(192 days)
3018-0010/3018-001B
No
The summary describes a biochemical assay and instrument for measuring enzyme activity, with no mention of AI or ML in the device description, intended use, or performance studies.
No.
The device is intended for the quantitative in vitro determination of human biotinidase activity in blood specimens to aid in screening newborns for biotinidase deficiency. It is a diagnostic device used for screening, not for treatment or therapy.
Yes
Explanation: The "Intended Use" section explicitly states that the kit is "an aid in screening newborns for biotinidase deficiency," which is a diagnostic purpose. The "Device Description" explains how it quantitatively measures biotinidase activity, and the "Summary of Performance Studies" further details its ability to identify deficient specimens.
No
The device description clearly outlines a kit containing reagents and describes a multi-step biochemical assay process involving enzyme reactions, immunofluorescence, and fluorescence measurement. This indicates a hardware component (the GSP instrument) is required to perform the assay and measure the results, making it a hardware-based medical device with associated software for analysis.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the kit is "intended for the quantitative in vitro determination of human biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency". The phrase "in vitro" is a key indicator of an IVD.
- Device Description: The description details a test system that measures biotinidase activity using a combination of enzyme reaction and a solid phase time-resolved immunofluorescence assay. This is a laboratory-based test performed on biological samples (blood specimens).
- Sample Type: The test is performed on "blood specimens dried on filter paper," which are biological samples.
- Purpose: The purpose is to aid in screening newborns for a specific medical condition (biotinidase deficiency). This is a diagnostic purpose.
All of these factors align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality.
N/A
Intended Use / Indications for Use
The GSP Neonatal Biotinidase kit is intended for the quantitative in vitro determination of human biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency using the GSP instrument.
Product codes
NAK
Device Description
The GSP Neonatal Biotinidase kit contains sufficient reagents to perform 1152 assays. The GSP Neonatal Biotinidase test system measures biotinidase activity, combining an enzyme reaction with a solid phase time-resolved immunofluorescence assay. The GSP Neonatal Biotinidase assay is based on the ability of the biotinidase enzyme to cleave the amide bond in Eu-labeled biotin. The enzyme reaction is stopped by addition of streptavidin which has high affinity for biotin (either Eu-labeled or free biotin). The streptavidin-biotin complexes are captured by the solid phase monoclonal antibody directed against streptavidin. DELFIA Inducer dissociates the molecules into the solution where the europium fluorescence is measured. The measured fluorescence is inversely proportional to the biotinidase activity of the sample.
The kit contains the following components:
Calibrators have been prepared from human whole blood using ProClin 300 as preservative. The biotinidase calibrators' activities range from 10 U/dl to 325 U/dL. As no internationally accepted reference material or a reference method for the determination of biotinidase activity is available, the calibrators have been calibrated against in-house primary calibrators (dried blood spots, stored at -80 to -60°C) prepared using adult human blood (endogenous biotinidase activity in serum) and washed red blood cells as blood matrices.
Controls have been prepared from human whole blood using ProClin 300 as preservative. The low control is approximately 40.0 U/dL and the high control approximately 160 U/dL.
All human source materials used in the preparation of kit components were tested and found to be negative for hepatitis B surface antigen, anti-hepatitis C and anti-HIV 1 and 2 derivatives by FDA approved methods.
Biotinidase Substrate Reagent - 3 ready-to-use vials, 2.8 ml each Biotinidase SA Reagent - 3 ready-to-use vials, 2.8 ml each Assay Buffer - 3 bottles, 120 ml each Anti-SA Microtitration Strips - 12 plates
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
The 3307-001U GSP Neonatal Biotinidase kit was compared to the 3018-0010/3018-001B Neonatal Biotinidase kit in a routine screening laboratory by measuring the biotinidase activity in a total of 2008 specimens. These included routine newborn screening specimens (n = 1988) and retrospective confirmed biotinidase deficiency specimens (n = 20).
Summary of Performance Studies
The variation of the GSP Neonatal Biotinidase assay was determined using dried blood spot samples, 3 kit lots, and 3 GSP instruments. The study was performed in 27 runs over 20 days, each run consisting of 2 plates with 4 replicates per sample. Total number of measurements was 216 per sample. Total variation ranged from 7.5 to 12.7 %CV.
