ASTORIA-PACIFIC SPOTCHECK BIOTINIDASE MICROPLATE REAGENT KIT

• K Number: K080294
• Device Name: ASTORIA-PACIFIC SPOTCHECK BIOTINIDASE MICROPLATE REAGENT KIT
• Manufacturer: ASTORIA-PACIFIC,INC.
• Date Cleared: 2008-11-04 ( 274 days)
• Product Code: NAK
• Regulation Number: 862.1118

Intended Use

This method is for the semi-quantitative determination of biotinidase, EC 3.5.1.12, activity in dried whole blood spots using a spectrophotometer. 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 in screening for decreased levels of biotinidase activity and not for monitoring purposes.

Device Description

Biotinidase activity is determined by measuring the color that develops from p-Aminobenzoic Acid (PABA) after PABA is released from Biotinyl-p-Aminobenzoate (Biotin-PAB). Samples with biotinidase activity develop a purple color. Samples without biotinidase activity remain straw-colored. Patient samples of whole blood collected on standardized filter paper are eluted in a standard 96 well microplate. The plate is incubated with Biotin-PAB in a buffer at 37℃ for 240 minutes on a combination incubator/shaker. Following incubation, TCA is added to the sample mixture and the resulting precipitate is removed through filtration. The PABA in the filtrate is subsequently diazotized and coupled to a napthol derivative to form an azo dye by the successive addition of sodium nitrite, acidic ammonium sulfamate and finally, N-1-naphthylethylenediamine dihydrochloride (NED). The azo dye is measured colorimetrically at 550 nm on a commercial microplate absorbance reader with a reference measurement at 690 mm.

Predicate Devices

K010844

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a chemical reaction and spectrophotometric measurement for determining enzyme activity. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis is based on direct measurement of color intensity, not algorithmic interpretation of complex data.

Therapeutic

No.
This device is for in vitro diagnostic use to screen for decreased levels of biotinidase activity, not for treatment or therapy.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states, "Measurement of biotinidase activity is primarily for the diagnosis and treatment of biotinidase deficiency in newborns." and "This method is intended for in vitro diagnostic use in screening for decreased levels of biotinidase activity". These statements clearly indicate the device's diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device description details a chemical assay involving reagents, incubation, filtration, and spectrophotometric measurement, indicating it is a hardware-dependent in vitro diagnostic kit, not software only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

• Intended Use: The "Intended Use / Indications for Use" section explicitly states: "This method is intended for in vitro diagnostic use in screening for decreased levels of biotinidase activity and not for monitoring purposes."
• Device Description: The description details a laboratory method for analyzing a biological sample (dried whole blood spots) to determine the activity of an enzyme (biotinidase) for the purpose of diagnosing a condition (biotinidase deficiency). This is a core characteristic of an in vitro diagnostic device.
• Sample Type: The device analyzes "dried whole blood spots," which is a biological specimen taken from the human body.
• Clinical Context: The measurement of biotinidase activity is stated to be "primarily for the diagnosis and treatment of biotinidase deficiency in newborns." This clearly links the device's use to a clinical purpose.
• Intended User: The intended users are "Trained, qualified clinical laboratory personnel," indicating use in a clinical laboratory setting for diagnostic purposes.

All of these factors align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

This method is for the semi-quantitative determination of biotinidase, EC 3.5.1.12, activity in dried whole blood spots using a spectrophotometer. 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 in screening for decreased levels of biotinidase activity and not for monitoring purposes.

Product codes (comma separated list FDA assigned to the subject device)

NAK

Device Description

Biotinidase activity is determined by measuring the color that develops from p-Aminobenzoic Acid (PABA) after PABA is released from Biotinyl-p-Aminobenzoate (Biotin-PAB). Samples with biotinidase activity develop a purple color. Samples without biotinidase activity remain straw-colored.

