(119 days)
K042613, PAXgene® Blood RNA System
No
The device description and performance studies focus on the chemical properties of a tissue preservation solution and its ability to maintain RNA integrity. There is no mention of AI or ML algorithms being used for analysis or interpretation.
No
The device is intended for the collection, storage, and transportation of fresh breast tissue specimens for subsequent RNA isolation and molecular diagnostic testing, not for treating a disease or condition.
No
The device is intended for the collection, storage, and transportation of specimens for subsequent molecular diagnostic testing, not for performing the diagnostic testing itself. It's a specimen preservation and transport device.
No
The device is a physical container with a preservation solution, not a software program.
Based on the provided information, the RNARetain® device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The device is specifically intended for the "collection, storage, and transportation of fresh breast tissue specimens for subsequent RNA isolation and further molecular diagnostic testing." This clearly indicates its use in the diagnostic process, even though it's a pre-analytical step.
- Device Description: The description highlights its role in preserving nucleic acids within the tissue, which is crucial for accurate molecular diagnostic testing.
- Performance Studies: The performance studies focus on the device's ability to maintain the quality and integrity of RNA for downstream diagnostic tests like the MammaPrint® Test (a molecular diagnostic test). The metrics evaluated (RNA purity, integrity, correlation with MammaPrint® outcomes) are directly related to its performance in a diagnostic workflow.
- Predicate Device: The predicate device listed, PAXgene® Blood RNA System, is also a device used for the collection and stabilization of blood for RNA isolation, which is a common pre-analytical step for IVD tests. This further supports the classification of RNARetain® as an IVD.
- Reference Device: The reference device, MammaPrint® Test, is a molecular diagnostic test that would utilize the RNA preserved by the RNARetain® device. This connection reinforces the device's role within a diagnostic pathway.
While the device itself doesn't perform the final diagnostic test, its function is essential for enabling accurate and reliable molecular diagnostic testing on the collected tissue specimen. Therefore, it falls under the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The RNARetain® device is a single-use, prefilled container intended for the collection, storage, and transportation of fresh breast tissue specimens for subsequent RNA isolation and further molecular diagnostic testing. For Professional Use Only.
Product codes
OZF
Device Description
The RNARetain® device consists of an aqueous, hypertonic tissue preservation solution that is provided in a single-use, non-sterile vial intended to serve as the container for the collection, storage, and transport of breast tissue specimens. The ability of the solution formulation to preserve fresh tissue and nucleic acids within the tissue is due to its rapid permeation of tissue to protect cellular nucleic acids from nucleases that would otherwise rapidly degrade the nucleic acids within the specimen. The demonstrated inhibitory effect of the RNARetain® solution on the growth of bacteria, yeast and mold protects the specimen from inadvertent microbial contamination during storage or usage of the device. The utility of the RNARetain® solution is to maintain high quality cellular RNA for downstream molecular testing. The collection of fresh breast tissue specimens into the RNARetain® device eliminates the need to immediately process these specimens, enabling RNA extraction and molecular testing at a later time and/or transport to a different location. RNARetain® eliminates the need to flash-freeze specimens and to keep specimens frozen throughout storage and transport, a process that is costly and involves manipulation of potentially hazardous agents. It also eliminates the need for formalin fixation, the most common method of clinical tissue preservation, that is both hazardous to work with and known to cross-link and sometimes degrade the nucleic acids rendering them unacceptable for specific downstream molecular applications.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
breast tissue specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
will be utilized in the healthcare facility/hospital/laboratory environment. For Professional Use Only.
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
Non-Clinical Analytical Performance: Precision/Reproducibility (K070675) - Reproducibility of multiple isolations starting from breast tissue sample collected in RNARetain®. Five previously analyzed tumor samples (one borderline, two high risk and two low risk) were isolated in duplicate over multiple days. No statistically significant difference in MammaPrint® risk group assignment or MammaPrint® index between the two separate RNA isolations was observed.
