(32 days)
No
The description mentions "ANALYSIS SOFTWARE algorithm" which converts genotypes to alleles based on literature, but there is no indication of AI or ML being used for learning or pattern recognition. The process is described as a standard PCR and hybridization-based assay with software for data processing.
No
Explanation: The device is an in vitro diagnostic test intended to aid in the diagnosis of A1AT deficiency by identifying genetic variants. It does not directly treat or alleviate a medical condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test results "are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD)." This directly indicates its role in diagnosis.
No
The device is a kit that includes reagent components and a CD containing software. It is an in vitro diagnostic test that requires laboratory processing of biological samples using hardware (Luminex 200 instrument) and reagents. The software is an analysis tool for the data generated by the hardware and reagents, not a standalone software-only medical device.
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 a "quantitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test".
- Purpose: The test is intended to be used with human samples (whole blood and saliva) to detect and identify genetic variants associated with Alpha-1 antitrypsin deficiency (A1ATD). This is a diagnostic purpose performed outside of the body.
- Aid in Diagnosis: The results are intended to be used "as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD)", which is a key characteristic of an IVD.
- Prescription Use: The indication for "prescription use only" further supports its classification as a medical device used for diagnostic purposes.
The "Device Description" also reinforces this by describing the process of extracting DNA from human samples and performing laboratory procedures (PCR, hybridization, detection) to obtain results.
N/A
Intended Use / Indications for Use
The Progenika A1AT genotyping kit is a quantitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200 instrument (with xPONENT software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The test intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spot (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect Dx model OCD-100. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD). The kit is indicated for prescription use only.
Product codes (comma separated list FDA assigned to the subject device)
PZH
Device Description
Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS or from human EDTA anticoagulated whole blood or from human saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.
The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the above mentioned processing steps, and a CD containing the A1AT Genotyping Test ANALYSIS SOFTWARE and other necessary files. Two kit configurations are available: for 48 or for 192 tests (different amounts of the same reagent components are provided in each case).
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
Not Found
Intended User / Care Setting
Prescription Use
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
A total of 147 DNA samples, representing all variants interrogated by the assay, were included in the study, distributed as follows: 140 archived left-over clinical genomic DNA samples obtained from human saliva collected as buccal swabs (ORAcollect Dx model OCD-100), 3 genomic DNA samples extracted from cell lines and 4 synthetic DNA samples. The sample panel covered all heterozygous and homozygous genotypes of each allelic variant and 12 compound heterozygous genotypes. The comparison (with bi-directional Sanger sequencing) showed 100% concordance.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Data:
- Precision/Reproducibility: See K171868 for Lot-to-Lot Variability and Site Reproducibility information.
- Reagent Stability: See K171868 for Real-Time and Open-Vial Stabilities information. Stability studies based on the same protocol, acceptance criteria and results as K171868 have proved up to 24 months reagent stability when stored at 2-8ºC and up to 9 months reagent stability after the vials were first opened.
- Specimen Stability: See K171868 for whole blood samples collected as DBS or in K2-EDTA stabilities. Saliva samples are collected in ORAcollect Dx model OCD-100. See K152464 for saliva samples stability information.
- Lower Limit of Detection (LoD): See K171868 for LoD information.
- DNA Extraction Variability: See K171868 for DNA Extraction Variability in whole blood samples collected as DBS or in K2-EDTA information. Twelve saliva samples collected as buccal swabs using ORAcollect Dx model OCD-100 were extracted three times by two operators on three different days and tested in duplicate with 3 different extraction methods. Results obtained for all samples tested with each extraction method were correct.
- Cross-reactivity and Cross-contamination: See K171868 for Cross-reactivity and Cross-contamination information.
- Interfering Substances: See K171868 for Interfering Substances information in whole blood samples collected as DBS or in K2-EDTA. Saliva samples from five (5) random donors (M/M except one M/Z) were spiked with salivary α-amylase, hemoglobin, immunoglobin A, and total protein. No inhibition of the assay was observed. Saliva samples from five (5) random donors (M/M except one M/F and one M/S) were collected before, immediately after, and 30 minutes after various activities (eating, drinking, smoking, chewing gum, mouth washing, brushing teeth). Results indicated samples should be collected at least 30 minutes after activity. DNAs from human cell lines were spiked with DNA of various microbes; no inhibition was observed.
- Method Comparison: The results obtained with the A1AT Genotyping Test were compared with bi-directional Sanger sequencing. A total of 147 DNA samples (140 archived left-over clinical genomic DNA samples from human saliva, 3 genomic DNA samples from cell lines, and 4 synthetic DNA samples) were included. The sample panel covered all heterozygous and homozygous genotypes of each allelic variant and 12 compound heterozygous genotypes. The comparison showed 100% concordance between A1AT Genotyping Test and bi-directional Sanger sequencing results.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Concordance shown as 100% in method comparison study (table)
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.