Patient samples of whole blood collected on standardized filter paper are eluted in a standard 96 well microplate. The plate is incubated with Biotin-PAB in a buffer at 37℃ for 240 minutes on a combination incubator/shaker. Following incubation, TCA is added to the sample mixture and the resulting precipitate is removed through filtration. The PABA in the filtrate is subsequently diazotized and coupled to a napthol derivative to form an azo dye by the successive addition of sodium nitrite, acidic ammonium sulfamate and finally, N-1-naphthylethylenediamine dihydrochloride (NED). The azo dye is measured colorimetrically at 550 nm on a commercial microplate absorbance reader with a reference measurement at 690 mm.

The color developed is proportional to the biotinidase activity in the sample. A standard curve prepared from a stock PABA solution is used to evaluate the results.

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

This device is for use by trained, qualified laboratory personnel.
This device is for use by trained, qualified clinical laboratory personnel.

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 performance of the SPOTCHECK Biotinidase Microplate Reagent Kit was evaluated against the predicate device by analyzing unclassified (564) and biotinidase deficient (2) patient samples and (10) deficient controls provided by the Centers for Disease Control (CDC). All deficient patient samples are from persons clinically-confirmed as such. Samples analyzed with the SPOTCHECK Biotinidase Microplate Reagent Kit were treated according to the procedures detailed under SPECMEN COLLECTION AND PREPARATION FOR ANALYSIS in the product insert.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

CLASSIFICATION of DEFICIENT and UNCLASSIFIED PATIENT SAMPLES
The performance of the SPOTCHECK Biotinidase Microplate Reagent Kit was evaluated against the predicate device by analyzing unclassified (564) and biotinidase deficient (2) patient samples and (10) deficient controls provided by the Centers for Disease Control (CDC). All deficient patient samples are from persons clinically-confirmed as such. Samples analyzed with the SPOTCHECK Biotinidase Microplate Reagent Kit were treated according to the procedures detailed under SPECMEN COLLECTION AND PREPARATION FOR ANALYSIS in the product insert.

	Predicate device
	Deficient	Partial Activity	Normal
Microplate Kit	Deficient	11 of 11	0	0
	Partial Activity	0	4 of 5*	1**
	Normal	0	1**	559 of 560

Note: 1 partial* and the 11 deficient represent the 2 clinically-confirmed patients and 10 CDC deficient controls. Discrepant results ** were not confirmed by follow-up testing.

PRECISION
To evaluate within-run and total precision (according to CLSI Document EPS-A2) for the new device, Astoria-Pacific's Quality Assurance Laboratory completed 2 analyses per day, of samples in duplicate, for 20 days. An additional low-activity precision study was performed over 5-days only on the Microplate Kit. A summary of the data is shown below compared to the historical performance evaluation of the predicate device. The predicate device evaluation utilized data from 2 runs per day for 8 days (deficient) to 11 days (normal and near deficient) according to NCCLS Document EPS-T.

Within-Run Precision, SWR
SPOTCHECK Biotinidase Microplate Reagent Kit

Biotinidase Activity, MRU	Low Activity n = 80	Moderate Activity n = 80	Normal n = 80
Average	18.3	50.7	124.9
S.D.	1.2	2.2	4.7
C.V.	6.3%	4.4%	3.8%

Predicate Device

Biotinidase Activity, ERU	Low Activity n = 32	Moderate Activity n = 44	Normal n = 44
Average	0.54	14.6	79.6
S.D.	0.09	0.47	3.8
C.V.	17%	3.2%	4.7%

Total Precision, ST
SPOTCHECK Biotinidase Microplate Reagent Kit

Biotinidase Activity, MRU	Low Activity n = 80	Moderate Activity n = 80	Normal n = 80
Average	18.3	50.7	124.9
S.D.	1.7	3.7	8.9
C.V.	9.4%	7.3%	7.1%

