(464 days)
No
The description mentions an "algorithmic composite" and a "Software Analyzer" that calculates a score based on gene expression data. While this involves computation and an algorithm, there is no mention of learning from data, training sets, or adaptive capabilities characteristic of AI/ML. The algorithm appears to be a fixed formula based on weighted gene expression.
No
The device is an in vitro diagnostic test that aids in identifying heart transplant recipients with a low probability of acute cellular rejection. It provides a score that helps clinicians evaluate the patient's condition, but it does not directly treat or prevent a disease.
Yes
The device is described as an "In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service" that is "intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing." This clearly indicates its purpose is to provide diagnostic information.
No
The device is an In Vitro Diagnostic (IVD) test service that involves laboratory procedures to analyze gene expression from blood samples using specific instruments (Roche LC480, ABI 7900HT). While it includes software for data analysis and scoring, it is fundamentally a hardware-dependent laboratory test service, not a standalone software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly Stated: The "Intended Use / Indications for Use" section clearly states: "AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service..."
- Definition of IVD: An IVD is a medical device used to examine specimens, such as blood, tissue, or urine, taken from the human body to provide information for diagnosis, monitoring, or screening. This description fits the AlloMap Heart Testing, which analyzes RNA from peripheral blood mononuclear cells.
- Purpose: The test is intended to "aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the of testing in conjunction with standard clinical assessment." This is a diagnostic purpose.
- Performed in a Laboratory: The testing is performed in a "single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC)." This is characteristic of IVD testing.
N/A
Intended Use / Indications for Use
AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service, performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Heart Testing is intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment.
Indicated for use in heart transplant recipients:
· 15 years of age or older
· At least 2 months (>55 days) post-transplant
Product codes
OJQ
Device Description
AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index Assay (IVDMIA) test service performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Heart Testing is a non-invasive blood test that uses genomic technologies to identify the absence of cardiac rejection. When used in conjunction with standard clinical assessments, AlloMap Heart Testing may help identify patients with stable allograft function who have a low probability of moderate to severe acute cellular rejection (ACR) at the time of Testing.
AlloMap is a panel of 20 gene assays, 11 informative and 9 used for normalization and quality control, which produces gene expression data used to calculate a reported AlloMap test score - an integer ranging from 0 to 40. The Score is an algorithmic composite of the expression of 11 differentially weighted informative genes that have a role in rejection and reflect host immune response, representing multiple diverse molecular pathways. The clinician uses the AlloMap Score and other standard clinical assessments to evaluate the patient's probability of rejection and the need for additional diagnostic evaluations. Compared with patients in the same post-transplant period, the lower the Score, the lower the probability of acute cellular rejection at the time of Testing. AlloMap Heart Testing is only performed at the CLIA-certified and CAP-accredited clinical laboratory at CareDx in Brisbane, California.
AlloMap Heart Test Process: A whole blood sample is collected at the patient site in a BD Vacutainer® CPT™ Cell Preparation tube with sodium citrate anticoagulant. Peripheral blood mononuclear cells (PBMC) are isolated and lysed, and frozen PBMC lysate is shipped using kits provided by CareDx to the CareDx laboratory in Brisbane, CA. RNA is purified from the PBMC lysate and converted to cDNA using commercial reagents on a thermal cycler following a standard reverse transcriptase protocol. Using liquid handling instruments, the cDNA is diluted and dispensed into a 384-well AlloMap HTx assay plate. The AlloMap plate comprises pre-aliquoted qRT-PCR reagents created by CareDx Manufacturing, containing sequence-specific primers, probes, and Universal Master Mix to measure each of the 20 genes in triplicate. Gene expression levels are determined via the qRT-PCR instrument for each of the eleven (11) informative and nine (9) control genes. The Analyzer Software, SAX, converts sample data generated from the qRT-PCR plate to an AlloMap Test Score. Multiple automated QC checks are performed on every sample. AlloMap scores are calculated for all samples that pass QC. The AlloMap Test Score is then reported to the physician.
