Search Results

The FINDER G6PD test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood specimens collected in lithium heparin tubes, for the identification of G6PD deficient samples. The FINDER G6PD test is intended to be used with the FINDER Instrument in point of care or clinical laboratory settings.

The FINDER G6PD test system measures G6PD quantitatively from a 50uL venous whole blood specimen. The blood specimen should be collected in lithium heparin anticoagulant. The G6PD test system is suitable for use in both a point-of-care setting and a clinical laboratory. The time to result is around 16 minutes from sample introduction. The FINDER G6PD test system consists of the FINDER G6PD Test Cartridge and the FINDER Instrument. The cartridge uses electrowetting-based digital microfluidics to integrate and automate all the sample and reagent handling steps. The instrument contains all the hardware and software required to operate the cartridge, providing electrowetting control, thermal control and detection capability, a touch-screen user interface and software necessary to perform the test and report results.

FINDER G6PD Test: Acceptance Criteria and Performance Study

The FINDER G6PD Test is intended for semi-quantitative measurement of glucose-6-phosphate dehydrogenase in venous whole blood to identify G6PD deficient samples. The device is used with the FINDER Instrument in point-of-care or clinical laboratory settings.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a separate section with specific numerical targets. However, the performance data presented from precision, linearity, interference, sensitivity, and method comparison studies collectively demonstrate the device's acceptable performance in comparison to the predicate device and established guidelines. For the purpose of this analysis, key performance metrics from the non-clinical and clinical studies will be presented as the "reported device performance."

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

For the Clinical Method Comparison Study (test set):

• Sample Size: 200 subjects. The results of 167 samples were used in the concordance analysis after the first 36 normal male samples were used to calculate the adjusted male median.
• Data Provenance: Venous whole blood samples were collected from 6 sites, including one biorepository. The samples were collected in lithium heparin tubes. The study design was based on CLSI EP09-c – Measurement Procedure Comparison and Bias Estimation Using Patient Samples. The subjects included 89 males and 92 females with ages ranging from 20 to 72 years. 19 contrived samples were also included in the study.

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 of experts or their qualifications used to establish the ground truth for the test set. Instead, the "ground truth" for the method comparison study was established by a comparator method: the Pointe Scientific Glucose-6-Phosphate Dehydrogenase Reagent Set (K024006), run on a Cobas Mira instrument. This predicate device served as the reference method.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving human experts for the test set. The comparison was made directly between the FINDER G6PD Test results and the results obtained from the predicate device (Pointe Scientific G6PD Reagent Set on Cobas Mira).

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

There is no indication of a multi-reader multi-case (MRMC) comparative effectiveness study being performed in this document. The study focuses on the performance of the device (FINDER G6PD Test) compared to a predicate device, not on human readers' improvement with or without AI assistance. The FINDER G6PD Test is an in vitro diagnostic device, not an imaging AI diagnostic tool for human readers.

6. Standalone Performance Study

Yes, a standalone performance study was conducted for the FINDER G6PD Test. All the non-clinical and clinical performance data presented (precision, linearity, interference, sensitivity, and method comparison) reflect the performance of the FINDER G6PD Test system (FINDER G6PD Test Cartridge + FINDER Instrument) operating by itself, without human interpretation of the primary result. The results are reported directly by the instrument in U/gHb and as a % of the site-specific Adjusted Male Median (AMM).

7. Type of Ground Truth Used

The ground truth for the clinical method comparison study was established using a comparator method, specifically the Pointe Scientific Glucose-6-Phosphate Dehydrogenase (G6PD) Reagent Set (K024006) run on a Cobas Mira instrument. This serves as a reference standard for measuring G6PD activity.

8. Sample Size for the Training Set

The document does not specify a distinct "training set" sample size for developing the FINDER G6PD Test. This is typical for IVD devices that measure an analyte directly, where the underlying principle is biochemical and validated through analytical and clinical performance studies, rather than a machine learning model that requires a labeled training dataset.

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

As there is no explicit "training set" described in the context of a machine learning model for this IVD device, the concept of establishing ground truth for a training set does not directly apply. The "training" for the device's underlying measurement methodology would involve established biochemical principles and extensive internal analytical validation prior to the formal performance studies presented in the 510(k) submission.

Ask a specific question about this device

The SEEKER System, including the SEEKER Instrument and the SEEKER LSD Reagent Kit-IDUA|GAA|GBA|GLA for use on the SEEKER Instrument, is intended for quantitative measurement of the activity of a-L-iduronidase, a-D-glucosidase, Bglucocerebrosidase and a-D-galactosidase A from newborn dried blood spot specimens as an aid in screening newborns for Mucopolysaccharidosis Type I, Pompe, Gaucher and Fabry diseases. Reduced activity of these enzymes may be indicative of these lysosomal storage diseases. The enzymes measured using the SEEKER LSD Reagent Kit-IDUA|GAA|GBA|GLA and their associated lysosomal storage diseases are listed below.

