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The SPOTCHECK® Neonatal Total Galactose Microplate Reagent Kit is for the quantitative determination of the concentration of Total Galactose (Gal) + galactose-1-phosphate (Gal-1-P)) in whole blood saturated filter paper disks, using a microplate absorbance reader or SPOTCHECK Pro. Measurements of Total Galactose are used primarily in the diagnosis and treatment of the hereditary disease galactosemia. This method is intended for in vitro diagnostic use as an aid in neonatal screening for increased concentrations of Total Galactose, and not for monitoring purposes.

The SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit is a galactose test system. It includes Extraction Solution, Enzyme Reagent, Coenzyme Reagent, Color Reagent, and Stock Standard. Total Galactose is measured colorimetrically following the completion of two enzyme assisted reactions and the color formation reaction. Patient samples of whole blood collected on standardized filter paper are placed into the wells of a 96 well filtration microplate. Extraction solution is added and samples are eluted and incubated. The contents are filtered into a clean flat-bottom microplate. Enzyme Reagent and Coenzyme Reagent are added and the plate is incubated. Color Reagent is then added and the plate is incubated. The absorbance is measured on a microplate reader at a wavelength of 600 nm for the measurement channel and 750 nm for the reference channel. Results are expressed as mg of total galactose per dL of whole blood.

The Astoria-Pacific SPOTCHECK® Neonatal Total Galactose Microplate Reagent Kit is a diagnostic device for quantitative determination of Total Galactose (Galactose + Galactose-1-Phosphate) in whole blood samples collected on filter paper disks. This information is gleaned from the provided 510(k) summary (K121101).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary compares the performance of the SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit to a legally marketed predicate device (Accuwell Total Galactose Model No. 6020-20 EGAL, 2000 Test Kit). The criteria for acceptance are primarily demonstrated through substantial equivalence to the predicate device in various analytical performance characteristics.

Study Proving Acceptance Criteria:

The studies described in the 510(k) summary were primarily focused on demonstrating "substantial equivalence" of the SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit to a legally marketed predicate device. This is the common pathway for 510(k) clearances. The acceptance criteria are "met" if the new device performs similarly and safely to the predicate, accounting for any differences.

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

• Method Comparison (Clinical Comparison Study):

  • Initial routine samples: 2037 (manual method) and 2036 (SPOTCHECK Pro method).
  • Manufactured elevated samples: 51.
  • Supplemental retrospective confirmed galactosemic newborn specimens: 11 (from Michigan Neonatal Biobank).
  • Total Test Set for Clinical Comparison:
    • Manual processing: 2037 + 51 + 11 = 2099 samples (with an overall total including the supplemental study given as 2209).
    • SPOTCHECK Pro processing: 2036 + 51 + 11 = 2098 samples (with an overall total including the supplemental study given as 2208).
  • Data Provenance: Routine samples were analyzed at a "state screening laboratory." The 11 confirmed galactosemic newborn specimens were obtained retrospectively from the "Michigan Neonatal Biobank." This indicates that the data is predominantly retrospective and originates from multiple sources/locations within the US.

• Precision Performance:

  • For the proposed device (SPOTCHECK Kit, both manual and SPOTCHECK Pro): 80 replicates for each of the three concentrations (Normal, Near Cutoff, Galactosemic). This implies 3 concentrations * 80 replicates = 240 measurements for each processing method.
  • For the predicate device: 40 replicates for each of four concentrations. This implies 4 concentrations * 40 replicates = 160 measurements.

• Analytical Sensitivity (LoD/LoQ): 180 determinations were used to calculate LoD.

• Linearity and Analytical Specificity: Sample sizes are not explicitly stated as specific numbers of unique patient samples but rather as "responses of the standards" for linearity and "interference evaluated" with corresponding concentrations for specificity.

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

The provided document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth for this diagnostic kit.

• For the clinical comparison study, the "ground truth" for the routine samples was likely based on their classification as "routine" and the results from a legally marketed predicate device.
• For the 51 manufactured elevated samples, the "ground truth" was established by their controlled, high Total Galactose concentration during manufacturing.
• For the 11 retrospective confirmed galactosemic newborn specimens, the "ground truth" was established by their prior diagnosis of galactosemia, likely through standard clinical and laboratory diagnostic procedures (which would be the "gold standard" for the disease).

