(244 days)
No
The summary describes a reagent kit and a mass spectrometry system for quantitative analysis of analytes. There is no mention of AI or ML in the intended use, device description, or performance studies. The analysis is based on the proportional relationship between analyte response and concentration, a standard analytical chemistry technique.
No.
The device is intended for the measurement and evaluation of analytes to aid in screening newborns for metabolic disorders, which is a diagnostic purpose, not a therapeutic one.
Yes
This device measures biomolecules (amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations) from newborn heel prick blood samples to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders, fitting the definition of a diagnostic device.
No
The device is a reagent kit used with a mass spectrometry system, indicating it is a physical product and not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the kit is for the "measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper." This involves testing a sample taken from the human body (blood) outside of the body to provide information about a person's health.
- Purpose: The purpose is to "aid in screening newborns for metabolic disorders" by providing "analyte concentration profiles." This is a diagnostic purpose, even though it's for screening rather than definitive diagnosis.
- Device Description: The description details a method for analyzing these analytes using a laboratory technique (tandem mass spectrometry) on a biological sample (dried blood spots).
These characteristics align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes.
N/A
Intended Use / Indications for Use
The Neobase Non-derivatized MSMS reagent kit (for use on the PerkinElmer TQD MSMS Screening System) is intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper. Quantitative analysis of these analytes (Table 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
Product codes
NQL
Device Description
The measurement of amino acids, succinylacetone, free carnitine, and acylcarnitines with the NeoBase assay involves extraction of dried blood spots from newborns with a solution containing stable-isotope labeled internal standards and analysis using a tandem mass spectrometry (MSMS) system. The response of each analyte relative to their internal stable-isotope labeled corresponding standard is proportional to analyte concentration.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Newborns
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Non-clinical: The performance of the NeoBase Non-derivatized MSMS kit on the PerkinElmer TQD Triple Quadrupole Mass Spectrometer System (PerkinElmer TQD platform) was compared to the predicate MS2 and PerkinElmer Quattro Micro platforms performance, K031878. All of these are tandem mass spectrometry platforms capable of measuring the NeoBase panel of amino acids and acylcarnitines from neonatal dried blood spots. The panel of analytes measured by all three platforms is the same. Analytically, all devices are identical regarding sample requirements, sample processing, analysis time and assay format (Tables 5.1 and 5.2). The performance of the NeoBase kit on the PerkinElmer TQD platform was compared against the corresponding characteristics reported in the predicate device product insert. A summary of the performance characteristics is presented in Tables 5.3 to 5.6. The NeoBase kit provides equivalent precision, recoveries and measurable ranges that cover all clinically significant ranges on all platforms tested. Therefore, the NeoBase kit provides performance levels that are adequate for its intended use on the MS2, PerkinElmer Quattro Micro and PerkinElmer TQD platforms
Clinical correlation studies involved the analysis of 2499 random newborn screening specimens and 17 specimens with true positive diagnoses. In addition, a set of enriched samples (five levels) was analyzed (as singlicates of each level) for 16 runs to provide a total of 80 individual measurements. All samples were evaluated in parallel on the TQD and the predicate MS- platforms using the NeoBase kit. Clinical correlation was established by assessing whether or not the platforms were concordant in determining the paired samples to have analyte concentration values above or below their corresponding cutoffs. Examination on the number of concordant pairs for each analyte (cases in which both methods agreed) provided the percent agreements shown in Table 5.9. The correlation between the test and predicate platforms included 17 samples with true positive diagnoses representing 14 disorders (Table 5.10). All of these cases were successfully detected by both platforms for 100% agreement in the clinical determination (Table 5.10).
Key Metrics
Precision:
- Amino acids: Average Total imprecision coefficients of variation (%CV) for QM, MS2, and TQD platforms range from 8% to 18%.
- Carnitine and acylcarnitines: Average Total imprecision coefficients of variation (%CV) for QM, MS2, and TQD platforms are not fully represented in the provided excerpt but generally show acceptable levels.
Recovery:
- Mean % Recovery for analytes:
- ALA: TQD 100%, QMicro 92%, MS2 83%
- ARG: TQD 86%, QMicro 87%, MS2 87%
- CIT: TQD 93%, QMicro 96%, MS2 95%
- GLY: TQD 90%, QMicro 93%, MS2 86%
- LEU: TQD 101%, QMicro 93%, MS2 88%
- MET: TQD 97%, QMicro 88%, MS2 86%
- ORN: TQD 98%, QMicro 91%, MS2 91%
- PHE: TQD 94%, QMicro 95%, MS2 89%
- PRO: TQD 97%, QMicro 93%, MS2 84%
- SA: TQD 57%, QMicro 64%, MS2 62%
- TYR: TQD 84%, QMicro 96%, MS2 102%
- VAL: TQD 90%, QMicro 88%, MS2 78%
- C0: TQD 104%, QMicro 91%, MS2 107%
- C2: TQD 95%, QMicro 93%, MS2 97%
- C3: TQD 93%, QMicro 94%, MS2 95%
- C4: TQD 93%, QMicro 91%, MS2 92%
- C5: TQD 86%, QMicro 91%, MS2 94%
- C5DC: TQD 99%, QMicro 99%, MS2 104%
- C6: TQD 91%, QMicro 91%, MS2 83%
- C8: TQD 100%, QMicro 90%, MS2 96%
- C10: TQD 92%, QMicro 97%, MS2 95%
- C12: TQD 102%, QMicro 93%, MS2 103%
- C14: TQD 92%, QMicro 92%, MS2 94%
- C16: TQD 92%, QMicro 93%, MS2 84%
- C18: TQD 89%, QMicro 91%, MS2 94%
Method Correlation (Mean ratio of measured concentration for MS2/TQD and Q Micro/TQD comparisons):
- MS2/TQD comparison: Ratios range from 0.89 to 1.09, indicating statistically equivalent results.