Stability of MammaPrint® outcomes in RNARetain® (K070675) - The effect of shipment of a tumor in RNARetain® on stability of MammaPrint® results was demonstrated. A tumor selected from which both immediately snap-frozen and RNARetain® preserved sections were available. Both samples were labeled 5 times and hybridized on MammaPrint® microarrays. Results showed that the incorporation of both Cy5 and Cy3 were significantly higher for samples shipped in RNARetain® (Unpaired T-tests, p=0.018 and p=0.001 respectively). The variance in MammaPrint® indices was smaller for samples that were stored in RNARetain® compared to the samples that were frozen immediately (Std dev 0.022 vs. 0.042). An unpaired T-test of the MammaPrint® index revealed no significant difference in the actual MammaPrint® indices for the RNARetain® and frozen samples (p=0.24). Based on these experiments, the stability in MammaPrint® index is greater in samples stored in RNARetain® than in samples that were immediately frozen. The difference in MammaPrint® index between RNARetain® and frozen tissue (Δ 0.027) was within the previously determined acceptable limit of index variation.
Comparison studies - Method comparison with predicate device (K070675): One set consisted of 33 breast tumor samples of which one part of the sample was immediately snap-frozen in liquid nitrogen and stored at -70 ℃, another part was stored in RNARetain® for 3 to 5 days at room temperature and subsequently removed from the preservation solution, snap frozen and stored at -70 ℃. Another set comprised of 18 tumors of which two parts were available for research that were immediately snap frozen and stored at -70 ℃. RNA isolation and DNAse treatment were performed. All samples were hybridized on MammaPrint® microarrays, and passed all sample, labeling and hybridization QCs. Analysis was performed. The median difference between the RNARetain® preserved and the snap frozen is 0.070. The Pearson correlation (0.94) and regression analysis indicate a high similarity (Re= 0.90). This finding is similar to the results of a series of tumors of which two frozen samples were available and were collected in the same time period. The median difference in MammaPrint® Index was 0.105. A comparison of the differences in both series (RNARetain -frozen vs. frozen-frozen) showed no significant difference (t-test, p=0.57) indicating no variation is introduced by RNARetain®.
Repeatability and Reproducibility (Asuragen) - Ten adjacent pairs of breast tissue were collected by Asuragen from 3 subjects. From each pair, one was stored in RNARetain® at 2 to 8 °C for 12 to 18 hours and the other was frozen in liquid nitrogen and stored at ≤ - 70 ℃. The RNARetain® and flash-frozen stored specimens were then shipped overnight. The samples were processed immediately upon receipt for RNA purification and RNA analysis. There was no significant difference between tissues from various storage methods, indicating that RNA quality from human breast tissue stored in RNARetain® is equivalent to flash-frozen specimens and that the two RNA preservation methods are compatible with downstream molecular analyses.
Sample stability - Human breast cancer cell line MCF-7 were grown and resuspended in RNARetain® incubated overnight at 2-8 °C, then subjected to up to 7 days at 35 to 39 °C, up to 15 days at 18 to 25 °C, up to 60 days at 2 to 8 °C, and up to 3 years at -15 to -30 °C. RNA Yield (A260), Purity (A260/A280), and Integrity (285:18S ratios) were compared to Fresh Frozen cells. Samples passed acceptance criteria up to 3 days at 35 to 39 ℃, 15 days at 18 to 25 ℃, 60 days at 2 to 8 ℃, and up to 3 years at -15 to -30 ℃.
RNARetain® reagent stability - Stability studies were performed with 3 lots of the 8mL vial (6 mL volume) up to 20 months with storage at room temperature (18 to 25 °C). Reagents passed acceptance criteria. Additional stability studies with the 6 mL vial (5 mL volume) and 2 mL vial (1 mL volume) configurations were also performed up to 36 months and passed acceptance criteria. RNARetain® is stable at room temperature up to 36 months.
Key Metrics
RNA Purity (A260/A280 ≥ 1.6); Integrity (28S:18S ≥ 1.0 or RIN ≥ 7.0); Pearson correlation (0.94); Regression analysis indicates high similarity (Re= 0.90); Median difference between RNARetain® preserved and snap frozen is 0.070.
Predicate Device(s)
K042613, PAXgene® Blood RNA System
Reference Device(s)
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.4070 RNA Preanalytical Systems.
