(120 days)
No
The device description details a microarray-based gene expression analysis and calculation of an index based on correlation to known risk templates. There is no mention of AI or ML algorithms being used in the analysis or risk determination process. The performance studies focus on analytical concordance and precision, not the performance of an AI/ML model.
No.
The device is described as a qualitative in vitro diagnostic test used to assess a patient's risk for distant metastasis, and its result is indicated for use by physicians as a prognostic marker. It does not provide treatment or directly affect the body's function to alleviate or cure a disease.
Yes
The device is described as a "qualitative in vitro diagnostic test" for assessing a patient's risk for distant metastasis. It involves the analysis of gene expression to produce a "molecular profile" and determination of a "MammaPrint index" which classifies risk, indicating its use in aiding diagnosis or prognosis.
No
The device description explicitly details a multi-step process involving the physical handling and analysis of tissue samples, including RNA isolation, amplification, labeling, hybridization, and scanning using specific hardware (microarray scanners). This indicates the device is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "MammaPrint® FFPE is a qualitative in vitro diagnostic test..."
This statement, along with the description of the test being performed on biological samples (breast cancer tissue) in a laboratory setting to provide information about a patient's condition (risk for distant metastasis), clearly identifies it as 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 clinicopathological factors.
Product codes (comma separated list FDA assigned to the subject device)
NYI
Device Description
The MammaPrint service is a microarray-based gene expression analysis of a tumor. The analysis is based on several processes: isolation of RNA from formalin-fixed paraffin embedded (FFPE) tumor tissue sections, DNase treatment of isolated RNA, amplification DNase treated RNA resulting in cDNA, labeling and purification of amplified cDNA, hybridization of the diagnostic microarray, scanning the MammaPrint microarray and data acquisition (Feature Extraction), calculation and determination of the risk of recurrence in breast cancer patients.
The MammaPrint analysis is designed to determine the gene activity of specific genes in a FFPE tissue sample. The result is an expression profile, or fingerprint, of the sample.
The molecular profile of the sample is determined (Low Risk) by calculating the MammaPrint index (MPI) by determining the correlation of the sample expression profile to the mean expression profiles of risk templates of tumors with a known good and poor outcome.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
breast cancer tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Physicians / central laboratory
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)
- Analytical Performance Compared to Predicate:
- Study Type: Technical equivalence of MammaPrint between scanner part #G2505 (C-scanner) and SureScan Dx microarray scanner, part #G5761AA (D-scanner).
- Sample Size: 92 8-pack arrays.
- Key Results: Concordance experiments were performed. MammaPrint indices were compared using Passing and Bablok regression. Passing and Bablok regression comparing MammaPrint indices between C-scanners and SureScan Dx scanner SG18309119 resulted in y=0.00 +1.00 x (95%Cl – slope: 1.000 – 1.002, 95%Cl intercept: -0.0002 to 0.000). For SG18449122, it was y=0.0010 +1.00 x (95%Cl – slope: 1.000 – 1.0021, 95%Cl intercept: 0.0014 to 0.001). The overall concordance in MammaPrint categorical result between C-scanners and SureScan Dx scanners, SG18309119 and SG18449122, is 99.7% and 100%, respectively. For C-scanners vs SG18449122, NPA is 100 % (95%Cl: 98.1-100) and 100% (95%Cl: 97.1 – 100), PPA is 99.3% (95%Cl: 96.0 – 99.9) and 100% (95%Cl: 97.5 - 100), respectively. All results were within predefined acceptance criteria.
- Test performance - precision assessment of the SureScan Dx scanners - SG18309119 and SG18449122:
- Study Type: Precision assessment.
- Sample Size: Four diagnostic control samples (PLEP3 [Low Risk], PHHE2 [High Risk], PHTR2 [High Risk], PBCL2 [Low Risk -close to classification threshold]).
- Key Results: The variability of repeated measurements of these controls were compared between both scanners using the F-test. F-test p-values for all four control samples were all well below the significance level of 0.05, indicating no significant difference in precision between C and D-scanners.