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
§ 866.5130
Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition,alpha -1-antitrypsin deficiency has been associated with pulmonary emphysema.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 5, 2019
Progenika Biopharma S.A., A Grifols Company Diego Tejedor Technical Director Ibaizabal bidea, Edificio 504, Parque Tecnologico de Bizkaia Derio, 48160 Es
Re: K192858
Trade/Device Name: A1AT Genotyping Test Regulation Number: 21 CFR 866.5130 Regulation Name: Alpha-1-antitrypsin immunological test system Regulatory Class: Class II Product Code: PZH Dated: October 1, 2019 Received: October 4, 2019
Dear Diego Tejedor:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 note: 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 either 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 Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Douglas Jeffery, Ph.D. Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K192858
Device Name A1AT Genotyping Test
Indications for Use (Describe)
The Progenika A1AT genotyping kit is a quantitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200 instrument (with xPONENT software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The test intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spot (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect Dx model OCD-100. The A1AT allelic variant genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD). The kit is indicated for prescription use only.
| Type of Use (Select one or both, as applicable) | For personal use (If you are a CFP Board Candidate, select this option) For Firm Use (If you are a Firm Administrator, select this option) | For personal use (If you are a CFP Board Candidate, select this option) | For Firm Use (If you are a Firm Administrator, select this option) |
|---|---|---|---|
| For personal use (If you are a CFP Board Candidate, select this option) | |||
| For Firm Use (If you are a Firm Administrator, select this option) |
X Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
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3
Progenika Biopharma, S.A.
Ibaizabal bidea, Edificio 504
Parque Tecnológico de Bizkaia
48160 Derio - Bizkaia - SPAIN
Phone: +34 94 406 45 25
Fax: +34 94 406 45 26
CIF: ESA95091799
www.progenika.com - www.grifols.com
Special 510(k) Summary
- A. Name of the device: A1AT Genotyping Test
- B. Common name: Test for SERPINA1 gene genotyping
- C. Regulatory information:
- a. Classification: Class II
- b. Regulation Section: 21 CFR 866.5130, Alpha-1-antitrypsin immunological test system
- c. Classification Product Code: PZH, SERPINA1 Variant Detection System
- d. Review panel: Immunology (82)
- D. Applicant: Progenika Biopharma S.A.
Address: Parque Tecnológico de Bizkaia Ibaizabal bidea, Edificio 504 C.P. 48160, Derio - Bizkaia (Spain) Telephone number: +34 94 406 45 25 Fax number: +34 94 406 45 26 Contact person: Diego Tejedor, Technical Director e-mail: diego.tejedor@grifols.com
E. Intended Use:
The Progenika A1AT genotyping kit is a qualitative, polymerase chain reaction (PCR) and hybridization-based in vitro diagnostic test to be used with the Luminex 200TM instrument (with xPONENT® software) for the simultaneous detection and identification of 14 allelic variants and their associated alleles found in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The test is intended for use with genomic DNA extracted from human whole blood samples collected as dry blood spots (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabs using ORAcollect.Dx model OCD-100. The A1AT allelic variant
4
www.progenika.com - www.grifols.com
genotypes and associated allele results, when used in conjunction with clinical findings and other laboratory tests, are intended as an aid in the diagnosis of individuals with A1AT deficiency (A1ATD).
The kit is indicated for prescription use only.
F. Device Description:
Alpha 1 antitrypsin (A1AT) Genotyping Test utilizes Luminex xMAP technology. Genomic DNA is extracted from DBS or from human EDTA anticoagulated whole blood or from human saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100. Extracted DNA is amplified and biotinylated by multiplex PCR and PCR products are denatured and hybridized to oligonucleotide probes coupled to color-coded beads. Hybridized DNA is labeled with a fluorescent conjugate and the resulting signal is detected with a Luminex® 200 system. Raw data obtained is processed with the A1AT Genotyping Test ANALYSIS SOFTWARE in order to obtain the final report. The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm converts the allelic variant genotypes into associated alleles, based on the current literature.
The A1AT Genotyping Test Kit is composed of 4 reagent components (A1AT PCR Master Mix, A1AT Beads Master Mix, SAPE, SAPE Dilution Buffer) required to perform all the above mentioned processing steps, and a CD containing the A1AT Genotyping Test ANALYSIS SOFTWARE and other necessary files. Two kit configurations are available: for 48 or for 192 tests (different amounts of the same reagent components are provided in each case).