(a)
Identification. RNA Preanalytical Systems are devices intended to collect, store, and transport patient specimens, and stabilize intracellular RNA from the specimens, for subsequent isolation and purification of the intracellular RNA for RT-PCR used in in vitro molecular diagnostic testing.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: RNA Preanalytical Systems (RNA Collection, Stabilization and Purification System for RT-PCR Used in Molecular Diagnostic Testing).” See § 866.1(e) for the availability of this guidance document.
0
MAR 1 6 2012
RNARetain® Asuragen, Inc Traditional 510(k) Submission
510(k) Summary
-
- Assigned 510(k) number The assigned 510(k) number is ________________________________________________________________________________________________________________________________________________ K113420
-
- Company Asuragen, Inc. 2150 Woodward Street, Suite 100 Austin, TX 78744
Tel: 512-681-5200 Fax: 512-681-5201
-
- Contact Luc Van Hove, M.D., Ph.D., CSSBB Senior Director Quality, Regulatory, Clinical & Medical Affairs
Address: See above Tel: 512-681-5280 Fax: 512-681-5201 Email: Ivanhove@asuragen.com
- Contact Luc Van Hove, M.D., Ph.D., CSSBB Senior Director Quality, Regulatory, Clinical & Medical Affairs
-
- Date Prepared March 8, 2012
-
- Proprietary Name Trade name (Proprietary name): RNARetain®
-
- Classification Name RNA Pre-Analytical System
-
- Common Name Common name (usual name): RNARetain® collection, storage, and transportation device
-
- Classification Class II Regulation: 21CFR 866.4070 Product code: OZF Panel: Immunology
-
- Predicate Device K042613, PAXgene® Blood RNA System
1
10. Device Description - Characteristics
The RNARetain® device consists of an aqueous, hypertonic tissue preservation solution that is provided in a single-use, non-sterile vial intended to serve as the container for the collection, storage, and transport of breast tissue specimens. The ability of the solution formulation to preserve fresh tissue and nucleic acids within the tissue is due to its rapid permeation of tissue to protect cellular nucleic acids from nucleases that would otherwise rapidly degrade the nucleic acids within the specimen. The demonstrated inhibitory effect of the RNARetain® solution on the growth of bacteria, yeast and mold protects the specimen from inadvertent microbial contamination during storage or usage of the device.
The utility of the RNARetain® solution is to maintain high quality cellular RNA for downstream molecular testing. The collection of fresh breast tissue specimens into the RNARetain® device eliminates the need to immediately process these specimens, enabling RNA extraction and molecular testing at a later time and/or transport to a different location. RNARetain® eliminates the need to flash-freeze specimens and to keep specimens frozen throughout storage and transport, a process that is costly and involves manipulation of potentially hazardous agents. It also eliminates the need for formalin fixation, the most common method of clinical tissue preservation, that is both hazardous to work with and known to cross-link and sometimes degrade the nucleic acids rendering them unacceptable for specific downstream molecular applications.
10 a. Device Description - Identification and Materials of Use
The RNARetain® device consists of an aqueous, hypertonic tissue preservation solution that is provided in a single-use, non-sterile vial intended to serve as the container for the collection, storage and transport of breast tissue specimens.
| Table 1. RNARetain® configurations. | |||||
|---|---|---|---|---|---|
| RNARetain® | |||||
| solution | Vial | ||||
| Capacity | Maximum | ||||
| Tissue Fill | Cap | Devices | |||
| per box | Comment | ||||
| .6 mL | 8 mL | 0.6 cc or | |||
| 0.6 g | Leak-proof polyethylene | ||||
| cap | 18 vials | Configuration of | |||
| MammaPrint® | |||||
| includes 1 vial of | |||||
| RNARetain® | |||||
| 5 mL | 6 mL | 0.5 cc or | |||
| 0.5 g | Leak-proof polyethylene | ||||
| cap | 18 vials | ||||
| 1 mL | 2 mL | 0.1 cc or | |||
| 0.1 g | Leak-proof | ||||
| polypropylene cap with | |||||
| O-ring | 24 vials |
10 b. Device Description - Environment of Use
The device will be utilized in the healthcare facility/hospital/laboratory environment.
2
10 c. Device Description - Kev Performance Specifications|Characteristics of the Device
- A single-use, prefilled container intended for fresh tissue collection, storage, and . transportation.
