linear operating range of TDM methods and instruments. Quality control/verification requirements should be determined in conformance with local, state and/or Federal regulations or accreditation requirements
medical device intended for use with automated and manual methods monitoring selected therapeutic drugs (TDM). AC/AD Linearity Verifiers is a five level, multiconstituent set of calibrators made in human serum and used to confirm the proper calibration, linear operating range and reportable range (linearity) of TDM methods. The "AC/AD" designation derives from AntiConvulsant, antiAnxiety and other Qrugs. AC/AD Linearity Verifiers contains concentrations of analytes extending over a wide analytical range. Level 1 is a zero level 5 has a concentration near the upper limit of instruments. Levels 1, 2, 3, and 4 are related by linear dilution. When assayed like patient samples, the verifiers assist in determination of calibration and linear operating range (linearity) of methods for the analytes included.
This 510(k) submission (K982217) describes the AC/AD^TM Linearity Verifiers, a device used to verify the calibration, linear operating range, and reportable range for therapeutic drug monitoring (TDM) methods. The submission focuses on demonstrating substantial equivalence to a predicate device, the ABC^TM Linearity Verifiers, rather than presenting a study against a pre-defined set of acceptance criteria for a novel device. Therefore, some of the requested information, particularly regarding specific numerical acceptance criteria and a detailed study design meeting such criteria, is not present in this document in the typical format for performance studies.
However, based on the provided text, we can infer some aspects and extract relevant information.
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly list numerical "acceptance criteria" for the AC/AD Linearity Verifiers in the way one might see for a diagnostic test. Instead, the performance assessment is geared towards demonstrating functional equivalence to the predicate device and confirming the "desired functionality."
Inference: The implicit acceptance criterion for the AC/AD Linearity Verifiers is to "demonstrate the desired functionality" of verifying calibration, linear operating range, and reportable range for TDM methods, similar to the predicate device. This functionality is demonstrated through testing on commonly used automated TDM systems and other analytical methods.
| Acceptance Criterion (Inferred) | Reported Device Performance |
|---|---|
| Verify Calibration | Demonstrated for most methods tested: The AC/AD Linearity Verifiers were tested on three commonly used automated TDM systems (Abbott TDx Assay System, Dade-Behring EMIT system, Roche-Boehringer CEDIA reagents), two colorimetric methods (GED reagents for acetaminophen, Sigma Diagnostic reagents for salicylate), and HPLC (for nordiazepam). For most of these, the product demonstrated its intended use in verifying calibration. Exceptions/Observations: - Carbamazepine by fluorescence polarization immunoassay: Demonstrated a "significant miscalibration believed to be real." This implies the verifiers successfully identified a miscalibration, fulfilling their intended purpose of verifying. - GED reagents for acetaminophen: Gave results that "might indicate incompatibility" or a miscalibration. However, a level-correlated, proportional colorimetric response was observed, suggesting the verifiers were providing expected responses within the method's context. - EMIT reagents for ethosuximide: Reacted with an interferent in the AC/AD base matrix, leading to the conclusion that "this product is not useful with the EMIT ethosuximide reagents." This identifies a specific limitation where the verifiers do not perform as intended, which is also a valuable outcome of a verification study. |
| Verify Linear Operating Range | Demonstrated for most methods tested: Similar to calibration, the verifiers were used to assess linearity. The text states: "Most methods tested demonstrated the desired functionality of the product," which encompasses verifying the linear operating range. For the methods where issues were noted (Carbamazepine, Acetaminophen GED, Ethosuximide EMIT), the verifiers either indicated a problem with linearity/calibration or a specific incompatibility, thereby fulfilling their role in assessing the linear operating range and reportable range, even if the result was a limitation. |
| Verify Reportable Range | Demonstrated for most methods tested: Similar to calibration and linearity, the verifiers' ability to assess the reportable range of TDM methods was implied as part of the "desired functionality" demonstrated across the tested systems. |
| Substantial Equivalence to Predicate Device | Conclusion: "Based upon the purpose of the device, the descriptions and labeling of the predicate device, and upon the safety and efficacy using multiple instruments and methods, and stability data generated for the AC/AD Linearity Verifiers, the product is substantially equivalent to the predicate device." |
2. Sample Size for the Test Set and Data Provenance
- Sample Size for Test Set: The document does not specify a numerical "sample size" in terms of how many individual tests or replicates were performed for each analyte on each system. It mentions that the verifiers contain "five levels" and were tested on "three commonly used automated therapeutic drug monitoring systems," "two colorimetric methods," and "HPLC."
