NEONATAL TOTAL GALACTOSE KIT; NEONTAL TOTAL GALACTOSE KIT, MODELS 3029-0010 AND 3029-110B

K071649 · Wallac OY · JIA · Aug 7, 2008 · Clinical Chemistry

Device Facts

• Record ID: K071649
• Device Name: NEONATAL TOTAL GALACTOSE KIT; NEONTAL TOTAL GALACTOSE KIT, MODELS 3029-0010 AND 3029-110B
• Applicant: Wallac OY
• Product Code: JIA · Clinical Chemistry
• Decision Date: Aug 7, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1310
• Device Class: Class 1
• Attributes: Pediatric

Intended Use

This kit is intended for the quantitative determination of total galactose (galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia.

Device Story

The Neonatal Total Galactose Kit is an in vitro diagnostic assay for screening newborns for galactosemia. It utilizes dried blood spot specimens collected on filter paper. The device employs a fluorescent enzymatic method: alkaline phosphatase converts galactose-1-phosphate to galactose; galactose oxidase then converts galactose to D-galacto-hexadialdose and hydrogen peroxide; finally, peroxidase reacts hydrogen peroxide with 3-(p-hydroxyphenyl)propionic acid (HPPA) to produce a fluorescent dimer. The fluorescence intensity is proportional to the total galactose concentration. The assay is performed using a Victor2 D Fluorometer or equivalent plate reader. Results are interpreted against a standard curve generated from six calibrator levels. Healthcare providers use these quantitative results to identify newborns requiring further diagnostic follow-up for galactosemia. The device provides a screening tool to facilitate early detection and intervention.

Clinical Evidence

Method comparison study using 2,109 prospective newborn specimens and 7 retrospective high-galactose samples (3 confirmed galactosemia). Compared against a commercially available kit. Overall percent agreement was 95.9% at the 95th percentile and 99.2% at the 99th percentile. Analytical performance included precision (CVs 8.4-12.7%), linearity (1.3-56 mg/dL), and LoD (1.3 mg/dL). Interference noted for lipids (over-recovery) and high glutathione (under-recovery).

Technological Characteristics

Enzymatic fluorescent assay. Components: calibrators/controls (human blood on Whatman 903 paper), Zinc Sulfate, Reconstitution Buffer, Substrate Reagent, Galactose Oxidase, Stop Solution. Requires fluorometer (340/405 nm). Linearity: 1.3-56 mg/dL. Traceable to HPLC-MS/MS. No software algorithm class specified; manual/instrument-based measurement.

Indications for Use

Indicated for the quantitative determination of total galactose (galactose and galactose-1-phosphate) in dried blood spot specimens from newborns as an aid in screening for galactosemia.

Regulatory Classification

Identification

A galactose test system is a device intended to measure galactose in blood and urine. Galactose measurements are used in the diagnosis and treatment of the hereditary disease galactosemia (a disorder of galactose metabolism) in infants.

Predicate Devices

• Quantase Total Galactose Screening Assay (k990654)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" symbol above the name "PerkinElmer". The "P" symbol is made up of a thick vertical line and a triangle shape. Below the name "PerkinElmer" is the word "precisely."

PerkinElme▶Life and Analytical Sciences Wallac Oy P.O. Box 10 FIN-20101 Turku, Finland Phone: +358 - (0)2 - 267 8111 Fax: +358 - (0)2 - 267 8357

### 510(k) Summary

## AUG - 7 2008

This summary of 510(k) safety and effectiveness information is being submitted in Introduction accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

| The assigned 510 (k) number is k071649 | | |
|----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------|
| Submitter | Name<br>Address | Wallac Oy<br>Mustionkatu 6<br>20750 Turku, Finland |
| | Phone<br>Fax | [phone]<br>[phone] |
| | Contact Person | Helena Lundström<br>Registration Manager |
| | Date of Preparation | July 31, 2008 |
| Device name | Trade Name | Neonatal Total Galactose Kit |
| | Common Name | Enzymatic Methods, galactose |
| | Classification Name | Galactose Test System (21 CFR 862.1310) Class I |
| | Product Code | JIA |
| Predicate device | BioRad QuantaseTM Neonatal Total Galactose Screening Assay (k990654) | |
| Description of<br>the device | The Neonatal Total Galactose kit makes use of a fluorescent galactose oxidase method.<br>The assay measures total galactose, i.e. both galactose and galactose-1-phosphate. The<br>following schematic summarizes the reactions that occur during the test procedure: | |