The SEEKER System employs digital microfluidic technology to measure multiple lysosomal enzymatic activities quantitatively from newborn dried blood spot specimens. The following components are provided:

• 1. SEEKER Instrument (including USB and power cables), Desktop PC with monitor, keyboard, mouse, and the Spot Logic software.
• 2. SEEKER LSD Reagent Kit IDUA|GAA|GBA|GLA containing enzyme specific substrate reagents, dried blood spot extraction buffer, reaction stop buffer, 4 levels of calibrators and quality control dried blood spots containing 4 levels of quality control (OC) material. Each Reagent Kit contains sufficient consumables for 1440 tests. The contents of the kit are listed below:

Other components needed to run tests include the following:

The composition of the enzyme reagents and buffers are summarized below:

The Seeker Calibrators are supplied as part of the SEEKER LSD Reagent Kit -IDUA|GAA|GBA|GLA. The calibrators consist of 4 levels of aqueous preparation of 4methylumbelliferone sodium salt (4-MU) in 0.6M sodium bicarbonate buffer, pH 11.0 with 0.01% Tween 20. The concentration of 4-MU in each of the 4 calibrators is indicated in the table below:

The quality control dried blood spots include 4 levels of control material: OC Low (QCL), QC Medium (QCM) and QC High (QCH). The composition of the 4 quality control dried blood spot (DBS) is summarized below. QCBP is used to fill empty wells on a cartridge.

The enzymatic activity values for the quality control DBS measured by the manufacturer are given on the lot specific quality control certificate included in each assay kit for all levels except QCBP. Each laboratory should establish its own mean and acceptable ranges for the quality control materials.

3. SEEKER Cartridges

• 4. Finnipipette Novus 8-channel automatic pipette 1-10 uL
• 5. Finnipipette Novus 1-channel automatic pipette 10-100 uL

The SEEKER System is a device designed for quantitative measurement of the activity of α-L-iduronidase (IDUA), α-D-glucosidase (GAA), β-glucocerebrosidase (GBA), and α-D-galactosidase A (GLA) from newborn dried blood spot specimens. This serves as an aid in screening newborns for Mucopolysaccharidosis Type I (MPS I), Pompe, Gaucher, and Fabry diseases.

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

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the SEEKER System are implicitly defined by the analytical and clinical performance standards required for its De Novo classification as a Class II device with special controls. These controls mandate thorough demonstration of performance characteristics, including clinical validity, reference intervals, carry-over, detection limits, and imprecision. The clinical validity is primarily demonstrated by the false positive and false negative rates observed in the pivotal clinical study.

Table: Acceptance Criteria (Implied by Regulatory Requirements) and Reported Device Performance

The studies described predominantly cover the analytical performance requirements (reproducibility, linearity, detection limits, analytical specificity, carry-over) and the clinical performance (false positive/negative rates).

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

The primary clinical effectiveness study (pivotal phase) involved screening 105,599 newborns.

Data Provenance: The study was performed over 24 months at a public state health laboratory that performs newborn screening. This implies the data were collected in the United States. The study was prospective in nature, as it involved actively screening newborns using the device over a defined period (pivotal phase 18 months). A preliminary study, prior to the pilot/pivotal studies, used approximately 13,000 presumed normal de-identified specimens and 29 known affected specimens, suggesting a mix of retrospective (de-identified) and potentially prospective collection for the known affected cases.

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 of experts" or their specific "qualifications" involved in establishing the ground truth for the clinical test set in a centralized, adjudicatory manner (e.g., as consensus readers for imaging). Instead, the ground truth was established through confirmatory diagnostic methods and clinical follow-up within the standard newborn screening program.

For patients referred for follow-up:

• "Babies considered to still be at high risk for the screened condition after the risk assessment were referred for confirmatory testing."
• "Confirmed positive specimens must have a diagnosis based on confirmatory diagnostic methods or clinically meaningful information regarding the status of the subject must be obtained."

The "risk assessment" itself was performed by the laboratory, and would involve experienced personnel (e.g., laboratory directors, genetic counselors, metabolic specialists). While not explicitly listed as "experts establishing ground truth," these individuals make the critical decisions leading to confirmatory diagnosis. The state public health laboratory also had an active surveillance program to track false negative results, which likely involves experts in metabolic diseases.