Predicate Device

Biotinidase Activity, ERU	Low Activity n = 32	Moderate Activity n = 44	Normal n = 44
Average	0.54	14.6	79.6
S.D.	0.30	0.94	4.5
C.V.	56%	6.4%	5.8%

Additional 5-day study results
SPOTCHECK Biotinidase Microplate Reagent Kit

Mean Biotinidase Activity, MRU (n = 80)	10.3
Sr (within-run precision)	0.6
C.V. (within-run)	5.8%
B (daily mean precision)	0.8
ST (total precision)	1.1
C.V. (total)	9.7%

The SPOTCHECK Biotinidase Microplate Reagent Kit is effective at screening out patient samples deficient in biotinidase activity. The precision is comparable and in some cases, greatly improved.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

LINEARITY
The calibration utilizing PABA standards ranges from 0 to 200 MRU with a typical correlation coefficient of at least 0.999. Additionally, the assay was deemed linear after evaluation over the range of 5 to 213 MRU adhering to CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

SENSITIVITY
The Limit of Blank (LoB) and Limit of Detection (LoD) for biotinidase activity are 2 and 3 MRU, respectively, determined using the guidelines in the CLSI EP17-A protocol. The total error is less than the LoD, and the CLSI document prescribes that the Limit of Quantitation (LoQ) is equal to the LoD. This correlates well with the sensitivity of the predicate device.

DETERMINATION of CLINICAL CUTOFF
The recommendation for determining the clinical action cutoff for profound deficiency are the same for both devices: 37 and 10% of the mean patient result, respectively. As with the predicate device, each laboratory must determine its range of normal, partial and deficient levels of biotinidase activity, based on its population and analytical variables. All samples below the partial activity cutoff require follow-up screening according to local, state and federal laws.

INTERFERING SUBSTANCES

Interference Evaluated	SPOTCHECK Biotinidase Microplate Reagent Kit	Predicate Device
Sulfonamides1	1.58 mmol/L (400 μg/mL) sulfamethoxazole has a clinically significant effect on biotinidase activity classification - patients treated with sulfonamides should be screened using an alternate method	No limit established, but a known interference is cited
Albumin	albumin concentrations above normal can show positive interference of 1.6 MRU per 1 g/dL albumin	25 g/L albumin showed no interference; > 25 g/L effected significant interference
Hemoglobin	2 g/L hemoglobin caused no clinically significant interference	1 g/L hemoglobin caused no clinically significant interference
Lipids	37 mmol/L (3270 mg/dL) lipids caused a decrease in response; may cause false positives - no risk to deficient patients	2.5 g/L lipids showed no clinically significant interference
Bilirubin	342 µmol/L direct (conjugated) or indirect (unconjugated) bilirubin (~0.3 and ~0.2 g/L, respectively) caused no clinically significant interference	0.25 g/L bilirubin showed no interference
Trimethoprim	138 µmol/L (40 µg/mL) trimethoprim caused a decrease in response; may cause false positives - no risk to deficient patients	No limit established
Gamma globulin	60 g/L gamma globulin caused no clinically significant intereference	No limit established

Phenytoin, ampicillin, gentamicyn sulfate, vitamin K, penicillin G potassium, kanamycin sulfate, adrenocorticotropic hornone, valproic acid and sodium phenobarbital do not interfere at therapeutic concentrations.

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.

K010844

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

Regulation Number and Section

§ 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.

Summary

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I N T E R N A T I O N A L

NOV - 4 2008

Summary, 510(k) No. K080294

1. Name, Address of Contact Person and Date of Preparation

Applicants name and address

Astoria-Pacific, Inc. FDA Establishment No. 3050015 15130 SE 82nd Drive Post Office Box 830 Clackamas, OR 97015-0830

Tel [phone] Fax [phone]

Charles A. Peterson CEO

Jason Reynolds Official Correspondent Director of Research & Development

Signature of Applicant:

Date: October 23, 2008

jason reynolds

Jason Reynolds

2. Name of the Device

Product Classification

Regulation Number 510(k) Number Classification Panel Product Code Device Classification

