(416 days)
This 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.
The Neonatal Total Galactose kit makes use of a fluorescent galactose oxidase method. The assay measures total galactose, i.e. both galactose and galactose-1-phosphate.
The provided information describes a medical device called the "Neonatal Total Galactose Kit" and its performance in a substantial equivalence study as submitted for 510(k) clearance (K071649).
Here's an analysis of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The submission focuses on demonstrating substantial equivalence to a predicate device (BioRad QuantaseTM Neonatal Total Galactose Screening Assay, K990654) rather than explicit acceptance criteria for a novel performance claim alone. However, performance characteristics are compared, which implicitly serve as acceptance benchmarks against the predicate.
For the purpose of this analysis, "acceptance criteria" are interpreted as the comparable performance metrics of the predicate device that the new device aims to match or demonstrate equivalency to. "Reported device performance" refers to the results obtained for the Neonatal Total Galactose Kit.
| Performance Metric | Predicate Device Performance | Neonatal Total Galactose Kit Performance | Acceptance Criteria (implied, based on predicate) |
|---|---|---|---|
| Analytical Sensitivity | 0.60 mg/dL | 1.3 mg/dL | Performance comparable to 0.60 mg/dL |
| Linearity | 0.6 to 55 mg/dL | 1.3 to 56 mg/dL | Performance comparable to 0.6 to 55 mg/dL |
| Measuring Range | 0.6 to 50 mg/mL | 1.3 to 40 mg/mL | Performance comparable to 0.6 to 50 mg/mL |
| Specificity/Recovery (D(+) galactose) | Mean recovery: 95.07% (S.D: 7.49%) in presence of various sugars/metabolites | Mean recovery: 79-81% in presence of galactose, galactose-1-phosphate or both | High recovery and low interference. Results within a clinically acceptable range compared to predicate. |
| Interference | No interference with known antibiotics, non-antibiotics, and metabolites | No interference with glucose, mannose, fructose, ascorbate, bilirubin, hemoglobin, protein BSA, and acetaminophen. Interference with Glutathione (60 mg/dL) and lipemic samples (0.25 - 1 g/dL). | Comparable lack of significant interference with common substances. Specific identified interferences for the new device must be manageable. |
| Intra-assay Precision (%CV) | Low: 3.94% (at 33.96 mg/dL) | Low: 5.3% (at 20.2 mg/dL) | Comparable or improved precision. |
| Total Assay Precision (%CV) | Low: 6.27% (at 6.97 mg/dL) | Low: 8.4% (at 23 mg/dL) | Comparable or improved precision. |
| Method Comparison (Correlation) | N/A (this is the predicate) | y = 0.6Sx + 1.73, r = 0.87 (n = 842) | Sufficient correlation with the predicate device (r > 0.85 is often considered acceptable). |
| Screening Summary (95th percentile) | Overall Percent Agreement: N/A | Positive agreement: 64% (73/114). Overall percent agreement: 95.9% ((73+1956)/2116). | High agreement with predicate for screening purposes. |
| Screening Summary (99th percentile) | Overall Percent Agreement: N/A | Positive agreement: 72.4% (21/29). Overall percent agreement: 99.2% ((21+2078)/2116). | High agreement with predicate for screening purposes, particularly at higher cut-offs. |
| True Positive Detection | Detected 3/3 true positives | Detected 3/3 true positives (at varying concentrations) | Detection of all known true positive cases. |
Note: The analytical sensitivity, linearity, and measuring range are numerically different between the predicate and the new device. The acceptance is implicitly based on these ranges being clinically acceptable for newborn screening and demonstrating equivalence in the overall clinical screening performance.
2. Sample Size Used for the Test Set and Data Provenance
Sample Size:
- Method Comparison: 842 samples for correlation analysis.
- Cut-off Value Determination & Screening Summary: 2109 routine newborn screening dried blood specimens + 7 retrospective specimens (3 diagnosed true positives for galactosemia), totaling 2116 samples.
Data Provenance:
- Country of Origin: The samples represented an "US population."
