PERKINELMER 226 SAMPLE COLLECTION DEVICES

K121864 · Perkinelmer, Inc. · PJC · Mar 12, 2013 · Clinical Chemistry

Device Facts

• Record ID: K121864
• Device Name: PERKINELMER 226 SAMPLE COLLECTION DEVICES
• Applicant: Perkinelmer, Inc.
• Product Code: PJC · Clinical Chemistry
• Decision Date: Mar 12, 2013
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.1675
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The PerkinElmer 226 Sample Collection Devices are intended to be used as a medium to collect and transport whole blood specimen spots to a laboratory, in newborn screening. The device includes a tear-apart form for the collection of demographic information.

Device Story

PerkinElmer 226 Sample Collection Device consists of filter paper printed with circles and affixed to a rigid carrier with a tear-apart demographic form. Used in clinical settings (hospitals) by nurses or phlebotomists to collect newborn whole blood samples. A drop of blood is applied to the filter paper, allowed to saturate, and air-dried. The dried blood spot (DBS) card is then transported to a laboratory for newborn screening analysis. The device serves as a passive collection medium; it does not perform analysis. Laboratory analysis of the DBS samples (using immunoassays, mass spectrometry, or HPLC) allows for the screening of various metabolic and genetic disorders. The device ensures uniform sample collection and transport, facilitating clinical decision-making regarding newborn health.

Clinical Evidence

Clinical performance was evaluated using a population comparison study of 2,000 patient samples per disorder. Samples were collected by nurses/phlebotomists from newborns and tested for 11 conditions (e.g., CAH, hypothyroidism, CF, PKU, hemoglobinopathies). Assays included immunoassays, mass spectrometry, and HPLC. Results showed median percent differences between the subject device and the predicate ranging from 2-10%. Hemoglobinopathy testing via HPLC showed overlapping 95% confidence intervals with no significant statistical differences, supporting clinical equivalence.

Technological Characteristics

Filter paper: 100% pure cotton linters, no wet-strength additives. Standards: CLSI LA4-A4, ASTM D646-96 (basis weight 110 lb), ISO 6599:1981 (pH 5.7-7.5), ASTM D586-97a (ash <0.1%). Form factor: Printed filter paper affixed to cardboard/plastic carrier with optional demographic form. Non-electronic, passive collection medium.

Indications for Use

Indicated for use as a medium to collect and transport whole blood specimen spots for newborn screening. No specific patient population contraindications are listed.

Regulatory Classification

Identification

A blood specimen collection device is a device intended for medical purposes to collect and to handle blood specimens and to separate serum from nonserum (cellular) components prior to further testing. This generic type device may include blood collection tubes, vials, systems, serum separators, blood collection trays, or vacuum sample tubes.

Predicate Devices

• Ahlstrom 226 filter paper (k062932)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k121864

B. Purpose for Submission:
New device

C. Measurand:
Not applicable – whole blood collection system

D. Type of Test:
Not applicable

E. Applicant:
PerkinElmer Inc.

F. Proprietary and Established Names:
PerkinElmer 226 Sample Collection Device

G. Regulatory Information:
1. Regulation section:
21CFR 862.1675 (Blood specimen collection device)
2. Classification:
Class II
3. Product code:
JKA
4. Panel:
75 (Chemistry)

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H. Intended Use:

1. Intended use(s):
See Indication for use below.

2. Indication(s) for use:
The PerkinElmer 226 Sample Collection Devices are intended to be used as a medium to collect and transport whole blood specimen spots to a laboratory, in newborn screening. The device includes a tear-apart form for the collection of demographic information.

3. Special conditions for use statement(s):
For prescription use only.

4. Special instrument requirements:
Not applicable.

I. Device Description:

PerkinElmer 226 Sample Collection Device is designed to provide a uniform surface for the collection of dried blood spots (DBS). The collection paper is in the format of a printed card that may be incorporated along with a tear-apart form for the collection of demographic information. A drop of blood is applied to the filter paper and allowed to soak through the paper. The sample is then air dried and sent to a laboratory for analysis in newborn screening.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Ahlstrom 226 filter paper

2. Predicate K number(s):
k062932

3. Comparison with predicate:

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| Similarities | | |
| --- | --- | --- |
| Item | Candidate device-PerkinElmer 226 | Predicate device-Ahlstrom 226 |
| Intended Use | Intended to be used as a medium to collect and transport whole blood specimen spots to a laboratory, in newborn screening. | same |
| Description | Filter paper printed and affixed to a carrier with a tear-apart form. | same |
| Matrix | Whole blood | same |
| Storage conditions for unused cards | Store in a cool dry space away from direct sunlight. | same |
| Specimen drying time | 3-4 hours | same |

K. Standard/Guidance Document Referenced (if applicable):

CLSI LA4 – A4: Blood Collection on Filter Paper for Newborn Screening Programs; Approved Standard

L. Test Principle:

The PerkinElmer 226 Sample Collection Device is intended to be used directly as a blood collection device for newborn screening. The device is filter paper card printed with circles and affixed to a rigid carrier device. The filter paper is touched to a sufficiently large blood drop to completely fill a preprinted circle. Blood should be applied to only one side of the filter paper and allowed to uniformly penetrate and fully saturate the filter paper. The filter paper is then placed in the horizontal position and allowed to air dry at room temperature away from direct sunlight.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:
a. Precision/Reproducibility:
Not applicable
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):

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The filter paper was shown to conform to Consensus Standard – CLSI LA4-A4: Blood Collection on Filter Paper for Newborn Screening Programs; Approved Standard.