- Correlation between MammaPrint Index and Clinical Outcome:
- Study Type: Based on the RASTER study (previously submitted in K141142).
- 1- Result distribution: Patients were binned into 4 MammaPrint Index levels. Bin 1 (0.36
§ 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/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services logo. The logo on the right is the FDA logo, which stands for U.S. Food & Drug Administration. The FDA logo is in blue.
November 05, 2020
Agendia Inc. Janice Hogan Partner Hogan Lovells US LLP 1735 Market Street Suite 2320 Philadelphia, PA 19103
Re: K201902
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: July 8, 2020 Received: July 8, 2020
Dear Janice Hogan:
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
1
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 803) 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 (OS) 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,
Soma Ghosh, Ph.D. Chief Molecular Pathology and Cytology Branch Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known)
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 I 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 clinicopathological factors.
Type of Use (Select one or both, as applicable)
Z 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 shows the Agendia logo. On the left is a colorful fingerprint graphic. To the right of the graphic is the word "AGENDIA" in bold, black letters. Below the word "AGENDIA" is the phrase "PRECISION ONCOLOGY" in smaller, gray letters.
510 (k) Summary
1.Submitter Agendia Inc. 22 Morgan Irvine, California 92618 Email: marcelo.trevino@agendia.com Telephone: +1 310 409 7828 Contact person: Marcelo Trevino, Global VP Regulatory & Quality Assurance Date prepared: November 3, 2020
- Device MammaPrint FFPE
3.Predicate Device
MammaPrint FFPE K141142
4. Device Description
The MammaPrint service is a microarray-based gene expression analysis of a tumor. The analysis is based on several processes: isolation of RNA from formalin-fixed paraffin embedded (FFPE) tumor tissue sections, DNase treatment of isolated RNA, amplification DNase treated RNA resulting in cDNA, labeling and purification of amplified cDNA, hybridization of the diagnostic microarray, scanning the MammaPrint microarray and data acquisition (Feature Extraction), calculation and determination of the risk of recurrence in breast cancer patients.
The MammaPrint analysis is designed to determine the gene activity of specific genes in a FFPE tissue sample. The result is an expression profile, or fingerprint, of the sample.
The molecular profile of the sample is determined (Low Risk) by calculating the MammaPrint index (MPI) by determining the correlation of the sample expression profile to the mean expression profiles of risk templates of tumors with a known good and poor outcome.
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Image /page/4/Picture/0 description: The image is a logo for Agendia Precision Oncology. The logo features a colorful fingerprint graphic on the left side. To the right of the graphic is the word "AGENDIA" in large, bold, black letters. Below "AGENDIA" is the phrase "PRECISION ONCOLOGY" in smaller, gray letters.
5. 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 clinicopathological factors.
6. Comparison to Predicate Device
The predicate is Agendia Inc's MammaPrint (K141142). The predicate device, with product code NYI, is regulated under 21CFR866.6040. The modified MammaPrint device subject of this 510(k) is substantially equivalent to Agendia's MammaPrint device covered under K141142. It has the identical indications for use and very similar technological features. The only difference is that the modified MammaPrint device allows the use of Agilent SureScan Dx microarray scanners, part #G5761AA. The minor change in the specific scanner that is used does not raise any new types of safety or effectiveness questions. Performance testing confirms that the change in scanner does not adversely impact functioning of the system compared to the predicate.
7. Performance Data
Analytical Performance Compared to Predicate
Analytical performance of MammaPrint was investigated by assessing concordance between results from Agilent scanners part #G2505 (C-scanner) and Agilent SureScan Dx microarray scanners, part #G5761AA (D-scanner). Additionally, precision was also assessed for the Agilent SureScan Dx microarray scanners, part #G5761AA.
1- Technical equivalence of MammaPrint between scanner part #G2505 and SureScan Dx microarray scanner, part #G5761AA
Concordance experiments were performed based on designs as previously included in K080252 as well as K101454.