The limit of blank, detection and quantity were determined according to the CLSI guideline EP17-A.The Limit of Blank (LoB) for GSP Neonatal Biotinidase kit is 9.5 U/dL, defined as the 95th percentile of a distribution of blank samples (n=150). The Limit of Detection (LoD) is 14.8 U/dL based on 360 determinations of five low level samples. The Limit of Quantitation (LoO) is 14.8 U/dL, defined as the lowest activity with a total CV equal or less than 20%.
Linearity was determined in accordance with CLSI document EP6-A. For GSP Neonatal Biotinidase, the method has been demonstrated to be linear throughout the measuring range (from 14.8 U/dL to 325 U/dL). Recovery cannot be determined as biotinidase is not commercially available in pure form.
Interference studies:
Ampicillin (1.4 mg/dL and above), sulfisoxazole (7.5 mg/dL and above) at low biotinidase activity levels (35 U/dL) and ampicillin (2.8 mg/dL) at high biotinidase activity levels (150 U/dL) were found to interfere with this test by increasing measured biotinidase activity by 19.9%, 32.1% and 15.6%, respectively. Elevated ampicillin and suffisoxazole levels near the biotinidase cut-off did not exhibit a significant effect ( 30 mg/dL) can interfere with this test by increasing biotinidase activity by 16.1% or more. This could result in the misclassification of a patient with a biotinidase result near the cut-off value as 'normal' when in fact the patient should be classified as 'deficient'. A patient with known or clinically suspected elevated blood glutathione concentration (>30 mg/dL)should be screened with an alternative method and confirmed according to local requirements for follow-up testing.
Unconjugated bilirubin (10 mg/dL) added to whole blood at low biotinidase activity levels (35 U/dL) were found to interfere with this test by increasing measured biotinidase activity by 18.7%. Elevated unconjugated bilirubin level (20 mg/dL) near the biotinidase cut-off did not exhibit a significant effect ( 67.6 U | Total |
| GSP
3307-001U
0.5th
percentile | Screen positive≤ 74.6 U/dL | 23* | 6 | 29 |
| | Screen negative> 74.6 U/dL | 2** | 1977 | 1979 |
| | Total | 25 | 1983 | 2008 |
- Includes 19 retrospective confirmed biotinidase deficiency specimens.
** One retrospective confirmed biotinidase deficiency specimen that initially tested as negative; tested as positive in 4 repeat tests
Key Metrics
Total variation ranged from 7.5 to 12.7 %CV.
LoB = 9.5 U/dL
LoD = 14.8 U/dL
LoQ = 14.8 U/dL
Overall percent agreement = 99. 6% (CI 99.2% - 99.8%)
Positive percent agreement = 92.0% (CI 74.0% - 99.0%)
Negative percent agreement = 99.7% (CI 99.3% - 99.9%)
Predicate Device(s)
PerkinElmer Neonatal Biotinidase kit [K090123]
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1118 Biotinidase test system.
(a)
Identification. The biotinidase test system is an in vitro diagnostic device intended to measure the activity of the enzyme biotinidase in blood. Measurements of biotinidase are used in the treatment and diagnosis of biotinidase deficiency, an inborn error of metabolism in infants, characterized by the inability to utilize dietary protein bound vitamin or to recycle endogenous biotin. The deficiency may result in irreversible neurological impairment.(b)
Classification. Class II (special controls). The special control is sale, distribution, and use in accordance with the prescription device requirements in § 801.109 of this chapter.
0
510k Summary
This 510k Summary information is supplied in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is K131284
Date: November 14, 2013
| Submitted by: | Wallac Oy, a subsidiary of PerkinElmer Inc.
940 Winter Street
Waltham, MA 02451 | NOV 14 2013 |
| --------------- | --------------------------------------------------------------------------------------- | ------------- |
|---|
| Submission Contact Person: | Jeanette Schier-Pugsley
Director, Regulatory and Clinical Affairs
Tel: 781-663-6025
Fax: 781-663-5969 |
|----------------------------|----------------------------------------------------------------------------------------------------------------|
| Trade Name: | GSP Neonatal Biotinidase kit |
| Common Name: | Biotinidase test system |
| Regulation: | 21 CFR 862.1118 |
| Classification Name: | Biotinidase test system |
| Classification: | II |
| Panel: | 75 Clinical Chemistry |
| Product Code: | NAK |
| Predicate device: | PerkinElmer Neonatal Biotinidase kit [K090123] |
Device Description:
The GSP Neonatal Biotinidase kit contains sufficient reagents to perform 1152 assays. The GSP Neonatal Biotinidase test system measures biotinidase activity, combining an enzyme reaction with a solid phase time-resolved immunofluorescence assay. The GSP Neonatal Biotinidase assay is based on the ability of the biotinidase enzyme to cleave the amide bond in Eu-labeled biotin. The enzyme reaction is stopped by addition of streptavidin which has high affinity for biotin (either Eu-labeled or free biotin). The streptavidin-biotin complexes are captured by the solid phase monoclonal antibody directed against streptavidin. DELFIA Inducer dissociates the molecules into the solution where the europium fluorescence is measured. The measured fluorescence is inversely proportional to the biotinidase activity of the sample.
