Who is the manufacturer of AFFYMETRIX GENE PROFILING REAGENTS?

Affymetrix, Inc. filed the 510(k) submission for AFFYMETRIX GENE PROFILING REAGENTS (K103112).

What is the FDA product code for AFFYMETRIX GENE PROFILING REAGENTS?

OVA. It is classified under 21 CFR 862.2570 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for AFFYMETRIX GENE PROFILING REAGENTS?

510(k) clearance (submission type: Traditional).

Who can help prepare an FDA 510(k) submission like AFFYMETRIX GENE PROFILING REAGENTS?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

AFFYMETRIX GENE PROFILING REAGENTS

K103112 · Affymetrix, Inc. · OVA · May 4, 2011 · Clinical Chemistry

Device Facts

Record ID	K103112
Device Name	AFFYMETRIX GENE PROFILING REAGENTS
Applicant	Affymetrix, Inc.
Product Code	OVA · Clinical Chemistry
Decision Date	May 4, 2011
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.2570
Device Class	Class 2

Intended Use

Affymetrix® Gene Profiling Reagents are intended for the preparation of labeled complementary RNA target from purified total RNA from fresh or frozen clinical tissue specimens for hybridization to Affymetrix GeneChip® microarrays and the measurement of fluorescence signals of labeled RNA target using the Affymetrix GeneChip® Microarray Instrumentation System. Intended for use with separately FDA-cleared Affymetrix GeneChip microarray assays specifying the use of the Affymetrix Gene Profiling Reagents.

Device Story

Affymetrix Gene Profiling Reagents are an accessory kit for the GeneChip Microarray Instrumentation System; used to prepare labeled cRNA targets from purified total RNA (100-1000 ng) extracted from fresh or frozen clinical tissue. The system processes RNA through three kits: RNA Control Kit (positive controls), Transcript Synthesis/Labeling Kit (amplification and biotinylation), and Transcript Detection Kit (fragmentation and hybridization cocktail preparation). The labeled cRNA is hybridized to Affymetrix GeneChip microarrays; the instrumentation system measures fluorescence signals. Used in clinical laboratory settings by trained personnel. Output consists of .CEL files generated by the scanner, which are subsequently analyzed by proprietary algorithms (e.g., Pathwork Tissue of Origin-Frozen algorithm) to provide clinical diagnostic information. The reagents ensure consistent target preparation, enabling standardized gene expression analysis for clinical decision-making.

Clinical Evidence

Clinical evidence includes a two-part prospective study comparing the subject reagents to the One-Cycle Reagent Kit using the Pathwork Tissue of Origin-Frozen Test. Part 1 tested 16 frozen tissue samples; Part 2 tested 45 total RNA samples. The primary endpoint was the success rate of generating test results and concordance of results between reagent sets. The integrated analysis demonstrated that the observed percent correct using the subject reagents was statistically equivalent to the expected percent correct using the predicate reagents (95% bootstrap CI: -5.9%, 3.4%).

Technological Characteristics

Kit-based reagents for RNA amplification and labeling. Includes RNA Control Kit (Poly-A control, dilution buffer), Transcript Synthesis/Labeling Kit (enzymes, biotinylated reagents), and Transcript Detection Kit (fragmentation reagents, hybridization cocktail). Designed for use with Affymetrix GeneChip microarrays and Fluidics Station 450/GCS3000 Dx scanner. Operates via enzymatic amplification and biotinylation of RNA targets. Analytical performance validated for 100-1000 ng input RNA.

Indications for Use

Indicated for preparation of labeled cRNA from purified total RNA (100-1000 ng) derived from fresh or frozen clinical tissue specimens for use with FDA-cleared Affymetrix GeneChip microarray assays.

Regulatory Classification

Identification

Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.

The special control is FDA's guidance document entitled "Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems."

