(265 days)
The GSP Neonatal Total Galactose kit is intended for the quantitative determination of total galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia using the GSP® instrument.
The GSP Neonatal Total Galactose test system measures total galactose, i.e. both galactose and galactose-1-phosphate, using a fluorescent galactose oxidase method. The fluorescence is measured using an excitation wavelength of 505 nm and an emission wavelength of 580 nm. The GSP Neonatal Total Galactose kit contains sufficient reagents to perform 1152 assays. The kit contains Calibrators, Controls, Neonatal Total Galactose Assay Reagent 1, Neonatal Total Galactose Assay Reagent 2, Neonatal Total Galactose Assay Buffer, Neonatal Total Galactose Assay Reconstitution Solution, and Neonatal Extraction Solution.
The provided document describes the K190335 submission for the GSP Neonatal Total Galactose kit, a device used for screening newborns for galactosemia. It primarily focuses on demonstrating the substantial equivalence of the new device (3309-002U) to a previously cleared predicate device (3309-001U).
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text, with the understanding that this is a medical device clearance document, not an AI/ML model acceptance study. Therefore, some of the requested information (like number of experts for AI ground truth, MRMC study, training set details) are not directly applicable to this type of device and submission.
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the comparison to the predicate device and standard analytical performance metrics for in vitro diagnostic tests. The goal is to show that the new device performs equivalently to the predicate.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (typically similar to predicate performance or within acceptable ranges) | Reported Device Performance (GSP Neonatal Total Galactose kit - 3309-002U) |
|---|---|---|
| Intended Use | Quantitative determination of total galactose and galactose-1-phosphate in dried blood specimens as an aid in screening newborns for galactosemia. | Same as predicate. |
| Test Methodology | Enzymatic assay | Enzymatic assay |
| Detection Method | Fluorescence – measured at 505 nm and 580 nm wavelengths | Fluorescence – measured at 505 nm and 580 nm wavelengths |
| Instrument Platform | GSP instrument, automated (K090846) | GSP instrument, automated (K090846) |
| Sample Type | Dried blood spot | Dried blood spot |
| Reportable Range | 1.15 - 50 mg/dL (Predicate) | 1.2 - 50 mg/dL |
| Limit of Blank (LoB) | 0.34 mg/dL (Predicate) | 0.3 mg/dL (17 umol/L) |
| Limit of Detection (LoD) | 0.97 mg/dL (Predicate) | 0.7 mg/dL (39 umol/L) |
| Limit of Quantitation (LoQ) | 1.15 mg/dL (Predicate) | 1.2 mg/dL (67 umol/L), defined as lowest concentration with total CV ≤ 20% |
| Calibrators | Specific values (0.5, 2.5, 5.0, 10.0, 20, 50 mg/dL) | Specific values (0.5, 2.5, 5.0, 10, 20, 50 mg/dL) |
| Total Variation (%CV) | Not explicitly stated as acceptance criteria, but demonstrates precision. | Ranged from 10.0 to 13.9 %CV |
| Linearity | Demonstrated to be linear throughout the measuring range. | Linear from 1.2 mg/dL to 50 mg/dL |
| Recovery | Not explicitly stated as acceptance criteria, but demonstrates accuracy. | Average recovery: Galactose 98%, Galactose-1-phosphate 115%, Combined 102% |
| Interference | Bias exceeding ±15% is considered significant interference. | Acetaminophen, Conjugated Bilirubin, Intralipid, Hemoglobin/Bilirubin combinations tested (see detailed tables in source for significant interference levels) |
| Hook Effect | No hook effect expected within relevant range. | No hook effect found up to 500 mg/dL |
| Method Comparison (vs. 3309-001U) | Close correlation with predicate device. | mg/dL: y = 1.00x + 0.33; 95% CI: slope (0.96; 1.04), intercept (0.25; 0.42) (n=545) |
| Overall Percent Agreement (95th percentile) | High agreement with predicate. | 98.7 % (95%CI 98.1 % - 99.1 %) |
| Positive Percent Agreement (95th percentile) | High agreement with predicate. | 87.7 % (95%CI 80.3 % - 93.1 %) |
| Negative Percent Agreement (95th percentile) | High agreement with predicate. | 99.3 % (95%CI 98.9 % - 99.6 %) |
| Overall Percent Agreement (99th percentile) | High agreement with predicate. | 99.4 % (95%CI 98.9 % - 99.6 %) |
| Positive Percent Agreement (99th percentile) | High agreement with predicate. | 74.1 % (95%CI 53.7% - 88.9 %) |
| Negative Percent Agreement (99th percentile) | High agreement with predicate. | 99.7 % (95%CI 99.3 % - 99.9 %) |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Analytical Validation (Precision, LoB, LoD, LoQ, Linearity, Recovery, Interference, Hook Effect): Various sample sizes specific to each experiment (e.g., 150 for LoB, 60 for LoD, 40 plates/80 results for repeatability, 15 plates/75 results for between-instrument, 15 plates/75 results for between-lot variation). Samples were human red blood cell enriched with galactose, human blood enriched with galactose and galactose-1-phosphate, whole blood with added substances, or contrived dried blood spot samples.