- Q Micro/TQD comparison: Ratios range from 0.92 to 1.08, indicating statistically equivalent results.
Clinical Determinations Percent Agreement between TQD and MS2 platforms:
- ALA: 99.6%
- ARG: 99.9%
- CIT: 99.8%
- GLY: 99.5%
- LEU: 99.6%
- MET: 100.0%
- ORN: 99.6%
- PHE: 99.9%
- PRO: 99.8%
- SA: 99.5%
- TYR: 99.2%
- VAL: 99.7%
- C0: 100.0%
- C2: 99.9%
- C3: 100.0%
- C4: 99.9%
- C5: 99.9%
- C5DC: 99.7%
- C6: 99.7%
- C8: 99.8%
- C10: 99.9%
- C12: 99.8%
- C14: 99.9%
- C16: 99.6%
- C18: 99.9%
- C4OH/C3DC: 99.9%
- C5OH/C4DC: 99.9%
- C5:1: 99.4%
- C6DC: 99.8%
- C8:1: 99.9%
- C10:1: 100.0%
- C10:2: 99.7%
- C12:1: 100.0%
- C14-OH: 99.7%
- C14:1: 99.8%
- C14:2: 99.8%
- C16-OH: 99.8%
- C16:1: 99.9%
- C16:1-OH: 99.8%
- C18-OH: 99.6%
- C18:1: 99.9%
- C18:1-OH: 99.2%
- C18:2: 100.0%
True Positive Sample Results: 100% agreement in clinical determination for all 17 true positive samples representing 14 disorders when compared between MS and TQD platforms.
Predicate Device(s)
Reference Device(s)
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1055 Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry.
(a)
Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry is a device that consists of stable isotope internal standards, control materials, extraction solutions, flow solvents, instrumentation, software packages, and other reagents and materials. The device is intended for the measurement and evaluation of amino acids, free carnitine, and acylcarnitine concentrations from newborn whole blood filter paper samples. The quantitative analysis of amino acids, free carnitine, and acylcarnitines and their relationship with each other provides analyte concentration profiles that may aid in screening newborns for one or more inborn errors of amino acid, free carnitine, and acyl-carnitine metabolism.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry.” See § 862.1(d) for the availability of this guidance document.
0
AUG 2 3 2010
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is supplied in accordance with the requirements of the SMDA of 1990 and 21 CFR 807.92
The assigned 510(k) number is K093916
Date: August 18, 2010
Submitted by:
Wallac Oy a subsidiary of PerkinElmer Mustionkatu 6 20750 Turku, Finland
Contact person:
Primary:
Kay A. Taylor Tele: 317-418-1735 Fax: 317-536-3064
Secondary:
Susan Hamann Tele: 781-633-5872 781-633-5983 Fax:
Trade Name:
NeoBase Non-derivatized MSMS Kit
NeoBase kit or Non-derivatized kit Common Name:
Newborn screening test system for amino acids, free Classification Name: carnitine, and acylcarnitines using tandem mass spectrometry (21 CFR § 862.1055 /Product code NQL)
NeoBase Non-derivatized MSMS Kit, K083130 Predicate device(s):
The measurement of amino acids, succinylacetone, Device description: free carnitine, and acylcarnitines with the NeoBase assay involves extraction of dried blood spots from newborns with a solution containing stable-isotope labeled internal standards and analysis using a tandem mass spectrometry (MSMS) system. The each analyte relative to their response of internal stable-isotope labeled corresponding standard is proportional to analyte concentration
1
1
Intended Use: Indications for Use
The Neobase Non-derivatized MSMS reagent kit (for use on the PerkinElmer TQD MSMS Screening System) is intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper.