21 CFR 862.1118 K080294 Clinical Chemistry NAK Class II

Product Nomenclature

Common Name Classification Name Proprietary Name

Model Number

Biotinidase Screening Test Biotinidase Test System Astoria-Pacific SPOTCHECK® Biotinidase Microplate Reagent Kit Astoria-Pacific Part No. 81-8000-13K

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Summary, 510(k) No. K080294

3. Identification of the legally-marketed device for which substantial equivalence is claimed

Product Classification

Regulation Number	21 CFR 862.1118
510(k) Number	K010844
Classification Panel	Clinical Chemistry
Product Code	NAK
Device Classification	Class II

Product Nomenclature

Common Name	Biotinidase Screening Test
Classification Name	Biotinidase Test System
Proprietary Name	Astoria-Pacific SPOTCHECK
Model Numbers	Biotinidase Kit, 50-Hour
Astoria-Pacific
Part Number 80-8000-13K

4. Description of the Device

SPOTCHECK Biotinidase Microplate Reagent Kit

API Part No. 81-8000-13K Biotinidase Test System

KIT CONTENTS:

Color Reagent 1 Color Reagent I Diluent Color Reagent 2 Color Reagent 2 Diluent Color Reagent 3 Substrate Substrate Diluent Substrate Buffer Stock Standard Trichloroacetic acid (TCA)

Biotinidase activity is determined by measuring the color that develops from p-Aminobenzoic Acid (PABA) after PABA is released from Biotinyl-p-Aminobenzoate (Biotin-PAB). Samples with biotinidase activity develop a purple color. Samples without biotinidase activity remain straw-colored.

Patient samples of whole blood collected on standardized filter paper are eluted in a standard 96 well microplate. The plate is incubated with Biotin-PAB in a buffer at 37℃ for 240 minutes on a combination incubator/shaker. Following incubation, TCA is added to the sample mixture and the resulting precipitate is

2

Biotinidase Reagent Kit

Image /page/2/Picture/2 description: The image shows the logo for Astoria-Pacific International. The text "Astoria-Pacific" is in a bold, stylized font, with a trademark symbol to the right of "Pacific". Below this, the word "INTERNATIONAL" is written in a smaller, sans-serif font. The logo is simple and professional, likely representing a company with a global reach.

Summarv, 510(k) No. K080294

removed through filtration. The PABA in the filtrate is subsequently diazotized and coupled to a napthol derivative to form an azo dye by the successive addition of sodium nitrite, acidic ammonium sulfamate and finally, N-1-naphthylethylenediamine dihydrochloride (NED). The azo dye is measured colorimetrically at 550 nm on a commercial microplate absorbance reader with a reference measurement at 690 mm.

Biotinidase Biotin-PAB ------------> Biotin + PABA

NO2, NH2SO2 PABA --------------> Purple chromophore NED

The color developed is proportional to the biotinidase activity in the sample. A standard curve prepared from a stock PABA solution is used to evaluate the results.

ર. Statement of Intended Use

This method is for the semi-quantitative determination of biotinidase, EC 3.5.1.12, activity in dried whole blood spots using a spectrophotometer. Measurement of biotinidase activity is primarily for the diagnosis and treatment of biotinidase deficiency in newborns. This method for in vitro diagnostic use to aid in screening for decreased levels of biotinidase activity and not for monitoring purposes.

This device is for use by trained, qualified laboratory personnel.

Summary of the Technological Characteristics of the Device 6.

DEVICE COMPARISON

The most significant difference between the SPOTCHECK Biotinidase Microplate Reagent Kit and the predicate device is the intended analyzer platform. The predicate device is used on a segmented-flow analyzer while the new reagent kit is for manual laboratory use only, applying simple bench chemistry techniques (e.g. pipetting) and utilizing a combination incubator/shaker and spectrophotometric microplate reader. The units used for the two assay kits are also different: microplate response units (MRU) for the new kit and enzyme response units (ERU) for the predicate device (1 MRU + 1 ERU).