- Method Comparison:
- Comparison with 3029-0010 Neonatal Total Galactose kit (different method): n=139 samples (routine newborn screening dried blood spot samples and dried adult human whole blood samples spiked with galactose and galactose-1-phosphate).
- Comparison with 3309-001U GSP Neonatal Total Galactose kit (predicate): n=545 routine newborn screening dried blood spot samples.
- Screening Performance Study:
- Test Set Size: 2161 samples.
- Data Provenance: Conducted at one newborn screening laboratory in the United States.
- Retrospective/Prospective: The samples included "routine newborn screening dried blood spot samples" (implying prospective collection in a screening program context) and "retrospective galactosemia diagnosed screening samples" (implying retrospective identification of confirmed positive cases). Specifically, the 95th percentile analysis included 5 retrospective galactosemia diagnosed screening samples and 1 retrospective galactosemia screening sample collected 22 hours after birth. The 99th percentile analysis included 4 retrospective galactosemia diagnosed screening samples, 1 retrospective galactosemia diagnosed screening sample collected 22 hours after birth, and 1 retrospective galactosemia diagnosed screening sample collected 16 hours after birth.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This is an in vitro diagnostic (IVD) device, not an AI/ML model for image interpretation. The "ground truth" for the screening performance study is clinical diagnosis of galactosemia, or the results from the predicate device using routine newborn screening samples.
- The document does not specify the number or qualifications of experts (e.g., radiologists) in the context of establishing ground truth, as this is not a study involving subjective interpretation like medical imaging by human experts. The 'truth' is derived from the biochemical measurements and clinical outcomes associated with galactosemia screening performed by a validated screening program.
4. Adjudication Method for the Test Set:
- Not applicable in the context of an IVD device. The 'comparison' and 'screening performance' results are based on quantitative measurements by both the new device and the predicate device compared to each other, and against known clinical results (for retrospective samples). There is no "adjudication" between human readers or AI outputs in the way it's understood for image interpretation or diagnosis.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No. An MRMC study is relevant for perception tasks like image interpretation where human readers' performance is evaluated. This is an in vitro diagnostic assay that produces quantitative results. The comparison is between the new device's quantitative output and the predicate device's quantitative output, as well as their agreement on screening classification (positive/negative) against the established screening program's outcomes.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The GSP Neonatal Total Galactose kit is a standalone in vitro diagnostic system. Its performance (accuracy, precision, linearity, etc.) is measured intrinsically and compared to the predicate, independent of human operators' subjective interpretation. The "screening performance study" evaluates the device's ability to classify samples as screen positive or negative based on its quantitative output, without direct human "interpretation" of the assay result itself. Human decision-making uses this quantitative result but isn't part of the direct device performance.
7. The Type of Ground Truth Used:
- For analytical performance (Precision, LoB, LoD, LoQ, Linearity, Recovery, Interference, Hook Effect): The ground truth is established by known concentrations of analytes (galactose, galactose-1-phosphate) in spiked samples, or by established measurement principles for blank and low-level samples.
- For Method Comparison: The ground truth is the measurement obtained from the predicate device and the 3029-0010 Neonatal Total Galactose kit. This establishes agreement.