- The RNARetain® solution is a non-toxic tissue preservation reagent that stabilizes . cellular nucleic acids.
- Eliminates the need to freeze tissue samples after harvesting. .
- The preserved tissue is applicable for subsequent nucleic acid isolation and . downstream molecular tests.
- The performance characteristics of RNARetain® have been established for RNA with . fresh breast tumor tissue and the MammaPrint® Test (K070675) and the additional Asuragen testing.
- Multiple vial configurations containing RNARetain® solution: 6 mL solution in a 8 . mL vial; 5 mL solution in a 6 mL vial; 1 mL solution in a 2 mL vial.
- Specimen content of 6 mL: ≤ 0.6 cc of solid tissue; Specimen content of 5 mL: ≤ 0.5 . cc of solid tissue; Specimen content of 1 mL: ≤ 0.1 cc of solid tissue. This is a specimen to solution ratio of 1:10 or less.
- . Device storage and stability: 5 mL and 1 mL configurations up to 36 months at room temperature (18 to 25 °C) and ≤ 85% humidity; 6 mL configuration up to 20 months at room temperature (18 to 25 °C) and ≤ 85% humidity.
- Tissue should be submerged in RNARetain® for at least 12 hours prior to freezing. .
- . Tissue can be stored in reagent for up to 3 days at 35 to 39 ℃, 7 days at 18 to 25 ℃, 30 days at 2 to 8 ℃, or 3 years at -15 to -30 ℃ before RNA extraction.
- . Median RNA purity, vield, integrity and corresponding %CVs between assay replicates are equivalent to flash frozen tissue.
- . RNA Purity (A260/A280 ≥ 1.6).
- . Integrity (28S:18S ≥ 1.0 or RIN ≥ 7.0).
- . Ambient temperature storage and shipping of device to end-user.
-
- Intended Use/Indications for Use
The RNARetain® device is a single-use, prefilled container intended for the collection, storage, and transportation of fresh breast tissue specimens for subsequent RNA isolation and further molecular diagnostic testing. For Professional Use Only.
11 a. Intended Use - general description of diseases and conditions
The device itself does not diagnose, treat, prevent, cure, or mitigate any disease or condition, but rather is intended for the collection, storage, and transportation of fresh breast tissue.
The difference in tissue type and vial closures from the predicate does not add additional risk to the use of the device.
Page 3 of 9
3
.
12. Table of Similarities and Differences of RNARetain® and Predicate device
| Item | Test Article | Predicate |
|---|---|---|
| Name | RNARetain® | PAXgene® Blood RNA System |
| 510(k) number | K113420 | K082150; K042613 |
| 510(k) holder | Asuragen, Inc. | |
| Austin, TX | PreAnalytiX GMBH | |
| Feldbachstrasse, | ||
| Hombrechtikon | ||
| Switzerland CH-8634 | ||
| Product Code | OZF | NTW |
| Intended Use | Pre-analytical specimen collection, storage and transportation device | SAME |
| RNARetain® is used to preserve fresh breast tissue and stabilize cellular RNA | SAME, but tissue type is blood | |
| The preserved tissue can be used for subsequent nucleic acid isolation and further molecular testing | SAME, but system also contains the nucleic acid purification kit for isolation of RNA | |
| RNA is used for molecular testing | SAME | |
| Technology | Deactivation of ribonucleases and preservation of RNA molecules | SAME |
| Principle of Operation | Tissue collection, preservation, storage and transportation | SAME, but also includes the isolation of RNA |
| Components | Single-use, specimen container prefilled with preservation solution | SAME, but the system also contains a blood RNA kit for the isolation of RNA |
| Risks | Chemical exposure risk to person who handles the material-minimum | SAME |
| RNA degradation risk to patient for misdiagnosis, delay in diagnosis and sample recollection | SAME | |
| Item | Test Article | Predicate |
| Sample types | Breast | DIFFERENT, |
| Tissue type is blood | ||
| Storage | ||
| Solution | ||
| Composition | Ammonium sulfate, | |
| sodium citrate and EDTA | ||
| at specific, proprietary | ||
| concentrations | DIFFERENT, formulated | |
| for blood tissue, but same | ||
| concept - | ||
| tetradecyltrimethyl- | ||
| ammonium oxalate and | ||
| tartaric acid | ||
| Sterility | Non-sterile | DIFFERENT, Sterile |
| Container | Transparent, | |
| polypropylene plastic | ||
| tube | DIFFERENT, | |
| Blood collection tube of | ||
| undeclared plastic | ||
| Closure | Leak-proof polyethylene | |
| cap for 6 mL in 8 mL vial | ||
| and for 5 mL in 6 mL vial | ||
| Polypropylene cap with | ||
| O-ring (for 2 mL vial) | DIFFERENT, | |
| Special blood collection | ||
| enclosure. |
Table 2. RNARetain and PAXgene blood system comparison table.