l
1
The kit contains the following components:
Calibrators have been prepared from human whole blood using ProClin 300 as preservative. The biotinidase calibrators' activities range from 10 U/dl to 325 U/dL. As no internationally accepted reference material or a reference method for the determination of biotinidase activity is available, the calibrators have been calibrated against in-house primary calibrators (dried blood spots, stored at -80 to -60°C) prepared using adult human blood (endogenous biotinidase activity in serum) and washed red blood cells as blood matrices.
Controls have been prepared from human whole blood using ProClin 300 as preservative. The low control is approximately 40.0 U/dL and the high control approximately 160 U/dL.
All human source materials used in the preparation of kit components were tested and found to be negative for hepatitis B surface antigen, anti-hepatitis C and anti-HIV 1 and 2 derivatives by FDA approved methods.
Biotinidase Substrate Reagent - 3 ready-to-use vials, 2.8 ml each Biotinidase SA Reagent - 3 ready-to-use vials, 2.8 ml each Assay Buffer - 3 bottles, 120 ml each Anti-SA Microtitration Strips - 12 plates
Intended Use:
The GSP Neonatal Biotinidase kit is intended for the quantitative in vitro determination of human biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency using the GSP® instrument.
Comparison Chart:
Comparison of the GSP Neonatal Biotinidase kit (proposed device) with its predicate:
| Characteristics | -- Proposed Device – GSP
Neonatal Biotinidase kit | Predicate (K090123) |
|----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended
Use/Indications for
Use | The GSP Neonatal Biotinidase kit
is intended for the quantitative in vitro determination of human
biotinidase activity in blood
specimens dried on filter paper as
an aid in screening newborns for
biotinidase deficiency using the
GSP® instrument. | This kit is intended for the semi-
quantitative determination of
biotinidase in blood specimen dried
on filter paper as an aid in screening
newborns for biotinidase deficiency. |
| Specimen Type | Dried blood spot | Same |
| Assay Technology | Enzymatic assay | Same |
| Kit Content | Calibrators, enzymatic reagents,
kit controls (additionally includes
mocrotiter plates and bar code
labels for use with the GSP
instrument) | Calibrators, enzymatic reagents, kit
controls (additionally includes
mocrotiter plates) |
2
| Interpretation of Results | Calibration Curve | Same |
|---|---|---|
| Test Principle | Combines an enzyme reaction with a solid phase time-resolved immunofluorescence assay. Biotinidase in the sample cleaves the amide bond in the Eu-labeled biotin substrate. The end product is captured using Streptavidin and Anti-streptavidin coated plate. DELFIA® Inducer dissociates the molecules into the solution where the europium fluorescence is measured | 1-step enzymatic assay were the biotinidase in the sample cleaves the substrate biotin 6- aminoquinoline generating a fluorescent 6- aminoquinoline product |
| Instrument Platform | GSP instrument, automated (K090846) | Fluorometer, manual |
| Detection Method | Time-resolved fluorescence | Fluorometer with excitation central wavelength of 355 nm and the emission central wavelength of 460 nm |
| Screening Outcome | Normal and Deficient | Same |
| Measuring Unit | U/dL | U |
| Calibrator Matrix | Dried blood spots prepared from human whole blood | Dried blood spots prepared from porcine blood |
| Calibrator Levels | Six levels, ready to use | Six levels, ready to use |
| 10 U/dL | ||
| 25 U/dL | ||
| 50 U/dL | ||
| 100 U/dL | ||
| 175 U/dL | ||
| 325 U/dL | 10 U | |
| 30 U | ||
| 130 U | ||
| 180 U | ||
| 250 U | ||
| 350 U | ||
| Measuring Range | 14.8 U/dL - 325 U/dL | 16 U - 350 U |
| Lower Limits of Measure | LoB = 9.5 U/dl | |
| LoD = 14.8 U/dl | ||
| LoQ = 14.8 U/dl | LoB = 12 U | |
| LoD = 16 U |
Summary of Non-Clinical Studies:
The variation of the GSP Neonatal Biotinidase assay was determined using dried blood spot samples, 3 kit lots, and 3 GSP instruments. The study was performed in 27 runs over 20 days, each run consisting of 2 plates with 4 replicates per sample. Total number of measurements was 216 per sample. Total variation ranged from 7.5 to 12.7 %CV.
