NEOPAC SOFTWARE, 3007 DIGITAL PHOTOMETER/FLUOROMETER MODEL NA, 307 AND 350D

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k101392 B. Purpose for Submission: New Device (SPOTCHECK Flow Analyzer) and three Modified Devices (SPOTCHECK Analyzer with three different detector combinations) for use with marketed reagents. C. Measurand: Uridyltransferase, Total Galactose, Phenylalanine, Glucose-6-Phosphate Dehydrogenase, Tyrosine and Biotinidase D. Type of Test: Quantitative fluorometric and/or photometric enzymatic assays E. Applicant: Astoria-Pacific, Inc. F. Proprietary and Established Names: Astoria-Pacific SPOTCHECK Flow Astoria-Pacific SPOTCHECK Analyzer with NeoPac, Fluorometer and Photometer Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Photometer Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Fluorometer G. Regulatory Information: | Device Classification Name | Device Classification | Regulation Number | Product Code | Panel | | --- | --- | --- | --- | --- | | Continuous flow sequential multiple chemistry analyzer for clinical use | Class I | 21 CFR § 862.2150 | JJC | Clinical Chemistry (75) | | Uridyltransferase (GALT) | Class II | 21 CFR § 862.1315 | KQP | Clinical Chemistry (75) | | Total Galactose | Class I, reserved | 21 CFR § 862.1310 | JIA | Clinical Chemistry (75) | | Phenylalanine | Class II | 21 CFR § 862.1555 | JNB | Clinical Chemistry (75) | | Glucose-6-Phosphate Dehydrogenase (G6PD) | Class II | 21 CFR § 864.7360 | JBL | Hematology (81) | | Tyrosine | Class I, reserved | 21 CFR § 862.1730 | CDR | Clinical Chemistry (75) | | Biotinidase | Class II | 21 CFR § 862.1118 | NAK | Clinical Chemistry (75) | {1} H. Intended Use: 1. Intended use(s): See indication(s) for use below. 2. Indication(s) for use: **Astoria-Pacific SPOTCHECK Flow** The SPOTCHECK Flow system is used for *in vitro* diagnostic newborn screening in conjunction with Astoria-Pacific’s SPOTCHECK family of reagent kits. The specific inborn errors in metabolism screened for (bold), and the respective Astoria-Pacific dried blood spot assays are: - Galactose-1-phosphate uridyltransferase (GALT) enzyme deficiency (Galactosemia); SPOTCHECK Uridyltransferase 50 Hour Reagent Kit - Galactose and galactose-1-phosphate, elevated total galactose concentration (Galactosemia); SPOTCHECK Total Galactose 50 Hour Reagent Kit - Phenylalanine, elevated concentration (Phenylketonuria); SPOTCHECK Phenylalanine 50 Hour Reagent Kit - Glucose-6-phosphate dehydrogenase enzyme deficiency; SPOTCHECK G6PD 50 Hour Reagent Kit - Tyrosine, elevated concentration (Tyrosinemia); SPOTCHECK Tyrosine 50 Hour Reagent Kit The system is intended for screening use only and is not intended for monitoring purposes. **Astoria-Pacific SPOTCHECK Analyzer with NeoPac, Fluorometer and Photometer** The SPOTCHECK Flow system is used for *in vitro* diagnostic newborn screening in conjunction with Astoria-Pacific’s SPOTCHECK family of reagent kits. The specific inborn errors in metabolism screened for (bold), and the respective Astoria-Pacific dried blood spot assays are: - Galactose-1-phosphate uridyltransferase (GALT) enzyme deficiency (Galactosemia); SPOTCHECK Uridyltransferase 50 Hour Reagent Kit - Biotinidase enzyme deficiency; SPOTCHECK Biotinidase 50 Hour Reagent Kit - Galactose and galactose-1-phosphate, elevated total Galactose concentration (Galactosemia); SPOTCHECK Total Galactose 50 Hour Reagent Kit {2} - Phenylalanine, elevated concentration (Phenylketonuria); SPOTCHECK Phenylalanine 50 Hour Reagent Kit - Glucose-6-phosphate dehydrogenase enzyme deficiency; SPOTCHECK G6PD 50 Hour Reagent Kit - Tyrosine, elevated concentration (Tyrosinemia); SPOTCHECK Tyrosine 50 Hour Reagent Kit The system is intended for screening use only and is not intended for monitoring purposes. ## Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Photometer The SPOTCHECK Analyzer system is used for in vitro diagnostic newborn screening in conjunction with Astoria-Pacific’s SPOTCHECK family of reagent kits. The specific inborn error in metabolism screened for (bold), and the respective Astoria-Pacific dried blood spot assay are: - Biotinidase enzyme deficiency; SPOTCHECK Biotinidase 50 Hour Reagent Kit The system is intended for screening use only and is not intended for monitoring purposes. ## Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Fluorometer The SPOTCHECK Analyzer system is used for in vitro diagnostic newborn screening in conjunction with Astoria-Pacific’s SPOTCHECK family of reagent kits. The specific inborn