4
RNARetain® Asuragen, Inc
13. Non-Clinical Analytical Performance
Analytical performance Agendia
13 a. Precision/Reproducibility (K070675)
Reproducibility of multiple isolations starting from breast tissue sample collected in RNARetain®.
In order to determine the reproducibility of the MammaPrint® device process from tissue processing to the end result, five previously analyzed tumor samples (one borderline, two high risk and two low risk) were isolated in duplicate. Over multiple days, the ten isolations from five tumors were processed according to standard MammaPrint® protocols.
| Sample | Original
index | Result | Index from
first
isolation | Index from
second
isolation |
|--------|-------------------|---------------------------|----------------------------------|-----------------------------------|
| S1 | 0.376 | High risk
(borderline) | 0.254 | 0.374 |
| S2 | 0.608 | Low risk | 0.564 | 0.553 |
| S3 | 0.659 | Low risk | 0.639 | 0.680 |
| S4 | -0.105 | High risk | 0.068 | 0.067 |
| S5 | -0.305 | High risk | -0.171 | -0.337 |
Table 3. Reproducibility
Page 5 of 9
5
Traditional 510(k) Submission
RNARetain® Asuragen, Inc
No statistically significant difference in MammaPrint® risk group assignment or MammaPrint® index between the two separate RNA isolations was observed.
13 b. Stability of MammaPrint® outcomes in RNARetain® (K070675)
The effect of shipment of a tumor in RNARetain® on stability of MammaPrint® results was demonstrated in K070675. The tumor was selected from which both immediately snapfrozen and RNARetain® preserved sections were available. Both sections of the turnor had a similar tumor cell percentage and similar RNA quality. Both samples were labeled 5 times and hybridized on MammaPrint® microarrays according to standard protocols. MammaPrint® Indices were compared to determine if samples shipped in RNARetain® have a greater stability than tumor sections which are immediately stored at -70 ℃ after excision. Results showed that the incorporation of both Cy5 and Cy3 were significantly higher for samples shipped in RNARetain" (Unpaired T-tests, p=0.018 and p=0.001 respectively). The variance in MammaPrint® indices was smaller for samples that were stored in RNARetain® compared to the samples that were frozen immediately (Std dev 0.022 vs. 0.042). An unpaired T-test of the MammaPrint® index revealed no significant difference in the actual MammaPrint® indices for the RNARetain® and frozen samples (p=0.24). Based on these
experiments, the stability in MammaPrint® index is greater in samples stored in RNARetain® than in samples that were immediately frozen. The difference in MammaPrint® index between RNARetain® and frozen tissue (Δ 0.027) was within the previously determined acceptable limit of index variation.
13 c. Comparison studies
Method comparison with predicate device (K070675):
The samples for this study were collected in 2003 as a pilot study for the Dutch Raster clinical trial sponsored by the Dutch Health Insurance Council where tissue would be shipped in RNARetain® from 20 hospitals. One set consisted of 33 breast tumor samples of which one part of the sample was immediately snap-frozen in liquid nitrogen and stored at -70 ℃, another part was stored in RNARetain® for 3 to 5 days at room temperature and subsequently removed from the preservation solution, snap frozen and stored at -70 ℃. Another set comprised of 18 tumors of which two parts were available for research that were immediately snap frozen and stored at -70 ℃. RNA isolation and DNAse treatment were performed in this same period. HE stained sections were re-examined by a pathologist to confirm invasive ductal carcinoma and sufficient tumor cell content. All samples were hybridized on MammaPrint® microarrays, and passed all sample, labeling and hybridization QCs. Analysis was performed using Feature Extraction version 8.5 and XPrint version 1.40. Results of MammaPrint® indices of paired RNARetain® and frozen samples are shown in Figure 2A. The median difference between the RNARetain® preserved and the snap frozen is 0.070. The Pearson correlation (0.94) and regression analysis indicate a high similarity (Re= 0.90).