Therefore, there were no human experts forming a consensus for the test set ground truth in the way described for imaging or subjective assessment devices. The ground truth was based on the predicate device's results, manufacturing specifications, or established clinical diagnoses.

4. Adjudication Method for the Test Set

Given that the ground truth was largely based on a predicate device, manufacturing, or existing clinical diagnoses, there was no explicit adjudication method (like 2+1 or 3+1 consensus) described for resolving discrepancies in measurements or classifications. The study likely focused on agreement/correlation between the new device and the established values/predicate.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is typically associated with imaging devices where human readers interpret results, and the AI's impact on reader performance is evaluated. This device is an in vitro diagnostic reagent kit, and its performance is assessed analytically and by comparison to a predicate device and known values, not by human reader interpretation.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone performance evaluation was done. The device's performance characteristics (LoQ, LoD, range, linearity, precision, analytical specificity) were assessed directly through laboratory studies, both when processed manually and using the "SPOTCHECK Pro" automated system. These are evaluations of the algorithm/reagent system itself, independent of interpretation by human clinicians for diagnostic purposes. The device generates a quantitative numerical result.

7. Type of Ground Truth Used

The types of "ground truth" used include:

• Predicate Device Results: For routine samples in the method comparison, the results from the legally marketed predicate device served as the comparative ground truth.
• Known Concentrations/Manufacturing Specifications: For manufactured samples with elevated Total Galactose and the samples used in linearity, precision, and interference studies, the ground truth was the known, spiked, or formulated concentrations.
• Clinical Diagnosis/Outcomes Data: For the 11 retrospective confirmed galactosemic newborn specimens, the ground truth was their established clinical diagnosis of galactosemia.

8. Sample Size for the Training Set

The document is a 510(k) summary for a reagent kit that measures an analyte. This type of device does not typically involve "training sets" in the context of machine learning or AI algorithms that learn from data. Therefore, the concept of a "training set" as it applies to AI/ML is not relevant here, and no training set size is mentioned. The device's performance is based on chemical reactions and spectrophotometric measurements, not on learning from a dataset.

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

As noted above, the concept of a "training set" does not apply to this type of diagnostic reagent kit. Therefore, the establishment of ground truth for a non-existent training set is not applicable.

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The SPOTCHECK Neonatal GALT Microplate Reagent Kit is for the quantitative determination of galactose-1-phosphate uridyltransferase, EC 2.7.7.12 (GALT), activity in whole blood saturated filter paper disks, using a microplate absorbance reader. Measurements of GALT enzyme activity are used primarily in the diagnosis and treatment of the hereditary disease galactosemia. This method is intended for in vitro diagnostic use as an aid in neonatal screening for decreased levels of GALT enzyme activity, and not for monitoring purposes.

The SPOTCHECK Pro is used for automated sample processing in the application of in vitro diagnostic assays. Specimens containing patient bodily substances are introduced and analyzed in microtiter plates using qualitative/quantitative determination through absorbance measurements.

These devices are intended for use by trained, qualified laboratory personnel.

SPOTCHECK Neonatal GALT Microplate Reagent Kit - 60 Plate: Four enzyme mediated reactions are employed in the determination of GALT activity. GALT activity is determined by measuring the colored formazan produced by the addition of the color reagent to the incubated blood/substrate mixture. Patient samples of whole blood collected on standardized filter paper are placed into the wells of a standard 96 well microplate. A buffered enzyme mixture is added to each well and the plate is incubated at 37 °C for 120 minutes on a plate shaker/incubator. Following incubation, an aliquot of the mixture from each well is transferred to the corresponding wells on a clean 96 well microplate. Color reagent is added to each well, the color is developed over the course of 10 minutes, and the absorbance of each sample is determined on the plate reader. A blank absorbance reading is made prior to the addition of the color reagent to correct for endogenous sample color. The color developed is proportional (1:1) to the GALT activity in the sample. A standard curve prepared from a stock NADH solution is used to quantitate the results. Results are expressed as units of GALT enzyme activity per gram of hemoglobin or U/g Hb.