Predicate Devices

Affymetrix GeneChip® Microarray Instrumentation System (K080995)

Reference Devices

Pathwork® Tissue of Origin-Frozen Test (K080896)

Related Devices

K080896 — PATHWORK DIAGNOSTICS TISSUE OF ORIGIN TEST · Pathwork Diagnostics, Inc. · Jul 30, 2008
K173839 — Tissue of Origin Test Kit-FFPE · Cancer Genetics, Inc. · Mar 15, 2018
K080995 — MODIFICATION TO AFFYMETRIX GENECHIP MICROARRAY INSTRUMENTATION SYSTEM · Affymetrix, Inc. · Jul 30, 2008
K120489 — TISSUE OF ORIGIN TEST KIT FFPE · Pathwork Diagnostics, Inc. · May 17, 2012
K092967 — PATHWORK TISSUE OF ORIGIN TEST KIT-FFPE (ORIGIN TEST KIT-FFPE · Pathwork Diagnostics · Jun 8, 2010

Submission Summary (Full Text)

{0}------------------------------------------------ K103112 Image /page/0/Picture/1 description: The image shows the Affymetrix logo, which includes the company name in a stylized font and a graphic element above it. Below the logo, the text "Gene Profiling Reagents Premarket Notification" is displayed. The text is in a smaller font size compared to the company name. April 28, 2011 ### Summary of Safety and Effectiveness MAY - 4 2011 l. Submitter Information - 21 CFR 807.92(a)(1): Submitter: Affymetrix, Inc. 3420 Central Expressway Santa Clara, CA 95051 Establishment Registration No: 3003314809 ' Contact: Phone: Fax: E-mail: Chief Medical Officer, Affymetrix : Phone: 408-731-5967 Fax: 408-731-5755 E-mail: Rick_Hockett@Affymetrix.com Rick Hockett Regulatory Contact: Maureen Mende MyRAQA, Inc. 3 Lagoon Drive, Suite 280 Redwood Shores, CA 94065 650-730-5020 650-730-5005 Maureen@myraqa.com April 17, 2011 Date Prepared: # II. Name of Device and Classification - 21 CFR 807.92(a)(2): Affymetrix Gene Profiling Reagents Name: Class II Classification: OVA Product Code: AFFYMETRIX, INC. {1}------------------------------------------------ Image /page/1/Picture/0 description: The image shows the Affymetrix logo, which includes a stylized DNA double helix and the company name in bold, sans-serif font. Below the logo, the text "Gene Profiling Reagents Premarket Notification" is displayed in a smaller, regular font. The text indicates that the image is related to the regulatory submission of gene profiling reagents by Affymetrix. ### III. Predicate Device - 21 CFR 807.92(a)(3): Affymetrix GeneChip® Microarray Predicate Device: Instrumentation System ## IV. Device Description - 21 CFR 807.92(a)(4): The Affymetrix® Gene Profiling Reagents were designed for in vitro diagnostic use as an accessory to the GeneChip® MicroArray Instrumentation System. Affymetrix® Gene Profiling Reagents are intended for the preparation of labeled complementary RNA target from purified total RNA from fresh or frozen clinical tissue specimens for hybridization to Affymetrix® GeneChip® microarrays and the measurement of fluorescence signals of labeled RNA target using the Affymetrix GeneChip microarray instrumentation system. Intended for use with separately FDA-cleared Affymetrix GeneChip microarray assays specifying the use of the Affymetrix Gene Profiling Reagents. The Affymetrix Gene Profiling Reagents consist of three kits. Kit 1 is the RNA Control Kit consisting of Poly-A Control and Dilution Buffer. These reagents are designed to provide exogenous positive controls to monitor the entire target labeling process. The Poly-A Control and Dilution Buffer are provided with the kit to prepare the appropriate serial dilutions. After the appropriate dilution of the Poly-A Control, they are added to the total RNA and then amplified and labeled together. Examining the hybridization intensities of these controls on the array helps to monitor the amplification and labeling processes. Kit 2 is comprised of the Transcript Synthesis and Labeling Kits A and B and includes enzyme mixes, labeling reagent, reaction buffers and purification reagents for the preparation of the {2}------------------------------------------------ labeled cRNA target. Kit 2 is optimized specifically for producing amplified and biotinylated cRNA targets to hybridize to arrays