(266 days)
No
The description details a microarray-based gene expression analysis and a calculation of an index based on this profile. There is no mention of AI, ML, or any learning algorithms used in the calculation or interpretation of the results. The process is described as a direct calculation based on the expression profile.
No.
This device is an in vitro diagnostic test used to assess a patient's risk for distant metastasis. It provides prognostic information to physicians but does not directly treat or alleviate a disease, injury, or disability.
Yes
The "Intended Use / Indications for Use" section explicitly states that MammaPrint® FFPE is a "qualitative in vitro diagnostic test." It is used to assess a patient's risk for distant metastasis, which is a diagnostic purpose.
No
The device description clearly outlines a multi-step process involving physical manipulation of tissue samples, including RNA isolation, reverse transcription, amplification, hybridization to a microarray, washing, scanning, and data acquisition. While software is used for data analysis and risk calculation, the core of the device involves laboratory-based hardware and biological processes.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly Stated in Intended Use: The very first sentence of the "Intended Use / Indications for Use" section clearly states: "MammaPrint® FFPE is a qualitative in vitro diagnostic test..."
- Performed in a Central Laboratory: The test is performed in a central laboratory, which is a common setting for IVD tests.
- Analyzes Biological Samples: The test uses "formalin-fixed paraffin embedded (FFPE) breast cancer tissue samples," which are biological specimens taken from the human body.
- Provides Information for Diagnosis/Prognosis: The test provides a "prognostic marker" to assess a patient's risk for distant metastasis, which is information used by physicians in the management of a patient's condition.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
MammaPrint® FFPE is a qualitative in vitro diagnostic test, performed in a central laboratory, using the gene expression profile obtained from formalin-fixed paraffin embedded (FFPE) breast cancer tissue samples to assess a patient's risk for distant metastasis within 5 years.
The test is performed for breast cancer patients, with Stage II disease, with tumor size ≤ 5.0 cm and lymph node negative. The MammaPrint® FFPE result is indicated for use by physicians as a prognostic marker only, along with other clinico-pathological factors.
Product codes
NYI
Device Description
The MammaPrint® FFPE test is a microarray based gene expression analysis of a tumor. The analysis is based on several processes: isolation of RNA from FFPE breast cancer tissue sections; elimination of gDNA, reverse transcription of RNA resulting in cDNA; amplification of the cDNA, purification and labeling of cDNA; hybridization of the amplified and labeled cDNA to the diagnostic microarray; washing and scanning the diagnostic microarray and data acquisition (feature extraction); calculation and determination of the risk of recurrence.
The MammaPrint® FFPE analysis is designed to determine the expression of specific genes in a tissue sample. The result is an expression profile, or "fingerprint", of the sample. Using this expression profile, the MammaPrint® FFPE Index is calculated and the molecular prognosis profile of the sample is determined (Low Risk, High Risk).
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
breast cancer tissue samples
Indicated Patient Age Range
Not Found
Intended User / Care Setting
central laboratory, physicians
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical performance:
- Concordance FFPE tissue samples and Fresh:
- First independent validation: n=122 tumor samples. One section preserved as Fresh, second part as FFPE. Fresh section subjected to MammaPrint assay (K101454), FFPE sections subjected to MammaPrint FFPE. Overall concordance in outcome between MammaPrint Fresh and FFPE is 89.34 %. If only true positives and negatives are considered (non-borderline samples), concordance is 92.7%. NPA = 88.4% (95% CI: 80.5 to 95), PPA = 90.6% (95% CI: 79.8 to 95.9).
- Second independent validation: (Raster study) n=345 samples. Fresh RNA and FFPE tissue available. Fresh RNA subjected to MammaPrint Fresh, FFPE tissues subjected to MammaPrint FFPE. Concordance was 89.28%. If only true positives (nonborderlines) are considered, concordance is 93.5%. NPA = 91.5% (95% CI: 86.7 to 94.7), PPA = 86.6% (95% CI: 80.4 to 91.1).
- Test Performance:
- I. Reproducibility assessed on multiple isolations from the same sample (report VR-TR-206a). 30 FFPE samples, four isolations performed. No significant difference in MammaPrint Indices over all four isolations (p=0.994). No significant difference in MammaPrint Outcome over the different isolations (p=0.290).