SPOTCHECK Pro: INSTRUMENT COMPONENTS: Tecan Freedom EVO and accessories necessary for assay.

This is a 510(k) premarket notification for a medical device, not an AI/ML device, therefore, some of the requested information (e.g., number of experts, adjudication method, MRMC study, sample size for training set) is not applicable or cannot be extracted from the provided text. The document describes the device's technical characteristics, performance studies performed to demonstrate substantial equivalence to a predicate device, and its intended use.

Here's an analysis of the provided information, tailored to what is available in the regulatory submission format:

1. Table of Acceptance Criteria (Performance Goals) and Reported Device Performance

The acceptance criteria are generally implied by the comparative studies to the predicate device and established CLSI guidelines for analytical performance. The studies aim to show the SPOTCHECK Kit performs comparably or better than the predicate device across various metrics.

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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.

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
• 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.

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
• 2. 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).

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

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.

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SPOTCHECK Blood Spot Controls are used for monitoring assay performance during in vitro diagnostic newborn screening for deficient Galactose-1-phosphate UridyItransferase (GALT) and/or Biotinidase enzyme activity. Enzyme response quantitation is provided in the product insert.

SPOTCHECK Blood Spot Controls. Part No. 80-0900P4K, Blood Spot Controls, Deficient; 4 cards. Part No. 80-0901P4K, Blood Spot Controls, Normal; 4 cards. The controls are prepared with mixtures of human serum and human red blood cells. adjusted to approximately 55% hematocrit. Enzyme activity in the Deficient Control is decreased by heating. Enzyme activity in the Normal Control is supported by the addition of dithioerythritol (DTE). The mixtures are spotted on Whatman 903A filter paper and allowed to air dry at room temperature. The suppliers of serum and red blood cells certify that the materials have been tested using FDA-approved assays and shown to be negative for infectious disease agents. The SPOTCHECK Blood Spot Controls provide an ongoing indication of the assay performance. The Deficient Control responds below the assay cutoff, and the Normal Control responds above the assay cutoff within normal limits.

The provided 510(k) summary (K090940) describes a medical device, the SPOTCHECK® Blood Spot Controls, which are quality control materials for newborn screening assays. The acceptance criteria and the study proving the device meets these criteria are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

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This method is for the semi-quantitative determination of biotinidase, EC 3.5.1.12, activity in dried whole blood spots using a spectrophotometer. Measurement of biotinidase activity is primarily for the diagnosis and treatment of biotinidase deficiency in newborns. This method is intended for in vitro diagnostic use in screening for decreased levels of biotinidase activity and not for monitoring purposes.

Biotinidase activity is determined by measuring the color that develops from p-Aminobenzoic Acid (PABA) after PABA is released from Biotinyl-p-Aminobenzoate (Biotin-PAB). Samples with biotinidase activity develop a purple color. Samples without biotinidase activity remain straw-colored. Patient samples of whole blood collected on standardized filter paper are eluted in a standard 96 well microplate. The plate is incubated with Biotin-PAB in a buffer at 37℃ for 240 minutes on a combination incubator/shaker. Following incubation, TCA is added to the sample mixture and the resulting precipitate is removed through filtration. The PABA in the filtrate is subsequently diazotized and coupled to a napthol derivative to form an azo dye by the successive addition of sodium nitrite, acidic ammonium sulfamate and finally, N-1-naphthylethylenediamine dihydrochloride (NED). The azo dye is measured colorimetrically at 550 nm on a commercial microplate absorbance reader with a reference measurement at 690 mm.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly present a formal "acceptance criteria" table with pre-defined thresholds for performance that the new device must meet. Instead, it compares the performance of the new device (SPOTCHECK Biotinidase Microplate Reagent Kit) against a legally marketed predicate device (K010844 Biotinidase Kit, 50-Hour) to demonstrate substantial equivalence, implying that performance comparable to the predicate device is the "acceptance criteria."