4. Adjudication Method for the Test Set

The adjudication method for the clinical test set was an elaborate, multi-step process ingrained in the newborn screening workflow of the state health laboratory:

• Initial Screening: DBS cards were tested in singlicate.
• Retesting for Borderline Results: DBS with at least one enzyme below the borderline cutoff were retested in duplicate.
• Visual Outlier Evaluation: The laboratory evaluated retest results for "visual outliers." If found, additional testing was performed.
• Average Calculation: The average of valid retest results (excluding visual outliers) was calculated.
• Risk Assessment: If the average was below the high-risk cutoff, a risk assessment was performed by the laboratory. This assessment included review of other newborn screening enzyme results, sample quality, transfusion status, health status, transit time, gestational age, family history, and age at sample collection.
• Referral for Confirmatory Testing: Babies still considered at high risk after the risk assessment were referred for confirmatory diagnostic methods.
• Presumed Normal: Babies with an average above the high-risk cutoff after retest, or those not referred after risk assessment, were presumed normal.

This is a complex, stepwise adjudication process, rather than a simple 2+1 or 3+1 consensus. It involves a combination of algorithmic cutoffs, repeat testing, visual inspection, and comprehensive clinical review.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not performed for the SEEKER System. This device is a quantitative enzymatic activity assay for newborn screening, not an imaging-based diagnostic aid or an AI system intended to be used directly by human readers in an interpretive capacity. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply in the context of this device. The SEEKER System performs the assay autonomously using digital microfluidic technology.

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

Yes, the primary function of the SEEKER System is standalone (algorithm only) in measuring enzyme activities. The results are reported as quantitative values (micromoles of 4-MU produced / liter of blood / hour of incubation).

However, the "human-in-the-loop" component comes into play with the interpretation of these quantitative results within the newborn screening program's workflow:

• The device generates raw data, which is then processed by its software (Spot Logic).
• The laboratory applies specific cutoff values (high risk, borderline), which were adjusted and refined during the study period by human experts based on observed performance and factors like age.
• Human judgment is involved in the "risk assessment" process for borderline cases.
• Human decision-making leads to referral for confirmatory testing.

So, while the initial measurement is standalone, the screening decision (positive/negative/retest/referral) is a combination of the device's quantitative output and a multi-step human-defined protocol.

7. The Type of Ground Truth Used

The ground truth used for determining true positives and true negatives in the clinical study was primarily based on confirmatory diagnostic methods and clinical follow-up/outcomes data.

• For positive cases, the "True Positives" are those confirmed by "other confirmatory diagnostic methods." This implies biochemical, genetic, or clinical diagnoses consistent with the respective lysosomal storage diseases.
• For negative cases, the "Presumptive False Positives" are those referred but not confirmed, or those deemed normal after risk assessment. The absence of reported false negatives through the active surveillance program and the assumption that early-onset cases would be clinically identified also contribute to the ground truth for true negatives (i.e., those who screened negative and did not later develop symptoms or receive a diagnosis).

8. The Sample Size for the Training Set

The document does not explicitly delineate a "training set" in the context of typical machine learning or AI models with a distinct number of samples. This device is an enzymatic assay system, not an algorithm that undergoes iterative training on a dataset.

However, the "cutoffs" used by the laboratory for interpreting the results can be thought of as parameters that were "tuned" or "trained" based on observational data:

• "A preliminary study was performed by the public state health laboratory prior to the pilot/pivotal studies to establish initial cutoff values. Approximately 13,000 presumed normal de-identified specimens and 29 known affected specimens were analyzed using the proposed device."
• "The cutoff values were adjusted during the course of the study in order to reduce the false negative and false positive rate and also to take into account seasonal changes..."

These initial 13,029 specimens and the ongoing refinement using data from the 48,813 newborns in the pilot phase could be considered analogous to a "training" or "development" dataset for establishing the operational parameters (cutoffs) of the screening algorithm.

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

For the "training" data (preliminary study and pilot phase used for cutoff adjustments):

• Known affected specimens (29 samples): These likely had their diagnosis confirmed by established diagnostic methods (e.g., enzyme assays, genetic testing) or clinical presentation from relevant patient populations prior to being used in the preliminary study.
• Presumed normal de-identified specimens (13,000 samples): These were likely samples from healthy newborns collected and de-identified, implicitly considered "normal" based on the absence of a disease diagnosis through routine clinical channels.
• Ongoing Adjustment: During the pilot and pivotal phases, the clinical outcomes (confirmatory diagnoses, absence of symptoms) informed the continuous adjustment of cutoffs, acting as a feedback mechanism for refining the test's interpretive ground truth. The "active surveillance program" for false negatives also served to validate the accuracy of the negative screening decisions.

Ask a specific question about this device