- For Screening Performance Study: The ground truth is a combination of:
- Predicate Device Results: For routine samples, the predicate device's classification (screen positive/negative) serves as the comparator.
- Clinical Diagnosis/Outcomes: For "retrospective galactosemia diagnosed screening samples," the confirmed clinical diagnosis of galactosemia (presumably through follow-up testing and clinical presentation) serves as the ultimate truth for these specific cases.
8. The Sample Size for the Training Set:
- This device is an IVD kit, not an AI/ML algorithm. Therefore, there is no "training set" in the context of machine learning. The device's calibration curve is established using known calibrators provided in the kit. The "training" of an IVD like this involves chemical formulation, assay optimization, and manufacturing process control, not data-driven learning from a "training set" like an AI model.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable, as there is no training set for this type of device. The calibrators have been prepared from human red blood cells enriched with galactose and calibrated against primary calibrators gravimetrically prepared using a U.S. Pharmacopeia Reference Standard Preparation for galactose. This establishes the "truth" for calibration.
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November 6, 2019
PerkinElmer Inc. Brian Ciccariello Head of Regulatory & Medical Affairs - Americas 940 Winter Street Waltham, MA 02451
Re: K190335
Trade/Device Name: GSP Neonatal Total Galactose kit Regulation Number: 21 CFR 862.1310 Regulation Name: Galactose test system Regulatory Class: Class I, Reserved Product Code: JIA Dated: September 27, 2019 Received: September 30, 2019
Dear Brian Ciccariello:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, M.T., Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K190335
Device Name GSP Neonatal Total Galactose kit
Indications for Use (Describe)
The GSP Neonatal Total Galactose kit is intended for the quantitative determination of total galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia using the GSP® instrument.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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GSP Neonatal Total Galactose Kit
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510(k) Summary
This 510(k) Summary information is supplied in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is K190335.
Date: November 5, 2019
| Submitted by: | PerkinElmer Inc.940 Winter StreetWaltham, MA 02451 |
|---|---|
| Contact Person: | Brian CiccarielloHead of Regulatory & Medical Affairs - AmericasEmail: brian.ciccariello@perkinelmer.comPhone: 781-663-5651 |
| Trade Name: | GSP Neonatal Total Galactose kit |
| Common Name: | Galactose test System |
| Regulation: | 21 CFR 862.1310 |
| Classification Name: | Galactose test System |
| Classification: | I, Reserved |
| Panel: | 75 Clinical Chemistry |
| Product Code: | JIA |
| Predicate Device: | GSP Neonatal Total Galactose kit [K133652] |
Device Description:
The GSP Neonatal Total Galactose test system measures total galactose, i.e. both galactose and galactose-1-phosphate, using a fluorescent galactose oxidase method. The fluorescence is measured using an excitation wavelength of 505 nm and an emission wavelength of 580 nm. The GSP Neonatal Total Galactose kit contains sufficient reagents to perform 1152 assays.
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The kit contains the following components:
Calibrators have been prepared from human red blood cells enriched with galactose, and with ProClin 300 as preservative. The hematocrit value is 50 - 55 % to correspond to a hematocrit of a newborn. The calibrators have been calibrated against primary calibrators gravimetrically prepared using a U.S. Pharmacopeia Reference Standard Preparation for galactose.
Controls have been prepared from human blood enriched with galactose and galactose-1phosphate, and with ProClin 300 as preservative. Prior to dispensing the blood onto the filter paper, the hematocrit value of blood used in the controls preparation is adjusted to 50 - 55 % to correspond to a hematocrit of a newborn. The low control is approximately 4.0 mg/dL and the high control approximately 12 mg/dL.
All human source materials used in the preparation of kit components were tested and found to be non-reactive for the presence of HBsAg, anti-HIV 1 and 2, and HCV by FDA approved methods.
Neonatal Total Galactose Assay Reagent 1 - 3 lyophilized vials Neonatal Total Galactose Assay Reagent 2 - 3 lyophilized vials Neonatal Total Galactose Assay Buffer - 3 bottles, 40 ml Neonatal Total Galactose Assay Reconstitution Solution - 1 bottle. 20 ml Neonatal Extraction Solution - 2 bottles, 60 ml
Intended Use:
The GSP Neonatal Total Galactose kit is intended for the quantitative determination of total galactose (galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia using the GSP® instrument.
