(288 days)
The NeoBase™ 2 Non-derivatized MSMS kit is intended for the measurement and evaluation of amino acid, succinylacetone, free carnitine, acylcarnitine, nucleoside and lysophospholipid concentrations (Table 1) with a tandem mass spectrometer from newborn heel prick blood specimens dried on filter paper. Quantitative analytis of these analytes and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
Not Found
The provided text describes the acceptance criteria and study results for the NeoBase 2 Non-derivatized MSMS kit.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria for the screening performance studies (e.g., minimum sensitivity or specificity targets). Instead, it states that "All verification studies were successfully concluded and met the respective study's predetermined acceptance criteria." The clinical studies for screening performance are presented as agreement between the new device (NeoBase 2) and the predicate device (NeoBase). The agreement is presented as contingency tables (e.g., "Screening positive" vs "Screening negative" for both devices).
The performance is demonstrated by the agreement between the NeoBase 2 Non-derivatized MSMS kit and the predicate device, NeoBase Non-derivatized MSMS kit, in detecting various metabolic disorders in newborn screening. The results are presented in terms of the number of positive and negative screens detected by each device, along with the number of confirmed positive specimens.
Summary of Device Performance (from Tables A, B, C, D):
| Disorder Group | Cut-off Type (Percentile) | NeoBase 2 Screening Positive (with Predicate Positive) | NeoBase 2 Screening Negative (with Predicate Negative) | Total Specimens | Confirmed Positive Specimens (detected by both methods) |
|---|---|---|---|---|---|
| Study 1 | |||||
| Amino acid disorders | 99th | 621 | 1591 | 1751 | 15 |
| Amino acid disorders | 99.5th | 452 | 1645 | 1751 | 15 |
| Amino acid disorders | 1st | 161 | 1687 | 1737 | 1 (OTCD) |
| Fatty acid oxidation | 99th | 801 | 1581 | 1746 | 10 |
| Fatty acid oxidation | 99.5th | 451 | 1661 | 1746 | 10 |
| Fatty acid oxidation | Low Percentile | 1732 | 1386 | 1738 | 2 (CUD) |
| Organic acid condition | 99th | 571 | 1660 | 1751 | 15 |
| Organic acid condition | 99.5th | 361 | 1697 | 1751 | 15 |
| ADA-SCID | 99th | 2 | 1661 | 1738 | 2 |
| ADA-SCID | 99.5th | 2 | 1700 | 1738 | 2 |
| X-ALD | 99th | 2 | 1724 | 1738 | 2 |
| X-ALD | 99.5th | 2 | 1731 | 1738 | 2 |
| Study 2 | |||||
| Amino acid disorders | 99th | 1161 | 2353 | 2648 | 19 |
| Amino acid disorders | 99.5th | 782 | 2474 | 2648 | 18 |
| Amino acid disorders | 1st | 141 | 2571 | 2631 | 2 (OTCD) |
| Fatty acid oxidation | 99th | 1601 | 2326 | 2641 | 12 |
| Fatty acid oxidation | 99.5th | 1081 | 2442 | 2641 | 12 |
| Fatty acid oxidation | Low Percentile | 1581 | 2363 | 2632 | 3 |
| Organic acid condition | 99th | 861 | 2479 | 2642 | 13 |
| Organic acid condition | 99.5th | 422 | 2561 | 2642 | 12 |
| ADA-SCID | 99th | 2 | 2563 | 2631 | 2 |
| ADA-SCID | 99.5th | 2 | 2578 | 2631 | 2 |
| X-ALD | 99th | 2 | 2626 | 2631 | 2 |
| X-ALD | 99.5th | 2 | 2628 | 2631 | 2 |
2. Sample Size Used for the Test Set and Data Provenance
-
Study 1 Sample Size:
- Amino acid disorders, Fatty acid oxidation, Organic acid conditions: 1751 samples (for 99th and 99.5th percentile cut-offs) and 1737-1746 samples (for 1st and low percentile cut-offs).
- ADA-SCID and X-ALD: 1738 samples.
-
Study 2 Sample Size:
- Amino acid disorders, Fatty acid oxidation, Organic acid conditions: 2631-2648 samples.
