(46 days)
The CEDIA® Tacrolimus Assay is an in vitro diagnostic medical device intended for the quantitative determination of tacrolimus in human whole blood using automated clinical chemistry analyzers as an aid in the management of kidney and liver transplant recipients receiving tacrolimus therapy.
CEDIA® Tacrolimus Calibrators are intended for calibration of the CEDIA® Tacrolimus Assay in whole blood.
The CEDIA® Tacrolimus Assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). 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.
In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment (ED) of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of analyte present in the sample.
The provided text describes the 510(k) summary for the CEDIA® Tacrolimus Assay, primarily focusing on its substantial equivalence to a predicate device rather than detailing specific acceptance criteria and a dedicated study proving its fulfillment. Therefore, some information, particularly regarding specific performance metrics and a standalone study to meet predefined acceptance criteria, is not explicitly present.
However, based on the context of a 510(k) submission and the information provided, we can infer and construct a response.
Here's a breakdown of the requested information based on the provided text:
Acceptance Criteria and Device Performance Study
The document states that the CEDIA® Tacrolimus Assay is substantially equivalent to the IMx® Tacrolimus II (MEIA). This equivalence is demonstrated by comparing device characteristics and, implicitly, performance, although specific performance acceptance criteria and direct comparative performance data against these criteria are not explicitly detailed in the provided summary. The guidance document "Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA", dated September 16, 2002, was followed to demonstrate this equivalence.
Given the nature of diagnostic assays, "acceptance criteria" generally involve analytical performance characteristics like precision, accuracy, linearity, lower limit of detection (LoD), upper limit of quantification (LoQ), and potential interferences. While these specific criteria and the detailed results against them are not provided, the claim of "substantial equivalence" implies that these were assessed and found comparable to the predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
As specific numerical acceptance criteria and direct performance metrics against them are not explicitly stated in the provided text, the table below will reflect the comparison made for "substantial equivalence" based on device characteristics. For a diagnostic assay, typical performance criteria would involve analytical accuracy, precision, and agreement with the predicate.
| Characteristic | Acceptance Criterion (Implicitly based on Predicate) | Reported Device Performance (CEDIA® Tacrolimus Assay) |
|---|---|---|
| Intended Use | Quantitative determination of tacrolimus in human whole blood as an aid in managing kidney and liver transplant patients receiving tacrolimus therapy with automated clinical chemistry analyzers. | Quantitative determination of tacrolimus in human whole blood using automated clinical chemistry analyzers as an aid in the management of kidney and liver transplant recipients receiving tacrolimus therapy. (Equivalent to Predicate) |
| Analyte | Tacrolimus | Tacrolimus |
| Matrix | Whole blood extract | Whole blood extract |
| Calibrator Form | Liquid | Liquid |
| Calibrator Levels | Not explicitly stated as acceptance criteria, but predicate has 6 levels (0, 3, 6, 12, 20, and 30 ng/mL). | Two (2) Levels (0 and 30 ng/mL) - Note: This is a difference compared to the predicate, but implied to be acceptable for substantial equivalence. |
| Storage (Reagents) | 2°C to 8°C until expiration. | Reagents are stored at 2°C to 8°C until expiration date. (Equivalent to Predicate) |
| Storage (Calibrators) | Frozen until expiration. | Calibrators are stored at -20°C until expiration date. (Equivalent to Predicate type of storage, though specific temperature differs: frozen vs. -20°C) |
| Stability | Until expiration date noted on vial label. | Until expiration date noted on vial label and Package Insert. (Equivalent to Predicate) |
| Accuracy / Agreement (Inferred) | Clinical agreement and correlation with the predicate device (IMx® Tacrolimus II). | "Data and results amply demonstrate that the CEDIA® Tacrolimus Assay is substantially equivalent to the IMx® Tacrolimus II assay for the quantitative determination of tacrolimus..." (Specific statistical metrics or performance data are not provided in the summary). |
| Precision (Inferred) | Acceptable within-run, between-run, and total precision for tacrolimus quantification. | Implied to be acceptable for substantial equivalence, but specific data not provided. |
| Linearity (Inferred) | Linear response across the claimed assay range. | Implied to be acceptable for substantial equivalence, but specific data not provided. |
2. Sample size used for the test set and the data provenance
The document does not specify the sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective). It broadly mentions that "Data and results provided in this premarket notification were collected and prepared, respectively, in accordance with the established guideline, 'Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA'". This guideline is likely to define the requirements for such studies, but the specific details are absent from this summary.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable and hence not provided. For an in vitro diagnostic (IVD) quantitative assay like the CEDIA® Tacrolimus Assay, ground truth is typically established through reference methods, certified calibrators, or established analytical techniques directly measuring tacrolimus concentration, rather than human expert interpretation of images or clinical assessments.