Newborn patient blood spots are punched into microplate wells, eluted and incubated with the same substrate and buffer system as on the predicate device. Extraction and incubation occur concurrently, whereas on the predicate device, samples are first eluted, then vacuum filtered and subsequently incubated on the analyzer system. The predicate device utilizes automated dialysis to remove interferences. The SPOTCHECK Biotinidase Microplate Reagent Kit however, uses a reagent not included with the predicate device to precipitate matrix interferences which are subsequently removed through vacuum filtration. The same reagent formulation is used on both devices to generate the azo dye measured at 550 nm.

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I N T E R N A T I O N A L

Summary, 510(k) No. K080294

Summary of Predicate Device and Microplate Kit Technological Characteristics

| | SPOTCHECK Biotinidase
Microplate Reagent Kit | Predicate Device |
|------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sample collection and
handling | Use standardized filter paper,
S&S®903TM
Follow CLSI document LA4-A5: Blood
Collection on Filter Paper for Newborn
Screening | Same collection and handling |
| Sample | 2 x 1/8" punched blood spot | Same patient sampling |
| Incubation | In microplate, on combination
incubator/shaker | On flow analyzer system |
| Matrix interference
mitigation | Chemical precipitation and
manual vacuum filtration | Manual vacuum filtration and
dialysis on the flow analyzer
system |
| Incubation Temp | 37°C | 40°C |
| Incubation Time | 240 minutes | ~120 minutes |
| Color Reagents | Sodium nitrite, acidic
ammonium sulfate, NED | Same formulation |
| Incubation substrate | Buffered Biotinyl-p-
Aminobenzoate | Same formulation |
| Absorbance
measurements | Spectrophotometric microplate
reader -
550 nm (reference at 690 nm) | Flow through split-beam
spectrophotometer - 550 nm |
| Units of measurement | Microplate response unit
(MRU)
1 MRU equals 1 umol of p-
aminobenzoic acid produced
from Biotin-PAB per dL per
240 minutes of incubation at
37°C | Enzyme response unit (ERU)
1 ERU defined as the azo dye
formed from 1 umol of p-
aminobenzoic acid produced
from Biotin-PAB per dL per
~120 min. of incubation at
40°C |
| Deficient cutoff | 10% mean activity of population | Same cutoff |
| Partial Activity cutoff -
Clinical decision level | 37% mean activity of population | Same cutoff |

LINEARITY

Calibration standards are analyzed at the beginning of each assay using the SPOTCHECK Biotinidase Microplate Kit, as with the predicate device. The calibration utilizing PABA standards ranges from 0 to 200 MRU with a typical correlation coefficient of at least 0.999. Additionally, the assay was deemed linear after evaluation over the range of 5 to 213 MRU adhering to CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

SENSITIVITY

The Limit of Blank (LoB) and Limit of Detection (LoD) for biotinidase activity are 2 and 3 MRU, respectively, determined using the guidelines in the CLSI EP17-A protocol. The total error is less than the LoD, and the CLSI document prescribes that the Limit of Quantitation (LoQ) is equal to the LoD. This correlates well with the sensitivity of the predicate device.

4

Summary, 510(k) No. K080294

DETERMINATION of CLINICAL CUTOFF

The recommendation for determining the clinical action cutoff for profound deficiency are the same for both devices: 37 and 10% of the mean patient result, respectively. As with the predicate device, each laboratory must determine its range of normal, partial and deficient levels of biotinidase activity, based on its population and analytical variables. All samples below the partial activity cutoff require follow-up screening according to local, state and federal laws.