- Retrospective/Prospective: Primarily retrospective, using "routine newborn screening dried blood spot specimens" and "retrospective specimens."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The documentation does not specify the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method for the Test Set
The documentation does not describe an adjudication method for the test set. The "ground truth" for the test set appears to be based on "diagnosed galactosemia" and routine screening results (implied by the comparison against a predicate device's findings).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study concerns an in-vitro diagnostic kit for measuring an analyte, not typically a visual interpretation task where human readers are involved. Therefore, there's no "human readers improve with AI vs. without AI assistance" effect size to report.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the study describes a standalone device performance. The Neonatal Total Galactose Kit is an in-vitro diagnostic assay. Its performance (analytical sensitivity, linearity, precision, method comparison, and screening summaries) is evaluated as the device itself, separate from human interpretation, although the results would be used by clinicians for decision-making.
7. The Type of Ground Truth Used
The ground truth implicitly used for the screening summary tables (which included "Diagnosed galactosemia") seems to be clinical diagnosis or outcomes data for the "true positives." For the majority of routine samples, the ground truth for comparison is the result obtained from the predicate device.
8. The Sample Size for the Training Set
The documentation does not explicitly mention a separate "training set" or its sample size. The studies described are performance evaluation studies for regulatory submission, typically focusing on validation rather than algorithm training for AI/ML devices. For IVD kits, the "development" or "optimization" phase might use internal samples, but these are not usually referred to as a "training set" in the context of the 510(k) submission.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned, the method for establishing its ground truth is also not described. For a traditional IVD kit, the "ground truth" for calibrators and controls (which might be seen as analogous to training data in a broader sense) would be established through a traceable reference method or gravimetric preparation with certified materials.
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Image /page/0/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" symbol above the name "PerkinElmer". The "P" symbol is made up of a thick vertical line and a triangle shape. Below the name "PerkinElmer" is the word "precisely."
PerkinElme▶Life and Analytical Sciences Wallac Oy P.O. Box 10 FIN-20101 Turku, Finland Phone: +358 - (0)2 - 267 8111 Fax: +358 - (0)2 - 267 8357
510(k) Summary
AUG - 7 2008
This summary of 510(k) safety and effectiveness information is being submitted in Introduction accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| The assigned 510 (k) number is K071649 | ||
|---|---|---|
| Submitter | NameAddress | Wallac OyMustionkatu 620750 Turku, Finland |
| PhoneFax | +358-2-2678575+358-2-2678357 | |
| Contact Person | Helena LundströmRegistration Manager | |
| Date of Preparation | July 31, 2008 | |
| Device name | Trade Name | Neonatal Total Galactose Kit |
| Common Name | Enzymatic Methods, galactose | |
| Classification Name | Galactose Test System (21 CFR 862.1310) Class I | |
| Product Code | JIA | |
| Predicate device | BioRad QuantaseTM Neonatal Total Galactose Screening Assay (K990654) | |
| Description ofthe device | The Neonatal Total Galactose kit makes use of a fluorescent galactose oxidase method.The assay measures total galactose, i.e. both galactose and galactose-1-phosphate. Thefollowing schematic summarizes the reactions that occur during the test procedure: |
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| GAL-1-P + H₂O | AP | GAL + P |
|---|---|---|
| GAL + O₂ | GAO | GHD + H₂O₂ |
| HPPA + H₂O₂ | POD | HPPA dimer* + H₂O |
| GAL-1-P | = | Galactose-1-phosphate |
| AP | = | Alkaline phosphatase |
| GAL | = | Galactose |
| P | = | Phosphate |
| GAO | = | Galactose oxidase |
| GHD | = | D-galacto-hexadialdose |
| POD | = | Peroxidase |
| HPPA | = | 3-( p -hydroxyphenyl)propionic acid |
| * | = | Fluorescent |
:
ﮨﮯ proportional to the concentration of galactose in the sample.
| Intended use | The Neonatal Total Galactose kit is intended for the quantitative determination of totalgalactose (galactose and galactose-1-phosphate) concentrations in blood specimens driedon filter paper as an aid in screening newborns for galactosemia. |
|---|---|
| SubstantialEquivalence | The Neonatal Total Galactose kit is substantially equivalent to the BioRad QuantaseTM |
| Neonatal Total Galactose Screening Assay (K990654). |
:
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Image /page/2/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" shape above the company name. Below the name is the word "precisely."