AlloMap Heart Test System: The test system consists of assay reagents, instruments, and system software. The test components have not changed from the predicate device K073482, including sample processing, reagents, formulations, and assay plates containing qRT-PCR reagents created by CareDx Manufacturing to measure each of the 20 genes. The difference between the subject device, the AlloMap Heart Testing, and the predicate device is the replacement of the current eight ABI 7900HT thermal cyclers in the CareDx laboratory with eight Roche LightCycler 480 II (LC480) thermal cyclers. Consequently, the Software Analyzer has been modified to support the LC480 Instrument and achieve AlloMap Heart test equivalency with the current ABI 7900HT instrument.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
15 years of age or older
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Software Verification and Validation Testing:
Verification of the Software Analyzer, SAX v1.2, was conducted per Verification Plan against its requirement specification, followed by a software validation test at CareDx in Brisbane, CA, including Analyzer QC Criteria, Analyzer Algorithm Score, and Integration with LIMS. As demonstrated by the V&V reports in this submission, the modified Software Analyzer v1.2 and its specifications (design outputs) meet the product requirements (design inputs) and conform to the user's needs and Intended Use.
Analytical Performance Validation Testing:
Four analytical validation studies were performed to evaluate the performance characteristics of the Roche LC480 Instrument (subject device) compared to the current AB17900HT Instrument (predicate device). Previously tested heart transplant patient samples with clinical relevance to AlloMap score were used after deidentification in the studies. The modified Analyzer Software SAX v1.2 was used for the LC480 workflow during the validation, and SAX v1.0 was used for the data analysis of 7900HT.
-
Precision – Between Instrument Variability:
Variance component analysis was performed to estimate the between-instrument variability for the AlloMap scores. This study demonstrated the between-instrument variability for LC480 to be comparable to that of the predicate device, the 7900HT instrument. The variance ratios of LC480 over 7900HT are less than ( 34), were used as input into the cDNA synthesis ranging from 150 to 500 ng (regular 300 ng). The linear regression method was used to analyze the mean of the normalized factors vs. the input log10RNA concentration. The result obtained an R2 value of 0.989. The variability of the raw scores at each RNA input level was examined using the acceptance criteria established for the predicate device. The result showed that the LC480 met the acceptance criteria and is comparable to the predicate device, 7900HT. The study demonstrated that linearity of the AlloMap Heart test across various RNA inputs is maintained using the Roche LC480 qRT-PCR instruments especially around the current RNA input of 300ng per patient sample. -
Method Comparison - Accuracy:
The study validated that AlloMap results measured by the Roche LC480 are equivalent across the reportable range to the results measured by the ABI 7900HT in the CareDx Laboratory. The analysis included a total of 163 patient RNA samples processed by 2 LC480 instruments and a single 7900HT. The paired scores were analyzed using Passing-Bablok regression models. All prespecified passing criteria were met at a two-sided significance level of 0.05 for the paired score differences and the regression parameters, i.e., intercept and slope.
For each LC480, over 95% of the samples across the entire clinical range fell within the ATD zones with a lower limit of 95% one-sided CI > 90%. Thus, the measurements by LC480 are within the analytical variation of the 7900HT and can be considered equivalent to the predicate.
Using the 300 samples in the original clinical validation study from the predicate device, K073482, we calculated projected NPV and PPV for each Roche LC480 as the mean of the 500 simulated NPV and PPV from the simulated AlloMap scores for the LC480 by adding random errors (estimated from Accuracy study or Reproducibility study) to the 7900HT scores. The projected NPV and PPV for the Roche LC480 were then compared with the NPV and PPV for the 7900HT. The absolute differences between the two system platforms were within 1% or 95% CI including 0 for NPV, and within 2% or 95% CI including 0 for PPV, for both 2-6 months (55-182 days) and >6 months (>182 days) post-transplant periods. These results demonstrated that the Roche LC480 produces AlloMap results that are statistically and clinically equivalent across the whole clinical range to those produced by the ABI 7900HT qRT-PCR thermal cycler in the CareDx Laboratory.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Projected NPV and PPV were calculated. For NPV, absolute differences were within 1% or 95% CI including 0. For PPV, absolute differences were within 2% or 95% CI including 0.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1163 Cardiac allograft gene expression profiling test system.
(a)
Identification. A cardiac allograft gene expression profiling test system is a device that measures the ribonucleic acid (RNA) expression level of multiple genes and combines this information to yield a signature (pattern, classifier, index, score) to aid in the identification of a low probability of acute cellular rejection (ACR) in heart transplant recipients with stable allograft function.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Cardiac Allograft Gene Expression Profiling Test Systems.” See § 862.1(d) for the availability of this guidance document.
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September 13, 2023
CareDx, Inc. Camilla Lu Associate Director, Regulatory Affairs 3260 Bayshore Boulevard Brisbane, CA 94005
Re: K221640
Trade/Device Name: AlloMap Heart Molecular Expression Testing Regulation Number: 21 CFR 862.1163 Regulation Name: Cardiac Allograft Gene Expression Profiling Test System Regulatory Class: Class II Product Code: OJQ Dated: April 7, 2023 Received: April 10, 2023
Dear Camilla Lu:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
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- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Paula V. Caposino -S
Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K221640
Device Name
AlloMap Heart Molecular Expression Testing
Indications for Use (Describe)
AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service, performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Heart Testing is intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the of testing in conjunction with standard clinical assessment.