errors in metabolism screened for (bold), and the respective Astoria-Pacific dried blood spot assays are: - Galactose-1-phosphate uridyltransferase (GALT) enzyme deficiency (Galactosemia); SPOTCHECK Uridyltransferase 50 Hour Reagent Kit - Galactose and galactose-1-phosphate, elevated total galactose concentration (Galactosemia); SPOTCHECK Total Galactose 50 Hour Reagent Kit - Phenylalanine, elevated concentration (Phenylketonuria); SPOTCHECK Phenylalanine 50 Hour Reagent Kit - Glucose-6-phosphate dehydrogenase enzyme deficiency; SPOTCHECK G6PD 50 Hour Reagent Kit - Tyrosine, elevated concentration (Tyrosinemia); SPOTCHECK Tyrosine 50 Hour Reagent Kit {3} The system is intended for screening use only and is not intended for monitoring purposes. 3. Special conditions for use statement(s): This device is intended for prescription use only. As with any other in vitro screening test, the data obtained using these screening kits should be used as an aid to other medically established procedures and results interpreted in conjunction with other clinical data available to the clinician. A diagnostic procedure should be used to confirm a diagnosis. 4. Special instrument requirements: Five neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) are for use on the SPOTCHECK FLOW analyzer. Six neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase, Glucose-6-Phosphate Dehydrogenase and Biotinidase) are for use on the SPOTCHECK analyzer. I. Device Description: One new device and three modified devices are described in this bundled submission. The new device (SPOTCHECK Flow) is a continuous flow analyzer consisting of a new detector (307 Digital Photometer/Fluorometer Detector) which does not require an Interface Unit for communication between detector and software, new software (NeoPac Software), computer, autosampler, peristaltic pump, assay cartridge and base module with power. The three modified devices are modifications to previously cleared continuous flow analyzers (SPOTCHECK Analyzers; k883020 and k851542) that consist of a detector (315 and/or 321 Detector), a new interface unit (350D Interface Unit), new software (NeoPac Software), computer, autosampler, peristaltic pump, assay cartridge and base module with power. NeoPac Software is new software update allowing compatibility with Microsoft based computers while the 350D Interface Unit is an updated component that allows communication between the 315 or 321 detector and new software. The 307 Digital Photometer/Fluorometer Detector is a new detector developed as an alternative to using the interface unit and 315/321 detectors. It is intended to be used with the new NeoPac software. The 307 Detector consists of a base module with up to 4 detection channels (not including a reference channel); each channel is either a fluorometer module or a photometric subassembly. The only significant differences between the new detector (307 Detector) and the original detectors (315 and 321 Detectors) are the use of LED light source for excitation (fluorometry) and a bandpass filter instead of a monochromator (photometry). NeoPac Software replaces Astoria-Pacific’s original software package, FASPac. It is 4 {4} intended for use with new components and Microsoft operating systems currently on the market. The software facilitates similar instrument controls as FASPac, while adding new minor functionality. The 350D Interface Unit facilitates electronic communication between NeoPac software and the detector(s), autosampler and pump. Each unit has 7 analog detector inputs on the front panel, a power cord connection, and cable connections for a PC, autosampler and pump. Its sole purpose is to provide a mechanism for commands and data to flow to and from the software and system components. The 350D Interface Unit is modified from the predicate device (350 Interface Unit) in order to communicate with new software. # J. Substantial Equivalence Information: | Predicate device name | Predicate 510(k) number | | --- | --- | | RFA300 Rapid Flow Analyzer w/ Computer (later renamed to SPOTCHECK Analyzer) | k851542 | | RFA300 Rapid Flow Analyzer w/ Computer (later renamed to SPOTCHECK Analyzer) | k883020 | {5} Comparison with predicates: | Similarities and Differences | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Item | New Device | Modified Device 1 | Modified Device 2 | Modified Device 3 | k883020 | k851542 | | Product Name | SPOTCHECK Flow | SPOTCHECK Analyzer with NeoPac, Photometer, and Fluorometer | SPOTCHECK Analyzer with