(408 days)
Not Found
No
The description details a biochemical assay and fluorescence measurement, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is a diagnostic kit used to screen newborns for biotinidase deficiency by measuring biotinidase activity in blood samples. It does not provide treatment or therapy.
Yes
The device aids in screening newborns for biotinidase deficiency by semi-quantitatively determining biotinidase activity, which is a diagnostic purpose.
No
The device description clearly outlines a chemical assay involving reagents, filter paper, microplates, and a fluorometer, indicating it is a hardware-based diagnostic kit, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "for the semiquantitative determination of biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency." This involves testing a sample taken from the body (blood) in vitro (outside the body) to provide information about a medical condition (biotinidase deficiency).
- Device Description: The description details a laboratory-based assay using reagents, microplates, and a fluorometer to analyze a blood sample. This is characteristic of an in vitro diagnostic test.
- Sample Type: The device uses "blood specimens dried on filter paper," which are biological samples taken from the patient.
- Purpose: The purpose is to "aid in screening newborns for biotinidase deficiency," which is a diagnostic purpose.
All these elements align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Neonatal Biotinidase kit is intended for the semiquantitative determination of biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency.
Product codes (comma separated list FDA assigned to the subject device)
NAK, JIT, JJX
Device Description
Biotinidase is found in the blood sample itself. Filter paper disks from newborn dried blood spot samples, calibrators and controls are punched into the wells of a microplate. When biotin substrate reagent containing biotin 6-aminoquinoline (6-AQ) is added to a well containing a punched dried blood spot, the reagent extracts and reconstitutes the proteins and enzymes in the spot. The biotinidase enzyme in the sample cleaves the substrate to biotin and fluorescent 6-AQ The addition of the ethanol stops the reaction and precipitates the proteins to cover the bottom of the well and the extracted spot. The fluorescent product (6-AQ) formed during the reaction is measured with a fluorometer. The biotinidase activity is defined against a calibration curve. The biotinidase activity of the sample is determined by comparing the fluorescence intensity of the sample to a calibration curve.
Mentions image processing
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Mentions AI, DNN, or ML
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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
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: The method comparison was determined in accordance with NCCLS document EP9-A2. The PerkinElmer Neonatal Biotinidase kit was compared with the Astoria-Pacific Biotinidase 50-Hour Reagent kit (K010844). The samples used in the study included 1516 newborn dried blood spot specimen representing US population analyzed as singlicates with the Neonatal Biotinidase kit and with a commercially available assay. The samples consisted of 1496 routine screening specimens and 20 retrospective specimens diagnosed positive for biotinidase deficiency. The cutoffs were determined according to each method's respective labeling (30% of mean ±2 SD for the Neonatal Biotinidase and 37% of the mean for predicate). All of the 20 clinically confirmed deficient samples were positive by both methods.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
The positive percent agreement was 90.9% (20/22) and the overall percent agreement was 99.8% ((20+1493)/1516).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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
510(k) Summary
This summary of 510(k) safety and effectiveness information is supplied in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510 (k) number is K090123
Kay A. Taylor
Tele: 317 418-1735 Fax: 317 536-3064
Helena Lundstrom
Tele: (011) +358-2-2678575 Fax: (011) +358-2-2678357
Neonatal Biotinidase kit
Neonatal Biotinidase kit
Date: March 5, 2010
Submitted by: Wallac Ov Mustionkatu 6 20750 Turku, Finland
Contact Person:
Primary:
Secondary:
Trade Name:
Common Name:
Classification Name:
System, Test, Biotinidase (21 CFR 862.1118/ Product Code NAK)
Astoria-Pacific SPOTCHECK® Biotinidase 50-Hour Reagent Predicate device: Kit, (K010844)
Biotinidase is found in the blood sample itself. Filter paper Device Description: disks from newborn dried blood spot samples, calibrators and controls are punched into the wells of a microplate. When biotin substrate reagent containing biotin 6-aminoquinoline (6-AQ) is added to a well containing a punched dried blood spot, the reagent extracts and reconstitutes the proteins and enzymes in the spot. The biotinidase enzyme in the sample cleaves the substrate to biotin and fluorescent 6-AQ The addition of the ethanol stops the reaction and precipitates the proteins to cover the bottom of the well and the extracted spot. The fluorescent product (6-AQ) formed during the reaction is measured with a fluorometer. The biotinidase activity is defined against a calibration curve. The biotinidase activity of the sample is
1
determined by comparing the fluorescence intensity of the sample to a calibration curve.
Intended Use:
The Neonatal Biotinidase kit is intended for the semiquantitative determination of biotinidase activity in blood specimens dried on filter paper as an aid in screening newborns for biotinidase deficiency.
Device Comparison:
Comparison of the PerkinElmer Neonatal Biotinidase kit with the predicate device.