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image shows the PerkinElmer logo. The logo consists of a stylized "P" and a right-pointing triangle above the company name "PerkinElmer" in a sans-serif font. Below the company name is the word "precisely."

| GAL-1-P + H₂O | AP | GAL + P |
|---------------|-----|--------------------------------------------|
| GAL + O₂ | GAO | GHD + H₂O₂ |
| HPPA + H₂O₂ | POD | HPPA dimer* + H₂O |
| GAL-1-P | = | Galactose-1-phosphate |
| AP | = | Alkaline phosphatase |
| GAL | = | Galactose |
| P | = | Phosphate |
| GAO | = | Galactose oxidase |
| GHD | = | D-galacto-hexadialdose |
| POD | = | Peroxidase |
| HPPA | = | 3-( <i>p</i> -hydroxyphenyl)propionic acid |
| * | = | Fluorescent |

:

ﮨﮯ proportional to the concentration of galactose in the sample.

| Intended use | The Neonatal Total Galactose kit is intended for the quantitative determination of total<br>galactose (galactose and galactose-1-phosphate) concentrations in blood specimens dried<br>on filter paper as an aid in screening newborns for galactosemia. |
|----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Substantial<br>Equivalence | The Neonatal Total Galactose kit is substantially equivalent to the BioRad QuantaseTM |
| | Neonatal Total Galactose Screening Assay (k990654). |

:

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" shape above the company name. Below the name is the word "precisely."

Device
Comparison The following table compares the Neonatal Total Galactose kit with the predicate device.

| Predicate Device | New Device | |
|--------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device characteristics | BioRad Quantase Total Galactose<br>Screening Assay | Perkin Elmer Neonatal Total Galactose Kit |
| Device Similarities | | |
| Intended use | The Quantase™ Neonatal Total<br>Galactose Screening Assay is<br>intended for use as a screening<br>method for measuring the total<br>D(+)galactose concentrations in<br>newborn blood spot specimens. | The kit is intended for the quantitative<br>determination of total galactose (galactose<br>and galacatose-1-phosphate)<br>concentrations in blood specimens dried<br>on filter paper as aid in screening<br>newborns for galactosemia. |
| Technology | Enzymatic assay | The same |
| Kit content | Calibrators/Standards, Controls and<br>Enzymatic Reagents | The same, plus Assay Plates |
| Specimen type | Newborn dried blood spot specimens | The same |
| Interpretation of<br>results | Standard curve | The same |
| Calibrator format | Dried blood spots | The same |
| Number of Controls | Two | The same |
| Control format | Dried blood spots | The same |
| Device Differences | | |
| Methodology | Colorimetric end point method | Prompt Fluorescence |
| Instrumentation | Plate reader | Victor2™ D Fluorometer or equivalent |
| Calibrators/standards:<br>Number of levels | Five<br>(Four standard levels + Standard 0<br>which is plain white paper) | Six<br>(six calibrator levels) |
| Analytical sensitivity | 0.60 mg/dL | 1.3 mg/dL |
| Linearity | 0.6 to 55 mg/dL | 1.3 to 56 mg/dL |
| Measuring Range | 0.6 to 50 mg/mL | 1.3 to 40 mg/mL |
| Expected values | Mean total galactose concentration<br>1.05 mg/dL (n=462) measured with a<br>punch size of 3/16". | Median total galactose concentration,<br>1.7 mg/dL (n=2109) measured with a punch<br>size of 1/8". |

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the PerkinElmer logo. The logo consists of a stylized "P" shape above the company name "PerkinElmer" in a bold, sans-serif font. Below the company name is the word "precisely."