Device
Comparison The following table compares the Neonatal Total Galactose kit with the predicate device.
| Predicate Device | New Device | |
|---|---|---|
| Device characteristics | BioRad Quantase Total GalactoseScreening Assay | Perkin Elmer Neonatal Total Galactose Kit |
| Device Similarities | ||
| Intended use | The Quantase™ Neonatal TotalGalactose Screening Assay isintended for use as a screeningmethod for measuring the totalD(+)galactose concentrations innewborn blood spot specimens. | The kit is intended for the quantitativedetermination of total galactose (galactoseand galacatose-1-phosphate)concentrations in blood specimens driedon filter paper as aid in screeningnewborns for galactosemia. |
| Technology | Enzymatic assay | The same |
| Kit content | Calibrators/Standards, Controls andEnzymatic Reagents | The same, plus Assay Plates |
| Specimen type | Newborn dried blood spot specimens | The same |
| Interpretation ofresults | Standard curve | The same |
| Calibrator format | Dried blood spots | The same |
| Number of Controls | Two | The same |
| Control format | Dried blood spots | The same |
| Device Differences | ||
| Methodology | Colorimetric end point method | Prompt Fluorescence |
| Instrumentation | Plate reader | Victor2™ D Fluorometer or equivalent |
| Calibrators/standards:Number of levels | Five(Four standard levels + Standard 0which is plain white paper) | Six(six calibrator levels) |
| Analytical sensitivity | 0.60 mg/dL | 1.3 mg/dL |
| Linearity | 0.6 to 55 mg/dL | 1.3 to 56 mg/dL |
| Measuring Range | 0.6 to 50 mg/mL | 1.3 to 40 mg/mL |
| Expected values | Mean total galactose concentration1.05 mg/dL (n=462) measured with apunch size of 3/16". | Median total galactose concentration,1.7 mg/dL (n=2109) measured with a punchsize of 1/8". |
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:
| Specificity/Recovery | Mean recovery of D(+) galactose inthe presense of 100mg/dL of thefollowing sugars and D(+)galactosemetabolites was 95.07% (S:D:7.49%).D-(+)-Gucosea-LactoseD(-)FructoseSucroseMaltoseD(+)MannoseD-MannitolGalactitolD-Galacturonic AcidD-Glucuronic AcidD(-)Ribose | Mean recovery of galactose in the presence ofgalactose, galactose-1-phosphate or galactose+ galactose-1-phosphate was 79 - 81 %. | |||||
|---|---|---|---|---|---|---|---|
| Interference | No interference observed withknown antibiotics, non-antibioticsand metabolites | No interference with glucose, mannose,fructose, ascorbate, bilirubin, hemoglobin,protein BSA and acetaminophen. Glutathione(60 mg/dL) and lipemic samples (0.25 -1g/dL) interfere with the assay. | |||||
| Precision | Intra-assay (1/8 punch size)Mean D(+)Galactoseconc.(mg/dL) | % CV | n | Intra-assay and total variationMeanGalactoseconc.(mg/dL) | Intra-assay(%CV) | Totalvariation(%CV) | n |
| 1.06 | 13.99 | 20 | 7.1 | 6.6 | 12.3 | 143 | |
| 6.81 | 10.02 | 20 | 13.8 | 6.5 | 10.8 | 144 | |
| 14.23 | 6.67 | 20 | 20.2 | 5.3 | 8.6 | 144 | |
| 33.96 | 3.94 | 20 | |||||
| Total Assay ( 1/8 punch size)Mean D(+)Galactoseconc.(mg/dL) | % CV | n | MeanGalactoseconc.(mg/dL) | Intra-assay(%CV) | Totalwithin lotvariation(%CV) | n | |
| 1.43 | 17.42 | 39 | 3.5 | 7.8 | 12.7 | 80 | |
| 6.97 | 6.27 | 40 | 11 | 7.2 | 11.8 | 80 | |
| 14.53 | 7.43 | 40 | 23 | 6.0 | 8.4 | 80 | |
| 33.58 | 8.53 | 40 | 36 | 5.2 | 8.6 | 80 |
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Image /page/4/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" symbol above the company name, with the word "precisely" written below. The "P" symbol is made up of a thick vertical line and an arrow pointing to the right. The word "PerkinElmer" is written in a bold, sans-serif font.