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Image /page/5/Picture/0 description: The image shows the Agendia logo. The logo consists of a fingerprint graphic on the left and the word "AGENDIA" in bold, black letters on the right. Below "AGENDIA" is the phrase "PRECISION ONCOLOGY" in smaller, gray letters. The fingerprint graphic is made up of concentric lines in a gradient of colors, ranging from red to blue.
nis validation, a set of 92 8-pack arrays were analyzed as part of regular diagnostics on the FDA cleared scanners (US45103019 and US811R3213). Subsequently, these were scanned a second time on the SureScan Dx scanners, SG18309119 and SG18449122. The text files generated as output were used to generate MammaPrint indices according to standard procedures.
The samples included in this dataset covered the entire MammaPrint readout range, including the borderline region. Additionally, there were four diagnostic control samples included that cover the MammaPrint categorical results; PLEP3 (Low Risk), PHHE2 (High Risk), PHTR2 (High Risk), PBCL2 (Low Risk -close to classification threshold).
MammaPrint indices were compared between both C and D-scanners using Passing and Bablok regression. The MammaPrint categorical results (High/Low Risk) were compared using a 2x2 contingency table after which concordance, Negative Percent Agreement (NPA) and Positive Percent (PPA) were determined. The Passing and Bablok regression comparing the MammaPrint indices between the Cscanners and SureScan Dx scanner SG18309119 is y=0.00 +1.00 x (95%Cl – slope: 1.000 – 1.002, 95%Cl intercept: -0.0002 to 0.000). The Passing and Bablok regression comparing the MammaPrint indices between the C-scanners and SureScan Dx scanner SG18449122 is y=0.0010 +1.00 x (95%Cl – slope: 1.000 – 1.0021, 95%Cl intercept: 0.0014 to 0.001). The overall concordance in MammaPrint categorical result between the C-scanners and the SureScan Dx scanners, SG18309119 and SG18449122 is 99.7% and 100%, respectively. For this comparison C-scanners versus SG18449122 the NPA is 100 % (95%Cl: 98.1-100) and 100% (95%Cl: 97.1 – 100), the PPA is 99.3% (95%Cl: 96.0 – 99.9) and 100% (95%Cl: 97.5 - 100), respectively.
The results of the Passing and Bablok regression of both D-scanners compared to the C-scanner are within the pre-defined acceptance criteria. Furthermore, the concordance, NPA and PPA determined for each Dscanner versus the FDA cleared C-scanners were all within the predefined acceptance criteria.
2- Test performance - precision assessment of the SureScan Dx scanners - SG18309119 and SG18449122
Precision assessment was performed using the four diagnostic control samples (PLEP3 [Low Risk], PHHE2 [High Risk], PHTR2 [High Risk], PBCL2 [Low Risk -close to classification threshold]) that were measured as
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Image /page/6/Picture/0 description: The image shows the logo for Agendia Precision Oncology. The logo features a colorful fingerprint graphic on the left, with the word "AGENDIA" in bold, black letters to the right. Below "AGENDIA" are the words "PRECISION ONCOLOGY" in a smaller, gray font. The fingerprint graphic is made up of concentric lines in shades of red, orange, yellow, green, and blue.
t of the validation. These control samples have a known MammaPrint result and cover all MammaPrint categorical results.
In order to assess the precision of both D-scanners versus the FDA cleared scanners, the variability of repeated measurements of these controls were compared between both scanners using the F-test. The F-test p-values for all four control samples were all well below the significance level of 0.05, indicating there is no significant difference in precision between C and D-scanners.
Correlation between MammaPrint Index and Clinical Outcome
Two analyses were conducted to show the correlation between the MammaPrint index and clinical outcome of the RASTER study (previously submitted in K141142):
1- Result distribution
In order to show a correlation between the MammaPrint index and clinical results were placed into bins consisting of 4 MammaPrint Index levels.
| Bin | MPI Range | Number
of
Patients | Percentage
of Patients | Observed 5-
yr DR risk |
|-------|-------------------|--------------------------|---------------------------|---------------------------|
| 1 | 0.36