:

| Specificity/Recovery | Mean recovery of D(+) galactose in<br>the presense of 100mg/dL of the<br>following sugars and D(+)galactose<br>metabolites was 95.07% (S:D:<br>7.49%).<br>D-(+)-Gucose<br>a-Lactose<br>D(-)Fructose<br>Sucrose<br>Maltose<br>D(+)Mannose<br>D-Mannitol<br>Galactitol<br>D-Galacturonic Acid<br>D-Glucuronic Acid<br>D(-)Ribose | | | Mean recovery of galactose in the presence of<br>galactose, galactose-1-phosphate or galactose<br>+ galactose-1-phosphate was 79 - 81 %. | | | |
|----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------|----|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|-------------------------------------------|-----|
| Interference | No interference observed with<br>known antibiotics, non-antibiotics<br>and metabolites | | | No interference with glucose, mannose,<br>fructose, ascorbate, bilirubin, hemoglobin,<br>protein BSA and acetaminophen. Glutathione<br>(60 mg/dL) and lipemic samples (0.25 -1<br>g/dL) interfere with the assay. | | | |
| Precision | Intra-assay (1/8 punch size)<br>Mean D(+)<br>Galactose<br>conc.(mg/dL) | % CV | n | Intra-assay and total variation<br>Mean<br>Galactose<br>conc.(mg/dL) | Intra-<br>assay<br>(%CV) | Total<br>variation<br>(%CV) | n |
| | 1.06 | 13.99 | 20 | 7.1 | 6.6 | 12.3 | 143 |
| | 6.81 | 10.02 | 20 | 13.8 | 6.5 | 10.8 | 144 |
| | 14.23 | 6.67 | 20 | 20.2 | 5.3 | 8.6 | 144 |
| | 33.96 | 3.94 | 20 | | | | |
| | Total Assay ( 1/8 punch size)<br>Mean D(+)<br>Galactose<br>conc.(mg/dL) | % CV | n | Mean<br>Galactose<br>conc.(mg/dL) | Intra-<br>assay<br>(%CV) | Total<br>within lot<br>variation<br>(%CV) | n |
| | 1.43 | 17.42 | 39 | 3.5 | 7.8 | 12.7 | 80 |
| | 6.97 | 6.27 | 40 | 11 | 7.2 | 11.8 | 80 |
| | 14.53 | 7.43 | 40 | 23 | 6.0 | 8.4 | 80 |
| | 33.58 | 8.53 | 40 | 36 | 5.2 | 8.6 | 80 |

{4}------------------------------------------------

Image /page/4/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" symbol above the company name, with the word "precisely" written below. The "P" symbol is made up of a thick vertical line and an arrow pointing to the right. The word "PerkinElmer" is written in a bold, sans-serif font.

#### Method Comparison

The PerkinElmer Neonatal Total Galactose kit (y) was compared with the BioRad Quantase™ Neonatal Total Galactose Screening Assay (k990654). using routine newborn screening dried blood spot specimens in the range of 72 umol/L to 1970 umo//L (1.3-3.5 mg/dL) (determined with the PerkinElmer kit). The correlation was found to be:

$$\mathbf{y} = \mathbf{0.6Sx} + \mathbf{1.73}, \quad \mathbf{r} = \mathbf{0.87} \text{ (n = 842)}$$

The total galactose cut-off values by percentile for both the PerkinFilmer Neonatal Total Galactose kit and the predicate were determined by analyzing 2109 routine newborn screening dried blood specimens representing an US population. The results are shown in the table below:

| Total galactose cut-off values by percentile | | | | |
|----------------------------------------------|-----------------|-------|-----------|-------|
| | PerkinElmer kit | | Predicate | |
| | µmol/L | mg/dL | µmol/L | mg/dL |
| Median | 94 | 1.7 | 33 | 0.6 |
| 95th percentile | 283 | 5.1 | 233 | 4.2 |
| 97.5th percentile | 355 | 6.4 | 316 | 5.7 |
| 99th percentile | 461 | 8.3 | 521 | 9.4 |
| 99.5th percentile | 549 | 9.9 | 678 | 12.2 |

The screening summaries using the 95th and 99th percented in the tables below. The samples used in the study, representing an US population, included 2116 newborn dricd blood samples (2109 routine screening specimens and seven restrospective specimens of which three were diagnosed true positives for galactosemia).