The filter paper’s physical composition was evaluated internally and results are summarized below:

| Lot # | Basis Weight (110 ± 5%) lbs /ream | pH (5.7 – 7.5) | Ash Percent |
| --- | --- | --- | --- |
| 5431001 | 111.24 | 7 | 0.047 |
| 6050501 | 110.05 | 7.5 | 0.04357 |
| 6460701 | 108.43 | 7.2 | 0.047 |
| Test Method Reference | ASTM D4646-96 | ISO 6588.1981 | ASTM D586-97a Method A |

Testing was performed to assess the absorption characteristics of the filter paper based on CLSI LA4-A4, Appendix B. Results for the PKI 226 paper are summarized below.

| Lot # | Mean blood absorption time (5-30 s/100 uL) | Mean blood spot diameter (15-17 mm) | Mean serum absorption volume (1.37-1.71 uL/punch) | Homogeneity (p > 0.05) |
| --- | --- | --- | --- | --- |
| 5431001 | 7.4 | 16.1 | 1.42 | p=0.937 |
| 6050501 | 14.1 | 16.3 | 1.47 | p=0.607 |
| 6460701 | 16.2 | 17.0 | 1.49 | p=0.984 |

d. Detection limit:

Not applicable

e. Analytical specificity:

An interference study was performed to show that printing ink used to manufacture the device would not interfere with newborn screening assays across representative platform and assay types. TSH, 17 α-OH-progesterone, T4 and total galactose assays (incorporating immunometric, competitive and enzymatic test methods) were run with samples punched to exclude (control) or include ink on commercially available platforms. Samples were DBS prepared from heparinized whole blood adjusted to a hematocrit of 47.5% spiked with analyte concentrations at low, high and near the relevant clinical decision point. Each concentration was tested in replicates of 12. Results of the study are summarized in the table below.

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| Analyte | Target Concentration | % Interference From Ink |
| --- | --- | --- |
| TSH (μU/mL) | 5 | 7.9 |
| | 15 | 0.3 |
| | 100 | -7.5 |
| 17-OHP (ng/mL) | 10 | 0.3 |
| | 45 | -0.9 |
| | 100 | -4.4 |
| T4 (μg/dL) | 3 | 1.5 |
| | 7 | -1.9 |
| | 15 | 0.8 |
| TGal (mg/dL) | 4 | 11.8 |
| | 8 | 1.1 |
| | 20 | 3.9 |

The sponsor also provided an additional analysis of the interference study data demonstrating that sample means and within-sample variation were not statistically different for unfinished paper, the finished device in the absence of ink, and the finished device in the presence of ink.

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study performed by an independent laboratory used adult whole blood adjusted to a hematocrit of 55% supplemented with various analytes spotted on both a commercially available device and PKI 226 and then tested with assays that screen for congenital adrenal hyperplasia (CAH), hypothyroidism, cystic fibrosis (CF), maple syrup urine disease, fatty acid oxidation disorders (FAO), and disorders of amino acid metabolism including phenylketonuria, tyrosinemia, and citrulinemia. The analytes were added at concentrations below, at, and above relevant clinical cutoffs. Dried blood spot samples on PKI 226 and the comparator were prepared at a central laboratory.

Six external laboratories performed testing in duplicate using routine testing assays and provided the line data to the independent lab for statistical analysis of mean and standard deviation. The assays tested included direct and

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competitive immunoassays using both fluorometric and colorimetric readouts as well as mass spectrometric-based assay methodologies.

All data from PKI 226 for each analyte shows a strong overlap at one standard deviation with the data derived with samples collected with the comparator device with a difference of 4-5%. Concurrent longitudinal testing of mean serum volume testing on six lots of the PKI 226 device showed a similar lot-to-lot variability (4.66%), therefore the difference between newborn screening assay data from the two DBS cards is not dissimilar from the lot-to-lot variability detected for the proposed device.

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

To support the use of PKI 226 in the intended use setting by the intended users with clinical patient samples, results from a clinical study were provided. In this study a central laboratory received dried blood spot samples collected by nurses and/or phlebomists from newborns in a hospital. These samples provided a population comparison study using 2000 randomly selected patient samples per disorder that included screening assays for biotinidase deficiency, congenital adrenal hyperplasia, hypothyroidism, cystic fibrosis, galactosemia, homocystinuria, maple syrup urine disease, phenylketonuria, tyrosinemia, citrulinemia, and hemoglobinopathies. The assays tested included direct and competitive immunoassays using fluorometry, mass spectrometry, and high performance liquid chromatography assay methodologies. The testing results for each assay were analyzed for the mean, median value of each analyte and SD as well as the observed ranges for the 2000 samples. Results for samples from PKI 226 and a commercially available device were compared based on the difference between their calculated medians for the 2000 samples. The median of each analyte for the PKI 226 data exhibits a percent difference from the predicate that's within 2-6% for the immunoassays and 2-10% for the mass spectrometric assays. PKI 226 Data and descriptive statistics are included below.