The limit of blank, detection and quantity were determined according to the CLSI guideline EP17-A.The Limit of Blank (LoB) for GSP Neonatal Biotinidase kit is 9.5 U/dL, defined as the 95th percentile of a distribution of blank samples (n=150). The Limit of Detection (LoD) is 14.8
3
3
U/dL based on 360 determinations of five low level samples. The Limit of Quantitation (LoO) is 14.8 U/dL, defined as the lowest activity with a total CV equal or less than 20%.
Linearity was determined in accordance with CLSI document EP6-A. For GSP Neonatal Biotinidase, the method has been demonstrated to be linear throughout the measuring range (from 14.8 U/dL to 325 U/dL). Recovery cannot be determined as biotinidase is not commercially available in pure form.
Ampicillin (1.4 mg/dL and above), sulfisoxazole (7.5 mg/dL and above) at low biotinidase activity levels (35 U/dL) and ampicillin (2.8 mg/dL) at high biotinidase activity levels (150 U/dL) were found to interfere with this test by increasing measured biotinidase activity by 19.9%, 32.1% and 15.6%, respectively. Elevated ampicillin and suffisoxazole levels near the biotinidase cut-off did not exhibit a significant effect ( 30 mg/dL) can interfere with this test by increasing biotinidase activity by 16.1% or more. This could result in the misclassification of a patient with a biotinidase result near the cut-off value as 'normal' when in fact the patient should be classified as 'deficient'. A patient with known or clinically suspected elevated blood glutathione concentration (>30 mg/dL)should be screened with an alternative method and confirmed according to local requirements for follow-up testing.
Unconjugated bilirubin (10 mg/dL) added to whole blood at low biotinidase activity levels (35 U/dL) were found to interfere with this test by increasing measured biotinidase activity by 18.7%. Elevated unconjugated bilirubin level (20 mg/dL) near the biotinidase cut-off did not exhibit a significant effect ( 67.6 U | Total |
| GSP
3307-001U
0.5th
percentile | Screen positive
≤ 74.6 U/dL | 23* | 6 | 29 |
| | Screen negative
74.6 U/dL | 2** | 1977 | 1979 |
| | Total | 25 | 1983 | 2008 |
- Includes 19 retrospective confirmed biotinidase deficiency specimens.
** One retrospective confirmed biotinidase deficiency specimen that initially tested as negative; tested as positive in 4 repeat tests
Overall percent agreement = 99. 6% (CI 99.2% - 99.8%) Positive percent agreement = 92.0% (CI 74.0% - 99.0%) Negative percent agreement = 99.7% (CI 99.3% - 99.9%)
Substantial Equivalency:
The proposed device and predicate device utilize similar enzymatic pathway and design which is shown to produce equivalent screening performance in a clinical setting. Both devices are intended for the quantitative in vitro determination of human biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency.
5
,
6
Conclusion:
The GSP Neonatal Biotinidase test system demonstrates analytical and screening performance that supports its substantial equivalency with the predicate device, the Neonatal Biotinidase test system (K090123).
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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized symbol resembling an eagle or bird with three curved lines representing its wings or feathers.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WORG-GB()s Silver Spring, MI) 20993-0002
November 14, 2013
Wallac Oy. a subsidiary of PerkinElmer Inc. Ms. Jeanette Schier-Pugsley Director, Regulatory and Clinical Affairs 940 Winter Street WALTHAM MA 02451
Re: K131284
Trade/Device Name: GSP Neonatal Biotinidase Kit Regulation Number: 21 CFR 862.1118 Regulation Name: Biotinidase test system Regulatory Class: II Product Code: NAK Dated: October 03, 2013 Received: October 04. 2013
Dear Ms. Schier-Pugsley:
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. Please notc: 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 cither class II (Special Controls) or class III (PMA). it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations. Title 21. Parts 800 to 898. In addition. FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA s issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Parts 801 and 809): medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.
7
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Carol C. Benson -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
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.
510(k) Number (if known)
Device Name
GSP Neonatal Biotinidase Kit Indications for Use (Describe)
The GSP Neonatal Biotinidase kit is intended for the quantitative in vitro determination of human biolinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency using the GSP instrument.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
_ Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
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