Quantitative analysis of these analytes (Table 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
Instruments: - PerkinElmer MS2 Tandem Mass Spectrometer System (MS2) - PerkinElmer MSMS Quattro Micro (Qmicro) Newborn Screening System
- PerkinElmer MSMS TQD Newborn Screening System
| ANALYTE NAME | ABBREVIATION |
|---|---|
| Amino acids | |
| Alanine | Ala |
| Arginine | Arg |
| Citrulline | Cit |
| Glycine | Gly |
| Leucine/Isoleucine/Hydroxyproline* | Leu/Ile/Pro-OH |
| Methionine | Met |
| Ornithine | Orn |
| Phenylalanine | Phe |
| Proline | Pro |
| Tyrosine | Tyr |
| Valine | Val |
| Carnitines | |
| Free carnitine | C0 |
| Acetylcarnitine | C2 |
| Propionylcarnitine | C3 |
| Malonylcarnitine / 3-Hydroxy-butyrylcarnitine* | C3DC/C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl / 3-Hydroxy-isovalerylcarnitine* | C4DC/C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine / 3-Hydroxy-hexanoylcarnitine* | C5DC/C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
Table 1. Analytes measured by the NeoBase Non-derivatized MSMS Kit
2
| Octenoylcarnitine | C8:1 |
|---|---|
| Decanoylcarnitine | C10 |
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
| ANALYTE NAME | ABBREVIATION |
| Carnitines | |
| Dodecenoylcarnitine | C12:1 |
| Tetradecanoylcarnitine (Myristoylcarnitine) | C14 |
| Tetradecenoylcarnitine | C14:1 |
| Tetradecadienoylcarnitine | C14:2 |
| 3-Hydroxy-tetradecanoylcarnitine | C14OH |
| Hexadecanoylcarnitine (palmitoylcarnitine) | C16 |
| Hexadecenoylcarnitine | C16:1 |
| 3-Hydroxy-hexadecanoylcarnitine | C16OH |
| 3-Hydroxy-hexadecenoylcarnitine | C16:1OH |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| Ketones | |
| Succinylacetone | SA |
*Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometry experiment.
Device Comparison:
Table 5.1: Comparison of the modified device (NeoBase Non-derivatized MSMS Assay on the TQD Platform_ and predicate device.
| GENERAL CHARACTERISTICS | ||
|---|---|---|
| Parameter | Modified Device | Predicate Device |
| Intended Use | The NeoBase Non-derivatized MSMS | |
| reagent kit is intended for the measurement | ||
| and evaluation of amino acids, | ||
| succinylacetone, free carnitine, and | ||
| acylcarnitine concentrations from newborn | ||
| heel prick blood samples dried on filter | ||
| paper. Quantitative analysis of these | ||
| analytes (Table 1) and their relationship | ||
| with each other is intended to provide | ||
| analyte concentration profiles that may aid | ||
| in screening newborns for metabolic | ||
| disorders. | ||
| (intended use employs a table to identify | ||
| each analyte detected) | Same | |
| Instrumentation | PerkinElmer MS2 Tandem Mass | |
| Spectrometer System (MS2) | ||
| PerkinElmer MSMS Quattro Micro (Qmicro) | - PerkinElmer MS2 Tandem | |
| Mass Spectrometer System |
- PerkinElmer MS/MS Qmicro |
3
| Newborn Screening System
PerkinElmer MSMS TQD Newborn
| Screening System | Screening System |
|---|---|
| ------------------------------------------------------------------------------ | ------------------ |
·
| GENERAL CHARACTERISTICS | ||
|---|---|---|
| Parameter | Modified Device | Predicate Device |
| Disorders Screened | Amino-, organic-, and fatty acid metabolic | |
| disorders | Same | |
| Analytes Measured | Amino acids, free carnitine, acylcarnitines, | |
| and succinylacetone | Same | |
| Methodology | Microplate based tandem mass | |
| spectrometric assay | Same | |
| Test Principle | Amino acids and carnitines in sample are | |
| measured by tandem mass spectrometry | ||
| through analyte-specific mass transitions | ||
| appropriate for each type of analyte. The | ||
| extracted analytes are measured for set | ||
| time periods and compared to the signal | ||
| intensities produced by the corresponding | ||
| isotope-labeled internal standards. The | ||
| concentrations are determined by | ||
| comparing the signal intensities of the | ||
| known standards to the measured analytes. | Same | |
| Quantitative Nature | Quantitative by internal standardization | Same |
| Sample Requirements | Newborn blood collected on Schleicher and | |
| Schuell 903 filter paper per NCCLS | ||
| standards | Same | |
| Throughput | Ninety-six tests per microtiter plate. Multiple | |
| plates can be analyzed | Same | |
| Analysis Time | 2 to 2.5 hours per plate. | Same |
| Controls | Controls are blood spots from processed | |
| human blood enriched with several amino | ||
| acids, carnitines and succinylacetone. | Same | |
| Calibrators | Internal calibration using several isotopically | |
| labeled standards, included as dried | ||
| material in vials. Internal standards must be | ||
| reconstituted with extraction solution prior to | ||
| their use. | Same | |
| Assay format | Non-derivatized (analytes measured in their | |
| native forms) | Same |
Analytes measured by the device
:
| ANALYTE NAME | ABBREVIATION |
|---|---|
| Amino acids | |
| Alanine | Ala |
| Arginine | Arg |
| Citrulline | Cit |
| Glycine | Gly |
| Leucine/Isoleucine/Hydroxyproline* | Leu/Ile/Pro-OH |
| Methionine | Met |
4
| Ornithine | Orn |
|---|---|
| Phenylalanine | Phe |
| Proline | Pro |
| Tyrosine | Tyr |
| Valine | Val |
| Carnitines | |
| Free carnitine | CO |
| Acetylcarnitine | C2 |
| Propionylcarnitine | C3 |
| Malonylcarnitine / 3-Hydroxy-butyrylcarnitine* | C3DC/C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl / 3-Hydroxy-isovalerylcarnitine* | C4DC/C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine / 3-Hydroxy-hexanoylcarnitine* | C5DC/C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
| Octenoylcarnitine | C8:1 |
| Decanoylcarnitine | C10 |
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
| Dodecenoylcarnitine | C12:1 |
| Tetradecanoylcarnitine (Myristoylcarnitine) | C14 |
| Tetradecenoylcarnitine | C14:1 |
| Tetradecadienoylcarnitine | C14:2 |
| 3-Hydroxy-tetradecanoylcarnitine | C14OH |
| Hexadecanoylcarnitine (palmitoylcarnitine) | C16 |
| Hexadecenoylcarnitine | C16:1 |
| 3-Hydroxy-hexadecanoylcarnitine | C16OH |
| 3-Hydroxy-hexadecenoylcarnitine | C16:1OH |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| Ketones | |
| Succinylacetone | SA or SUAC |
*Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometry experiment.