- II. Reproducibility assessed on multiple labeling/hybridizations by measuring FFPE control samples overtime (report VR-TR-233a). Standard deviations passed predefined acceptance criteria (stdevs: PHTR=0.045 (n=54), PLEP=0.056 (n=52), PHHE=0.072 (n=52)).
- Precision and Evaluation (P&E) experiment (NCCLS, Evaluation of Precision Performance of Quantitative Measurement methods, EP5-A2) to determine Repeatability and Method Precision (report VR-TR-223a). Repeated runs over 20 days. Results for Repeatability and Method Precision meet predefined acceptance criteria.
- Sample ID 11003290 (High Risk): Repeatability Std dev = 0.036, Var = 0.0013. Method Precision Std dev = 0.044, Var = 0.0019.
- Sample ID 11003347 (High Risk): Repeatability Std dev = 0.046, Var = 0.0021. Method Precision Std dev = 0.057, Var = 0.0033.
- Sample ID 11003810 (Low Risk): Repeatability Std dev = 0.042, Var = 0.0018. Method Precision Std dev = 0.050, Var = 0.0025.
- Sample ID 11003860 (Low Risk - Borderline): Repeatability Std dev = 0.049, Var = 0.0024. Method Precision Std dev = 0.066, Var = 0.0044.
- Inter-laboratory comparison of MammaPrint FFPE between Irvine and Amsterdam laboratories: 25 FFPE samples. MammaPrint FFPE results generated by diagnostic departments in Agendia Irvine and Amsterdam. Irvine: Kappa score = 0.90, Amsterdam: Kappa Score = 0.9. Passing and Bablok regression analysis showed high agreement in MammaPrint Index.
- Validation of use of multiple microarray scanners for MammaPrint FFPE Irvine and Amsterdam:
- Amsterdam: 25 samples hybridized on two scanners. Pearson correlation = 1.0. Kappa score = 1.0, NPA = 100% (95% CI: 67.6 to 100), PPA = 100% (95% CI: 81.6 to 99.0). Passing and Bablok regression analysis showed high agreement.
- Irvine: 27 samples hybridized on two scanners. Pearson correlation = 1.0. Kappa score = 1.0, NPA = 100% (95% CI: 77.2 to 100), PPA = 100% (95% CI: 78.5 to 100). Passing and Bablok regression analysis showed high agreement.
- Determine minimum input in hybridization of MammaPrint FFPE: Dilution study performed on three samples and three control samples. MammaPrint FFPE results showed very stable results even at low input of cDNA.
Clinical Performance:
- Part of Raster study. Comparison of MammaPrint FFPE to MammaPrint Fresh. Samples with 5 years clinical follow-up. Endpoints: Distant Recurrence Free Interval (DRFI) and 5 year Distant Metastasis as first event (DM1st).
- Comparison based on DRFI: Kaplan-Meier curves showed a significant difference in DRFI low and High Risk groups (LogRank p=0.001). Performance of MammaPrint FFPE falls within 95% CI of MammaPrint Fresh and complies with predefined acceptance criteria.
- MammaPrint Fresh 2013: Low Risk Signature 0.976 (95% CI: 0.952 to 1.000), High Risk Signature 0.891 (95% CI: 0.840 to 0.942).
- MammaPrint FFPE: Low Risk Signature 0.977 (95% CI: 0.955 to 0.999), High Risk Signature 0.885 (95% CI: 0.830 to 0.940).
- Comparison based on DM 1st: Performance of MammaPrint FFPE falls within 95% CI of MammaPrint Fresh and complies with predefined acceptance criteria.
- MammaPrint Fresh 2013: Low Risk Signature 0.976 (95% CI: 0.952 to 1.000), High Risk Signature 0.907 (95% CI: 0.860 to 0.954).
- MammaPrint FFPE: Low Risk Signature 0.977 (95% CI: 0.955 to 0.999), High Risk Signature 0.903 (95% CI: 0.854 to 0.952).