Comparison Chart:
Comparison of the GSP Neonatal Total Galactose device with its predicate:
| GSP Neonatal Total Galactose kit | ||
|---|---|---|
| Characteristics | Proposed Device | Predicate Device (K133652) |
| IntendedUse/Indications forUse | The GSP Neonatal TotalGalactose kit is intended for thequantitative determination of totalgalactose (galactose andgalactose-1-phosphate)concentrations in blood specimensdried on filter paper as an aid inscreening newborns forgalactosemia using the GSP®instrument. | Same |
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| Test Methodology | Enzymatic assay | Same |
|---|---|---|
| Detection Method | Fluorescence – measured at 505nm and 580 nm wavelengths | Same |
| Instrument Platform | GSP instrument, automated(K090846) | Same |
| Sample Type | Dried blood spot | Same |
| Reportable Range | 1.2 - 50 mg/dL | 1.15 - 50 mg/dL |
| Lower Limits ofMeasure | LoB = 0.3 mg/dLLoD = 0.7 mg/dLLoQ = 1.2 mg/dL | LoB = 0.34 mg/dLLoD = 0.97 mg/dLLoQ = 1.15 mg/dL |
| Calibrators | A - 0.5 mg/dLB - 2.5 mg/dLC - 5.0 mg/dLD - 10 mg/dLE - 20 mg/dLF - 50 mg/dL | A - 0.5 mg/dLB - 2.5 mg/dLC - 5.0 mg/dLD - 10.0 mg/dLE - 20 mg/dLF - 50 mg/dL |
| Part Number | 3309-002U | 3309-001U |
Summary of Non-Clinical Studies:
The variation of the 3309-002U GSP Neonatal Total Galactose assay was determined in three different studies using dried blood spot samples. The repeatability (within-plate variation) and within-laboratory variation were determined with 40 plates (2 sample replicates/plate) of a single kit lot measured over 20 working days with a single GSP instrument (80 results/sample). The between-instrument variation was determined with 15 plates (5 sample replicates/plate) of a single kit lot measured over 5 working days with three GSP instruments (75 results/sample). The between-lot variation was determined with 15 plates (5 sample replicates/plate) of three kit lots measured over 5 working days with a single GSP instrument (75 results/sample). Total variation ranged from 10.0 to 13.9 %CV.
The Limit of Blank (LoB) for total galactose is 0.3 mg/dL (17 umo//L), defined as the 95th percentile of a distribution of blank samples (n = 150). The Limit of Detection (LoD) is 0.7 mg/dL (39 umol/L) based on 60 determinations of 6 low level samples. The Limit of Quantitation (LoQ) is 1.2 mg/dL (67 umol/L), defined as the lowest concentration with a total CV equal to or less than 20 %.
For total galactose, the method has been demonstrated to be linear throughout the measuring range (from 1.2 mg/dL (67 umol/L) to 50 mg/dL (2775 umol/L)).
The recovery of galactose, galactose-1-phosphate, and both combined was determined from three contrived dried blood spot samples with an average recovery of 98%, 115% and 102% respectively.
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The potentially interfering substances were added to whole blood with three total galactose concentrations (5, 10, and 15 mg/dL). The substances indicated in the table below were found not to interfere with the assay. A bias exceeding ±15% is considered a significant interference.