Method Comparison
The PerkinElmer Neonatal Total Galactose kit (y) was compared with the BioRad Quantase™ Neonatal Total Galactose Screening Assay (K990654). using routine newborn screening dried blood spot specimens in the range of 72 umol/L to 1970 umo//L (1.3-3.5 mg/dL) (determined with the PerkinElmer kit). The correlation was found to be:
$$\mathbf{y} = \mathbf{0.6Sx} + \mathbf{1.73}, \quad \mathbf{r} = \mathbf{0.87} \text{ (n = 842)}$$
The total galactose cut-off values by percentile for both the PerkinFilmer Neonatal Total Galactose kit and the predicate were determined by analyzing 2109 routine newborn screening dried blood specimens representing an US population. The results are shown in the table below:
| Total galactose cut-off values by percentile | ||||
|---|---|---|---|---|
| PerkinElmer kit | Predicate | |||
| µmol/L | mg/dL | µmol/L | mg/dL | |
| Median | 94 | 1.7 | 33 | 0.6 |
| 95th percentile | 283 | 5.1 | 233 | 4.2 |
| 97.5th percentile | 355 | 6.4 | 316 | 5.7 |
| 99th percentile | 461 | 8.3 | 521 | 9.4 |
| 99.5th percentile | 549 | 9.9 | 678 | 12.2 |
The screening summaries using the 95th and 99th percented in the tables below. The samples used in the study, representing an US population, included 2116 newborn dricd blood samples (2109 routine screening specimens and seven restrospective specimens of which three were diagnosed true positives for galactosemia).
In the tables below the screening positives (+) are samples ≥ cut-off and the screening negatives (-) arc samples < cut-off.
| Screening summary using the 95th percentile | ||||
|---|---|---|---|---|
| Predicate | PerkinElmer kit | Total | Diagnosedgalactosemia | No diagnosedgalactosemia |
| + | + | 73 | 3 | 70 |
| + | - | 41 | 0 | 41 |
| - | + | 46 | 0 | 46 |
| - | - | 1956 | 0 | 1956 |
| Total | 2116 | 3 | 2113 |
| Screening summary usingthe 95th percentile | Predicate | Total | |||
|---|---|---|---|---|---|
| + | - | ||||
| PerkinElmer kit | + | 73 | 46 | 119 | |
| - | 41 | 1956 | 1997 | ||
| Total | 114 | 2002 | 2116 |
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Image /page/5/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" shape above the company name. The word "PerkinElmer" is in bold, and below it is the word "precisely."
When the 95th percentile was used as a cut-off for both methods, the positive percent was 64% (73/114) and the overall percent agreement was 95.9% ((73+1956)/2116).
| Screening summary using the 99th percentile | ||||
|---|---|---|---|---|
| Predicate | PerkinElmer kit | Totalsubjects | Diagnosedgalactosemia | No diagnosedgalactosemia |
| + | + | 21 | 3 | 18 |
| + | - | 8 | 0 | 8 |
| - | + | 9 | 0 | 9 |
| - | - | 2078 | 0 | 2078 |
| Total | 2116 | 3 | 2113 |
| Screening summary usingthe 99th percentile | Predicate | |||
|---|---|---|---|---|
| + | - | Total | ||
| PerkinElmer kit | + | 21 | 9 | 30 |
| - | 8 | 2078 | 2086 | |
| Total | 29 | 2087 | 2116 |
When the 99" percentile was used as a cut-off for both methods, the positive percent agreement was 72.4%
(21/29) and the overall percent agreement was 99.2% ((21+2078)/2116).
The total galactose concentrations of the three true galactosemia specimens used in the study were as shown in the table below:
| Total Galactose concentrations of true positive specimens | ||
|---|---|---|
| Specimen no. | PerkinElmer kit(mg/dL) | Commercially available kit(mg/dL) |
| 1 | 16.6 | 23.9 |
| 2 | 12.1 | 14.6 |
| 3 | 22.2 | 39.1 |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The logo is black and white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Wallac Oy c/o Ms. Helena Lundstrom Regulatory Affairs Manager Mustionkatu 6, PO Box 10 Turku 20750, Finland
Re: K071649
Trade/Device Name: Neonatal Total Galactose Kit Regulation Number: 21 CFR 862.1310 Regulation Name: Galactose Test System Regulatory Class: Class I Product Code: JIA Dated: July 21, 2008 Received: July 24, 2008
AUG - 7 2008
Dear Ms. Lundstrom:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known): K071649
Device Name: Neonatal Total Galactose Kit
Indication For Use:
This 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.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use __ (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Carol C. Benam
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K071649
§ 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.