Indicated for use in heart transplant recipients:
· 15 years of age or older
· At least 2 months (>55 days) post-transplant
| Type of Use (Select one or both, as applicable) | ||
|---|---|---|
| X Prescription Use (Part 21 CFR 201 Subpart D) Over-The-Counter Use (21 CFR 201 Subpart C) | X Prescription Use (Part 21 CFR 201 Subpart D) | Over-The-Counter Use (21 CFR 201 Subpart C) |
| X Prescription Use (Part 21 CFR 201 Subpart D) | Over-The-Counter Use (21 CFR 201 Subpart C) |
| > Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/3/Picture/0 description: The image is a logo for CareDx. The logo features a stylized red blood drop with white squares inside, followed by the company name "CareDx" in black font. Below the company name is the tagline "Your Partner in Transplant Care".
TRADITIONAL 510(K) SUMMARY
(Complying with 21 CFR 807.92)
I. SUBMITTER
CareDx, Inc. 3260 Bayshore Boulevard Brisbane, CA 94005 USA
Phone : (415) 287-2300 x 5336 FAX : (415) 287 2427
| Contact Person: | Camilla Lu, PhD. |
|---|---|
| Date Prepared: | September 6, 2023 |
II. DEVICE
| Trade Name: | AlloMap Heart Molecular Expression Testing |
|---|---|
| Common Name: | AlloMap Heart Testing |
| Classification Name: | Cardiac Allograft Gene Expression Profiling Test System |
| Regulatory Class: | Class II |
| Regulation Number: | 21 CFR 862.1163 |
| Product Code: | OJQ |
| 510(K) Number: | K221640 |
III. PREDICATE DEVICE
| Trade Name: | AlloMap Molecular Expression Testing |
|---|---|
| Common Name: | AlloMap Testing |
| De Novo Number: | DEN080007 |
| 510(K) Number: | K073482 |
IV DEVICE DESCRIPTION
Principle of Operation: AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index Assay (IVDMIA) test service performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Heart Testing is a non-invasive blood test that uses genomic technologies to identify the absence of cardiac rejection. When used in conjunction with standard clinical assessments, AlloMap Heart Testing may help identify patients with stable allograft function who have a low probability of moderate to severe acute cellular rejection (ACR) at the time of Testing.
AlloMap is a panel of 20 gene assays, 11 informative and 9 used for normalization and quality control, which produces gene expression data used to calculate a reported AlloMap test score - an integer ranging from 0 to 40. The Score is an algorithmic composite of the expression of 11
4
differentially weighted informative genes that have a role in rejection and reflect host immune response, representing multiple diverse molecular pathways. The clinician uses the AlloMap Score and other standard clinical assessments to evaluate the patient's probability of rejection and the need for additional diagnostic evaluations. Compared with patients in the same post-transplant period, the lower the Score, the lower the probability of acute cellular rejection at the time of Testing. AlloMap Heart Testing is only performed at the CLIA-certified and CAP-accredited clinical laboratory at CareDx in Brisbane, California.
AlloMap Heart Test Process: A whole blood sample is collected at the patient site in a BD Vacutainer® CPT™ Cell Preparation tube with sodium citrate anticoagulant. Peripheral blood mononuclear cells (PBMC) are isolated and lysed, and frozen PBMC lysate is shipped using kits provided by CareDx to the CareDx laboratory in Brisbane, CA. RNA is purified from the PBMC lysate and converted to cDNA using commercial reagents on a thermal cycler following a standard reverse transcriptase protocol. Using liquid handling instruments, the cDNA is diluted and dispensed into a 384-well AlloMap HTx assay plate. The AlloMap plate comprises pre-aliquoted qRT-PCR reagents created by CareDx Manufacturing, containing sequence-specific primers, probes, and Universal Master Mix to measure each of the 20 genes in triplicate. Gene expression levels are determined via the qRT-PCR instrument for each of the eleven (11) informative and nine (9) control genes. The Analyzer Software, SAX, converts sample data generated from the qRT-PCR plate to an AlloMap Test Score. Multiple automated QC checks are performed on every sample. AlloMap scores are calculated for all samples that pass QC. The AlloMap Test Score is then reported to the physician.