NeoPac and Photometer | SPOTCHECK Analyzer with NeoPac and Fluorometer | SPOTCHECK Analyzer | SPOTCHECK Analyzer | | Intended Use | Is used for in vitro diagnostic newborn screening in conjunction with Astoria-Pacific's SPOTCHECK family of reagent kits | Same | Same | Same | Same | Same | | Software Package | NeoPac | NeoPac | NeoPac | NeoPac | FASPac | FASPac | | Interface Unit | None | 350D | 350D | 350D | 350 | 350 | | Detector | 307 | 315 and 321 | 315 | 321 | 321 | 315 | | Detection Method | Fluorometric | Fluorometric and Photometric | Photometric | Fluorometric | Fluorometric | Photometric | | Light Source | LED and Tungsten-halogen | Quartz-halogen and Tungsten-halogen | Tungsten-halogen | Quartz-halogen | Quartz-halogen | Tungsten-halogen | | Other system components | Same | Same | Same | Same | Same | Computer w/ software, autosampler, peristaltic pump, base module w/ power and assay cartridge | | Neonatal Screening Assays run on Device | Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase G6PD | Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase G6PD Biotinidase | Biotinidase | Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase G6PD | Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase G6PD | Biotinidase | K. Standard/Guidance Document Referenced (if applicable): CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods. CLSI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples. CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation L. Test Principle: Continuous flow analysis technology can be considered automated bench chemistry in which {6} continuously flowing reagents are mixed with the sample, ultimately producing a detectable product that correlates to analyte concentration. Regardless of the test, a system consists of an autosampler, a pump for reagents and sample streams, a module where assay chemistry occurs, a detector (including flowcell), and an interface unit that facilitates communication with the software (providing the detector does not directly interface with a computer). Proper conditions for chemical reactions are controlled by using a variety of techniques such as specific reagent input timing, mixing, incubation at specific temperatures, and sample dialysis. As the reaction stream enters the detector's flowcell, the fluorescence or absorbance increase is simultaneously observed onscreen and recorded by the software. The software package is designed to recognize the increase and marks the sample peak, identifying it to a particular sample based on its arrival time. Calibration and results determination are also computed by the software. The new instrument uses an LED light source for analyte excitation during fluorometric analysis which does not affect the assay as the peak excitation wavelength remains unchanged. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: #### a. Precision/Reproducibility: The sponsor performed a precision study that is modified from the recommendations in CLSI Guideline EP5-A2; four or five days of precision studies were performed. Precision studies were conducted for five neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) on a single SPOTCHECK FLOW analyzer (new device) using a single reagent lot. The evaluation of precision for Total Galactose, Phenylalanine, Tyrosine and Uridyltransferase was conducted using adult dried blood spot samples spiked at different three different levels (generally; low, medium and high). Samples were analyzed 8 replicates per run, 1 run per day for 5 days (total of 40 replicates per sample). The precision study for Glucose-6-Phosphate Dehydrogenase used adult dried blood spot samples spiked at three different levels (low, medium and high), however the samples were analyzed over 4 days with 1 run per day for 3 days and 2 runs on one day (total of 40 replicates per sample). Summary of Precision Study Data | Assay | Sample | Number of Observations | Mean (mg/dL) | Within-run Variation (CV%) | Total Variation (CV%) | | --- | --- | --- | --- | --- | --- | | Total Galactose | 1 | 40 | 6.2 | 0.82 | 3.4 | | | 2 | 40 | 11.3 | 1.05 | 1.6 | | | 3 | 40 | 31.4 | 0.53 | 2.0 | | Phenylalanine | 1 | 40 | 2.0 | 0.70 | 3.3 | | | 2 | 40 | 4.5 | 0.63 | 2.3 | | | 3 | 40 | 15.3 | 0.42 | 1.1 | | Tyrosine | 1 | 40 | 1.8 | 1.99 | 4.3 | | | 2 | 40 | 7.7 | 0.79 | 2.4 | | | 3 | 40 | 18.5 | 0.96 | 4.2 | {7} 8 | Assay | Sample | Number of Observations | Mean (μM NADPH) | Within-run Variation (CV%) | Total Variation (CV%) | | --- | --- | --- | --- | --- | --- | | Uridyltransferase | 1 | 40 | 6.6 | 5.18 | 6.5 | | | 2 | 40 | 62.5 | 1.67 | 4.6 | | | 3 | 40 | 122.0 | 0.99 | 3.7 | | Glucose-6-Phosphate Dehydrogenase | 1 | 40 | 3.4 | 8.15 | 8.7 | | | 2 | 40 | 39.7 | 1.33 | 5.1 | | | 3 | 40 | 83.1 | 1.42 | 6.5 | b. Linearity/assay reportable range: The linearity of the individual assays (k990957, k970277, k970093, k894011 and k891070) was previously established. c. Traceability, Stability, Expected values (controls, calibrators, or methods): The traceability, stability and expected values of the individual assays (k990957, k970277, k970093, k894011 and k891070) were previously established. d. Detection limit: The Detection Limit studies were conducted for five neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) on the SPOTCHECK FLOW analyzer (new device). The study was conducted according to CLSI EP17-A. Adult whole dried blood samples were precisely spotted (not diluted) on filter paper and dried. Evaluation of the five neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) utilized 3 low-level samples analyzed over 3 days in batches of 20 low-level replicates and 20 blank replicates per run (for each method). Evaluation of Uridyltransferase utilized 2 low level samples analyzed over 3 days in batches of 20 low-level replicates and 20 blank replicates per run (1 low level sample was used in 2 of 3 runs, 40 replicates in total). Results were used to determine the sensitivity of the analytical system for each method. | Limit of Blank | | | | | | --- | --- | --- | --- | --- | | Assay | Number of Observations | Mean | Standard Deviation | LoB | | Total Galactose | 60 | -0.012 mg/dl | 0.064 | 0.092 mg/dl | | Phenylalanine | 60 | 0.013 mg/dl | 0.029 | 0.060 mg/dl | | Tyrosine | 60 | -0.019 mg/dl | 0.076 | 0.11 mg/dl | | Uridyltransferase | 60 | 0.48 μM NADPH | 0.59 | 1.5 μM NADPH | | Glucose-6-Phosphate Dehydrogenase | 60 | -0.44 μM NADPH | 0.34 | 0.12 μM NADPH | {8} | Limit of Detection and Limit of Quantitation | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Assay | Number of Observations | Number of Levels | Standard Deviation | Cβ | LoD | LoQ | | Total Galactose | 60 | 3 | 0.040 | 1.652 | 0.16 mg/dL | 0.16 mg/dL | | Phenylalanine | 60 | 3 | 0.027 | 1.652 | 0.10 mg/dL | 0.10 mg/dL | | Tyrosine | 60 | 3 | 0.049 | 1.652 | 0.19 mg/dL | 0.19 mg/dL | | Uridyltransferase | 60 | 2 | 0.77 | 1.652 | 2.7 μM NADPH | 2.7 μM NADPH | | Glucose-6-Phosphate Dehydrogenase | 60 | 3 | 0.34 | 1.652 | 0.7 μM NADPH | 0.7 μM NADPH | The detection limits for the three modified devices described in this submission are not affected by the modifications to the instrument. e. Analytical specificity: The analytical specificity of the individual assays (k990957, k970277, k970093, k894011 and k891070) was previously established. f. Assay cut-off: Not applicable. 2. Comparison studies: a. Method comparison with predicate device: Method Comparison studies were conducted for five neonatal screening assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) on the SPOTCHECK FLOW analyzer (new device). To demonstrate comparable performance between the new (307 Detector) and predicate detectors (321 Detector) on SPOTCHECK Flow analyzer, sequential measurements employing two different detection schemes (i.e. new and predicate detectors) were performed for five neonatal screening assays using neonatal dried blood spots, adult and control blood spot samples. The results of the method comparisons are summarized in the following table. {9} | Assay | Total Number of Samples | Number of Newborn Dried Bloodspots | Linear Regression | Correlation Coefficient (R2) | | --- | --- | --- | --- | --- | | Total Galactose | 107 | 91 | y = 0.99x - 0.83 | 0.99 | | Phenylalanine | 112 | 96 | y = 0.99x + 0.01 | 1.00 | | Tyrosine | 101 | 88 | y = 1.01x - 0.06 | 1.00 | | Uridyltransferase | 96 | 94 | y = 1.03x - 7.62 | 0.97 | | Glucose-6-Phosphate Dehydrogenase | 92 | 92 | y = 0.97x - 1.77 | 1.00 | b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Newborn screening using these assays (Total Galactose, Phenylalanine, Tyrosine, Uridyltransferase and Glucose-6-Phosphate Dehydrogenase) requires a decision of the screening policy, cut-off values and follow-up for each condition being screened for. In the labeling the sponsor makes the recommendation that the laboratory needs to establish its own cut-off values for each assay, which can be based on a percentile, or on the basis of a normal range depending on the condition being screened for. In the labeling the sponsor