4. Adjudication method for the test set
This information is not applicable and hence not provided for a quantitative IVD assay. Adjudication methods like "2+1" or "3+1" are relevant for subjective interpretations, often in imaging or pathology, where human experts might disagree.
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
This information is not applicable. The CEDIA® Tacrolimus Assay is an in vitro diagnostic (IVD) device for quantitative biochemical analysis, not an AI-assisted diagnostic tool that aids human readers (e.g., radiologists interpreting images). Therefore, an MRMC study with human readers and AI assistance is not relevant to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance assessment was implicitly done. The CEDIA® Tacrolimus Assay is an automated enzyme immunoassay system. Its performance evaluation would have been conducted as an "algorithm only" (or assay-only) study to determine its analytical characteristics (accuracy, precision, linearity) and compare them to the predicate device. The claim of "substantial equivalence" is based on the standalone performance of the assay. The summary does not detail the specifics of this standalone study, but it is integral to the submission.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For this type of quantitative diagnostic assay, the "ground truth" would be established by:
- Reference materials/calibrators: Tacrolimus concentrations would be measured against highly pure, certified reference standards.
- Comparison to a legally marketed predicate device: The submitted study directly aims to show substantial equivalence to the IMx® Tacrolimus II, implying the predicate device's results serve as a comparative standard or "ground truth" for evaluating the novel assay's performance.
8. The sample size for the training set
The document does not provide details on a "training set." The development of an IVD assay typically involves internal development and validation, which might use various samples (clinical, spiked, controls) for optimization and preliminary testing. However, the term "training set" is more commonly used in machine learning and AI contexts. For an immunoassay, the samples used for validating performance are usually referred to as "validation sets" or "test sets" as outlined in question 2.
9. How the ground truth for the training set was established
As there is no explicit mention of a "training set" in the context of machine learning for this IVD device, this question is not directly applicable in the sense of establishing ground truth for AI model training. The ground truth for assay development and validation (if considered broadly analogous to "training/validation" in an AI sense) would be established as described in point 7 (reference materials/calibrators, comparison to predicate).
{0}------------------------------------------------
MAR 1 5 2005
Section II
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFRS807 92.
510(k) Number:
Submitter:
Microgenics Corporation 46360 Fremont Blvd Fremont, CA 94538 Telephone: (510)-979-5142 Facsimile: (510) 979-5455
Contact Person:
Lisa Charter Research and Development Supervisor Telephone: (510)-979-5142 Facsimile: (510) 979-5455
Alternate Contact: Candice Betz Manager of Regulatory and Quality Affairs Telephone: (510)-979-5169
Preparation Date:
January 27, 2005
Device Information:
| Proprietary Name: | CEDIA® Tacrolimus Assay |
|---|---|
| Device Description: | Enzyme Immunoassay, Tacrolimus |
| Product Code: | MLM |
| Regulation Number: | 21 CFR§862.1678. |
| Regulatory Class: | Class 2 (special controls) |
Predicate Device(s):
The data and results described herein demonstrate that the CEDIA® Tacrolimus Assay is substantially equivalent to IMx® Tacrolimus II (MEIA) for the quantitative determination of tacrolimus (FK506) concentration in human whole blood as an aid in the management of kidney and liver transplant patients receiving therapy with tacrolimus.
{1}------------------------------------------------
Device Description:
The CEDIA® Tacrolimus Assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). 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.
In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment (ED) of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of analyte present in the sample.
Intended Use:
The CEDIA® Tacrolimus Assay is an in vitro diagnostic medical device intended for the quantitative determination of tacrolimus in human whole blood using automated clinical chemistry analyzers as an aid in the management of kidney and liver transplant recipients receiving tacrolimus therapy.
CEDIA® Tacrolimus Calibrators are intended for calibration of the CEDIA® Tacrolimus Assay in whole blood.
Comparison to Predicate Device(s):
The CEDIA® Tacrolimus Assay is substantially equivalent to IMx® Tacrolimus II (MEIA) in its intended use and in for the quantitative determination of tacrolimus (FK-506) concentration as an aid in the management of kidney and liver transplant patients receiving therapy with tacrolimus.