- ADA-SCID and X-ALD: 2631 samples.
-
Data Provenance: The data was obtained from "routine newborn screening" in "two CLIA-certified state laboratories." The confirmed positive specimens were described as "retrospective" for Study 2. This suggests a retrospective study design using existing samples and accompanying diagnostic information. The country of origin is not explicitly stated but is implied to be the US due to "CLIA-certified state laboratories."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. It mentions "confirmed positive specimens," implying a definitive diagnostic process was followed to establish the true disease status of these samples, but details on the experts involved are not provided.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the test set, such as 2+1 or 3+1. The acceptance is based on the agreement between the new device and the predicate device, using established cut-offs derived from routine newborn screening data.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This device is a diagnostic kit measuring analyte concentrations, not an AI system assisting human readers. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" is not applicable.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
The study described is a comparison of the new device (NeoBase 2) to a predicate device (NeoBase) in obtaining analyte concentrations. While not explicitly stated as an "algorithm only" study, it's a standalone performance comparison of two test kits. The results (analyte concentrations and screening positive/negative classifications) are derived directly from the kit's operation with a tandem mass spectrometer, without human interpretation being part of the primary measurement process itself. The interpretation of the analyte profiles to aid in screening for metabolic disorders would typically involve medical professionals, but the performance data presented is on the analytical and classification output of the device.
7. Type of Ground Truth Used
The ground truth for the test set was based on "confirmed positive specimens." This implies that the true disease status of these specimens was established through clinical diagnosis and follow-up, which would typically involve a combination of clinical outcomes, biochemical testing, and/or genetic testing, ultimately confirmed by clinical experts. For ADA-SCID and X-ALD, it explicitly states "comparing the result... to the clinical condition."
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. The term "cut-offs for both methods were determined by calculating the 99.5th and 99th percentile for all analytes" using "data from routine newborn screening." This large volume of routine newborn screening data could be considered analogous to a training or reference population used to establish the operating characteristics of the screening test. The specific sample size for this cut-off determination is not given, but it is implied to be a large dataset from the "two CLIA-certified state laboratories."
9. How the Ground Truth for the Training Set Was Established
As discussed in point 8, there isn't a traditional "training set" for an AI model. However, the cut-off values (e.g., 99th, 99.5th, 1st, 10th percentiles) used to define "screening positive" or "screening negative" were established using "data from routine newborn screening." This means the ground truth for establishing these cut-offs would inherently come from the statistical distribution of analyte levels in a large, presumably healthy and general newborn population, along with the understanding of what analyte levels are indicative of various metabolic disorders. The document states that the cut-off values "only apply to these studies."
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in a stacked format.
September 4, 2018
Wallac Ov, Subsidiary of PerkinElmer, Inc. Anne Marie Whalen Director, Regulatory Affairs 940 Winter Street Waltham, MA 02451
Re: K173568
Trade/Device Name: NeoBase 2 Non-derivatized MSMS 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 Code: NQL Dated: August 24, 2018 Received: August 27, 2018
Dear Anne Marie Whalen:
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
{1}------------------------------------------------
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K173568
Device Name NeoBase™ 2 Non-derivatized MSMS kit
Indications for Use (Describe)
The NeoBase™ 2 Non-derivatized MSMS kit is intended for the measurement and evaluation of amino acid, succinylacetone, free carnitine, acylcarnitine, nucleoside and lysophospholipid concentrations (Table 1) with a tandem mass spectrometer from newborn heel prick blood specimens dried on filter paper. Quantitative analytis of these analytes and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
Table 1. Analytes measured by the NeoBase 2 Non-derivatized MSMS kit.