However, we can infer some criteria and report the device's performance based on the provided data:

Punctuation for specific values in the table above can be found in the excerpt itself.

2. Sample size used for the test set and the data provenance:

• Test Set Sample Size:
  • Classification Study: 564 unclassified patient samples, 2 biotinidase deficient patient samples, and 10 deficient controls. Total of 576 samples.
  • Precision Study:
    • Within-Run & Total Precision (main): n = 80 for each activity level (Low, Moderate, Normal) for the Microplate Kit. n = 32 (Low), n = 44 (Moderate), n = 44 (Normal) for the Predicate Device.
    • Additional 5-day Low Activity Precision: n = 80 for the Microplate Kit.
• Data Provenance:
  • Classification Study: The 2 deficient patient samples were "clinically-confirmed." The 10 deficient controls were "provided by the Centers for Disease Control (CDC)." The 564 unclassified patient samples are not explicitly stated in terms of specific country of origin, but generally, patient samples for such studies imply a clinical setting.
  • Prospective/Retrospective: The text implies a retrospective analysis as samples "were treated according to the procedures detailed under SPEDMEN COLLECTION AND PREPARATION FOR ANALYSIS in the product insert," suggesting these were existing samples processed with the new kit.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

• The document implies that the ground truth for the two "clinically-confirmed" deficient patient samples was established by clinical diagnosis, as they are referred to as "persons clinically-confirmed as such."
• For the 10 deficient controls, the ground truth was "provided by the Centers for Disease Control (CDC)," which suggests these are established and certified deficient samples.
• The "experts" themselves and their specific qualifications are not detailed in the provided text. The predicate device's classification served as a comparative ground truth for other samples and for discrepancies.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

• The document mentions "Discrepant results ** were not confirmed by follow-up testing." This indicates that for samples where the new Microplate Kit and the Predicate Device yielded different classifications (e.g., Microplate Kit: Normal, Predicate Device: Partial Activity), no explicit expert adjudication or further follow-up gold standard testing was performed to resolve the discrepancy for the purpose of this study report. The discrepancy is simply noted. Therefore, an explicit adjudication method (like 2+1 or 3+1) was not described or applied to resolve discrepancies for the reported results. The predicate device's classification was primarily used as a comparative benchmark, not an adjudicated ground truth in cases of disagreement.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

• No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) reagent kit that measures biotinidase activity, not an AI-powered diagnostic imaging tool or a system involving human readers interpreting outputs. It's a chemical assay. The comparison is between the new kit and a predicate kit (both laboratory assays), not between humans with and without AI assistance.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

• Yes, the performance presented is standalone for the device (algorithm/assay only). The kit measures biotinidase activity using a spectrophotometer, which is an automated reading of a chemical reaction. The results described (linearity, sensitivity, precision, classification) are direct outputs of the assay kit itself without human interpretation influencing the measurable outcome, although trained laboratory personnel are required for manual steps (e.g., pipetting, filtration). The "human-in-the-loop" would be the technician performing the assay and reviewing the numerical results, but the performance metrics reported are for the assay's output itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

• Clinical Confirmation/Certified Controls and Predicate Device Comparison:
  • For deficient patient samples, "clinical confirmation" of biotinidase deficiency was the ground truth.
  • For deficient controls, the "Centers for Disease Control (CDC)" provided samples with established deficiency.
  • For the bulk of the samples (564 unclassified), the predicate device's classification served as the comparative benchmark. While not a "true" independent ground truth for every sample, it's used as the standard against which the new device's classifications are measured for substantial equivalence.

8. The sample size for the training set:

• The document does not explicitly mention a separate "training set" in the context of machine learning or AI. As a reagent kit for a chemical assay, it does not typically involve explicit "training data" in the AI sense. The development of such kits often involves extensive R&D and optimization, but this is usually not referred to as a "training set" in the same way an AI model would have one.

9. How the ground truth for the training set was established:

• As a "training set" in the AI sense is not specified, the method for establishing its "ground truth" is also not applicable or described within the document. The development of the assay would rely on established biochemical principles and validation using known concentrations and clinical samples.