for expression analysis. Kit 3 is comprised of Transcript Detection Kits A, B and C and includes all of the reagents to perform fragmentation of the labeled cRNA target, prepare the hybridization cocktail (including Oligo B2 and hybridization controls) and process the arrays in the Affymetrix Fluidics Station 450. The arrays are then ready to be scanned by the Affymetrix GeneChip Scanner. # V. Intended Use/Indications for Use - 21 CFR 807.92(a)(5): Affymetrix® Gene Profiling Reagents are intended for the preparation of labeled complementary RNA target from purified total RNA from fresh or frozen clinical tissue specimens for hybridization to Affymetrix® GeneChip® microarrays and the measurement of fluorescence signals of labeled RNA target using the Affymetrix GeneChip microarray instrumentation system. # Special Conditions For Use Statement(s): Intended for use with separately FDA-cleared Affymetrix GeneChip microarray assays specifying the use of the Affymetrix Gene Profiling Reagents. # VI. Performance Data - 21 CFR 807.92(b): - A. Non-Clinical Test Summaries 21 CFR 807.92(b)(1): - i. Analytical Performance: - 1. Precision/Reproducibility - To demonstrate reproducibility studies were conducted in which three lots of Gene Profiling Reagents were tested AFFYMETRIX, INC. {3}------------------------------------------------ using 100 ng and 1000 ng of MAQC A and B total RNAs in quadruplicate by three different operators. Three lots of Pathwork® Expression 3'-Amplification One-Cycle Target Reagents were tested using 1000 ng of MAQC A and B total RNAs in quadruplicate by three different operators for comparison. In addition, one lot of the Gene Profiling Reagents was tested using 100 ng and 1000 ng of MAQC A and B total RNAs in quadruplicate. One lot of the One-Cycle Reagent Kit was tested using 1000 ng of MAQC A and B total RNAs in quadruplicate for comparison. The testing was repeated on three different days. The median probeset signal %CV from detected probesets was calculated both between lots and between days within a lot and is reported in Table 6-1 (a - d), The acceptance criterion of %CV less than 20% was met for all combinations. ### Table 6-1 | a - %CV between days within a lot for MAQC A | | | | |----------------------------------------------|--|--|--| |----------------------------------------------|--|--|--| | Data Sets | One-Cycle Days 1, 2 and 3 MAQC A | Gene Profiling 1000 ng Days 1, 2 and 3 MAOC A | Gene Profiling 100 ng Days 1, 2 and 3 MAQC A | |------------|----------------------------------------|--------------------------------------------------------|-------------------------------------------------------| | Median CV% | 7.97 % | 7.17 % | 7.03 % | ### b - %CV between days within a lot for MAQC B | Data Sets | One-Cycle Days 1, 2 and 3 MAQC B | Gene Profiling 1000 ng Days 1, 2 and 3 MAQC B | Gene Profiling 100 ng Days 1, 2 and 3 MAQC B | |------------|----------------------------------------|--------------------------------------------------------|-------------------------------------------------------| | Median CV% | 7.68 % | 7.24% | 9.33 % | #### c - %CV between lots for MAQC A | Data Sets | Gene Profiling | Gene Profiling | |----------------------------------------|--------------------------------------|-------------------------------------| | One-Cycle Lots 1, 2 and 3 MAQC A | 1000 ng Lots 1, 2 and 3 MAQC A | 100 ng Lots 1, 2 and 3 MAQC A | | Median CV% 8.70 % | 9.54 % | 8.74 % | {4}------------------------------------------------ | d - %CV between lots for MAQC B | | | | |---------------------------------|----------------------------------------|--------------------------------------------------------|--------------------------------------------------------| | Data Sets | One-Cycle Lots 1, 2 and 3 MAQC B | Gene Profiling 1000 ng Lots 1, 2 and 3 MAQC B | Gene Profiling - 100 ng Lots 1,2 and 3 MAQC B | | Median CV% | 9.52 % | 9.93 % | 11.72 % | # 2. Repeatability To demonstrate repeatability, the samples described in the Reproducibility section of this