FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The devices described herein are intended to be used with Astoria-Pacific's SPOTCHECK family of neonatal screening reagent kits. Assays currently offered on the system included Uridyltransferase (GALT), Biotinidase**, Total Galactose, Phenylalanine, G6PD, and Tyrosine. They are intended for use by qualified clinical laboratory professionals.

** Astoria-Pacific is not currently seeking FDA-clearance for Biotinidase on the 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 UridyItransferase 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.

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 UridyItransferase 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
Phenylalanine, elevated concentration (Phenvlketonuria); 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.

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.

Galactose-1-phosphate uridyltransferase (GALT) enzyme deficiency (Galactosemia); SPOTCHECK UridyItransferase 50 Hour Reagent Kit
Galactose and galactose-1-phosphate, elevated total galactose concentration (Galactosemia); SPOTCHECK Total Galactose 50 Hour Reagent Kit
Phenylalanine, elevated concentration (Phenviketonuria); 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.

Device Description

The SPOTCHECK continuous flow analyzer consists of various devices that interact together to provide a complete in vitro diagnostic (IVD) instrument system for use with Astoria-Pacific's neonatal screening assays. The technology can be considered automated bench chemistry in which continuously flowing reagents are mixed with the sample, ultimately producing a detectable product that correlates to analyte concentration. Proper conditions for reactions are controlled by using a variety of techniques such as specific timing for reagent inputs, incubation at specific temperatures, and/or dialysis. Depending upon the particular IVD assay, system components may differ slightly. In each case however, 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.

The proposed modifications to the analyzer system components allow for 2 new unique system options; they are as follows:

1. 350D Interface Unit: The predicate interface unit used for communications between detectors and software has been updated to accommodate the new software*.
  OR
1. 307 Digital Photometer/Fluorometer: A new detector has been developed as an alternative to using the interface unit and predicate fluorometric detector. It is intended to be used with the new software*.
  AND
  *NeoPac: A new software package has been developed to replace outdated software. The 2 options listed above both depend on this software to complete the system.

Each new or modified component is briefly described below:
NeoPac Software: NeoPac is a newly developed software package designed to replace Astoria-Pacific's predicate software package. It is intended for use with new components and Microsoft® operating systems currently on the market. The software facilitates similar instrument controls as the predicate package, while adding minor but important functionality.

350D Interface Unit: The 350D 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 is modified from the predicate device (350 Interface Unit) in order to communicate with new software.

307 Digital Photometer/Fluorometer: The 307 detector is a newly developed detection platform intended to provide an alternative option to the interface unit and one or more detectors in the SPOTCHECK analyzer system. Aside from providing a state-of-the-art option for detection, its spatial requirements are significantly less than the predicate device. It can be manufactured with up to 4 unique photometric or fluorometric detection channels and an additional analog input (offering the ability to connect to a standalone detector). In conjunction with NeoPac software, it facilitates the communication of data and commands between a PC, autosampler and pump.
The 307 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 fluorometer module is a removable device that contains a flowcell, excitation LED, and emission bandpass filter. Each fluorometer module is manufactured according to the specifications of the assay it is intended to be used with. The photometric subassembly is not removable by the user.
The only significant differences between the 307 and the predicate detectors (321 and 315) are the use of LEDs for excitation (fluorometry) and a bandpass filter instead of a monochromator (photometry).

AI/ML Overview

Here's a summary of the acceptance criteria and the studies that prove the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The core acceptance criteria for the new SPOTCHECK Flow system components (350D Interface Unit, 307 Digital Photometer/Fluorometer, and NeoPac Software) are that their performance is equivalent to or improved compared to the predicate SPOTCHECK Analyzer system components (350 Interface Unit, 321 Fluorometer, and 315 Photometer, with FASPac software). This equivalence is demonstrated across various performance metrics including method comparison (bias), sensitivity (limits of detection), and precision.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit: Equivalent or Improved to Predicate)	SPOTCHECK Flow (New Device) Performance	Predicate Device Performance Notes
Method Comparison (EP9-A2 Study)	No clinically significant bias compared to predicate.	Total Galactose: m=1.02, b=-0.58, R²=1.00, Bias at Xc=-0.3
UT (GALT): m=0.96, b=-1.49, R²=0.99, Bias at Xc=-3.8
Phenylalanine: m=1.01, b=-0.02, R²=1.00, Bias at Xc=0.02
G6PD: m=1.00, b=-1.24, R²=1.00, Bias at Xc=-1.1
Tyrosine: m=1.01, b=-0.05, R²=1.00, Bias at Xc=0.01	"Performed nearly identical on both the 307 and predicate detector." "No clinically-significant bias."
Sensitivity (CLSI EP17-A)	Equivalent or improved sensitivity compared to predicate.	TGal: 0.2 mg/dl
Phe: 0.1 mg/dl
Tyr: 0.2 mg/dl
GALT: 3 µM NADPH
G6PD: 1 µM NADPH	TGal: 0.3 mg/dl
Phe: 0.2 mg/dl
Tyr: 0.2 mg/dl
GALT: 5 µM NADPH
G6PD: 2 µM NADPH
Conclusion: Equivalent or improved sensitivity.
Precision (CLSI EP5-A2)	Equivalent or improved precision compared to predicate (acceptable imprecision at very low G6PD levels).	Generally improved precision across all assays and levels compared to predicate (see detailed tables for each assay/level).	"Each method's results demonstrated an improvement in precision over the predicate device... The only exception is an observed increase in imprecision at very low levels of G6PD enzyme activity, however, said imprecision is acceptable and not clinically significant."