Substantial equivalency:
(1) Non-clinical
The performance of the NeoBase Non-derivatized MSMS kit on the PerkinElmer TQD Triple Quadrupole Mass Spectrometer System (PerkinElmer TQD platform) was compared to the predicate MS2 and PerkinElmer Quattro Micro platforms performance, K031878. All of these are tandem mass spectrometry platforms capable of measuring the NeoBase panel of amino acids and acylcarnitines from neonatal dried blood spots. The panel of analytes measured by all three platforms is the same. Analytically, all devices are identical regarding sample
5
requirements, sample processing, analysis time and assay format (Tables 5.1 and 5.2).
The performance of the NeoBase kit on the PerkinElmer TQD platform was compared against the corresponding characteristics reported in the predicate device product insert. A summary of the performance characteristics is presented in Tables 5.3 to 5.6. The NeoBase kit provides equivalent precision, recoveries and measurable ranges that cover all clinically significant ranges on all platforms tested. Therefore, the NeoBase kit provides performance levels that are adequate for its intended use on the MS2, PerkinElmer Quattro Micro and PerkinElmer TQD platforms
Precision
Table 5.3: Averaged Total imprecision for amino acids. Data shown are average Total imprecision coefficients of variation (%CV) for each platform.
| Assav | ALA | ARG | CIT ' | GLY | LEU | MET | ORN | PHE | SA | TYR | VAL |
|---|---|---|---|---|---|---|---|---|---|---|---|
| QM | 10 | 8 | 13 | 10 | |||||||
| MS2 | 14 | 10 | 15 | 10 | 13 | 8 | |||||
| TQD | 10 | 10 | 10 | The Children Children Children Children Children Children Children Station Children Children Station of Children Station of Children Station of Children Station of Children | 10 | 18 | 12 |
Table 5.4: Averaged Total imprecision for carnitine and acylcarnitines. Data shown are average Total imprecision coefficients of variation (%CV) for each platform.
| on the first and the collection and the consisted to the consisted to the continues | -------------------------------------------------------------------- | ------------------------ | стание в приводство в с с с с в полниками своемника в можно в | C16 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| -------------------------------------------------- | . | ------------------------------------ | A mond anno a month and contract and collection and all development to | ------------------------------------ | |||||||
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | And 11 the American Andrew of American Andrew of | . | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | STATIS A . A . A . C | |||||||
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | |||||||||||
| 1 | ------------------ |
Recovery
Table 5.5: Averaged analyte percent recovery and recovery ranges for all platforms
| Mean % Recovery | Recovery SD, % | 95% Confidence interval | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Analyte | TQD | QMicro | MS2 | TQD | QMicro | MS2 | TQD | QMicro | MS2 |
| ALA | 100 | 92 | 83 | 7 | 12 | 10 | 85-115 | 69-116 | 63-104 |
| ARG | 86 | 87 | 87 | 7 | 8 | 7 | 72-100 | 72-102 | 73-100 |
| CIT | 93 | 96 | 95 | 6 | 7 | 11 | 82-104 | 83-109 | 73-116 |
| GLY | 90 | 93 | 86 | 19 | 12 | 17 | 51-128 | 69-117 | 51-120 |
| LEU | 101 | 93 | 88 | 14 | 10 | 8 | 73-128 | 72-113 | 72-103 |
| MET | 97 | 88 | 86 | 6 | 6 | 6 | 85-110 | 75-101 | 73-98 |
| ORN | 98 | 91 | 91 | 10 | 8 | 6 | 78-117 | 75-108 | 78-103 |
| PHE | 94 | 95 | 89 | 8 | 7 | 6 | 78-109 | 81-109 | 76-101 |
| PRO | 97 | 93 | 84 | 6 | 8 | 8 | 84-110 | 78-108 | 68-100 |
| SA | 57 | 64 | 62 | 6 | 6 | 7 | 44-70 | 52-77 | 48-76 |
| TYR | 84 | 96 | 102 | 6 | 9 | 10 | 72-95 | 79-114 | 81-122 |
| VAL | 90 | 88 | 78 | 9 | 9 | 10 | 72-109 | 69-106 | 58-97 |