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| Disease | Galactosemia | | Hypothyroidism | |
| --- | --- | --- | --- | --- |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator |
| % Difference between medians | 4% | | 6% | |
| Median | 9.1 | 9.5 | 14.6 | 15.6 |
| Mean | 9.1 | 9.5 | 14.5 | 15.7 |
| SD | 1.7 | 1.9 | 4.4 | 4.7 |
| Observed Ranges; Lower and Upper Percentiles | | | | |
| Disease | Galactosemia | | Hypothyroidism | |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator |
| 2.5% | 6.0 | 5.6 | 5.6 | 6.4 |
| 5% | 6.6 | 6.4 | 7.0 | 7.9 |
| 10% | 7.1 | 7.2 | 8.7 | 9.7 |
| 90% | 11.2 | 11.7 | 19.9 | 21.7 |
| 95% | 11.9 | 12.5 | 21.5 | 23.8 |
| 97.5% | 12.6 | 13.1 | 23.2 | 25.7 |
| Disease | Biotinidase Deficiency | | CF | | CAH | |
| --- | --- | --- | --- | --- | --- | --- |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator | PKI 226 | Comparator |
| % Difference between medians | 5% | | 2% | | 5% | |
| Median | 192 | 201 | 25.8 | 26.2 | 5.2 | 5.5 |
| Mean | 197.4 | 206.4 | 30.9 | 32.1 | 7.69 | 7.35 |
| SD | 49.1 | 52.4 | 18.0 | 22.9 | 8.61 | 6.96 |
| Observed Ranges; Lower and Upper Percentiles | | | | | | |
| Disease | Biotinidase Deficiency | | CF | | CAH | |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator | PKI 226 | Comparator |
| 2.5% | 111 | 116 | 16.3 | 16.4 | 2.0 | 2.0 |
| 5% | 127 | 126 | 16.7 | 16.7 | 2.3 | 2.4 |
| 10% | 141 | 142 | 17.5 | 17.6 | 2.7 | 2.9 |
| 90% | 265 | 278 | 49.1 | 50.9 | 14.9 | 13.2 |
| 95% | 291 | 302 | 60.2 | 64.1 | 22.9 | 18.2 |
| 97.5% | 314 | 320 | 75.4 | 81.9 | 29.4 | 26.8 |

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| Disease | Citrulinemia | | Maple Syrup Urine Disease | |
| --- | --- | --- | --- | --- |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator |
| % Difference between medians | 6% | | 2% | |
| Median | 16 | 17 | 102 | 104 |
| Mean | 16.8 | 18.2 | 11 | 113 |
| SD | 5.5 | 6.4 | 39.3 | 41.8 |
| Observed Ranges; Lower and Upper Percentiles | | | | |
| Disease | Citrulinemia | | Maple Syrup Urine Disease | |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator |
| 2.5% | 9 | 9 | 62 | 62 |
| 5% | 10 | 11 | 67 | 68 |
| 10% | 11 | 12 | 74 | 74 |
| 90% | 24 | 25 | 155 | 159 |
| 95% | 26 | 28 | 179 | 189 |
| 97.5% | 29 | 32 | 200 | 224 |
| Disease | Homocystinuria | | Phenylketonuria | | Tyrosinemia | |
| --- | --- | --- | --- | --- | --- | --- |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator | PKI 226 | Comparator |
| % Difference between medians | 5% | | 5% | | 5% | |
| Median | 19 | 20 | 55 | 58 | 89 | 94 |
| Mean | 20.0 | 21.3 | 57.2 | 60.4 | 95.6 | 101 |
| SD | 6.7 | 9.7 | 14.3 | 17.5 | 4.9 | 43.1 |
| Observed Ranges; Lower and Upper Percentiles | | | | | | |
| Disease | Homocystinuria | | Phenylketonuria | | Tyrosinemia | |
| Filter Paper | PKI 226 | Comparator | PKI 226 | Comparator | PKI 226 | Comparator |
| 2.5% | 11 | 12 | 36 | 38 | 40 | 44 |
| 5% | 12 | 13 | 39 | 41 | 45 | 51 |
| 10% | 13 | 14 | 42 | 44 | 53 | 58 |
| 90% | 27 | 29 | 75 | 79 | 147 | 154 |
| 95% | 31 | 33 | 82 | 87 | 168 | 180 |
| 97.5% | 35 | 38 | 90 | 98 | 193 | 205 |

This population comparison study was also used to provide results to show

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that PKI 226 appears to recover the same results for hemoglobinopathies. From a larger population, 2000 samples were randomly selected for PKI 226 and a commercially available paper for comparison in an HPLC-based method to detect hemoglobinopathies. The frequency results showed that the 95% confidence intervals for each paper overlapped and had no significant statistical differences.

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Not applicable

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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