In the tables below the screening positives (+) are samples ≥ cut-off and the screening negatives (-) arc samples < cut-off.

| Screening summary using the 95th percentile | | | | |
|---------------------------------------------|-----------------|-------|---------------------------|------------------------------|
| Predicate | PerkinElmer kit | Total | Diagnosed<br>galactosemia | No diagnosed<br>galactosemia |
| + | + | 73 | 3 | 70 |
| + | - | 41 | 0 | 41 |
| - | + | 46 | 0 | 46 |
| - | - | 1956 | 0 | 1956 |
| Total | | 2116 | 3 | 2113 |

| Screening summary using<br>the 95th percentile | | Predicate | | | Total |
|------------------------------------------------|-------|-----------|------|--|-------|
| | | + | - | | |
| PerkinElmer kit | + | 73 | 46 | | 119 |
| | - | 41 | 1956 | | 1997 |
| | Total | 114 | 2002 | | 2116 |

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for PerkinElmer. The logo consists of a stylized "P" shape above the company name. The word "PerkinElmer" is in bold, and below it is the word "precisely."

When the 95th percentile was used as a cut-off for both methods, the positive percent was 64% (73/114) and the overall percent agreement was 95.9% ((73+1956)/2116).

| Screening summary using the 99th percentile | | | | |
|---------------------------------------------|-----------------|-------------------|---------------------------|------------------------------|
| Predicate | PerkinElmer kit | Total<br>subjects | Diagnosed<br>galactosemia | No diagnosed<br>galactosemia |
| + | + | 21 | 3 | 18 |
| + | - | 8 | 0 | 8 |
| - | + | 9 | 0 | 9 |
| - | - | 2078 | 0 | 2078 |
| Total | | 2116 | 3 | 2113 |

| Screening summary using<br>the 99th percentile | Predicate | | | |
|------------------------------------------------|-----------|----|-------|------|
| | + | - | Total | |
| PerkinElmer kit | + | 21 | 9 | 30 |
| | - | 8 | 2078 | 2086 |
| | Total | 29 | 2087 | 2116 |

When the 99" percentile was used as a cut-off for both methods, the positive percent agreement was 72.4%
(21/29) and the overall percent agreement was 99.2% ((21+2078)/2116).

The total galactose concentrations of the three true galactosemia specimens used in the study were as shown in the table below:

| Total Galactose concentrations of true positive specimens | | |
|-----------------------------------------------------------|----------------------------|---------------------------------------|
| Specimen no. | PerkinElmer kit<br>(mg/dL) | Commercially available kit<br>(mg/dL) |
| 1 | 16.6 | 23.9 |
| 2 | 12.1 | 14.6 |
| 3 | 22.2 | 39.1 |

{6}------------------------------------------------

### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The logo is black and white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Wallac Oy c/o Ms. Helena Lundstrom Regulatory Affairs Manager Mustionkatu 6, PO Box 10 Turku 20750, Finland

Re: k071649

Trade/Device Name: Neonatal Total Galactose Kit Regulation Number: 21 CFR 862.1310 Regulation Name: Galactose Test System Regulatory Class: Class I Product Code: JIA Dated: July 21, 2008 Received: July 24, 2008

AUG - 7 2008

Dear Ms. Lundstrom:

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).

{7}------------------------------------------------

Page 2 -

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 Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [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

{8}------------------------------------------------

# Indication for Use

510(k) Number (if known): k071649

Device Name: Neonatal Total Galactose Kit

Indication For Use:

This kit is intended for the quantitative determination of total galactose (galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia.

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 (OVD)

Carol C. Benam

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

510(k) k071649