6
RNARetain® Asuragen, Inc
Image /page/6/Figure/2 description: The image contains two scatter plots, labeled A and B, showing correlations between different variables. Plot A shows the correlation between 'Frozen' and 'RNAleler', with a regression equation of y=0.9361x-0.0324, an R-squared value of 0.902, and a Pearson correlation coefficient of 0.94. Plot B shows the correlation between 'mzen 1' and 'mzen 2', with a regression equation of y=0.9472x-0.0314, an R-squared value of 0.838, and a Pearson correlation coefficient of 0.92.
Figure 2: Comparison of MammaPrint® Indices between two samplings of the same tumor. A RNARetain®-frozen; B frozen-frozen.
This finding is similar to the results of a series of tumors of which two frozen samples were available and were collected in the same time period (Figure 2B). The median difference in MammaPrint® Index was 0.105. A comparison of the differences in both series (RNARetain -frozen vs. frozen-frozen) showed no significant difference (t-test, p=0.57) indicating no variation is introduced by RNARetain®.
Image /page/6/Figure/5 description: The image is a scatter plot comparing MammaPrint Index RNALater and MammaPrint Index Frozen. The x-axis represents the MammaPrint Index Frozen, ranging from -1.0 to 1.0, while the y-axis represents the MammaPrint Index RNALater, also ranging from -1.0 to 1.0. The plot contains data points scattered around a diagonal line, indicating a correlation between the two indices. There are also a few regression lines plotted on the graph.
Figure 3: A Passing and Bablok regression analysis on the RNARetain® vs. frozen samples.
7
Analytical Performance Asuragen:
13 d. Repeatability and Reproducibility
Ten adjacent pairs of breast tissue were collected by Asuragen from 3 subjects. From each pair, one was stored in RNARetain® at 2 to 8 °C for 12 to 18 hours and the other was frozen in liquid nitrogen and stored at ≤ - 70 ℃. The RNARetain® and flash-frozen stored specimens were then shipped overnight on blue ice or dry ice, respectively. The samples were processed immediately upon receipt for RNA purification and RNA analysis. The average yield, integrity, and purity values for each subject (10 replicates), together with their associated standard deviation (SD) are presented in Table 4. There was no significant difference between tissues from various storage methods, indicating that RNA quality from human breast tissue stored in RNARetain® is equivalent to flashfrozen specimens and that the two RNA preservation methods are compatible with downstream molecular analyses.
| | Subject | Storage | Integrity
(28S:18S) | | Purity
(A260/A280) | | Yield |
|--|---------|-----------|------------------------|-----|-----------------------|------|-------|
| | 1 | RNARetain | AVG | SD | AVG | SD | AVG |
| | | RNARetain | 1.5 | 0.3 | 1.97 | 0.03 | 148 |
| | | Frozen | 1.6 | 0.2 | 1.92 | 0.06 | 131 |
| | 2 | RNARetain | 1.6 | 0.2 | 2.03 | 0.04 | 62 |
| | | Frozen | 1.5 | 0.2 | 2.01 | 0.11 | 43 |
| | 3 | RNARetain | 1.5 | 0.2 | 1.96 | 0.14 | 101 |
| | | Frozen | 1.5 | 0.1 | 1.96 | 0.09 | 81 |
Table 4. Mean results for the 3 breast tissue replicates.
13 e. Sample stability
Human breast cancer cell line MCF-7 were grown and resuspended in RNARetain® incubated overnight at 2-8 °C, then subjected to up to 7 days at 35 to 39 °C, up to 15 days at 18 to 25 °C, up to 60 days at 2 to 8 °C, and up to 3 years at -15 to -30 °C. RNA Yield (A260), Purity (A260/A280), and Integrity (285:18S ratios) were compared to Fresh Frozen cells. Samples passed acceptance criteria up to 3 days at 35 to 39 ℃, 15 days at 18 to 25 ℃, 60 days at 2 to 8 ℃, and up to 3 years at -15 to -30 ℃.