CLASSIFICATION of DEFICIENT and UNCLASSIFIED PATIENT SAMPLES

The performance of the SPOTCHECK Biotinidase Microplate Reagent Kit was evaluated against the predicate device by analyzing unclassified (564) and biotinidase deficient (2) patient samples and (10) deficient controls provided by the Centers for Disease Control (CDC). All deficient patient samples are from persons clinically-confirmed as such. Samples analyzed with the SPOTCHECK Biotinidase Microplate Reagent Kit were treated according to the procedures detailed under SPECMEN COLLECTION AND PREPARATION FOR ANALYSIS in the product insert.

Classification of Samples during Device Comparison

	Predicate device
	Deficient	Partial Activity	Normal
Microplate Kit	Deficient	11 of 11	0	0
	Partial Activity	0	4 of 5*	1**
	Normal	0	1**	559 of 560

Note: 1 partial* and the 11 deficient represent the 2 clinically-confirmed patients and 10 CDC deficient controls. Discrepant results ** were not confirmed by follow-up testing.

PRECISION

To evaluate within-run and total precision (according to CLSI Document EPS-A2) for the new device, Astoria-Pacific's Quality Assurance Laboratory completed 2 analyses per day, of samples in duplicate, for 20 days. An additional low-activity precision study was performed over 5-days only on the Microplate Kit. A summary of the data is shown below compared to the historical performance evaluation of the predicate device. The predicate device evaluation utilized data from 2 runs per day for 8 days (deficient) to 11 days (normal and near deficient) according to NCCLS Document EPS-T.

5

Astoria-Pacific, Inc.

N T E R N A T I O N A L

Summary, 510(k) No. K080294

Within-Run Precision, SWR

SPOTCHECK Biotinidase Microplate Reagent Kit

| Biotinidase
Activity,
MRU | Low
Activity
n = 80 | Moderate
Activity
n = 80 | Normal
n = 80 |
|---------------------------------|---------------------------|--------------------------------|------------------|
| Average | 18.3 | 50.7 | 124.9 |
| S.D. | 1.2 | 2.2 | 4.7 |
| C.V. | 6.3% | 4.4% | 3.8% |

Predicate Device
Biotinidase
Activity,
ERU	Low
Activity
n = 32	Moderate
Activity
n = 44	Normal
n = 44
Average	0.54	14.6	79.6
S.D.	0.09	0.47	3.8
C.V.	17%	3.2%	4.7%

Total Precision, ST

SPOTCHECK Biotinidase Microplate Reagent Kit

| Biotinidase
Activity,
MRU | Low
Activity
n = 80 | Moderate
Activity
n = 80 | Normal
n = 80 |
|---------------------------------|---------------------------|--------------------------------|------------------|
| Average | 18.3 | 50.7 | 124.9 |
| S.D. | 1.7 | 3.7 | 8.9 |
| C.V. | 9.4% | 7.3% | 7.1% |
| Biotinidase
Activity,
ERU | Low
Activity
n = 32 | Moderate
Activity
n = 44 | Normal
n = 44 |
| Average | 0.54 | 14.6 | 79.6 |
| S.D. | 0.30 | 0.94 | 4.5 |
| C.V. | 56% | 6.4% | 5.8% |

Predicate Device

Additional 5-day study results

SPOTCHECK Biotinidase Microplate Reagent Kit

| Mean Biotinidase Activity,

MRU (n = 80)	10.3
Sr (within-run precision)	0.6
C.V. (within-run)	5.8%
B (daily mean precision)	0.8
ST (total precision)	1.1
C.V. (total)	9.7%

The SPOTCHECK Biotinidase Microplate Reagent Kit is effective at screening out patient samples deficient in biotinidase activity. The precision is comparable and in some cases, greatly improved.