Study Details

2. Sample Size Used for the Test Set and Data Provenance

EP9-A2 Method Comparison Study:
- Total Galactose: 69 samples, 2 replicates per sample.
- UT (GALT): 58 samples, 2 replicates per sample.
- Phenylalanine: 70 samples, 2 replicates per sample.
- G6PD: 60 samples, 2 replicates per sample.
- Tyrosine: 71 samples, 2 replicates per sample.
- Data Provenance: Dried blood spots representing normal and deficient conditions. Patient samples supplemented with dried blood spot controls from manufacturers (including Astoria-Pacific and the Centers for Disease Control) to ensure adequate distribution, especially for rare deficient/partially-deficient conditions.
Additional Study of Newborn Specimens:
- Total Galactose, Phenylalanine, Tyrosine, UT (GALT): Minimum of 88 newborn dried blood spots (ranging from 94 to 96 newborns contributing to 96-112 measurements).
- G6PD: 50 newborn specimens for the new study; 42 measurements from the previous study (described above) were included, making the total N=92.
- Data Provenance: Domestic newborn screening laboratories (retrospective, obtained for testing purposes).
Sensitivity Study (CLSI EP17-A):
- TGal, Phe, Tyr, G6PD: 3 low-level samples analyzed over 3 days, with batches of 20 low-level replicates and 20 blank replicates per run for each method.
- GALT: 2 low-level samples analyzed over 3 days (1 low-level sample used in 2 of 3 runs, 40 replicates total), with batches of 20 low-level replicates and 20 blank replicates per run.
Precision Study (CLSI EP5-A2):
- TGal, Phe, Tyr, GALT: 3 samples at different levels (low, medium, high) for each method. Analyzed over 5 days, 1 run per day, 8 replicates per sample per run.
- G6PD: 3 samples (low, medium, high). Analyzed over 4 days (1 run per day for 3 days, 2 runs on one day), 8 replicates per sample per run.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number or qualifications of experts used to establish a "ground truth" for the test set in the traditional sense (e.g., radiologists interpreting images). Instead, the studies rely on quantitative measurements compared against known concentrations or activity levels, and medical decision levels established in Astoria-Pacific's quality control laboratory. The dried blood spot controls from manufacturers and the CDC serve as reference materials based on established values.

4. Adjudication Method for the Test Set

Not applicable. The studies are quantitative comparisons of numerical results from the new device versus a predicate device or reference measurements, not interpretations requiring adjudication by experts.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic instrument system, not an imaging device or AI-supported diagnostic tool that involves human readers. The studies performed focused on analytical performance characteristics comparing the new instrument components to previous versions.

6. If a Standalone Study Was Done

Yes, the studies assessed the standalone performance of the new device's analytical capabilities through method comparison, sensitivity, and precision evaluations against a predicate device. The device is a continuous flow analyzer for in vitro diagnostics and its performance is inherently standalone in this context.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies (method comparison, sensitivity, precision) was based on:

Predicate Device Measurements: For method comparison, the results from the new device were compared directly to measurements obtained from the legally marketed predicate device (321 Fluorometer).
Known Concentrations/Activity Levels: For sensitivity and precision, samples were prepared at specific low, medium, and high concentrations or enzyme activity levels. Dried blood spot controls from manufacturers (including Astoria-Pacific) and the Centers for Disease Control (CDC) were used to represent normal and deficient conditions with established values.
Medical Decision Levels: Cut-offs established in Astoria-Pacific's quality control laboratory were used as reference points for evaluating bias.

8. The Sample Size for the Training Set

The document does not mention a separate "training set" as this device is a hardware/software system for analytical measurement, not a machine learning or AI model that requires a distinct training phase with a dedicated dataset. The software (NeoPac) is a replacement for an outdated package, providing similar instrument controls with minor functionality updates, rather than an algorithm trained on data.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no mention of a distinct training set in the provided document.

Summary

Regulation Number and Section

§ 862.1315 Galactose-1-phosphate uridyl transferase test system.

(a)
Identification. A galactose-1-phosphate uridyl transferase test system is a device intended to measure the activity of the enzyme galactose-1-phosphate uridyl transferase in erythrocytes (red blood cells). Measurements of galactose-1-phosphate uridyl transferase are used in the diagnosis and treatment of the hereditary disease galactosemia (disorder of galactose metabolism) in infants.(b)
Classification. Class II.