AlloMap Heart Test System: The test system consists of assay reagents, instruments, and system software. The test components have not changed from the predicate device K073482, including sample processing, reagents, formulations, and assay plates containing qRT-PCR reagents created by CareDx Manufacturing to measure each of the 20 genes. The difference between the subject device, the AlloMap Heart Testing, and the predicate device is the replacement of the current eight ABI 7900HT thermal cyclers in the CareDx laboratory with eight Roche LightCycler 480 II (LC480) thermal cyclers. Consequently, the Software Analyzer has been modified to support the LC480 Instrument and achieve AlloMap Heart test equivalency with the current ABI 7900HT instrument.
V. INTENDED USE
1. Intended Use (s):
The Intended Use of the subject device is the same as the predicate device, K073482. See Indications for Use below.
2. Indications (s) for Use:
AlloMap Heart Molecular Expression Testing is an In Vitro Diagnostic Multivariate Index assay (IVDMIA) test service, performed in a single laboratory, assessing the gene expression profile of RNA isolated from peripheral blood mononuclear cells (PBMC). AlloMap Heart Testing is intended to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection (ACR) at the time of testing in conjunction with standard clinical assessment.
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Indicated for use in heart transplant recipients:
- 15 years of age or older ●
- At least 2 months (≥55 days) post-transplant ●
VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE
Similarities
First, the subject device has the same Intended Use as the predicate device. Second, the subject device has the same technological characteristics as the predicate device. At a high level, the subject and predicate devices are based on the following same technological elements:
- Sample processing
- . Reagents used for RNA purification and cDNA synthesis
- The panel of 20 genes (11 informative and 9 control genes)
- . AlloMap HTx assay plates containing qRT-PCR reagents created by CareDx Manufacturing measure the expression of each of the 20 genes
- . Instruments used for RNA Quantification, cDNA Synthesis Pipetting, and cDNA Synthesis Reaction
- . The Assay Quality Control rules and criteria for the AlloMap Heart test: rules of Data quality, PCR success, Genomic DNA contamination, Sample quality & quantity, Efficiency, Assay Ranges, Normalization genes, and Process control expected values
- . The LIS software used to manage the workflow for the processing, reporting AlloMap Heart tests, and the AlloMap Score has not changed
- . AlloMap Heart Report software has not changed
- Analyzer Software, SAX, which converts sample data to an AlloMap score, has not . changed its primary functions, and the four modules, including the Algorithm to calculate the AlloMap Score, remain unchanged
Differences
The following assay component differences exist between the subject and predicate devices:
- The predicate device uses eight ABI 7900 HT thermal cyclers, which are replaced with eight Roche LightCycler 480 II (LC480) for the subject device in the CareDx laboratory.
- . The Software Analyzer, SAX, has been modified in the subject device to support the LC480 Instrument and achieve AlloMap test equivalency with the current ABI 7900HT instrument. SAX changed its version from SAX v1.0 (for predicate device) to v1.2 (for subject device) to update existing modules:
- SAX v1.2 extracts the raw fluorescence data generated by the LC480 from the resulting o XML Summary output files
- O SAX v1.2 applies two gene-level correction factors additive correction coefficient (oga) and multiplicative correction coefficient (Sgb) - to map the LC480 response to the ABI 7900 HT response.
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PERFORMANCE DATA VII.
The following performance data were provided in support of the substantial equivalence determination.
Software Verification and Validation Testing
Verification of the Software Analyzer, SAX v1.2, was conducted per Verification Plan against its requirement specification, followed by a software validation test at CareDx in Brisbane, CA, including Analyzer QC Criteria, Analyzer Algorithm Score, and Integration with LIMS. As demonstrated by the V&V reports in this submission, the modified Software Analyzer v1.2 and its specifications (design outputs) meet the product requirements (design inputs) and conform to the user's needs and Intended Use.
Analytical Performance Validation Testing
Four analytical validation studies were performed to evaluate the performance characteristics of the Roche LC480 Instrument (subject device) compared to the current AB17900HT Instrument (predicate device). Previously tested heart transplant patient samples with clinical relevance to AlloMap score were used after deidentification in the studies. The modified Analyzer Software SAX v1.2 was used for the LC480 workflow during the validation, and SAX v1.0 was used for the data analysis of 7900HT.