G. Substantial Equivalence Information:
Predicate Device: A1AT Genotyping Test
510(k) number: K171868
Applicant: Progenika Biopharma S.A.
Main conclusion: The similarities among the candidate device and the predicate device show that A1AT Genotyping Test for use with human saliva samples
5
Progenika Biopharma, S.A. lbaizabal bidea. Edificio 504 Parque Tecnológico de Bizkaia 48160 Derio - Bizkaia - SPAIN Phone: +34 94 406 45 25 Fax +34 94 406 45 26 CIF: ESA95091799 www.progenika.com - www.grifols.com
collected as buccal swabs using ORAcollect-Dx model OCD-100 is substantially equivalent to the predicate.
Based on the risk assessment and performance data, it can be considered that the differences due to new sample matrix do not raise different questions of safety and effectiveness.
6
Progenika Biopharma, S.A.
Ibaizabal bidea, Edificio 504 Parque Tecnológico de Bizkaia
48160 Derio - Bizkaia - SPAIN
Phone: +34 94 406 45 25
Fax: +34 94 406 45 25
Fax: +34 94 406 45 26 ClF: ESA95091799
www.progenika.com - www.grifols.com
| Item | Candidate Device
Modified A1AT Genotyping Test | Predicate Device
A1AT Genotyping Test (K171868) |
|-------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Progenika A1AT genotyping kit is a qualitative, polymerase
chain reaction (PCR) and hybridization-based in vitro diagnostic
test to be used with the Luminex 200TM instrument (with
xPONENT® software) for the simultaneous detection and
identification of 14 allelic variants and their associated alleles found
in the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. The
test is intended for use with genomic DNA extracted from human
whole blood samples collected as dry blood spots (DBS) or in K2-
EDTA or from human saliva samples collected as buccal swabs
using ORAcollect-Dx model OCD-100. The A1AT allelic variant
genotypes and associated allele results, when used in conjunction
with clinical findings and other laboratory tests, are intended as an
aid in the diagnosis of individuals with A1AT deficiency (A1ATD).
The kit is indicated for prescription use only. | The Progenika A1AT genotyping kit is a qualitative, polymerase chain
reaction (PCR) and hybridization-based in vitro diagnostic test to be
used with the Luminex 200TM instrument (with xPONENT® software)
for the simultaneous detection and identification of 14 allelic variants
and their associated alleles found in the Alpha-1 antitrypsin (A1AT)
codifying gene SERPINA1. The test is intended for use with genomic
DNA extracted from human whole blood samples collected as dry
blood spots (DBS) or in K2-EDTA. The A1AT allelic variant genotypes
and associated allele results, when used in conjunction with clinical
findings and other laboratory tests, are intended as an aid in the
diagnosis of individuals with A1AT deficiency (A1ATD).
The kit is indicated for prescription use only. |
| Specimen Type | Genomic DNA extracted from human whole blood samples
collected as DBS or in K2-EDTA and human saliva samples
collected as buccal swabs using ORAcollect-Dx model OCD-100. | Genomic DNA extracted from human whole blood samples collected
as DBS or in K2-EDTA. |
| Target | Same. | Qualitative identification of A1AT alleles (which represent the
phenotypes) causing A1ATD. |
| Item | Candidate Device
Modified A1AT Genotyping Test | Predicate Device
A1AT Genotyping Test (K171868) |
| Device
components | Same. | The test is composed of four reagent components (A1AT PCR Master
Mix, A1AT Beads Master Mix, SAPE and SAPE Dilution Buffer) in
sufficient quantity for either 48 or 192 tests and a CD containing the
A1AT Genotyping Test ANALYSIS SOFTWARE. |
| Technology | Polymerase chain reaction (PCR) and hybridization-based in vitro
diagnostic test to be used with the Luminex 200TM instrument (with
xPONENT® software). | Polymerase chain reaction (PCR) and hybridization-based in vitro
diagnostic test to be used with the Luminex 200TM instrument (with
xPONENT® software). |
| | DNA is extracted from human whole blood samples collected as
dry blood spots (DBS) or in K2-EDTA or from human saliva
samples collected as buccal swabs using ORAcollect-Dx model
OCD-100, amplified and biotinylated by multiplex PCR and PCR
products are denatured and hybridized to oligonucleotide probes
coupled to color coded beads. Hybridized DNA is labeled with a
fluorescent conjugate and resulting signal is detected with a
Luminex 200TM system. The raw data obtained is finally
processed with the A1AT Genotyping Test ANALYSIS
SOFTWARE in order to obtain the final report. | DNA is extracted from human whole blood samples collected as dry
blood spots (DBS) or in K2-EDTA, amplified and biotinylated by
multiplex PCR and PCR products are denatured and hybridized to
oligonucleotide probes coupled to color coded beads. Hybridized DNA
is labeled with a fluorescent conjugate and resulting signal is
detected with a Luminex 200TM system. The raw data obtained is
finally processed with the A1AT Genotyping Test ANALYSIS
SOFTWARE in order to obtain the final report. |
| Performance
specifications | Lower Limit of Detection: same.