ANALYTE NAME
ABBREVIATION
Amino acids
| Alanine | Ala |
|---|---|
| Arginine | Arg |
| Argininosuccinic acid | Asa |
| Citrulline | Cit |
| Glutamine\Lysine (*) | Gln\Lys |
| Glutamic acid | Glu |
| 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 |
| Octenoylcarnitine | C8:1 |
| Decanoylcarnitine | C10 |
{3}------------------------------------------------
| 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\ | |
| Heptadecanoylcarnitine (*) | C16:1OH\C17 |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| 3-Hydroxy-octadecadienoylcarnitine | C18:2OH |
| Ketones | |
| Succinylacetone | SA |
| Nucleotides | |
| Adenosine | ADO |
| 2'-deoxyadenosine | D-ADO |
| Lysophospholipids | |
| C24:0 lysophosphatidylcholine | C24:0-LPC |
| C26:0 lysophosphatidylcholine | C26:0-LPC |
(*) Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectrometty experiment.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
[ ] Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
{4}------------------------------------------------
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{5}------------------------------------------------
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 K173568
Date: August 24, 2018
Submitted by:
Wallac Oy, a subsidiary of PerkinElmer Inc. 940 Winter Street Waltham, MA 02451
Wallac Oy Mustionkatu 6 Turku Finland 20750
Submission Contact Person:
| Primary: | Anne Marie Whalen, PhDDirector, Regulatory AffairsTel:781-663-5651Fax: 781- 663-5969 |
|---|---|
| Trade Name: | NeoBase 2 Non-derivatized MSMS kit |
| Common Name: | Newborn screening test system for amino acids, succinylacetone,free carnitine, acylcarnitines, nucleosides, and lysophospholipidsusing tandem mass spectrometry |
| Regulation: | 21 CFR 862.1055 |
| Classification: | II |
| Panel: | Clinical Chemistry (75) |
| Product Code: | NQL |
| Predicate device: | PerkinElmer NeoBase Non-derivatized MSMS reagent kit(K093916) |
{6}------------------------------------------------
Intended Use:
The NeoBase™ 2 Non-derivatized MSMS kit is intended for the measurement and evaluation of amino acid, succinylacetone, free carnitine, acylcarnitine, nucleoside and lysophospholipid concentrations (Table 1) with a tandem mass spectrometer from newborn heel prick blood specimens dried on filter paper. Quantitative analysis of these 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 |
| Argininosuccinic acid | Asa |
| Citrulline | Cit |
| Glutamine\Lysine1 | Gln\Lys |
| Glutamic acid | Glu |
| Glycine | Gly |
| Leucine\Isoleucine\Hydroxyproline1 | 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-butyrylcarnitine1 | C3DC\C4OH |
| Butyrylcarnitine | C4 |
| Methylmalonyl\3-Hydroxy-isovalerylcarnitine1 | C4DC\C5OH |
| Isovalerylcarnitine | C5 |
| Tiglylcarnitine | C5:1 |
| Glutarylcarnitine\3-Hydroxy-hexanoylcarnitine1 | C5DC\C6OH |
| Hexanoylcarnitine | C6 |
| Adipylcarnitine | C6DC |
| Octanoylcarnitine | C8 |
| Octenoylcarnitine | C8:1 |
| Decanoylcarnitine | C10 |
| Decenoylcarnitine | C10:1 |
| Decadienoylcarnitine | C10:2 |
| Dodecanoylcarnitine | C12 |
Table 1. Analytes measured by the NeoBase 2 Non-derivatized MSMS kit:
{7}------------------------------------------------
| 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\C17 |
| Heptadecanoylcarnitine¹ | |
| Octadecanoylcarnitine (Stearoylcarnitine) | C18 |
| Octadecenoylcarnitine (Oleylcarnitine) | C18:1 |
| Octadecadienoylcarnitine (Linoleylcarnitine) | C18:2 |
| 3-Hydroxy-octadecanoylcarnitine | C18OH |
| 3-Hydroxy-octadecenoylcarnitine | C18:1OH |
| 3-Hydroxy-octadecadienoylcarnitine | C18:2OH |
| Ketones | |
| Succinylacetone | SA |
| Nucleosides | |
| Adenosine | ADO |
| 2'-deoxyadenosine | D-ADO |
| Lysophospholipids | |
| C24:0 lysophosphatidylcholine | C24:0-LPC |
| C26:0 lysophosphatidylcholine | C26:0-LPC |
1 Analytes in these rows are either isomers or isobars and cannot be distinguished in the tandem mass spectroment.
{8}------------------------------------------------
Summary of Non-Clinical Studies:
A summary of the verification studies is presented below:
| Study | CLSI Guidance | Number of kit lots |
|---|---|---|
| Precision | EP5-A3 | Precision study 1:1 Instrument, 1 kit lotPrecision study 2:1 Instrument, 3 kit lotsPrecision study 3:2 Instruments, 1 kit lot |
| Analytical Sensitivity | N/A | 2 Instruments, 3 kit lots |
| Linearity | EP06-A | 1 Instrument, 3 kit lots |
| Interference | EP7-A2 | Mass transition overlap study:1 Instrument |
| Paired-difference study:2 Instruments, 3 kit lot | ||
| Dose-response study:2 Instruments, 3 kit lot | ||
| Drift | N/A | 1 Instrument, 1 kit lot |
| Recovery | N/A | 1 Instrument, 3 kit lots |
| Method Comparison | EP9-A3 | 2 Instruments, 3 kit lots |
| Carry-over | N/A | 2 Instruments, 1 kit lot |
| Incubation times andtemperatures | N/A | 1 Instrument, 1 kit lot |
| Real Time/TransportStability | EP25-A | 2 Instruments, 3 kit lots |
| Accelerated Stability | EP25-A | 2 Instruments, 2 kit lots |
| Study | CLSI Guidance | Number of kit lots |
| In-use, On-board Stability | EP25-A | 1 Instrument, 1 kit lot |
| Sample Stability | EP25-A | 1 Instrument, 1 kit lot |
{9}------------------------------------------------
All verification studies were successfully concluded and met the respective study's predetermined acceptance criteria.
Summary of Clinical Studies:
The 3044-0010U NeoBase 2 Non-derivatized MSMS kit was compared to 3040-001U NeoBase Non-derivatized MSMS kit by measuring analyte concentrations with a tandem quadrupole detector (TQD) in two CLIA-certified state laboratories responsible for routine newborn screening. Using data from routine newborn screening, the cut-offs for both methods were determined by calculating the 99.5th and 99th percentile for all analytes except C2. For C2, C3, C16, C18, C18:1 and Cit the low cut-off applied is based on 1st percentile. For C0, the low cut-off applied is based on 10th percentile. Please note that the cut-off values used in evaluating screening performance only apply to these studies.
The disorders and amount of confirmed positive specimens included in the studies 1 and 2 are listed in Tables A and B (study 1), and Tables C and D (study 2). In total, there were 37 specimens included in the group of amino acid disorders, 26 in the group of fatty acid oxidation disorders and 28 in the group of organic acid conditions. In addition, the group of other disorder contains adenosine deaminase severe combined immunodeficiency (ADA-SCID) and X-linked adrenoleukodystrophy (X-ALD) of which 8 specimens, 4 of each disorder, were included.
The results for the screening performance data including confirmed positive specimens tested with TQD in the study 1 are presented in Table A.
The screening performance for adenosine deaminase severe combined immunodeficiency (ADA-SCID) and X-linked adrenoleukodystrophy (X-ALD) was done by comparing the result of NeoBase 2 Non-derivatized MSMS kit to the clinical condition. Results of the study 1 are presented in Table B.
{10}------------------------------------------------
| Table A. Agreement between NeoBase 2 Non-derivatized MSMS kit and NeoBase Non- | |||||
|---|---|---|---|---|---|
| derivatized MSMS kit in the study 1. |
| Amino acid disorders(AA) | NeoBase | ||||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screening positive | Screening negative | Total | Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 621 | 70 | 132 | 452 | 41 | 86 |
| Screening negative | 28 | 1591 | 1619 | 20 | 1645 | 1665 | |
| Total | 90 | 1661 | 1751 | 65 | 1686 | 1751 |
¹ Includes all 15 specimens confirmed positive for AA detected with both methods using 99ᵗʰ percentile cut-offs.