| C0 | 104 | 91 | 107 | 5 | 11 | 14 | 95-114 | 70-112 | 80-134 |
6
| C2 | 95 | 93 | 97 | 7 | 7 | 8 | 82-108 | 79-108 | 80-113 |
|---|---|---|---|---|---|---|---|---|---|
| C3 | 93 | 94 | 95 | 4 | 8 | 10 | 85-102 | 78-110 | 76-115 |
| C4 | 93 | 91 | 92 | 4 | 9 | 14 | 85-101 | 72-109 | 64-121 |
| C5 | 86 | 91 | 94 | 5 | 7 | 10 | 75-97 | 78-105 | 74-114 |
| C5DC | 99 | 99 | 104 | 4 | 8 | 8 | 90-107 | 83-115 | 87-121 |
| C6 | 91 | 91 | 83 | 6 | 5 | 10 | 80-103 | 82-101 | 63-103 |
| C8 | 100 | 90 | 96 | 8 | 11 | 13 | 84-117 | 68-113 | 70-121 |
| C10 | 92 | 97 | 95 | 3 | 5 | 9 | 85-99 | 86-108 | 78-112 |
| C12 | 102 | 93 | 103 | 5 | 9 | 14 | 93-111 | 75-112 | 75-130 |
| C14 | 92 | 92 | 94 | 6 | 5 | 6 | 81-104 | 82-102 | 81-107 |
| C16 | 92 | 93 | 84 | 5 | 13 | 15 | 83-101 | 68-118 | 55-114 |
| C18 | 89 | 91 | 94 | 10 | 7 | 13 | 70-109 | 77-105 | 69-119 |
Measurable Ranges
Table 5.6: Measurable ranges for both assays and corresponding clinically significant ranges (all in
μML).
| Analyte | TQD Range (µM) | QMicro Range (µM) | MS² Range (µM) | Cutoff Range (µM) | |||
|---|---|---|---|---|---|---|---|
| Lower | Upper | Lower | Upper | Lower | Upper | ||
| Ala | 452 | 4841 | 387 | 4090 | 444 | 4203 | 975-1625 |
| Arg | 27 | 4140 | 25 | 3721 | 27 | 3806 | 180-300 |
| Cit | 28 | 1716 | 27 | 1683 | 26 | 1655 | 113-188 |
| Gly | 309 | 4350 | 334 | 4487 | 365 | 4504 | 975-1625 |
| Leu | 266 | 2992 | 218 | 2545 | 219 | 2463 | 263-438 |
| Met | 31 | 1252 | 30 | 1185 | 28 | 1100 | 120-200 |
| Orn | 110 | 3914 | 115 | 3771 | 110 | 3645 | 360-600 |
| Phe | 79 | 2607 | 71 | 2341 | 73 | 2169 | 225-375 |
| Pro | 248 | 3735 | 251 | 3659 | 238 | 3327 | 450-750 |
| SA | 0.6 | 164.9 | 0.4 | 158.1 | 0.4 | 155.0 | 4-7.0 |
| Tyr | 75 | 2980 | 72 | 2816 | 75 | 2857 | 578-963 |
| Val | 197 | 2300 | 205 | 2358 | 176 | 1902 | 300-500 |
| C0 | 51 | 2930 | 42 | 2274 | 43 | 2386 | 90-150 |
| C2 | 35 | 743 | 35 | 735 | 37 | 745 | 128-213 |
| C3 | 3.3 | 96 | 3.1 | 88 | 3.2 | 94 | 9.75-16.25 |
| C4 | 0.20 | 70.8 | 0.14 | 59.8 | 0.13 | 57 | 2.25-3.75 |
| C5 | 0.20 | 62.9 | 0.18 | 59.1 | 0.17 | 59.9 | 1.88-3.13 |
| C5DC | 0.18 | 32.6 | 0.13 | 28.9 | 0.10 | 29.2 | 0.6-1 |
| C6 | 0.03 | 67.6 | 0.03 | 61.5 | 0.03 | 66.6 | 0.98-1.63 |
| C8 | 0.05 | 39.8 | 0.04 | 35.2 | 0.04 | 35.8 | 1.2-2 |
| C10 | 0.07 | 29.8 | 0.07 | 28.9 | 0.06 | 27.9 | 1.35-2.25 |
| C12 | 0.05 | 50.8 | 0.05 | 42.7 | 0.05 | 41.7 | 1.88-3.13 |
| C14 | 0.1 | 42.7 | 0.1 | 41.8 | 0.1 | 42.3 | 1.5-2.5 |
| C16 | 2.3 | 90.5 | 2.8 | 107.3 | 2.9 | 106.7 | 11.25-18.75 |
7
7
| | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
LAND AND LAND LAND | | | | | | 1
State of the American
1 | |
| -- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | -- | -- | -- | -- | -- | --------------------------------- | -- |
|---|
Method Correlation
An additional measure of the equivalency in the results obtained when the assay is executed using three platforms is the comparison of the actual measured concentrations for each of the analytes included in dried blood spots enriched with the analytes of interest. The raw data was matched per run per level for two comparisons: 1) MS2 to PerkinElmer TQD; and 2) PerkinElmer Q Micro to TQD. Means were calculated per run per analyte per spiked level, to result in 25 means per platform for each analyte (5 levels times 5 runs per analyte). The results were averaged over the five spiked levels and the ratios of the means (per analyte) were then determined for the two comparisons (MS2/TQD and Q Micro/TQD). If the two platforms being compared give equivalent concentration measurements, then the ratio will be 1.0. The mean ratio (averaged over five levels) of each analyte is presented in Tables 5.7 and 5.8 for the MS2/TQD and Q Micro/TQD comparisons, respectively.