1. Precision - Between Instrument Variability
Variance component analysis was performed to estimate the between-instrument variability for the AlloMap scores. This study demonstrated the between-instrument variability for LC480 to be comparable to that of the predicate device, the 7900HT instrument. The variance ratios of LC480 over 7900HT are less than ( 34), were used as input into the cDNA synthesis ranging from 150 to 500 ng (regular 300 ng). The linear regression method was used to analyze the mean of the normalized factors vs. the input log10RNA concentration. The result obtained an R2 value of 0.989. The variability of the raw scores at each RNA input level was examined using the acceptance criteria established for the predicate device. The result showed that the LC480 met the acceptance criteria and is comparable to the predicate device, 7900HT. The study demonstrated that linearity of the AlloMap Heart test across various RNA inputs is maintained using the Roche LC480 qRT-PCR instruments especially around the current RNA input of 300ng per patient sample.
4. Method Comparison - Accuracy
The study validated that AlloMap results measured by the Roche LC480 are equivalent across the reportable range to the results measured by the ABI 7900HT in the CareDx Laboratory. The analysis included a total of 163 patient RNA samples processed by 2 LC480 instruments and a single 7900HT. The paired scores were analyzed using Passing-Bablok regression models. All prespecified passing criteria were met at a two-sided significance level of 0.05 for the paired score differences and the regression parameters, i.e., intercept and slope. See Table 4-1.
| Estimate and 95% CI | Acceptance Criteria | ||
|---|---|---|---|
| Parameters | LC480_7296 vs 7900HT | LC480_7371 vs 7900HT | 95% CI of the slope includes 1.0 and |
| 95% CI of the intercept includes 0.0 | |||
| Intercept | 0 (-0.53, 0.53) | 0 (-0.34, 0.34) | PASS |
| Slope | 1 (0.99, 1.01) | 1 (0.99, 1.01) | PASS |
| Table 4-1: Passing-Bablok Regression Results | |||
|---|---|---|---|
| -- | -- | ----------------------------------------------- | -- |
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| CAREDX INC. | ALLOMAP HEART MOLECULAR EXPRESSION TESTING |
|---|---|
| September 2023 | TRADITIONAL 510(K) SUBMISSION |
Following FDA Guidance for Assay Migration Studies, allowable total difference (ATD) zone were constructed separately for low, medium and high score ranges using reproducibility results for the 7900HT to define the limits for 95% of the differences between repeated measures by the 7900HT. For each LC480, over 95% of the samples across the entire clinical range fell within the ATD zones with a lower limit of 95% one-sided CI > 90%. Thus, the measurements by LC480 are within the analytical variation of the 7900HT and can be considered equivalent to the predicate. (see Table 4-2).
| | AlloMap Score Ranges
(7900HT) | Low
6 months (>182 days) post-transplant periods. These results demonstrated that the Roche LC480 produces AlloMap results that are statistically and clinically equivalent across the whole clinical range to those produced by the ABI 7900HT qRT-PCR thermal cycler in the CareDx Laboratory.
Compliance with FDA Recognized Standards and Guidelines
- . CLSI EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition. Section 6 Measurement Procedure Comparison Studies; Section 7, Considerations for Clinical Laboratories; Section 10.2, Other Comparisons. Clinical and Laboratory Standards Institute; 2013
- . CLSI EP31-A-IR Verification of Comparability of Patient Results Within One Health Care System; Approved Guideline (Interim Revision). Section 6.1, Commutability; Section 7.1, Evaluation of Comparability Based on Clinical Outcomes; Section 8.2, Statistical Analysis of Comparability Data. Clinical and Laboratory Standards Institute; 2012
- CLSI-EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A ● Statistical Approach; Approved Guideline. Sections 5.3, Determination of the Linear Range and 5.3.1, Summary of Methods - The Polynomial Evaluation of Linearity Wayne, PA: Clinical and Laboratory Standards Institute; 2003.
- CLSI EP05-A3, Evaluation of Precision Performance of Quantitative Measurement . Procedures: Approved Guideline Chapter 3, Single-Site Precision Evaluation Study, Wayne, PA: Clinical and Laboratory Standards Institute, 2014.
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- . FDA Guidance: Assay Migration Studies for In Vitro Diagnostic Devices. Document issued on April 25, 2013
- . FDA Guidance: Cardiac Allograft Gene Expression Profiling Test Systems – Class II Special Controls Guidance for Industry and FDA Staff. Document issued on October 21, 2009
CONCLUSIONS VIII.
CareDx has demonstrated through its evaluation and performance testing that the AlloMap Heart Testing using the Roche LC480 instruments is substantially equivalent to the legally marketed AlloMap Testing using the ABI 7900HT. Same as the predicate device, AlloMap Heart Testing is safe and effective for its intended Use.