1 Includes all 15 specimens confirmed positive for AA detected with both methods using 99th percentile cut-offs.
2 Includes all 15 specimens confirmed positive for AA detecte
| Amino acid disorders (AA) | NeoBase | |||
|---|---|---|---|---|
| 1st percentile | ||||
| Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 161 | 18 | 34 |
| Screening negative | 16 | 1687 | 1703 | |
| Total | 32 | 1705 | 1737 |
1 Includes 1 specimen confirmed positive for OTCD with both methods using 1st percentile cut-offs.
{11}------------------------------------------------
| Fatty acid oxidation (FAO) | NeoBase | ||||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screening positive | Screening negative | Total | Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 801 | 40 | 120 | 451 | 17 | 62 |
| Screening negative | 45 | 1581 | 1626 | 23 | 1661 | 1684 | |
| Total | 125 | 1621 | 1746 | 68 | 1678 | 1746 |
1 Includes all 10 specimens confirmed positive for FAO detected with both methods using 99th and 99.5 percentile cut-offs.
| Fatty acid oxidation (FAO) | NeoBase | |||
|---|---|---|---|---|
| Low percentile | ||||
| Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 1732 | 29 | 202 |
| Screening negative | 150 | 1386 | 1536 | |
| Total | 322 | 1415 | 1738 |
I "Low Percentile" reflects the positive C0 specimens detected with a 10% cut-off with other carnitine-positive samples at the 1% cut-off 2 Includes 2 specimens confirmed positive for CUD detected with both methods using low percentile cut-offs.
{12}------------------------------------------------
| Organic acid condition(OA) | NeoBase | NeoBase | |||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screening positive | Screening negative | Total | Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 571 | 23 | 80 | 361 | 13 | 49 |
| Screening negative | 11 | 1660 | 1671 | 5 | 1697 | 1702 | |
| Total | 68 | 1683 | 1751 | 41 | 1710 | 1751 |
1 Includes all 15 specimens confirmed positive for OA detected with both methods using 99th and 99.50 percentile cut-offs.
| Table B. Screening performance for ADA-SCID and X-ALD using 99th and 99.500 percentile in | ||||
|---|---|---|---|---|
| study 1. |
| ADA-SCID | 99th percentile | 99.5th percentile | |||||
|---|---|---|---|---|---|---|---|
| Positive | Normal | Total | Positive | Normal | Total | ||
| NeoBase 2 | Screening positive | 21 | 75 | 77 | 21 | 36 | 38 |
| Screening negative | 0 | 1661 | 1661 | 0 | 1700 | 1700 | |
| Total | 2 | 1736 | 1738 | 2 | 1736 | 1738 |
1 Includes both specimens confirmed positive for ADA-SCID.
| X-ALD | 99th percentile | 99.5th percentile | |||||
|---|---|---|---|---|---|---|---|
| Positive | Normal | Total | Positive | Normal | Total | ||
| NeoBase 2 | Screening positive | 21 | 12 | 14 | 21 | 5 | 7 |
| Screening negative | 0 | 1724 | 1724 | 0 | 1731 | 1731 | |
| Total | 2 | 1736 | 1738 | 2 | 1736 | 1738 |
1 Includes both specimens confirmed positive for X-ALD.
{13}------------------------------------------------
The results for the screening performance data including retrospective confirmed positive specimens tested with TQD in the study 2 are presented in Table C.
The screening performance for Adenosine deaminase severe combined immunodeficiency (ADA-SCID) and X-linked adrenoleukodystrophy (X-ALD) was done by comparing the result of NeoBase_2 Non-derivatized MSMS kit to the clinical condition. Results of the study 2 are presented in Table D.
Table C. Agreement between NeoBase_2 Non-derivatized MSMS kit and NeoBase Nonderivatized MSMS kit in the study 2.
| Amino acid disorders (AA) | NeoBase | ||||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screening positive | Screening negative | Total | Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 1161 | 138 | 254 | 782 | 67 | 145 |
| Screening negative | 41 | 2353 | 2394 | 29 | 24743 | 2503 | |
| Total | 157 | 2491 | 2648 | 107 | 2541 | 2648 |
Includes all 19 specimens confirmed positive for AA detected with both methods using 99th percentile cut-offs.
4 Includes 18 specimens confirmed positive for AA detected with both method using 99.5" percentile cut-offs.
3 Includes 1 specimen confirmed positive for AA not detected with
³Includes 1 specimen confirmed positive for AA not detected with either method using 99.5ᵗʰ percentile cut-offs.