| ALA | ARG | CIT | GLY | LEU | MET | ORN | PHE | ||
|---|---|---|---|---|---|---|---|---|---|
| Mean | 1.09 | 1.01 | 0.93 | 1.04 | 0.98 | 0.98 | 0.99 | 0.89 | |
| SD | 0.07 | 0.02 | 0.03 | 0.07 | 0.03 | 0.03 | 0.02 | 0.03 | |
| % CV | 6 | 2 | 3 | 7 | 3 | 3 | 2 | 3 | |
| LCL | 0.96 | 0.96 | 0.86 | 0.90 | 0.92 | 0.92 | 0.94 | 0.83 | |
| UCL | 1.22 | 1.05 | 0.99 | 1.17 | 1.04 | 1.05 | 1.04 | 0.95 | |
| PRO | SA | TYR | VAL | C0 | C2 | C3 | C4 | ||
| Mean | 0.94 | 1.08 | 1.01 | 1.08 | 0.98 | 0.99 | 1.04 | 0.92 | |
| SD | 0.03 | 0.05 | 0.03 | 0.06 | 0.03 | 0.03 | 0.03 | 0.03 | |
| % CV | 3 | 5 | 3 | 6 | 3 | 3 | 3 | 3 | |
| LCL | 0.87 | 0.98 | 0.95 | 0.96 | 0.92 | 0.92 | 0.98 | 0.86 | |
| UCL | 1.00 | 1.17 | 1.06 | 1.19 | 1.05 | 1.05 | 1.10 | 0.98 | |
| C5 | C5DC | C6 | C8 | C10 | C12 | C14 | C16 | C18 | |
| Mean | 0.92 | 0.97 | 0.89 | 0.97 | 0.94 | 0.98 | 1.01 | 0.99 | 0.99 |
| SD | 0.03 | 0.04 | 0.03 | 0.04 | 0.03 | 0.04 | 0.04 | 0.03 | 0.04 |
| % CV | 3 | 4 | 4 | 4 | 3 | 4 | 4 | 3 | 4 |
| LCL | 0.85 | 0.88 | 0.82 | 0.90 | 0.87 | 0.89 | 0.94 | 0.93 | 0.92 |
| UCL | 0.99 | 1.06 | 0.96 | 1.04 | 1.00 | 1.06 | 1.09 | 1.06 | 1.06 |
Table 5.7: Mean ratio of measured concentration for MS2TTQD comparison. Mean ratios of 25 measurements shown along with corresponding SD, %CV, and upper and lower 95% confidence limits.
Table 5.8: Mean ratio of measured concentration for Q Micro/TQD comparison. Mean ratios of 25 measurements shown along with corresponding SD, %CV, and upper and lower 95% confidence limits.
| ALA | ARG | CIT | GLY | LEU | MET | ORN | PHE | ||
|---|---|---|---|---|---|---|---|---|---|
| Micr | |||||||||
| 01/0 | Mean | 0.92 | 1.00 | 1.00 | 0.98 | 1.01 | 1.08 | 1.06 | 0.97 |
| SD | 0.04 | 0.05 | 0.06 | 0.05 | 0.06 | 0.04 | 0.04 | 0.06 |
8
| % CV | 4 | 5 | 6 | 5 | 6 | 4 | 4 | 6 | |
|---|---|---|---|---|---|---|---|---|---|
| LCL | 0.84 | 0.90 | 0.87 | 0.88 | 0.90 | 1.00 | 0.98 | 0.84 | |
| UCL | 0.99 | 1.11 | 1.13 | 1.07 | 1.12 | 1.16 | 1.14 | 1.09 | |
| PRO | SA | TYR | VAL | C0 | C2 | C3 | C4 | ||
| Mean | 1.02 | 1.04 | 1.00 | 1.08 | 0.99 | 0.94 | 0.95 | 1.03 | |
| SD | 0.03 | 0.04 | 0.05 | 0.07 | 0.03 | 0.04 | 0.04 | 0.04 | |
| % CV | 3 | 4 | 5 | 7 | 3 | 4 | 4 | 4 | |
| LCL | 0.95 | 0.96 | 0.91 | 0.95 | 0.93 | 0.86 | 0.87 | 0.96 | |
| UCL | 1.09 | 1.13 | 1.10 | 1.21 | 1.05 | 1.02 | 1.04 | 1.10 | |
| C5 | C5DC | C6 | C8 | C10 | C12 | C14 | C16 | C18 | |
| Mean | 0.97 | 0.97 | 1.00 | 1.00 | 0.98 | 1.02 | 1.00 | 1.00 | 1.02 |
| SD | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.03 | 0.04 | 0.04 | 0.04 |
| % CV | 3 | 3 | 3 | 3 | 3 | 3 | 4 | 4 | 4 |
| LCL | 0.91 | 0.91 | 0.93 | 0.94 | 0.92 | 0.96 | 0.93 | 0.93 | 0.95 |
| UCL | 1.03 | 1.03 | 1.07 | 1.07 | 1.05 | 1.09 | 1.07 | 1.08 | 1.10 |
The ratios range from 0.89 to 1.09 for the MS2/TQD comparison. Taking into account the small variation, the results indicate these two platforms give statistically equivalent results. Likewise, the ratios range from 0.92 to 1.08 for the Q Micro/TQD comparison and noting the small variation in the mean ratios, the results indicate these two platforms give statistically equivalent results.