INTERFERING SUBSTANCES

No known significant differences that would affect safety and effectiveness were observed when compared to the predicate device during the evaluation of interfering substances. The SPOTCHECK Biotinidase Microplate Reagent Kit was evaluated according to CLSI EP7-A2: Interference Testing in Clinical Chemistry, Approved Guideline. A summary of the findings and comparison to the predicate device is presented below.

| Interference Evaluated | SPOTCHECK Biotinidase Microplate
Reagent Kit | Predicate Device |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------|
| Sulfonamides1 | 1.58 mmol/L (400 $ $\mu$ $ g/mL)
sulfamethoxazole has a clinically
significant effect on biotinidase activity
classification - patients treated with
sulfonamides should be screened using
an alternate method | No limit established, but a
known interference is cited |

6

Astoria-Pacific, Inc.

Astoria-PacificTM
INTERNATIONAL

| Albumin | albumin concentrations above normal can
show positive interference of 1.6 MRU
per 1 g/dL albumin | 25 g/L albumin showed no
interference; > 25 g/L effected
significant interference |
|----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|
| Hemoglobin | 2 g/L hemoglobin caused no clinically
significant interference | 1 g/L hemoglobin caused no
clinically significant
interference |
| Lipids | 37 mmol/L (3270 mg/dL) lipids caused a
decrease in response; may cause false
positives - no risk to deficient patients | 2.5 g/L lipids showed no
clinically significant
interference |
| Bilirubin | 342 µmol/L direct (conjugated) or
indirect (unconjugated) bilirubin (~0.3
and ~0.2 g/L, respectively) caused no
clinically significant interference | 0.25 g/L bilirubin showed no
interference |
| Trimethoprim | 138 µmol/L (40 µg/mL) trimethoprim
caused a decrease in response; may cause
false positives - no risk to deficient
patients | No limit established |
| Gamma globulin | 60 g/L gamma globulin caused no
clinically significant intereference | No limit established |

Phenytoin, ampicillin, gentamicyn sulfate, vitamin K, penicillin G potassium, kanamycin sulfate, adrenocorticotropic hornone, valproic acid and sodium phenobarbital do not interfere at therapeutic concentrations. 1.2

7. Determination of Substantial Equivalency

Based on performance characteristics and comparison data, we believe this device to be safe, effective, and substantially equivalent to the legally-marketed predicate device. The indications for use are for the SPOTCHECK Biotinidase Microplate Reagent Kit and the predicate device. Technological characteristics are very similar to the predicate device and there is sufficient evidence demonstrating that the differences do not significantly affect safety and effectiveness when analyzing clinical patients.

l. Gregory S. Heard, J. S. McVoy and B. Wolf, A Screening Method for Biotinidase Deficiency in Newborns, Clinical Chemistry, 30, 125-127, 1984.

2. Barry Wolf, G. S. Heard, K. A. Weissbecker, J. R. Secor MeVoy, R. E. Gricr and R. T. Leshner, Biotinidase Deficiency: Initial Clinical Features and Rapid Diagnosis, Annals of Neurology, 18, 614-617, 1985.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol with three wing-like shapes. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird symbol.

Public Health Service

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

Astoria-Pacific, Inc. c/o Mr. Jason Revnolds Official Correspondent 15130 SE 82nd Drive P.O. Box 830 Clackamas, Oregon 97015

NOV - 4 2008

Re: K080294

Trade/Device Name: Spotcheck Biotinidase Microplate Reagent Kit Regulation Number: 21 CFR 862.1118 Regulation Name: Biotinidase test system Regulatory Class: Class II Product Code: NAK Dated: October 23, 2008 Received: October 27, 2008

Dear Mr. Reynolds:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the r Division of Small Manufacturers, International and Consumer Assistance at its toll frea mober [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.v.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE

510(k) K080294

SPOTCHECK® Biotinidase Microplate Reagent Kit

INTENDED USE

This method is for the semi-quantitative determination of biotinidase, EC 3.5.1.12, activity in dried whole blood spots using a spectrophotometer. 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 in screening for decreased levels of biotinidase activity and not for monitoring purposes.

This device is for use by trained, qualified clinical laboratory personnel.

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Carol C. Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K080294

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