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The Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit is intended for the semi-quantitative determination of glucose-6-phosphate dehydrogenase activity in erythrocytes using the Astoria-Pacific SPOTCHECK Analyzer. Measurements of glucose-6-phosphate dehydrogenase activity are used primarily in the diagnosis and treatment of nonspherocytic congenital hemolytic anemia or drug-induced hemolytic anemia associated with a G6PD deficiency. It is for in vitro diagnostic use primarily as an aid in screening for decreased levels of G6PD enzyme activity. This device is for use by trained, qualified laboratory personnel.

The Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit is a reagent kit used for the semi-quantitative determination of glucose-6-phosphate dehydrogenase activity in erythrocytes. The method is based on the spectrophotometric method where enzyme activity is measured by observing NADP+ reduction to NADPH when glucose-6-phosphate is present as a substrate. Maleimide is added to inhibit the production of NADPH by 6-phosphogluconate dehydrogenase. The fluorescent NADPH produced is proportional to the G6PD enzyme activity. The kit contains Extraction Buffer, Tris Buffer, G6PD Substrate, and NADH Stock Std reagents.

The provided text describes the G6PD 50-Hour Reagent Kit and its performance characteristics. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal "acceptance criteria" for regulatory approval in the typical sense of numerical thresholds for sensitivity, specificity, etc., that the device had to meet to be cleared. Instead, it presents performance characteristics that demonstrate the device is substantially equivalent to a predicate. The key performance aspects highlighted are:

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

• Sample Size for Correlation/Comparison Study: 30 samples (16 normal, 4 intermediate, 10 G6PD deficient).
• Sample Size for Expected Values:
  • Normal population of neonates: 17 observations
  • G6PD deficient population: 10 observations
  • Intermediate G6PD activity population: 4 observations
• Data Provenance: Not explicitly stated (e.g., country of origin). It's reasonable to infer these were collected for the purpose of the study. The study design (clinical samples, comparison to a competitive device) suggests prospective collection or at least retrospective use of stored clinical samples specifically for this performance evaluation.

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

• The document does not mention the use of "experts" in the sense of clinicians or radiologists adjudicating results.
• The ground truth for the comparison study (normal, intermediate, G6PD deficient) was established by analyzing samples "known to be normal (16), intermediate (4), and G6PD deficient (10)". It implies these classifications were based on prior clinical diagnosis or established laboratory methods, rather than real-time expert consensus for the purpose of this specific study.

4. Adjudication Method for the Test Set

• Not applicable/Not mentioned. The study compares the device's results to a "competitive device" and pre-classified samples, rather than an adjudication process among multiple readers for image interpretation or similar tasks.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic reagent kit, not an AI-powered diagnostic system involving human readers.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, the performance characteristics described are for the Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit as a standalone device, for use by trained laboratory personnel. Its output (µM NADPH) is a quantitative measurement, and its interpretation (e.g., normal, deficient) is based on established ranges. There is no "human-in-the-loop" AI component.

7. The Type of Ground Truth Used

• The ground truth for the performance studies was based on:
  • Prior clinical classification/diagnosis: Samples were "known to be" normal, intermediate, or G6PD deficient before being tested by the device.
  • Comparison to a predicate/competitive device: The device's results were compared against an existing, legally marketed G6PD assay.
  • Controlled conditions for precision and linearity: Known concentrations of NADH for linearity, and samples with stable activity levels for precision.

8. The Sample Size for the Training Set

• Not applicable. This is not a machine learning or AI device that requires a "training set." It's a chemical reagent kit with established biochemical principles.

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

• Not applicable, as there is no training set for this type of device.

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This method is for the quantitative determination of the amino acid tyrosine in whole blood saturated filter paper disks using the APF™ 300 SPOTCHECK® Analyzer or the RFA 300 System. Measurements obtained by this device are used primarily to screen newborns for congenital tyrosinemia, a disease that can cause liver/kidney disorders.