.
| Parameter | Neonatal Biotinidase kit | Predicate Device |
|---|---|---|
| Intended Use | The Neonatal Biotinidase kit is | |
| intended for the semi-quantitative | ||
| determination of biotinidase | ||
| activity in blood specimens dried | ||
| on filter paper as an aid in | ||
| screening newborns for | ||
| biotinidase deficiency. | The Astoria-Pacific® | |
| SPOTCHECK Biotinidase 50 | ||
| Hour Reagent Kit (K010844) is | ||
| intended for the semi-quantitative | ||
| determination of biotinidase, EC | ||
| 3.5.1.12, activity in dried whole | ||
| blood spots using the Astoria- | ||
| Pacific SPOTCHECK® Analyzer. | ||
| Measurement of biotinidase activity | ||
| is primarily for the diagnosis and | ||
| treatment of biotinidase deficiency | ||
| in newborns. This method is | ||
| intended for in vitro diagnostic use | ||
| to aid in screening for decreased | ||
| levels of biotinidase activity and | ||
| not for monitoring purposes. | ||
| Specimen type | Whole blood specimen spotted on | |
| filter paper | Same | |
| Assay | ||
| Technology | Enzymatic | Same |
| Kit content | Calibrators and enzymatic | |
| reagents. (additionally includes kit | ||
| controls and microtiter plates) | Same | |
| Interpretation of | ||
| results | Calibration curve | Same |
| Test Principle | 1-step enzymatic assay were the | |
| biotinidase in the sample cleaves | ||
| the substrate biotin 6- | ||
| aminoquinoline generating a | ||
| fluorescent 6-aminoquinoline | ||
| product. | 2-step assay were biotinidase | |
| releases p-Aminobenzoic acid | ||
| (PABA) from biotinyl-p- | ||
| aminobenzoate. The PABA is | ||
| diazotized and coupled to a napthol | ||
| derivative to form a purple | ||
| chromophore. | ||
| Parameter | Neonatal Biotinidase kit | Predicate Device |
| Detection | ||
| technique | Fluorometric | Colorimetric |
| Instrumentation | ||
| requirement | Fluorometer with excitation | |
| central wavelength of 355 nm and | ||
| the emission central wavelength | ||
| of 460 nm | Astoria-Pacific SPOTCHECK® | |
| Analyzer | ||
| Screening | ||
| Outcome | Normal and Deficient | Normal, Partial Deficient and |
| Profound Deficient | ||
| Measuring Unit | U | ERU |
| Calibrator | ||
| Matrix | Dried Blood Spots prepared from | |
| porcine blood. | Liquid standards. PABA stock | |
| standard. 1.0 mM p-Aminobenzoic | ||
| acid diluted with Tris Buffer. | ||
| Calibrator | ||
| Levels | Six levels, ready to use | Six levels to be prepared from |
| PABA stock standard | ||
| 10 U | ||
| 30 U | ||
| 130 U | ||
| 180 U | ||
| 250 U | ||
| 350 U | 0 ERU | |
| 5 ERU | ||
| 25 ERU | ||
| 50 ERU | ||
| 100 ERU | ||
| 200 ERU | ||
| Kit controls | Included in the kit. | |
| Dried blood spots prepared from | ||
| human blood. | ||
| Normal 275 U | ||
| Abnormal 50 U | Provided separately | |
| Analytical | ||
| sensitivity/Lower | ||
| limits of | ||
| detection | Limit of Blank = 12 U | |
| Limit of Detection = 16 U | Sensitivity = 1 ERU | |
| Linearity | 16 to 390 U | Not defined in predicate labeling |
| Measuring | ||
| Range | 16 to 350 U | Not defined in predicate labeling |
| Expected values | Normal Population | |
| Range: 31.5 - 388 U | ||
| Mean: 163.8 U | ||
| Median: 160.9 U | Normal Population | |
| Range: 19 to 121 ERU | ||
| Average: 54 ERU | ||
| Parameter | Neonatal Biotinidase kit | Predicate Device |
| Interference | Neonate albumin levels above normal (2.8 to 4.4 g/dL) can interfere with this test by increasing biotinidase activity. 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 albumin concentration should be screened with an alternative method and confirmed according to local requirements for follow-up testing. | |
| Kanamycin sulphate, glutathione, sulfamethoxazole, sulfisoxazole, and trimethoprim can interfere with this test by increasing biotinidase activity. 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'. Patients or mothers known to have received kanamycin sulphate, glutathione, sulfamethoxazole, sulfisoxazole or trimethoprim should be screened with an alternative method and confirmed according to local requirements for follow-up testing. |
Gammaglobulin (1.8 g/dL at biotinidase activity level of 55 U and 1.5 g/dL at biotinidase activity levels of 80 U and 160 U) caused a decrease in biotinidase activity. This could result in a false positive result (biotinidase deficient) in normal patients with biotinidase | Sulfonamides react with color developing reagents.
Phenytoin, ampicillin, gentamycin sulfate, vitamin K, penicillin G potassium, kanamycin sulphate, adrenocorticotropic hormone, valproic acid and sodium phenobarbital do not interfere at therapeutic concentrations.
Samples spiked with up to 2.5 g/dL of combined albumin and globulin do not interfere as protein added above that level increased the response.