| Total Galactoseconc. (mg/dL) | Acetaminophenconcentrationtested mg/dL | Percent change inmeasured galactose(%) | Significantchange |
|---|---|---|---|
| 5 | 1.38 | -6.7 | No |
| 2.75 | -13.5 | No | |
| 4.13 | -23.7 | Yes | |
| 5.5 | -24.3 | Yes | |
| 10 | 1.38 | -9.8 | No |
| 2.75 | -16.3 | Yes | |
| 4.13 | -20.3 | Yes | |
| 5.5 | -22.0 | Yes | |
| 15 | 1.38 | -10.3 | No |
| 2.75 | -18.5 | Yes | |
| 4.13 | -25.9 | Yes | |
| 5.5 | -29.5 | Yes |
| Total Galactoseconc. (mg/dL) | Conjugated bilirubinconcentrationtested mg/dL | Percent change inmeasured galactose(%) | Significantchange |
|---|---|---|---|
| 5 | 8.3 | -7.8 | No |
| 16.6 | -44.8 | Yes | |
| 24.9 | -90.5 | Yes | |
| 33.2 | -93.7 | Yes | |
| 10 | 8.3 | -5.0 | No |
| 16.6 | -13.9 | No | |
| 24.9 | -38.2 | Yes | |
| 33.2 | -84.5 | Yes | |
| 15 | 8.3 | -1.4 | No |
| 16.6 | -8.0 | No | |
| 24.9 | -24.5 | Yes | |
| 33.2 | -75.4 | Yes |
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Intralipid was found not to interfere up to added concentrations of 125 mg/dL total galactose, up to 375 mg/dL at 10 mg/dL total galactose, and up to 500 mg/dL at 15 mg/dL total galactose. When present above these amounts Intralipid may cause a false positive screening result for a sample with measured total galactose concentration close to the cut-off value.
| Total Galactoseconc. (mg/dL) | Intralipidconcentration testedmg/dL | Percent change inmeasured galactose (%) | Significantchange |
|---|---|---|---|
| 5 | 125 | 1.1 | No |
| 250 | 21.1 | Yes | |
| 375 | 29.7 | Yes | |
| 500 | 40.8 | Yes | |
| 750 | 58.2 | Yes | |
| 1130 | 97.1 | Yes | |
| 1500 | 126.0 | Yes | |
| 10 | 125 | 6.2 | No |
| 250 | 9.4 | No | |
| 375 | 11.8 | No | |
| 500 | 22.0 | Yes | |
| 750 | 40.2 | Yes | |
| 1130 | 53.0 | Yes | |
| 1500 | 67.6 | Yes | |
| 15 | 125 | -4.3 | No |
| 250 | 0.7 | No | |
| 375 | 8.7 | No | |
| 500 | 8.2 | No | |
| 750 | 22.3 | Yes | |
| 1130 | 37.2 | Yes | |
| 1500 | 50.2 | Yes |
In addition, hemoglobin in combination with elevated bilirubin concentration of 15 mg/dL was found to interfere with the assay by increasing the measured total galactose concentration (see the table below). Therefore, hemoglobin level at 237 g/L and above in combination with elevated bilirubin level may cause a false positive screening result for a sample with measured total galactose concentration close to the cut-off value.
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| Total Galactose conc.(mg/dL) | Hemoglobinconcentration tested g/Lat bilirubin level15 mg/dL | Percent change inmeasured galactose (%) | Significant change |
|---|---|---|---|
| 5 | 103 | -11.7 | No |
| 204 | 10.3 | No | |
| 223 | 7.1 | No | |
| 237 | 17.6 | Yes | |
| 10 | 103 | -5.9 | No |
| 204 | 14.2 | No | |
| 223 | 12.1 | No | |
| 237 | 17.6 | Yes | |
| 15 | 103 | -12.3 | No |
| 204 | 6.9 | No | |
| 223 | 12.0 | No | |
| 237 | 13.2 | No |
Hematocrit levels from 35% to 65% (Hemoglobin levels 12-22 g/dL, i.e. 120-220 g/L) were found not to interfere at total galactose concentrations of 5, 10, and 15 mg/dL.