summary were used to calculate the median probeset signal %CV from detected probesets for the replicates. Table 6-2 (a - f) shows the results for all sets of replicates using the Gene Profiling Reagents and the One-Cycle Reagent Kits. The acceptance criterion for %CV less than 10% for Repeatability was met for all conditions. ### Table 6-2 a - %CV for the replicates of 3 lots of the One-Cycle Reagent Kit, and one lot tested on 3 different days using 1000 ng of MAQC A. | Data Sets | Lot1 Day1 One-Cycle MAQC A | Lot1 Day2 One-Cycle MAQC A | Lot1 Day3 One-Cycle MAQC A | Lot2 Day1 One-Cycle MAQC A | Lot3 Day1 One-Cycle MAQC A | |------------|----------------------------------|----------------------------------|----------------------------------|----------------------------------|----------------------------------| | Median CV% | 5.06% | 4.55% | 4.85% | 3.67% | 4.30% | b - %CV for the replicates of 3 lots of the Gene Profiling Reagents, and one lot tested on 3 different days using 100 ng of MAQC A. | Data Sets | Lot1 | Lot2 | Lot3 | Lot3 | Lot3 | |------------|--------|--------|--------|--------|--------| | | 100ng | 100ng | 100ng | 100ng | 100ng | | | Day1 | Day1 | Day1 | Day2 | Day3 - | | | MAOC A | MAQC A | MAQC A | MAQC A | MAOC A | | Median CV% | 5.31% | 5.81% | 5.41% | 4.24% | 4.04% | {5}------------------------------------------------ Image /page/5/Picture/0 description: The image shows the Affymetrix logo, which includes the company name and a symbol resembling a DNA strand made of squares. Below the logo, the text "Gene Profiling Reagents Premarket Notification" is displayed. The text indicates that the image is related to the premarket notification of gene profiling reagents produced by Affymetrix. c - %CV for the replicates of 3 lots of the Gene Profiling Reagents, and one lot tested on 3 different days using 1000 ng of MAQC A. | Data Sets | Lot1 | Lot2 | . Lot3 | Lot3 | Lot3 | |------------|--------|--------|--------|--------|--------| | | 1000ng | 1000ng | 1000ng | 1000ng | 1000ng | | | Day1 - | Day1 - | Day1 - | Day2 - | Day3 - | | | MAQCA | MAQCA | MAQCA | MAQCA | MAQCA | | Median CV% | 5.5% | 4.38% | 5.88% | 4.54% | 5.44% | d - %CV for the replicates of 3 lots of the One-Cycle Reagent Kit, and one lot tested on 3 different days using 1000 ng of MAQC B. | Data Sets | Lot1 Day1 One-Cycle MAQC B | Lot1 Day2 One-Cycle MAQCB | Lot1 Day3 One-Cycle MAQC B | Lot2 Day1 One-Cycle MAQC B | Lot3 Day1 One-Cycle MAQC B | |------------|----------------------------------|---------------------------------|----------------------------------|----------------------------------|----------------------------------| | Median CV% | 4.57% | 4.11% | 4.35% | 4.88% | 4.64% | e - %CV for the replicates of 3 lots of the Gene Profiling Reagents, and one lot tested on 3 different days using 100 ng of MAQC B. | Data Sets | Lot1 100ng Day1 MAQC B | Lot2 100ng Day1 MAQC B | Lot3 100ng Day1 MAQC B | Lot3 100ng Day2 MAQC B | Lot3 100ng Day3 MAQC B | |------------|---------------------------------|---------------------------------|---------------------------------|---------------------------------|---------------------------------| | Median CV% | 8.77% | 4.42% | 5.15% | 5.46% | 4.79% | f - %CV for the replicates of 3 lots of the Gene Profiling Reagents, and one lot tested on 3 different days using 1000 ng of MAQC B. | Data Sets | Lot1 1000ng Day1 MAQCB | Lot2 1000ng Day1 MAQCB | Lot3 1000ng Day1 MAQCB | Lot3 1000ng Day2 MAQCB | Lot3 1000ng Day3 MAQCB | |------------|---------------------------------|---------------------------------|---------------------------------|---------------------------------|---------------------------------| | Median CV% | 5.74% | 5.33% | 4.23% | 4.37% | 5.64% | Repeatability was also demonstrated in the testing conducted at two external sites where eight replicates using 100 ng and 1000 ng of MAQC A and B total RNAs in batches of a minimum of 8 samples were tested. The median probeset signal %CV from detected probesets was calculated for the replicates and the acceptance