13 f. RNARetain® reagent stability
Stability studies were performed with 3 lots of the 8mL vial (6 mL volume) up to 20 months with storage at room temperature (18 to 25 °C). Reagents passed acceptance criteria. Additional stability studies with the 6 mL vial (5 mL volume) and 2 mL vial (1 mL volume) configurations were also performed up to 36 months and passed acceptance criteria. RNARetain® is stable at room temperature up to 36 months.
8
Summary of clinical studies for the determination of substantial equivalence
Not Applicable.
Summary of Substantial Equivalence to Predicate
The studies above demonstrate that RNARetain® is safe and effective in the collection, storage and transport of fresh breast tissue; preserving the nucleic acids to allow for high quality RNA isolation and accurate clinical outcome test results with a cleared assay. RNARetain was compared to the fresh-frozen method for tissue transportation and RNA preservation and determined to be safe, effective, and equivalent to its performance in the Agendia MammaPrint® (K070675) submission.
RNARetain® is substantially equivalent to the predicate - PAXgene® Blood RNA System. With the exception of the RNA isolation kit (which is not a component of the RNARetain® product), the two devices have the same technology, and principle of operation - that is the collection, preservation, storage and transportation of a specific tissue. Both devices are single-use specimen plastic containers prefilled with preservation solution. The risks are the same, which is risk to the patient for misdiagnosis, delay in diagnosis, or sample recollection due to RNA degradation. As the two devices are specific for different tissues (breast vs. blood), a direct comparison between the two devices was not performed; rather each device was compared to the pre-amendment test method utilized for that specific tissue. RNARetain® was compared to the fresh-frozen method of tissue preservation, transportation and storage and PAXgene® was compared to k2EDTA collected blood in an applicable collection vessel. However, the methods used to evaluate the comparison with the preamendment test methods were similar: RNA yield (A260) and purity (A260/280). Repeatability and reproducibility evaluations also utilizing RNA vield and purity, and finally a functional evaluation of the RNA quality by molecular diagnostic test assays. Both devices met their acceptance criteria demonstrating these two devices can preserve RNA molecules to yield high quality RNA for subsequent RNA isolation and further molecular diagnostic testing.
The differences in the devices are primarily due to the specific tissue type the device is intended for. PAXgene® has a vial closure that is conducive to drawing blood and the collection vial is sterile as this is a critical parameter for blood which coats the vial during collection. RNARetain® has a vial closure that is closer in composition to the vial and can be sealed after the breast tissue is placed in the vial is non-sterile as the tissue does not coat the vial during collection and the device solution has been shown to protect against microbial growth in anti-microbial challenge studies. The differences in the devices do not impact their similar intended use, technology, or principle of operation.
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
9
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Asuragen, Inc. c/o Luc Van Hove, M.D., Ph.D., CSSBB Senior Director Medical/Clinical, Regulatory & Quality 2150 Woodward Street, Suite 100 Austin, TX 78744
Re: K113420
Trade/Device Name: RNARetain® Regulation Number: 21 CFR §866.4070 Regulation Name: RNA Preanalytical Systems Regulatory Class: Class II Product Code: OZF Dated: January 19, 2012 Received: January 20, 2012
MAR 1 6 2012
Dear Dr. Van Hove:
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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code 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 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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing
10
Page2 – Dr. Luc Van Hove
vour device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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
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 Small Manufacturers, International and Consumer Assistance at its tolli-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
ia-m Chen
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
11
Indications for Use
510(k) Number (if known): K113420
Device Name: RNARetain®
Indications For Use:
The RNARetain® device is a single-use, prefilled container intended for the collection, storage, and transportation of fresh breast tissue specimens for subsequent RNA isolation and further molecular diagnostic testing.
For Professional Use Only.
Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use N.A. . (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)
Maria M Chan
Division Sign-Off
Page 1 of _
Office of in Vitro Dlagnostic Device Evaluation and Saffery
510(k) /