Hook Effect:
No hook effect has been found with total galactose concentrations up to 500 mg/dL (27750 umol/L)
Summary of Method Comparison:
The 3309-002U GSP Neonatal Total Galactose kit (y) was compared with the 3029-0010 Neonatal Total Galactose kit (x) using routine newborn screening dried blood spot samples and dried adult human whole blood samples spiked with galactose and galactose-1-phosphate in the range of 1.2-50 mg/dL (67-2775 umol/L) when determined with the 3309-002U GSP Neonatal Total Galactose kit. The correlation from weighted Deming regression was found to be:
mg/dL: y= 1.05x - 0.29; 95% CI: slope (0.97; 1.12), intercept (-0.48; -0.10) (n=139) umol/L: y= 1.05x - 16; 95% CI: slope (0.97; 1.12), intercept (-27; -6) (n=139)
The 3309-002U GSP Neonatal Total Galactose kit (y) was compared with the 3309-001U GSP Neonatal Total Galactose kit (x) using routine newborn screening dried blood spot samples in the range of 1.2-50 mg/dL (67-2775 µmol/L) when determined with the 3309-002U GSP Neonatal Total Galactose kit. The correlation from Deming regression was found to be:
mg/dL: y = 1.00x + 0.33; 95% CI: slope (0.96; 1.04), intercept (0.25; 0.42) (n=545) umol/L: y = 1.00x + 18.6; 95% CI: slope (0.96; 1.04), intercept (13.7; 23.4) (n=545)
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Summary of screening performance study:
In a study conducted at one newborn screening laboratory in the United States, the screening performance of the new and predicate device was evaluated with a total of 2161 samples (7 confirmed positive samples and 2154 routine samples). The screening performance is shown below based on 95th and 99th percentile values.
Screening performance of GSP Neonatal Total Galactose test system (95th percentile)
| 3309-001U | ||||
|---|---|---|---|---|
| Screeningpositive≥ 3.9 mg/dL | Screeningnegative< 3.9 mg/dL | Total | ||
| 3309-002U | Screening positive≥ 4.1 mg/dL | 100* | 14 | 114 |
| Screening negative< 4.1 mg/dL | 14 | 2033** | 2047 | |
| Total | 114 | 2047 | 2161 |
- Includes 5 retrospective galactosemia diagnosed screening samples.
** Includes 1 retrospective galactosed screening sample that was collected 22 hours after birth. . According to CLSI guideline [5], for laboratories measuring galactose it may be necessary to wait at least 24 hours of milk intake to transpire to minimize false-negative results.
** Includes 1 Duarte variant sample, see Limitations of the Procedure for details.
Overall percent agreement = 98.7 % (95%CI 98.1 % - 99.1 %) Positive percent agreement = 87.7 % (95%CI 80.3 % - 93.1 %) Negative percent agreement = 99.3 % (95%CI 98.9 % - 99.6 %)
Screening performance of GSP Neonatal Total Galactose test system (99th percentile)
| 3309-001U | ||||
|---|---|---|---|---|
| Screeningpositive≥ 7.0 mg/dL | Screeningnegative< 7.0 mg/dL | Total | ||
| 3309-002U | Screening positive≥ 6.8 mg/dL | 20* | 7 | 27 |
| Screening negative< 6.8 mg/dL | 7*** | 2127** | 2134 | |
| Total | 27 | 2134 | 2161 |
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- Includes 4 retrospective galactosemia diagnosed screening samples.
** Includes 1 retrospective galactosemia diagnosed screening sample that was collected 22 hours after birth. . According to CLSI guideline [5], for laboratories measuring galactose it may be necessary to wait at least 24 hours of milk intake to transpire to minimize false-negative results.
** Includes 1 Duarte variant sample, see Limitations of the Procedure for details.
*** Includes 1 retrospective galactosemia diagnosed screening sample that was collected 16 hours after birth. According to CLSI guideline [5], for laboratories measuring galactose it may be necessary to wait at least 24 hours of milk intake to transpire to minimize false-negative results.
Overall percent agreement = 99.4 % (95%CI 98.9 % - 99.6 %) Positive percent agreement = 74.1 % (95%CI 53.7% - 88.9 %) Negative percent agreement = 99.7 % (95%CI 99.3 % - 99.9 %)
Substantial Equivalency:
The proposed device and predicate device utilize similar enzymatic pathway and design shown to produce equivalent screening performance in a clinical setting. Both devices are intended for use in for the quantitative determination of total galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia.
Conclusion:
The GSP Neonatal Total Galactose test system demonstrates analytical and screening performance that supports its substantial equivalency with the predicate device, the 3309-001U GSP Neonatal Total Galactose test system (K133652).
§ 862.1310 Galactose test system.
(a)
Identification. A galactose test system is a device intended to measure galactose in blood and urine. Galactose measurements are used in the diagnosis and treatment of the hereditary disease galactosemia (a disorder of galactose metabolism) in infants.(b)
Classification. Class I.