criteria of % CV of < 10% was met for both sites. {6}------------------------------------------------ #### 3. Input Total RNA The range for the amount of starting material to be used with the Gene Profiling Reagents was determined to be between 100 ng to 1000 ng (1ug) of total RNA. The reagents were tested in both internal and external studies using total RNA at the minimum and maximum amount of the range of input total RNA. The testing demonstrated the reagents performed as expected using 100 ng and 1000 ng of input total RNA and the amount of cRNA produced was sufficient for the hybridization of one microarray (≥ 20 µg). The clinical study which utilized the Pathwork Tissue of Origin Test - Frozen used 200 ng of total RNA as the starting material. When the reagents were tested with 200 ng, the amount of cRNA produced was sufficient for the hybridization of one Pathchip™ microarray (≥ 15μg). #### 4. cRNA Yield To demonstrate cRNA yield of the Gene Profiling Reagents testing was conducted internally by Affymetrix and at two external sites as part of the Design Validation. The internal testing included 100 ng of total RNA from ten commercially available human tissues run in triplicate using the Transcript Synthesis and Labeling Kit (Kit 2). The test assessed the ability of the kit to vield ≥ 20 µg cRNA for greater than 90% of the total RNA samples tested and a cRNA concentration of ≥0.625 µg/µL. 100% (30/30) of the samples tested yielded greater than ≥ 20 µg cRNA and a cRNA concentration ≥0.625 µg/µL. Data is provided in Table 6-3. The testing conducted at the two external sites included eight replicates using 100 ng and 1000 ng of MAQC A and MAQC B total RNAs in batches of a minimum of 8 samples. AFFYMETRIX, INC. {7}------------------------------------------------ The acceptance criterion for this study was cRNA yield of ≥96 % of samples prepared must produce > 20 µg cRNA and cRNA concentration ≥0.625 µg/µL. 'All 32 samples (100%) at both sites achieved yields of ≥ 20 µg cRNA and cRNA concentration of ≥0.625 µg/µL. | | cRNA Concentration | Adjusted cRNA yields | Average cRNA yields | |---------------------------------|--------------------------------|---------------------------------|--------------------------------| | Sample ID | μg/μL | (μg) | (μg) | | Kidney Total RNA_R1 | 2.250 | 69.6 | | | Kidney Total RNA_R2 | 2.112 | 65.4 | 67.1 | | Kidney Total RNA_R3 | 2.141 | 66.3 | | | Pancreas Total RNA_R1 | 1.796 | 55.6 | | | Pancreas Total RNA_R2 | 1.792 | 55.5 | 54.2 | | Pancreas Total RNA_R3 | 1.664 | 51.5 | | | Heart Total RNA_R1 | 2.241 | 69.4 | | | Heart Total RNA_R2 | 2.338 | 72.4 | 69.2 | | Heart Total RNA_R3 | 2.126 | 65.8 | | | MAQCB Total RNA_R1 | 2.443 | 75.6 | | | MAQCB Total RNA_R2 | 2.441 | 75.6 | 74.4 | | MAQCB Total RNA_R3 | 3.009 | 72.1 | | | Liver Total RNA_R1 | 1.985 | 61.4 | | | Liver Total RNA_R2 | 1.843 | 57.0 | 57.1 | | Liver Total RNA_R3 | 1.705 | 52.8 | | | Breast Total RNA_R1 | 2.161 | 66.9 | | | Breast Total RNA_R2 | 1.844 | 58.9 | 62.2 | | Breast Total RNA_R3 | 1.965 | 60.8 | | | Testicle Total RNA_R1 | 2.207 | 68.3 | | | Testicle Total RNA_R2 | 2.268 | 70.2 | 69.5 | | Testicle Total RNA_R3 | 2.261 | 70.0 | | | HeLa Total RNA_R1 | 2.401 | 74.3 | | | HeLa Total RNA_R2 | 2.277 | 72.8 | 73.7 | | HeLa Total RNA_R3 | 2.390 | 74.0 | | | Thyroid Total RNA_R1 | 1.689 | 52.2 | | | Thyroid Total RNA_R2 | 1.562 | 48.3 | 50.5 | | Thyroid Total RNA_R3 | 1.644 | 50.8 | | | Skeletal Muscle Total RNA | | | 62.3 | | Sample ID | cRNA Concentration μg/μL | Adjusted cRNA yields (μg) | Average cRNA yields (μg) | | Skeletal Muscle Total RNA R2 | 2.043 | 63.2 | | | Skeletal Muscle Total RNA R3 | 1.931 | 59.8 | | #### Table 6-3 AFFYMETRIX, INC. {8}------------------------------------------------ Image /page/8/Picture/0 description: The image shows the logo for Affymetrix. The logo consists of the word "Affymetrix" in a sans-serif font, with a stylized double helix symbol above the letters "ff" and a series of black squares to the right of the helix. The squares are arranged