{2}------------------------------------------------
| DeviceCharacteristics | Subject Device(CEDIA® Tacrolimus Assay) | Predicate DeviceAbbott Laboratories IMx®Tacrolimus II (MEIA) |
|---|---|---|
| Intended Use | The CEDIA® Tacrolimus Assayis an in vitro diagnostic medicaldevice intended for thequantitative determination oftacrolimus in human wholeblood using automated clinicalchemistry analyzers as an aidin the management of kidneyand liver transplant recipientsreceiving tacrolimus therapy.CEDIA® Tacrolimus Calibratorsare intended for calibration ofthe CEDIA® Tacrolimus Assayin whole blood. | The IMx® Tacrolimus II assay isan in vitro reagent system forthe quantitative determinationof tacrolimus and somemetabolites in human wholeblood and as an aid in themanagement of liver allograftpatients receiving tacrolimustherapy.The IMx® Tacrolimus IICalibrators are for calibration ofthe IMx® analyzer when usedfor the quantitativedetermination of tacrolimus inhuman whole blood. |
| Analyte | Tacrolimus | Tacrolimus |
| Matrix | Whole blood extract | Whole blood extract |
| CalibratorForm | Liquid | Liquid |
| CalibratorLevel | Two (2) Levels (0 and 30ng/mL) | Six (6) Levels (0, 3, 6, 12, 20,and 30 ng/mL) |
| Storage | Reagents are stored at 2°C to8°C until expiration date.Calibrators are stored at -20°Cuntil expiration date. | Reagents are stored at 2°C to8°C until expiration date.Calibrators are stored frozenuntil expiration date. |
| Stability | Until expiration date noted onvial label and Package Insert. | Until expiration date noted onvial label. |
Summary:
The information provided in this pre-market notification demonstrates that the CEDIA® Tacrolimus Assay is substantially equivalent to the IMx® Tacrolimus II assay. The IMx® Tacrolimus II assay is commonly used for determination of tacrolimus concentration in whole blood samples obtained from patients receiving tacrolimus for post-operative management following hepatic transplant. Data and results provided in this premarket notification were collected and prepared, respectively, in accordance with the established guideline, "Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA", dated September 16, 2002. , These data and results amply demonstrate that the CEDIA® Tacrolimus Assay is substantially equivalent to the IMx® Tacrolimus II assay for the quantitative determination of tacrolimus (FK506) in human whole blood using automated clinical chemistry analyzers as an aid in the management of kidney and liver transplant patients receiving therapy with tacrolimus.
CEDIA® is a registered trademark of Roche Diagnostics.
{3}------------------------------------------------
Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name encircling a symbol. The symbol consists of a stylized caduceus, which is a staff with two snakes entwined around it, and three horizontal lines above it.
MAR 15 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Lisa Charter Research and Development Microgenics Corp. 46360 Fremont Blvd Fremont, CA 94538
K050206 Re: Resoleco
Trade/Device Name: CEDIA® Tacrolimus Assay CEDIA® Tacrolimus Calibrators Regulation Number: 21 CFR 862.1678 Regulation Name: Tacrolimus test system Regulatory Class: Class II Product Code: MLM, JIT Dated: January 27, 2005 Received: January 28, 2005
Dear Ms. Charter:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your because in and the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encreate) to togals) the enactment date of the Medical Device Amendments, or to commerce pror to they 20, 2017, 11:12
devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, de necs mat have occh require approval of a premarket approval application (PMA). and Cosmetic For , recy that the device, subject to the general controls provisions of the Act. The r ou may, mererors, mains of the Act include requirements for annual registration, listing of general controls provisions gractice, 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 it may be subject to Sach adde 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 ana + Federal statutes and regulations administered by other Federal agencies. You must or any I caeral statues and equirements, 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).
{4}------------------------------------------------
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) I his letter will anow you to ocgin marketing your intial equivalence of your device to a legally premarket notification. "The PDA Imang of cassification 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, If you desn't specific information actually of your device, please contact the Office of In of questions on the promotion and Safety at (240)276-0484. Also, please note the Vill o Diagnostic Dovies Dranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I ou may obtain other general memational 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/industry/support/index.html
Sincerely yours,
Jean M. Cooper MS, 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
{5}------------------------------------------------
SECTION III
INDICATIONS FOR USE STATEMENT
510(k) Number (if known): K050206
CEDIA® Tacrolimus Assay Device name: CEDIA® Tacrolimus Calibrators
Indications for Use:
The CEDIA® Tacrolimus Assay is an in vitro diagnostic device intended for use with The CEDIA - Tacrolinius Assay is an the quantitative determination of tacrolimus in a automated cifilioar of charj2019 and liver transplant of kidney and liver transplant recipients receiving tacrolimus therapy.
CEDIA® Tacrolimus Calibrators are intended for calibration of the CEDIA® Tacrolimus Assay in whole blood.
Prescription Use × (Part 21 CFR §801 Subpart D) AND/OR .
Over-the Counter Use (21 CFR §807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Carol C. Benson
Premarket Notification - CEDIA® Tacrolimus Assay Microgenics Corporation
$
49
§ 862.1678 Tacrolimus test system.
(a)
Identification. A tacrolimus test system is a device intended to quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving therapy with this drug. This generic type of device includes immunoassays and chromatographic assays for tacrolimus.(b)
Classification. Class II (special controls). The special control is “Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA.” See § 862.1(d) for the availability of this guidance document.