- Data Provenance: The document does not explicitly state the country of origin. Given the submission to the FDA in the US, it is highly likely that the testing was conducted in the US. The data appears to be retrospective in the sense that the studies were performed to validate the product before market submission, rather than a prospective trial of a new clinical diagnostic method.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of device (linearity verifier for analytical instruments) does not typically involve human experts establishing ground truth in the way a diagnostic imaging study would. The "ground truth" for the linearity verifiers is established through their intrinsic formulation (gravimetrically and traceable calibration) and their expected behavior when analyzed on instrument systems. The "experts" in this context would be the analytical chemists or laboratorians who designed the product and interpreted the results of the performance testing on the various instrument platforms. The document does not specify the number or qualifications of these individuals, but their expertise is implied by the technical nature of the submission.
4. Adjudication Method for the Test Set
Not applicable. As described above, the "ground truth" is analytical/technical, not based on expert adjudication of clinical cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is an in vitro diagnostic reagent (linearity verifier), not a diagnostic algorithm or imaging device requiring a MRMC study. Its function is to assess instrument performance, not to aid human readers in interpreting clinical cases.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This concept is not directly applicable. The "device" itself is a set of calibrators (reagents). It interacts with instruments to produce results. The "performance" is how reliably these calibrators allow the instrument and method to demonstrate proper calibration, linearity, and reportable range without human intervention in the result generation, although human interpretation of these instrument results is required. The testing described focuses on this standalone performance of the verifiers across different instrument platforms.
7. Type of Ground Truth Used
The ground truth used for the AC/AD Linearity Verifiers is based on:
- Intrinsic formulation: Gravimetric and traceable calibration of the analytes within the verifiers. This means the true concentration of each analyte at each level is known by design.
- Expected analytical response: The verifiers are designed to produce a linear and proportional response when tested on properly calibrated and functioning TDM methods and instruments. Deviations from this expected response (e.g., miscalibration, non-linearity, interference) reveal issues with the method/instrument, which is the intended purpose of the verifiers.
8. Sample Size for the Training Set
Not applicable. This device is a linearity verifier, not an algorithm that requires a "training set" in the machine learning sense. The concentrations within the verifiers are pre-determined by design and chemical formulation.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device. The "ground truth" (i.e., the exact concentration of each analyte at each level within the verifier vials) is established through precise manufacturing processes, including gravimetric measurements and traceability to reference standards.
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K982217
July 2, 1998
510(k) SUMMARY
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:
Roy F. Schall, Jr., Ph.D. Contact Name:
June 11, 1998 Date:
Product Name: AC/ADtm Linearity Verifiers
Calibration Verifiers, Linearity Verifiers Common Names:
Predicate Devices: ABC:m Linearity Verifiers by SC Calibrators & Controls LLC
Description of the Device: medical device intended for use with automated and manual methods monitoring selected therapeutic drugs (TDM). AC/AD Linearity Verifiers is a five level, multiconstituent set of calibrators made in human serum and used to confirm the proper calibration, linear operating range and reportable range (linearity) of TDM methods. The "AC/AD" designation derives from AntiConvulsant, antiAnxiety and other Qrugs. AC/AD Linearity Verifiers contains concentrations of analytes extending over a wide analytical range. Level 1 is a zero level 5 has a concentration near the upper limit of instruments. Levels 1, 2, 3, and 4 are related by linear dilution. When assayed like patient samples, the verifiers assist in determination of calibration and linear operating range (linearity) of methods for the analytes included.