in a pattern that resembles a grid or a barcode. The logo is simple and modern, and it is likely used to represent the company's focus on genomics and biotechnology. ## Gene Profiling Reagents Premarket Notification April 28, 2011 # 5. Linearity/Assay Reportable Range Not Applicable. Traceability, Stability Expected Values (controls, 6. calibrators or methods) # a. Performance of the Controls Performance of the Poly-A Control, Oligo B2 and hybridization controls were evaluated by testing conducted internally at Affymetrix and at two external sites as part of Design Validation. The internal testing to evaluate the performance of the Poly-A Control, Oligo B2 and hybridization controls included three lots of Gene Profiling Reagents that were tested using 100 ng and 1000 ng of MAQC A and B total RNAs and tested in quadruplicate. The testing conducted at the two external sites included eight replicates using 100 ng and 1000 ng of MAQC A and B total RNAs in batches of a minimum of 8 samples. In both studies .CEL files were generated by successful automatic gridding for all samples tested demonstrating that the Oligo B2 performed as expected. The analysis of the Poly-A Control showed the 3' AFFX-r2-Bs probe sets {9}------------------------------------------------ Image /page/9/Picture/1 description: The image shows the Affymetrix logo and the text "Gene Profiling Reagents Premarket Notification". The Affymetrix logo is a stylized double helix with a series of squares above it. The text is in a simple, sans-serif font, with the company name in a larger size than the rest of the text. for all three spikes (lys, phe and dap) were present. Signal intensities and r-squared values for the correlation of the 3' AFFX-r2-Bs signal intensities with the relative ratio for each spike, followed the relative concentration in the Poly-A Control mixture: lys < phe< dap and the rsquared values met the acceptance criteria of ≥ 0.900 for both studies. The 3' AFFX-r2 probeset for bioB was called present for all samples in both studies. The signal intensity for the hybridization controls (bioB, bioC, bioD and cre) followed the relative concentration in the mixture: bioB < bioC < bioD < cre for all samples tested in both studies. 100 % (80/80) of the samples passed the acceptance criteria for the performance of the controls in the internal study and 100% (64/64) in the external study. In addition the performance of the controls was evaluated in the clinical studies. 45 total RNA samples were tested at each of the 3 clinical sites and 100% (135/135) passed the acceptance criteria for the Poly-A Control, Oligo B2 and hybridization controls. 16 total RNA samples from 16 frozen tissues were tested at one site and 100 % (32/32) passed the acceptance criteria for performance of the controls. ## b. Stability Studies Real-time stability studies are being conducted on the RNA Control Kit, the Transcript Synthesis and Labeling Kit and the Transcript Detection Kit. Based on the results of these studies, a shelf life from the date of manufacturing has been established for each of the Gene AFFYMETRIX, INC. {10}------------------------------------------------ Image /page/10/Picture/1 description: The image shows the Affymetrix logo, which includes the company name in a stylized font and a DNA-like graphic. Below the logo, the text "Gene Profiling Reagents Premarket Notification" is displayed. The text is left-aligned and appears to be part of a document or presentation header. The overall image is clean and professional, likely representing a formal announcement or document related to gene profiling reagents. Profiling Reagents. On-going stability studies are being conducted according to established procedures. Open-vial stability studies have been completed for all reagent kits. Freeze-thaw stability studies have also been completed for the applicable reagents. The results of these studies support the freeze-thaw and open-vial stability recommended in the package inserts for the Gene Profiling Reagents. # c. Shipping