Samples spiked with up to 100 mg/dL hemoglobin showed no interference.
Samples spiked with up to 250 mg/dL of lipids showed no interference. Lipids added above that level decreased the response. |
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and the control control control of the control of the control of
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| values near the cut-off value.
| However, no interference was observed with gammaglobulin (6 g/dL) at a biotinidase activity level of 20 U. |
|---|
| Triglycerides (Intralipid at 150 mg/dL for biotinidase activity levels of 55 U and 80 U, 300 mg/dL at biotinidase activity of 20 U and 400 mg/dL at biotinidase activity of 160 U) caused a decrease in biotinidase activity. This could result in a false positive result (biotinidase deficient) in normal patients with biotinidase values near the cut-off value. |
| Biotin (500 ng/dL) at biotinidase activity level of 55 U caused a decrease in biotinidase activity. This could result in a false positive result (biotinidase deficient) in normal patients with biotinidase values near the cut-off value. |
| Ampicillin (0.56 mg/dL), penicillin G potassium (18.75 mg/dL), sodium phenobarbital (5.5 mg/dL), and phenytoin (1.88 mg/dL) at biotinidase activity level of 160 U caused an increase in response, whereas no interference was observed at biotinidase levels of 20 U, 55 U and 80 U. |
| Valproic acid (25 mg/dL) at biotinidase activity levels of 80 U and 160 U caused an increase in response, whereas no interference was observed at biotinidase activity levels of 20 U and 55 U. |
| The following substances were found not to interfere at the concentrations indicated; adreno- |
・
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:
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| corticotropic hormone (15 ng/dL),
ampicillin (2.8 mg/dL for
biotinidase activities of 20 U, 55 U
and 80 U), ascorbic acid (3
mg/dL), biotin (500 ng/dL for
biotinidase activities of 20 U, 80 U
and 160 U), conjugated bilirubin
(30 mg/dL), unconjugated
bilirubin (20 mg/dL), EDTA (1
g/dL), gentamicin sulphate (0.5
mg/dL), hemoglobin (200 mg/dL),
heparin
(37.5 mg/dL), penicillin G
potassium (25 mg/dL at
biotinidase activities of 20 U, 55 U
and 80 U), phenytoin (2.5 mg/dL
for biotinidase activities of 20 U,
55 U and 80 U), sodium
phenobarbital (5.5 mg/dL for
biotinidase activities of 20 U, 55 U
and 80 U) and vitamin K1 (0.2
mg/dL). | Precision
Precision
Within-Run, Within-Lot and Total Precision Sample
mean (U) 23 54 75 95 144 287 n 108 108 108 108 108 108 Min (U)
measured 17 44 50 71 112 217 Max (U)
measured 29 72 97 121 175 358 Within
run SD 1.4 4.4 5.9 7.9 10 21 Within
run CV% 6.3 8.2 7.9 8.3 7.2 7.4 Within lot
SD 2 5.2 7.8 10 14 30 Within lot
CV% 8.8 9.7 10 11 9.8 11 Total SD 2.3 5.5 8.4 11 16 35 Total
CV% 9.9 10 11 11 11 12 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Precision
Within-Run and Total Precision Deficient
(Profound) Partial
Activity Normal n 32 44 44 Average BTD*
activity (ERU) 0.54 14.6 3.2 Within-Run Precision, SWR SD 0.09 0.47 3.8 CV% 17 3.2 4.7 Total Precision, ST Average 0.54 14.6 79.6 SD 0.30 0.94 4.6 CV%
*Biotinidase 56 6.4 5.8 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
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Method Comparison
The method comparison was determined in accordance with NCCLS document EP9-A2.
The PerkinElmer Neonatal Biotinidase kit was compared with the Astoria-Pacific Biotinidase 50-Hour Reagent kit (K010844). The samples used in the study included 1516 newborn dried blood spot specimen representing US population analyzed as singlicates with the Neonatal Biotinidase kit and with a commercially available assay. The samples consisted of 1496 routine screening specimens and 20 retrospective specimens diagnosed positive for biotinidase deficiency. The cutoffs were determined according to each method's respective labeling (30% of mean ±2 SD for the Neonatal Biotinidase and 37% of the mean for predicate). All of the 20 clinically confirmed deficient samples were positive by both methods. The observed activities are shown in the following figure.
Image /page/6/Figure/3 description: This image is a scatter plot comparing PerkinElmer Biotinidase Activity (U) on the y-axis and Commercially available assay (ERU*) on the x-axis. The plot shows a cluster of data points, with most points concentrated in the lower-left to middle region of the graph. There are also some data points in the upper-right region, indicating a positive correlation between the two assays. The plot also indicates positive samples (n=20).
The evaluation data (n = 1516) with routine and known positive samples. The routine samples are illustrated with (o) and the known positive samples with (v). The cut-offs are presented with solid lines.
- Enzyme response unit (ERU)
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The screening summaries according to each method's respective labeling are presented in the tables below. The screening positives (+) are samples