- Univariate analysis: MammaPrint FFPE significantly associated with risk recurrence. Multivariate analysis did not conclusively demonstrate prognostic significance beyond other clinicopathological factors due to study design and low event rate.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- NPA (Negative Percent Agreement)
- PPA (Positive Percent Agreement)
- Kappa score
- Pearson correlation
- Standard deviation
- Variance
- P-value
- LogRank p-value
- 95% CI
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.6040 Gene expression profiling test system for breast cancer prognosis.
(a)
Identification. A gene expression profiling test system for breast cancer prognosis is a device that measures the ribonucleic acid (RNA) expression level of multiple genes and combines this information to yield a signature (pattern or classifier or index) to aid in prognosis of previously diagnosed breast cancer.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Gene Expression Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this guidance document.
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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around a symbol. The symbol consists of three stylized human profiles facing right, with flowing lines above them, resembling a bird in flight.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Agendia NV Mr. Guido Brink Vice President Regulatory Affairs & Compliance Science Park 406, 1098XH Amsterdam, The Netherlands
Re: K141142 Trade/Device Name: MammaPrint® FFPE Regulation Number: 21 CFR §866.6040 Regulation Name: Gene Expression Profiling Test System for Breast Cancer Prognosis Regulatory Class: Class II Product Code: NYI Dated: December 8, 2014 Received: December 10, 2014
Dear Mr. Guido Brink:
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. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set
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forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Reena Philip -S
Reena Philp, Ph.D. Director Division of Molecular Genetics and Pathology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K141142
Device Name MammaPrint® FFPE
Indications for Use (Describe)
MammaPrint® FFPE is a qualitative in vitro diagnostic test, performed in a central laboratory, using the gene expression profile obtained from formalin-fixed paraffin embedded (FFPE) breast cancer tissue samples to assess a patient's risk for distant metastasis within 5 years.
The test is performed for breast cancer patients, with Stage II disease, with tumor size ≤ 5.0 cm and lymph node negative. The MammaPrint® FFPE result is indicated for use by physicians as a prognostic marker only, along with other clinico-pathological factors.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
I. Submitter
Agendia NV Science Park 406 1098XH Amsterdam The Netherlands Telephone: 31 20 462 1500 Contact person: Guido Brink, VP Regulatory Affairs and EU Market Access Date Prepared: January 22nd, 2015
II. Device
Name of Device: MammaPrint® FFFPE Common or Usual Name: Multivariate device for cancer prognosis Classification Name: Gene expression profiling test system, for breast cancer prognosis (21 CFR 866.6040) Requlatory Class: Class II Product Code: NYI
III. Predicate Device Agendia NV's MammaPrint (K101454)
IV. Device Description
The MammaPrint® FFPE test is a microarray based gene expression analysis of a tumor. The analysis is based on several processes: isolation of RNA from FFPE breast cancer tissue sections; elimination of gDNA, reverse transcription of RNA resulting in cDNA; amplification of the cDNA, purification and labeling of cDNA; hybridization of the amplified and labeled cDNA to the diagnostic microarray; washing and scanning the diagnostic microarray and data acquisition (feature extraction); calculation and determination of the risk of recurrence.
The MammaPrint® FFPE analysis is designed to determine the expression of specific genes in a tissue sample. The result is an expression profile, or "fingerprint", of the sample. Using this expression profile, the MammaPrint® FFPE Index is calculated and the molecular prognosis profile of the sample is determined (Low Risk, High Risk).
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Image /page/4/Picture/1 description: The image shows the logo for Agendia. The logo consists of a colorful fingerprint above the word "agendia" in a stylized, lowercase font. The fingerprint is made up of concentric lines in various colors, including red, orange, yellow, green, blue, and purple. The word "agendia" is written in a modern, sans-serif font with rounded corners.
V. Intended Use
MammaPrint® FFPE is a qualitative in vitro diagnostic test, performed in a central laboratory, using the gene expression profile obtained from formalin-fixed paraffin embedded (FFPE) breast cancer tissue samples to assess a patient's risk for distant metastasis within 5 years.
The test is performed for breast cancer patients, with Stage II disease, with tumor size ≤ 5.0 cm and lymph node negative. The MammaPrint® FFPE result is indicated for use by physicians as a prognostic marker only, along with other clinico-pathological factors.