Intended Use: AC/AD Linearity Verifiers are intended to be used to verify the calibration, linear operating range and reportable range (linearity) of methods used to determine the concentration of therapeutic drugs.
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Technical Characteristics Compared to Predicate Device:
Comparison of Features of AC/AD Linearity Verifiers and the predicate device: ABC Linearity Veriflers.
| Attribute | AC/AD Linearity Verifiers | ABC Linearity Verifiers |
|---|---|---|
| No of Analytes | 11 | 12 |
| No of Levels | 5 | 5 |
| Vol per level (mL) | 5 | 5 |
| Type of Analytes | Therapeutic Drugs | Therapeutic Drugs |
| Method(s) | Automated, ManualImmunoassay, other(except EMIT ethosuximide) | Automated, ManualImmunoassay, other |
| Base Matrix | Human Serum | Human Serum |
| Preservative | Non-Azide (proprietary) | Non-Azide (proprietary) |
| Calibration | Gravimetric & Traceable | Gravimetric + Some,Traceable |
| Use | Verification of Calibration,Linear Operating Range (OR),Reportable RangeAll Methods(except EMIT ethosuximide) | Verification of Calibration,Linear Operating Range (OR),Reportable RangeAll Methods |
Technical Characteristics by Assessment of Performance: The performance of AC/AD Verifiers has been tested on three commonly used automated therapeutic drug monitoring systems (Abbott TDx Assay System, Dade-Behring (formerly Syva) EMIT system, and Roche-Boehringer CEDIA reagents), by two colorimetric methods (GED reagents for acetaminophen and Sigma Diagnostic reagents for salicylate) and by HPLC (for nordiazepam) to validate their use. Most methods tested demonstrated the desired functionality of the product. Carbamazepine by fluorescence polarization immunoassay demonstrated a significant miscallbration believed to be real. GED reagents for acetaminophen gave results which might indicate incompatibility with AC/AD vertfiers. However, the GED reagents gave a level-correlated, proportional colorimetric response with the verifiers, and it was not possible to rule out a miscalibration. EMIT reagents for ethosuximide reacted with an interferent in the AC/AD base matrix, and this product is not useful with the EMIT ethosuximide reagents.
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Based upon the purpose of the device, the descriptions and label-Conclusions: ing of the predicate device, and upon the safety and efficacy using multiple instruments and methods, and stability data generated for the AC/AD Linearity Verifiers, the product is substantially equivalent to the predicate device.
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Image /page/3/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with its wings spread, and three curved lines representing the feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle image.
2 1898 JUL
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
SC Calibrators & Controls LLC C/O Ms. Carole Stamp TUV Product Service 1775 Old Highway 8 NW, Suite 104 New Brighton, Minnesota 55112-1891
Re: K982217 Trade Name: AC/ADTH Linearity Verifiers Requlatory Class: I Product Code: DIF Dated: June 23, 1998 Received: June 24, 1998
Dear Ms. Stamp:
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 aqainst 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 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" (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 "dsmo@fdadr.cdrh.fda.gov".
Sincerely yours.
Steven Sutman
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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Page
510 (k) NUMBER (if KNOWN) : _
DEVICE NAME: AC/AD Linearity Verifiers
Indications for Use of the Subject Device: AC/AD Linearity Verifiers should be used any time it is necessary to confirm the proper callbration and linear operating range of TDM methods and instruments. Quality control/verification requirements should be determined in conformance with local, state and/or Federal regulations or accreditation requirements
(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)
A
§ 862.3280 Clinical toxicology control material.
(a)
Identification. A clinical toxicology control material is a device intended to provide an estimation of the precision of a device test system and to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects. This generic type of device includes various single, and multi-analyte control materials.(b)
Classification. Class I (general 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.