The proposed device, Tyrosine 50-Hour Reagent Kit, is a set of reagents to be used with the API™ 300 SPOTCHECK® Analyzer or the RFA 300 System for the quantitative determination of the amino acid tyrosine (Tyr) in whole blood saturated filter paper disks. The amount of Tvr is determined by measuring the fluorescent compound produced in the reaction of tyrosine with 1-nitroso-2-naphthol, catalyzed by nitrous acid at 80°C. The excitation wavelength of the product is 450 nm and emission is measured at 550 nm. The method is specific for para-substituted phenolic compounds. Excess 1-nitroso-2-naphthol is removed from the reaction mixture by reduction with sodium m-bisulfite.

The method is designed for mass screening, with enough reagents in each 50-Hour ' Reagent Kit for 1 week plus start-up (50 hours total) of run time. It is packaged to reduce storage space and to require a minimum of time to prepare. Each component is packaged with the correct weight to prepare the required volume of reagent. The standard is in a concentrated form, to permit easy dilution to prepare a standard curve.

Here's an analysis of the provided text to extract the acceptance criteria and study information:

Acceptance Criteria and Device Performance for Tyrosine 50-Hour Reagent Kit

The provided document describes the Tyrosine 50-Hour Reagent Kit, which is a set of reagents for the quantitative determination of the amino acid tyrosine in whole blood saturated filter paper disks. The device is intended for mass screening, primarily for newborns, to diagnose and treat diseases such as congenital tyrosinemia.

The submission claims substantial equivalence to a predicate device, the Technicon Tyrosine test. The acceptance criteria are implicitly based on demonstrating performance as well as or better than this predicate device, particularly through clinical correlation.

1. Table of Acceptance Criteria and Reported Device Performance

Given the nature of the submission (510(k) for a reagent kit claiming substantial equivalence), explicit numerical acceptance criteria (e.g., minimum sensitivity, specificity thresholds) are not formally stated in the provided text. Instead, the performance is evaluated by demonstrating good correlation with expected values and accurate identification within normal ranges, in comparison to the predicate device.

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

• Test Set Sample Size: 1,096 specimens
  • Normal Neonatal Blood Samples: 532
  • Spiked Samples: 521
• Data Provenance: The specimens were analyzed by the State of California's Genetic Disease Laboratory. The data appears to be retrospective as the samples were "analyzed" by an existing laboratory. The country of origin is the USA.

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

• The document does not specify the number of experts or their qualifications used to establish ground truth for the test set.
• However, the samples were analyzed by the "State of California's Genetic Disease Laboratory," implying analysis by qualified laboratory personnel, but no explicit number or credentialing of medical experts (e.g., geneticists, pathologists) involved in establishing the 'true' tyrosine levels for the samples is provided.

4. Adjudication Method

• The document does not specify an adjudication method (e.g., 2+1, 3+1, none). The ground truth for spiked samples would be based on the known concentration of the spike, and for normal samples, on established normal ranges from the collaborating laboratory.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described.
• The study focuses on the performance of the device itself in quantitative measurements, rather than human reader interpretation with or without AI assistance. The device is a reagent kit for an automated system, not an AI-powered image interpretation tool where human-in-the-loop studies are common.

6. Standalone Performance Study

• Yes, a standalone performance study was done for the algorithm (the reagent kit and its associated method). The clinical tests described (1,096 specimens) represent the performance of the proposed device without human intervention beyond the standard operation of the API™ 300 SPOTCHECK® Analyzer or the RFA 300 System.
• The study demonstrated that the device correlated well with expected values and produced results within the normal range for normal neonatal samples.

7. Type of Ground Truth Used

• For Spiked Samples: The ground truth was based on the known concentration of the spiked tyrosine.
• For Normal Neonatal Blood Samples: The ground truth was based on established normal ranges for tyrosine in neonatal blood, as determined by the State of California's Genetic Disease Laboratory. This could be considered a form of clinical consensus/laboratory reference range.

8. Sample Size for the Training Set

• The document does not explicitly mention a separate "training set" for the device, as it is a reagent kit and not a machine learning algorithm in the modern sense that requires explicit training data to learn parameters from scratch.
• The development of such a kit typically involves internal validation and optimization, but not a distinct 'training set' as used in AI/ML terminology. The "clinical tests" described are implicitly the demonstration of the final product's performance, which in a regulatory context serves as the validation against ground truth.