states that laboratories are to follow local requirements for follow-up testing. {10} 5. Expected values/Reference range: The expected values of the individual assays (k990957, k970277, k970093, k894011 and k891070) were previously established. In the labeling, the sponsor recommends that each laboratory establishes its own reference range for each assay from a representative sample population. N. Instrument Name: Astoria-Pacific SPOTCHECK Flow Astoria-Pacific SPOTCHECK Analyzer with NeoPac, Fluorometer and Photometer Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Photometer Astoria-Pacific SPOTCHECK Analyzer with NeoPac and Fluorometer O. System Descriptions: 1. Modes of Operation: Astoria-Pacific's SPOTCHECK analyzer uses neonatal patient blood samples dried on approved paper for its testing medium. Punched blood spots are eluted into extraction solution in individual wells of standard microplates. Up to 4 microplates are placed on a random access autosampler and patient identifiers are either imported or typed directly into NeoPac software's sample table. Once a run begins, samples are analyzed sequentially via continuous flow analysis and the data is handled, manipulated, and reported using the software. The software allows for samples to be added during a run, however because of the pre-analytical extraction process, this requires working with additional microplates. 2. Software: NeoPac software is capable of running on all of Microsoft operating systems currently on the market. Software capabilities include interfacing with laboratory management systems, using both import and export functions. The user primarily interfaces with the software by inputting sample identifiers and positions; monitoring detector response; starting and stopping analyses; exporting or printing reports; and reviewing calculated values for clinical-decision making purposes. Additional data management capabilities include ongoing trending for specific samples or quality control material. FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types: Yes ☐ X ☐ or No ☐ 3. Specimen Identification: Samples are identified in several ways: The user can manually input both sample identifiers and positions directly in the software's sample table (correlating to where dried blood spots are punched into the microplate). As samples are entered, by default NeoPac software will automatically add sample positions sequentially according to a microplate layout. Alternatively, sample positions can be imported along with sample identifiers from a spreadsheet or laboratory management system export file. This may or may not 11 {11} involve barcoding; however the software does not interface with barcodes directly. NeoPac software is flexible such that a combination of both methods is possible, allowing for the various levels of sample handling automation in clinical laboratories. 4. Specimen Sampling and Handling: Neonatal patient dried blood spots are punched (the size of the punch is dependent on the assay or number of assays) into 96-well filterplates and extracted with a specific eluent (dependent on the assay). After an extraction time specified in the assay's product insert, samples are filtered into clean microplates. The microplate containing each eluted sample is placed on the autosampler tray and individual wells are sampled sequentially correlating with their order of entry in NeoPac software. 5. Calibration: Calibration on the SPOTCHECK analyzer system is achieved using calibrators specific to the assay; this can be accomplished using the analyte or calibrators that mimic the analyte's response. NeoPac software applies the values entered by the user for the calibrators and, using regression analysis, generates a curve. This curve is used to calculate the results for all subsequent samples or quality control material. 6. Quality Control: Quality control samples, typically dried blood spots with specific or qualitative concentrations, are generally analyzed throughout a run to ensure that each assay continues to produce appropriately accurate results. In the labeling the sponsor provides recommendations for testing external quality control materials. P. Other Supportive Instrument Performance Characteristics Data Not Covered In the "Performance Characteristics" Section above: The software documentation for the modified and new device was reviewed and it supports that the device was developed under good software cycle processes. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 12