VI Comparison of technological characteristics with the predicate device
MammaPrint FFPE shares the same principles of operation, overall technical and functional capabilities as the predicate device covered under K101454. The only difference concerns the pre-analytical sample preparation; the use of formalin-fixed paraffin embedded (FFPE) breast tumor tissue in addition to fresh breast tumor tissue as is used in the predicate device.
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Image /page/5/Picture/1 description: The image shows the logo for Agendia. The logo features a colorful fingerprint design above the word "agendia" in a stylized, lowercase font. The fingerprint is made up of concentric lines in various colors, including red, orange, yellow, green, blue, and purple. The word "agendia" is written in a gray, sans-serif font with rounded edges.
VII. Performance Testing (Bench)
Analytical performance
MammaPrint analytical (i.e., non-clinical) performance characteristics investigated comprise concordance between FFPE tissue samples and Fresh as well as Precision and Reproducibility performance assessment. Also inter-laboratory and microarray scanner comparisons are included.
1 - Concordance FFPE tissue samples and Fresh
First independent validation: n=122
In order to extend the intended use of MammaPrint to FFPE samples as well as Fresh a concordance comparison was performed. A selection of 122 tumor samples was used from which one section of the tumor was preserved as Fresh and a second part as FFPE. The Fresh section of the tumor was subjected to latest design controlled version (internal version US09.1 / EU09.1) of the latest FDA cleared MammaPrint assay (K101454) and the FFPE sections were subjected to MammaPrint FFPE (internal version US01.1 / EU01.1). The MammaPrint results from Fresh and FFPE sections for each sample were compared.
The overall concordance in outcome between MammaPrint Fresh and FFPE is 89.34 %. If only the true positives and negatives are considered (non-borderline samples), there is a concordance of 92.7%. For this comparison the NPA is equal to 88.4% (95%C): 80.5 to 95) and the PPA was 90.6% (95%C1: 79.8 to 95.9).
Second independent validation: n=345 (Raster study)
A second concordance comparison between MammaPrint Fresh and FFPE was performed using the Raster study. A selection of 345 samples was used from which Fresh RNA as well as FFPE tissue was available. The Fresh RNA was subjected to MammaPrint Fresh version US09.1/EU09.1 and the FFPE tissues were subjected to MammaPrint FFPE version US01.1/EU01.1.
The concordance in this Raster sample set was 89.28%. If only the true positives (nonborderlines) are considered the concordance is equal to 93.5%. For this comparison the NPA is equal to 91.5% (95%C1: 86.7 to 94.7) and the PPA was 86.6% (95%C1: 80.4 to 91.1).
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Image /page/6/Picture/1 description: The image shows the logo for Agendia. The logo features a stylized fingerprint composed of concentric lines in various colors, including red, orange, yellow, green, blue, and purple. Below the fingerprint is the word "agendia" in a lowercase, sans-serif font with rounded edges.
2 - Test Performance
Test performance of MammaPrint FFPE was assessed on different levels.
- l. Reproducibility was assessed on multiple isolations from the same sample (report VR-TR-206a). For 30 FFPE samples four isolations were performed: 11, 12, 13 and 14. All 4 isolations were further processed to generate MammaPrint FFPE results.
A repeated Measurements ANOVA was used to determine if there was a difference in MammaPrint Indices over all four isolations. The results show that there is no significant difference (p=0.994).
A Cochran's Q test was used to assess the difference in MammaPrint Outcome over the four isolations. The results of this test show that there is no significant difference in MammaPrint Outcome over the different isolations (p=0.290).
- II. Reproducibility was assessed on multiple labeling/hybridizations by measuring FFPE control samples overtime (report VR-TR-233a):
- Paraffin, High risk ● PHTR:
- PLEP: Paraffin, Low risk
- РННЕ: Paraffin, High risk ●
This was performed on a daily basis in order to obtain overtime MammaPrint FFPE results for all three controls. The standard deviations passed the predefined acceptance criteria (stdevs: PHTR=0.045 (n=54), PLEP=0.056 (n=52), PHHE=0.072 (n=52)).