(2) Clinical
CLINICAL CORRELATION STUDIES
The clinical correlation studies involved the analysis of 2499 random newborn screening specimens and 17 specimens with true positive diagnoses. In addition, a set of enriched samples (five levels) was analyzed (as singlicates of each level) for 16 runs to provide a total of 80 individual measurements. All samples were evaluated in parallel on the TQD and the predicate MS- platforms using the NeoBase kit. Clinical correlation was established by assessing whether or not the platforms were concordant in determining the paired samples to have analyte concentration values above or below their corresponding cutoffs. Examination on the number of concordant pairs for each analyte (cases in which both methods agreed) provided the percent agreements shown in Table 5.9.
| Analyte | Total # of
observations | %
agreement | Analyte | Total # of
observations | %
agreement |
|---------|----------------------------|----------------|-----------|----------------------------|----------------|
| ALA | 2598 | 99.6% | C14 | 2598 | 99.9% |
| ARG | 2598 | 99.9% | C16 | 2598 | 99.6% |
| CIT | 2598 | 99.8% | C18 | 2598 | 99.9% |
| GLY | 2598 | 99.5% | C4OH/C3DC | 2518* | 99.9% |
| LEU | 2598 | 99.6% | C5OH/C4DC | 2518* | 99.9% |
| MET | 2598 | 100.0% | C5:1 | 2518* | 99.4% |
Table 5.9: Percent agreement in clinical determinations between the TQD and MS2 platforms.
9
| ORN | 2598 | 99.6% | C6DC | 2518* | 99.8% |
|---|---|---|---|---|---|
| PHE | 2598 | 99.9% | C8:1 | 2518* | 99.9% |
| PRO | 2598 | 99.8% | C10:1 | 2518* | 100.0% |
| SA | 2598 | 99.5% | C10:2 | 2518* | 99.7% |
| TYR | 2598 | 99.2% | C12:1 | 2518* | 100.0% |
| VAL | 2598 | 99.7% | C14-OH | 2518* | 99.7% |
| C0 | 2598 | 100.0% | C14:1 | 2518* | 99.8% |
| C2 | 2598 | 99.9% | C14:2 | 2518* | 99.8% |
| C3 | 2598 | 100.0% | C16-OH | 2518* | 99.8% |
| C4 | 2598 | 99.9% | C16:1 | 2518* | 99.9% |
| C5 | 2598 | 99.9% | C16:1-OH | 2518* | 99.8% |
| C5DC | 2598 | 99.7% | C18-OH | 2518* | 99.6% |
| C6 | 2598 | 99.7% | C18:1 | 2518* | 99.9% |
| C8 | 2598 | 99.8% | C18:1-OH | 2518* | 99.2% |
| C10 | 2598 | 99.9% | C18:2 | 2518* | 100.0% |
| C12 | 2598 | 99.8% |
ً For these analytes, newborn screening samples (presumptive negative data set, n=2499) and true positives (n=19, include the newly acquired NKH and H-ALA samples) were used.
COMPARISON OF TRUE POSITIVE SAMPLE RESULTS BETWEEN PLATFORM
The correlation between the test and predicate platforms included 17 samples with true positive diagnoses representing 14 disorders (Table 5.10). All of these cases were successfully detected by both platforms for 100% agreement in the clinical determination (Table 5.10).