Studies Shipping studies under actual and simulated conditions have been conducted to confirm that the products have been designed, manufactured and packaged in such a way that they maintain transport storage conditions and packaging integrity. Additional shipping studies are being conducted to confirm that product performance is not affected under recommended storage and transportation conditions. ## 7. Detection Limit Not applicable. ## 8. Assay Cut-Off Not Applicable. ## VII. Clinical Study Summary - 21 CFR 807.92(b)(2): ## A. Comparison Studies: i. Method Comparison: AFFYMETRIX, INC. {11}------------------------------------------------ The performance of the Affymetrix Gene Profiling Reagents was demonstrated utilizing a previously cleared expression assay on the Affymetrix GeneChip Microarray Instrumentation System. A two part prospective clinical study was conducted demonstrating performance of the Affymetrix Gene Profiling Reagents using the Pathwork® Tissue of Origin-Frozen Test (k080896) and the Affymetrix GeneChip® MicroArray Instrumentation System cleared for RNA analysis (k080995). Both studies evaluated the performance of the Pathwork® Tissue of Origin-Frozen Test with the Gene Profiling Reagents compared to performance of the assay demonstrated in K080896 using the One-Cycle Reagent Kit. The first part of the prospective clinical study was conducted at 1 external site and included testing of 16 frozen tissues from RNA extraction to hybridization to the Pathchip 100 microarray and scanning of the microarray on the Affymetrix GCS3000 Dx Instrument System. The 16 tissues, representing each of the 15 tumor types included in the Pathwork Tissue of Origin - Frozen cleared intended use, were tested twice using each of the Affymetrix Gene Profiling Reagents and the One-Cycle Reagent Kit included in Pathwork's K080896. The site was blinded to the available diagnosis of each tissue specimen. The resulting .CEL files were sent to Pathwork Diagnostics for analysis using proprietary Pathwork Tissue of Origin-Frozen algorithm. Pathwork Diagnostics was also blinded to the tissue sources. The second part of the prospective clinical study was conducted at 3 clinical sites. The clinical study included the preparation of 45 total RNA samples using the Affymetrix Gene Profiling Reagents, with hybridization to the Pathchip™ microarray and scanning of the microarray on the Affymetrix GCS3000 Dx Instrument System. The resulting .CEL files were sent to Pathwork Diagnostics for analysis using proprietary AFFYMETRIX, INC. ` {12}------------------------------------------------ Pathwork Tissue of Origin-Frozen algorithm. The clinical sites and Pathwork Diagnostics were both blinded to the available diagnosis for each specimen. The study included 39 samples that had been tested using One-Cycle Kit reagents in the Pathwork Reproducibility study, as discussed in K080896 and 6 samples that had previously been tested with One-Cycle Kit reagents at one of the test sites. Results using One-Cycle Kit reagents were available from two sites for the 39 samples and 1 site for the 6 additional samples. The acceptance criteria for both prospective studies were for the specimen processing specifications defined in the protocol to be met and the overall success rate for generating Tissue of Origin Test - Frozen results to be greater than 90%. Lastly, when data from these two studies were combined, the observed percent correct when using Gene Profiling Reagents could be no different from expected percent correct when using One-Cycle Reagent Kit (α = 0.05). Table 6-4 below shows the numbers of samples used in this comparison of One-Cycle Reagents and Gene Profiling Reagents. | Protocol (unique samples) | Gene Profiling Reagents Reactions | | | One-Cycle Kit Reactions | | |------------------------------|--------------------------------------|--------|--------|----------------------------|--------| | | | | | | | | | Site 1 | Site 2 | Site 3 | Site 1 | Site 4 | | Total RNA Study (n = 45) | 45 | 45 | 45 | 45 | 39 | | Tissue Study (n = 16) | 32 | | | 32 | | | Total Reactions by Site | 77 | 45 | 45 | 77 | 39 | | Total Reactions by Reagent | 167 | | | 116 | | TABLE 6-4 DISTRIBUTION OF SAMPLES USED FOR ANALYSIS {13}------------------------------------------------ In an integrated clinical analysis the performance of the Affymetrix Gene Profiling Reagents intended for in vitro diagnostic use were compared to the One-Cycle Reagent Kit intended for research use only which were utilized by Pathwork Diagnostics in the 510(k) for the Tissue of Origin Test - Frozen (K080896). The acceptance criteria for this analysis were for the observed percent correct when using IVD reagents should be no different from expected percent correct when using One-Cycle Kit reagents (α = 0.05). The results from this integrated analysis showed that the observed percent correct when using the Affymetrix Gene Profiling Reagents was no different (α = 0.05) from the expected percent correct when using the One-Cycle Reagent Kit (95% bootstrap confidence limits are given by (-5.9%, 3.4%)). The acceptance criteria were achieved in support of substantial equivalence for the IVD and One-Cycle Kit reagents. The combined data from these studies demonstrated the performance of the TOO assay was comparable with both sets of reagents. ii. Matrix Comparison: Not Applicable. iii. Clinical Sensitivity: Not Applicable. ### iv. Clinical Specificity: Not Applicable. v. Clinical Cut-Off: Not Applicable. AFFYMETRIX, INC. {14}------------------------------------------------ # vi. Expected Values/Reference Range: Not Applicable. - vii. Other Clinical Supportive Data: Not Applicable. # VIII. Conclusion The submitted information in this premarket notification is complete and supports a substantial equivalence decision for the Gene Profiling Reagents. {15}------------------------------------------------ Image /page/15/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an emblem featuring a stylized depiction of an eagle or bird-like figure. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Affymetrix, Inc. c/o Maureen Mende, RAC, MBA Senior Director and Regulatory Consultant MyRAQA, Inc. 3 Lagoon Drive. Suite 280 Redwood Shores, CA 94065 MAY - 4 2011 Re: k103112 Trade/Device Name: Affymetrix® Gene Profiling Reagents Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation for Clinical Multiplex Test Systems Regulatory Class: Class II Product Code: OVA Dated: April 22, 2011 Received: April 25, 2011 Dear Ms. Mende: 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 (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice {16}------------------------------------------------ Page 2 – Ms. Maureen Mende requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your 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 toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrl/industry/support/index.html. Sincerely yours. Maurice M. Charn 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 {17}------------------------------------------------ 510(k) Number (if known): k103112 Device Name: Affymetrix® Gene Profiling Reagents Indications for Use: Affymetrix® Gene Profiling Reagents are intended for the preparation of labeled complementary RNA target from purified total RNA from fresh or frozen clinical tissue specimens for hybridization to Affymetrix GeneChip® microarrays and the measurement of fluorescence signals of labeled RNA target using the Affymetrix GeneChip® Microarray Instrumentation System. Intended for use with separately FDA-cleared Affymetrix GeneChip microarray assays specifying the use of the Affymetrix Gene Profiling Reagents. Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR Over-The-Counter Use _ (21 CFR 801 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) Reena Philip Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) _k103112 ______________________________________________________________________________________________________________________________________________________________ Page __ of __ ]