- ============================================================================================================================================================================== A Precision and Evaluation (P&E) experiment (NCCLS, Evaluation of Precision Performance of Quantitative Measurement methods, EP5-A2) was performed to determine the Repeatability and Method Precision of MammaPrint FFPE test (report VR-TR-223a). This experiment set up consists of repeated runs over 20 days in which all test outcome levels are represented by one test sample. After collecting the data from 20 successive days, statistical analysis was performed to determine the repeatability and within-lab precision per sample level:
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| Repeatability (Within-Run) | Method Precision (within-Laboratory) | ||||
|---|---|---|---|---|---|
| Sample ID | Sample level: outcome | Standard deviation | Variance | Standard deviation | Variance |
| 11003290 | High Risk | 0.036 | 0.0013 | 0.044 | 0.0019 |
| 11003347 | High Risk | 0.046 | 0.0021 | 0.057 | 0.0033 |
| 11003810 | Low Risk | 0.042 | 0.0018 | 0.050 | 0.0025 |
| 11003860 | Low Risk - Borderline | 0.049 | 0.0024 | 0.066 | 0.0044 |
The P&E results for Repeatability and Method Precision meet the predefined acceptance criteria.
3 - Inter-laboratory comparison of MammaPrint FFPE between Irvine and Amsterdam laboratories
For this validation 25 FFPE samples were selected from which MammaPrint FFPE results were previously generated using standard FFPE protocols in Amsterdam. From these samples sections were taken and processed from isolation onwards by the diagnostic departments in both Agendia Irvine and Amsterdam according to standard protocols.
The MammaPrint FFPE results generated for these 25 samples at Irvine and Amsterdam locations were compared to the previously generated results. These results meet the predefined acceptance criteria (Irvine: Kappa score = 0.90, Amsterdam: Kappa Score = 0.9).
Furthermore, the Passing and Bablok regression analysis also showed that there is high agreement in MammaPrint Index within this inter-laboratory comparison of Amsterdam and Irvine Operations. For both locations the intercept is close to zero and the slope is close to 1.
4 - Validation of use of multiple microarray scanners for MammaPrint FFPE Irvine and Amsterdam
For the validation of both micro-array scanners in central lab in Amsterdam, 25 samples were hybridized two times; first on the originally validated scanner, serial number US810R3210 and in addition using the scanner with serial number US22502555. MammaPrint Indices were compared between both scanners. The comparison of MammaPrint indices between both scanners meet the predefined acceptance criteria (Pearson correlation = 1.0). Also the comparison of MammaPrint Outcome meet the predefined acceptance criteria (Kappa score =1.0, NPA= 100% (95%C): 67.6 to 100), PPA= 100% (95%C):81.6 to 99.0)).
Furthermore, the Passing and Bablok regression analysis also showed that there is high agreement in MammaPrint Index between both scanners located in Amsterdam. For this comparison the intercept is close to zero and the slope is close to 1.
For the validation of both micro-array scanners in central lab in Irvine, 27 samples were hybridized two times; first on the originally validated scanner, serial number US811R3213 and in addition using the scanner with serial number US45103019. MammaPrint Indices were compared between both scanners.
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The comparison of MammaPrint indices between both scanners meet the predefined acceptance criteria (Pearson correlation = 1.0). Also the comparison of MammaPrint Outcome meet the predefined acceptance criteria (Kappa score =1.0 NPA= 100% (95%C): 77.2 to 100), PPA= 100% (95%C):78.5 to 100)).
Furthermore, the Passing and Bablok regression analysis also showed that there is high agreement in MammaPrint Index between both scanners located in Irvine. For this comparison the intercept is close to zero and the slope is close to 1.
5 – Determine minimum input in hybridization of MammaPrint FFPE
A dilution study was performed to determine the minimum input of labeled cDNA in a hybridization of MammaPrint FFPE. In this dilution study three samples as well as three MammaPrint FFPE control samples were each labeled five times and per sample to generate sufficient amount of labeled material. Samples were then diluted in 8 steps with water to reach the specific yield (ng),in which step 8 reflects a hybridization with no labeled material.
MammaPrint FFPE results were compared over the different dilution and showed very stable results even at low input of cDNA.
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Image /page/9/Picture/1 description: The image shows the logo for Agendia. The logo features a colorful, fingerprint-like design above the word "agendia" in a lowercase, sans-serif font. The fingerprint design has a gradient of colors, including red, orange, yellow, green, blue, and purple, arranged in a swirling pattern.