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

• As a distinct training set (in the AI/ML sense) is not mentioned, therefore, how its ground truth was established is not applicable or described in the document. The development of the kit would be based on established chemical principles and optimization to match the performance of the predicate device.

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This Astoria-Pacific SPOTCHECK® Undyttransferase 50-Hour Reagent Kit is for the qualifative determination of galactose-1-phosphate uridyttransferase, EC 2.7.12 (GALT) activity in whole blood saturated filter paper disks (S&S 903 filter paper or equivalent), using the API™ 300 SPOTCHECK® Analyzer or the RFA-300 System. Measurements of galactose-1-phosphate undyttransferase are used in the diagnosis and treatment of the hereditary disease galactosemia. This method is intended for in vitro diagnostic use as an aid in screening for decreased levels of GALT activity in infants. This method is not for monitoring purposes.

The proposed device, Unidyttransferase 50-Hour Reagent Kit, is a set of reagents to be used with the API™ 300 SPOTCHECK® Analyzer or the RFA-300 System for the quantitative determination of the enzyme galactose-1-phosphate uridyttransferase (UT) in whole blood saturated filter paper disks. The amount of unidyltransferase activity is determined by measuring the fluorescent compound produced in the reaction of UT with galactose and UDP Glucose, followed by NADP reduction at 37°C. The excitation wavelength of the reaction product is 450 nm, and it's emission is measured at 550 nm. The method is specific for uridy transferase.

The method is designed for mass screening, with enough reagents in each 50-Hour Reagent Kit for 1 week plus start-up (50 hours total) of run time. It is packaged to reduce space and to require a minimum of time to prepare. Each component is packaged with the correct weight to prepare the required volume of reagent. The standard is in a concentrated form, to permit easy dikition to prepare a standard curve.

This document describes the Astoria-Pacific Uridyltransferase 50-Hour Reagent Kit, a device for in vitro diagnostic use to screen for decreased levels of GALT activity in infants. The information provided is sparse regarding detailed acceptance criteria and study particulars, particularly from a modern regulatory submission perspective.

Here's an attempt to extract and interpret the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state quantitative acceptance criteria (e.g., specific sensitivity, specificity, or accuracy thresholds). Instead, it relies on a qualitative assessment of "correlation" with known samples.

2. Sample size used for the test set and the data provenance

• Sample Size for Test Set: 27 specimens
  • 20 normal neonatal blood samples
  • 7 deficient samples from juveniles and adults
• Data Provenance: Not specified, but implied to be from a clinical setting, given the use of "normal neonatal blood samples" and "deficient samples from juveniles and adults." It is highly likely to be retrospective given the submission date and the limited details.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not provide any information regarding the number or qualifications of experts used to establish the ground truth for the test set.

4. Adjudication method for the test set

The document does not describe any adjudication method.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This is not applicable. The device is a reagent kit for assaying enzyme activity, not an AI or imaging diagnostic device requiring human reader interpretation in the context of an MRMC study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is not applicable in the typical sense of algorithm-only performance for an AI/CADe device. The device itself is an in vitro diagnostic assay kit. Its performance is measured by its ability to accurately detect GALT activity, which is a "standalone" measurement in its own right, without human interpretation of complex outputs.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the deficient samples and normal samples would likely have been established by a reference method for GALT deficiency diagnosis or existing clinical records for those individuals. The document does not explicitly state the specific method used for ground truth establishment, but it implies a pre-existing clinical classification ("normal neonatal blood samples" and "deficient samples").

8. The sample size for the training set

The document does not mention a separate training set. The "clinical tests" described appear to be the entirety of the evaluation. For a reagent kit, the development and calibration process would typically involve internal studies, but these are not disclosed as a "training set" in the context of this summary.

9. How the ground truth for the training set was established

Not applicable, as a separate training set is not explicitly mentioned. If the 27 clinical samples were used for both development and "testing" (which is common in older 510(k) submissions but not ideal by current standards), then the ground truth would have been established as described in point 7.

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