| Table 5.10: Summary of the analysis of true Positive samples by the NeoBase assay when performed | ||
|---|---|---|
| on the MS and TQD platforms | ||
| And American American Participant Production Comprehensive Children Comments of Children Comments of Children Comments of Children | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| Sample | Disorder | Cases Detected | Elevated Analytes Detected by each Platform | ||
|---|---|---|---|---|---|
| TQD | Sciex | TQD | Sciex | ||
| 1 | TYR I | yes | yes | SA, TYR | SA, TYR |
| 2 | CPT II | yes | yes | C12, C14, C16, C16:1, C16:1 OH, C16-OH, C18, C18:1, C18:1-OH | C14, C14:OH, C16, C16:1, C16:1 OH, C16-OH, C18, C18:1, C18:1-OH, C18-OH |
| 3 | MMA | yes | yes | C3, C6, | C3 |
| 4 | HMG | yes | yes | C5OH/C4DC, C6DC | C5OH/C4DC |
| 5 | VLCAD | yes | yes | C14:1 | C14:1 |
| 6 | IVA | yes | yes | C5 | C5 |
| 7 | MCC | yes | yes | C5OH/C4DC | C5OH/C4DC |
| 8 | BTK | yes | yes | C0, C4, C5:1, C6, C8 | C0, C4, C5:1, |
10
| 9 | MSUD | yes | yes | LEU | LEU |
|---|---|---|---|---|---|
| 10 | MCAD | yes | yes | C6, C8, C10:1 | C0 low, C8, C10:1 |
| 11 | PPA | yes | yes | C3, C16:1 OH | C3, C16:1 OH |
| 12 | PKU | yes | yes | PHE | PHE |
| 13 | CIT | yes | yes | CIT | CIT |
| 14 | PKU | yes | yes | PHE | PHE |
| 15 | MCAD | yes | yes | C6, C6DC, C8, C10, | |
| C10:1, C12:1 | C6, C6DC, C8, C10, | ||||
| C10:1 | |||||
| 16 | GAI | yes | yes | C5DC | C5DC |
| 17 | PKU | yes | yes | PHE | PHE |
Finally, the established performance characteristics and method comparison at the analytical and clinical levels show that using the Neo Base Non-derivatized MSMS kit on the PerkinElmer TQD platform provides performance that is equivalent to the performance of the kit when used on the predicate platforms.
the country of the
1
11
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/11/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like figure with outstretched wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird.
Public Health Service
Building 66
Food & Drug Administration
Silver Spring, MD 20993
10903 New Hampshire Avenue
PerkinElmer c/o Kay Taylor Director, Regulatory and Clinical Affairs 8275 Carloway Road Indiannapolis, IN 46236
AUG 2 3 2010
Re: K093916
Trade Name: NeoBase Non-derivatized MSMS reagent kit Regulation Number: 21 CFR 862.1055
Regulation Name: Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry
Regulatory Class: Class II Product Codes: NQL Dated: August 10, 2010 Received: August 11, 2010
Dear Ms. Taylor:
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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
12
Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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 ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
CA
Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
13
Indications for Use Form
510(k) Number (if known): K093916
Device Name: NeoBase Non-derivatized MSMS Kit
Indications for Use:
The Neobase Non-derivatized MSMS reagent kit (for use on the PerkinElmer TQD MSMS Screening System) is intended for the measurement and evaluation of amino acids, succinylacetone, free carnitine, and acylcarnitine concentrations from newborn heel prick blood samples dried on filter paper.
Quantitative analysis of these analytes (Table 1) and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
| ANALYTE NAME | ABBREVIATION |
|---|---|
| Amino acids | |
| Alanine | Ala |
| Arginine | Arg |
| Citrulline | Cit |
| Glycine | Gly |
| Leucine/Isoleucine/Hydroxyproline* | Leu/Ile/Pro-OH |
| Methionine | Met |
| Ornithine | Orn |
| Phenylalanine | Phe |
| Proline | Pro |
| Tyrosine | Tyr |
| Valine | Val |
Table 1. Analytes measured by the NeoBase™ Non-derivatized MSMS Kit.
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Carol C. Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
KO939112 510(k)
Page 1 of 3
14
| ANALYTE NAME (continued) | ABBREVIATION |
|---|---|
| Carnitines | |
| Free carnitine | C0 |
| Acetylcarnitine | C2 |
| Propionylcarnitine | C3 |
| Malonylcarnitine / 3-Hydroxy-butyrylcarnitine* | C3DC/C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl / 3-Hydroxy-isovalerylcarnitine* | C4DC/C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine / 3-Hydroxy-hexanoylcarnitine* | C5DC/C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
| Octenoylcarnitine | C8:1 |
| Decanoylcarnitine | C10 |
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
| Dodecenoylcarnitine | C12:1 |
| Tetradecanoylcarnitine (Myristoylcarnitine) | C14 |
| Tetradecenoylcarnitine | C14:1 |
| Tetradecadienoylcarnitine | C14:2 |
| 3-Hydroxy-tetradecanoylcarnitine | C14OH |
| Hexadecanoylcarnitine (Palmitoylcarnitine) | C16 |
| Hexadecenoylcarnitine | C16:1 |
| 3-Hydroxy-hexadecanoylcarnitine | C16OH |
| 3-Hydroxy-hexadecenoylcarnitine | C16:1OH |
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Carol C. Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K093916
Page 2 of 3
15
| ANALYTE NAME (continued) | ABBREVIATION |
|---|---|
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| Ketones | |
| Succinylacetone | SA |
- Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometry experiment.
Prescription Use XXXX (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Carol C. Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K693916
Page 3 of 3