{14}------------------------------------------------
| Amino acid disorders (AA) | NeoBase | |||
|---|---|---|---|---|
| 1st percentile | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 141 | 40 | 54 |
| Screening negative | 6 | 2571 | 2577 | |
| Total | 20 | 2611 | 2631 |
1 Includes 2 specimens confirmed positive for OTCD detected with both methods using 1* percentile cut-offs.
| Fatty acid oxidation(FAO) | NeoBase | ||||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screening positive | Screening negative | Total | Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 1601 | 83 | 243 | 1081 | 37 | 145 |
| Screening negative | 72 | 2326 | 2398 | 54 | 2442 | 2496 | |
| Total | 232 | 2409 | 2641 | 162 | 2479 | 2641 |
1 Includes all 12 specimens confirmed positive for FAO detected with both methods using 99th and 99.50 percentile cut-offs.
{15}------------------------------------------------
| NeoBase | ||||
|---|---|---|---|---|
| Fatty acid oxidation (FAO) | Low percentile | |||
| Screening positive | Screening negative | Total | ||
| NeoBase 2 | Screening positive | 1581 | 45 | 203 |
| Screening negative | 66 | 2363 | 2429 | |
| Total | 224 | 2408 | 2632 |
1 "Low Percentile" reflects positive C0 specimens detected with a 10% cut-off with other camples at the 1% cut-off 2 Includes 3 specimens confirmed positive for FAO detected with both methods using low percentile cut-offs. CPT II was confirmed positive with both methods with each of the 99th, 99.5th and 1st percentile cut-offs.
| Organic acid condition(OA) | NeoBase | ||||||
|---|---|---|---|---|---|---|---|
| 99th percentile | 99.5th percentile | ||||||
| Screeningpositive | Screeningnegative | Total | Screeningpositive | Screeningnegative | Total | ||
| NeoBase 2 | Screeningpositive | 861 | 52 | 138 | 422 | 27 | 69 |
| Screeningnegative | 25 | 2479 | 2504 | 12 | 25613 | 2573 | |
| Total | 111 | 2531 | 2642 | 54 | 2588 | 2642 |
1 Includes all 13 specimens confirmed positive for OA detected with both methods using 99th and 99.50 percentile cut-offs.
2 Includes 12 specimens confirmed positive for OA detected with both methods using 99.5th percentile cut-offs.
3 Includes 1 specimen confirmed positive for OA not detected with either method using 99.54 percentile cut-offs.
{16}------------------------------------------------
| Table D. Screening performance for ADA-SCID and X-ALD using 99th and 99.5th percentile in | |
|---|---|
| the study 2. |
| ADA-SCID | 99th percentile | 99.5th percentile | |||||
|---|---|---|---|---|---|---|---|
| Positive | Normal | Total | Positive | Normal | Total | ||
| NeoBase 2 | Screening positive | 21 | 66 | 68 | 21 | 51 | 53 |
| Screening negative | 0 | 2563 | 2563 | 0 | 2578 | 2578 | |
| Total | 2 | 2629 | 2631 | 2 | 2629 | 2631 |
1 Includes both specimens confirmed positive for ADA-SCID.
| X-ALD | 99th percentile | 99.5th percentile | |||||
|---|---|---|---|---|---|---|---|
| Positive | Normal | Total | Positive | Normal | Total | ||
| NeoBase 2 | Screeningpositive | 21 | 3 | 5 | 21 | 1 | 3 |
| Screeningnegative | 0 | 2626 | 2626 | 0 | 2628 | 2628 | |
| Total | 2 | 2629 | 2631 | 2 | 2629 | 2631 |
1 Includes both specimens confirmed positive for X-ALD.
Substantial Equivalency:
The proposed device and predicate device utilize similar design shown to produce equivalent screening performance in a clinical setting. Both devices are intended for the measurement and evaluation of multiple metabolite concentrations from newborn heel prick blood samples dried on filter paper. Quantitative analysis of these analytes and their relationship with each other is intended to provide analyte concentration profiles that may aid in screening newborns for metabolic disorders.
{17}------------------------------------------------
Conclusion:
The NeoBase 2 Non-derivatized MSMS kit demonstrates analytical and screening performance that supports its substantial equivalency with the predicate device, NeoBase 2 Non-derivatized MSMS kit (K093916).
§ 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.