VIII. Performance testing-Clinical
As part of this submission of MammaPrint FFPE the clinical performance of MammaPrint FFPE was compared to MammaPrint Fresh. For this comparison samples were used that were part of the Raster study that were processed on MammaPrint Fresh between 2004 and 2007 and currently have a clinical follow-up of 5 years. For the clinical performance evaluation of MammaPrint FFPE on RASTER FFPE samples, endpoints were defined as Distant Recurrence Free Interval (DRFI) as presented for the Raster study1 as well as the 5 year Distant Metastasis as first event (DM1®).
Comparison based on DRFI
(Figure 5.1 A and B respectively).
For both the Fresh version of MammaPrint as well as the FFPE version, Kaplan-Meier curves showed a significant difference in DRFI the Low and High Risk groups LogRank p=0.001)
Image /page/9/Figure/6 description: The image contains two Kaplan-Meier plots comparing the DRFI probability over time (in months) for low-risk and high-risk patients based on MammaPrint analysis. Plot A shows the results for the FRESH 2013 cohort, while plot B shows the results for the FFPE cohort. In both plots, the green line represents the low-risk group, and the red line represents the high-risk group, with a p-value of 0.001 indicating a statistically significant difference between the two risk groups in both cohorts.
F igure 5.1: Kaplan-Meier analysis of the 5 year DRFI probability among 345 patients with LN0 breast cancer that were part of the Raster study for A) MammaPrint F resh and B) MammaPrint F F PE
The 5-year DFRI of both MammaPrint Fresh and FFPE is shown in below. The performance of MammaPrint FFPE falls within the 95% Cl of MammaPrint Fresh and therefore complies with the predefined acceptance criteria.
| MammaPrint Fresh 2013 | MammaPrint FFPE | |||||
|---|---|---|---|---|---|---|
| 95% CI | 95% CI | |||||
| Low Risk Signature | 0.976 | 0.952 | 1.000 | 0.977 | 0.955 | 0.999 |
| High Risk Signature | 0.891 | 0.840 | 0.942 | 0.885 | 0.830 | 0.940 |
Based on the results shown MammaPrint FFPE is clinically equivalent to the predicate device MammaPrint Fresh (K101454).
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Image /page/10/Picture/1 description: The image shows the logo for Agendia. The logo features a stylized fingerprint above the word "agendia." The fingerprint is made up of concentric lines in a variety of colors, including red, orange, yellow, green, blue, and purple. The word "agendia" is written in a lowercase, sans-serif font.
Comparison based on DM 1st
The 5-year DM1st survival of both MammaPrint Fresh and FFPE is shown below. The performance of MammaPrint FFPE falls within the 95% Cl of MammaPrint Fresh and therefore complies with the predefined acceptance criteria.
| MammaPrint Fresh 2013 | MammaPrint FFPE | ||||||
|---|---|---|---|---|---|---|---|
| 95% CI | 95% CI | ||||||
| Low Risk Signature | 0.976 | 0.952 | 1.000 | Low Risk Signature | 0.977 | 0.955 | 0.999 |
| High Risk Signature | 0.907 | 0.860 | 0.954 | High Risk Signature | 0.903 | 0.854 | 0.952 |
Prognostic assessment of MammaPrint® FFPE was further investigated using a univariate and multivariate analysis. In the univariate analysis MammaPrint FFPE is significantly associated with risk recurrence. Multivariate analysis did not conclusively demonstrate prognostic significance for MammaPrint FFPE beyond that of other clinicopathological factors. This is attributable to the RASTER study design, in which MammaPrint result was included along with all relevant clinic-pathological factors, and treatment decisions were guided by assessed prognostic risk and the standard of practice. In this real-world context, the overall cohort experienced a low event rate which, despite the favorable trend, diminishes independent contribution of MammaPrint.
IX. Conclusion
MammaPrint FFPE and its predicate device MammaPrint Fresh (K101454) are a clinically and analytically accurate prognostic marker for providing a risk assessment of distant metastasis of breast cancer when performed in either Agendia's European or US central laboratory.
END OF DOCUMENT