Interferences: α-amylase, hemoglobin, immunoglobin A, total
protein, microbes, eating food without beef, eating food with
beef, drinking, smoking, chewing gum, mouth washing and
brushing teeth. | Lower Limit of Detection: 0.0310 ng/µl DNA.
Interferences: hemoglobin, bilirubin, triglycerides and short blood
draw. |
| Item | Candidate Device
Modified A1AT Genotyping Test | Predicate Device
A1AT Genotyping Test (K171868) |
| | - Lot-to-Lot and External Reproducibility studies: same. | - Lot-to-Lot and external reproducibility studies. |
| | - Accuracy: 147 samples, comparator: Bi-directional Sanger sequencing. | - Accuracy: 116 samples, comparator: Bi-directional Sanger sequencing. |
| Intended
population | Same. | Prescription use only. |
| DNA extraction
method | Whole blood samples collected as DBS or in K2-EDTA: same. | Whole blood samples collected in K2-EDTA: QIAamp DNA Blood Mini Kit (Qiagen) |
| | Saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100:
- QIAamp DNA Blood Mini Kit (Qiagen)
- Commercial lysis and neutralization solutions (Sigma)
- QIAsymphony DNA Mini Kit (Qiagen) | Whole blood samples collected as DBS:
- Commercial lysis and neutralization solutions (Sigma)
- Home-made buffer |
| Specimen
Stability | - Whole blood samples collected in K2-EDTA: same. - Whole blood samples collected as DBS: same.
- Saliva samples collected as buccal swabs using ORAcollect-Dx model OCD-100 (DNA Genotek): up to 60 days when stored at ambient temperature. | - Whole blood samples collected in K2-EDTA: up to 24 days before DNA extraction at 2-8°C.
- Whole blood samples collected as DBS: up to 6 months at ambient temperature. |
Comparison table:
7
Progenika Biopharma GRIFOLS
Progenika Biopharma, S.A.
lbaizabal bidea, Edificio 504
Parque Tecnológico de Bizkaia
48160 Derio Bickordo de Bizkaia
48160 Derio Bizkaisa Sirkai Siria SiriAlN
Fax: +34 94 406 45 25 CIF: ESA95091799
www.progenika.com - www.grifols.com
8
Progenika Biopharma GRIFOLS
Progenika Biopharma, S.A.
lbaizabal bidea, Edificio 504
Parque Tecnológico de Bizkaia
48160 Derio Bickordo de Bizkaia
48160 Derio Bizkaisa Sirkai Siria SiriAlN
Fax: +34 94 406 45 25 CIF: ESA95091799
www.progenika.com - www.grifols.com
9
H. Performance Data:
Analytical Data:
-
a) Precision/Reproducibility:
See K171868 for Lot-to-Lot Variability and Site Reproducibility information. -
b) Reagent Stability:
See K171868 for Real-Time and Open-Vial Stabilities information. Stability studies based on the same protocol, acceptance criteria and results as K171868 have proved up to 24 months reagent stability when stored at 2-8ºC and up to 9 months reagent stability after the vials were first opened. -
c) Specimen Stability:
See K171868 for whole blood samples collected as DBS or in K2-EDTA stabilities.
Saliva samples are collected in ORAcollect Dx model OCD-100. See K152464 for saliva samples stability information.
- d) Lower Limit of Detection (LoD): See K171868 for LoD information.
- e) DNA Extraction Variability:
See K171868 for DNA Extraction Variability in whole blood samples collected as DBS or in K2-EDTA information.
With the aim of testing the possible impact of 3 different extraction methods on assay performance, twelve saliva samples (covering >95% of cases worldwide where allelic variants have been identified in the A1AT coding gene) collected as buccal swabs using ORAcollect Dx model OCD-100 were extracted three
10
times by two operators on three different days and tested in duplicate. Results obtained for all samples tested with each extraction method were correct.
-
f) Cross-reactivity and Cross-contamination:
See K171868 for Cross-reactivity and Cross-contamination information. -
g) Interfering Substances:
See K171868 for Interfering Substances information in whole blood samples collected as DBS or in K2-EDTA.
Saliva samples collected in ORAcollect-Dx model OCD-100 from five (5) random donors (M/M except one M/Z) were spiked with salivary a-amylase at 395 U/mL; hemoglobin at 226 mg/dL; immunoglobin A at 0.43 mg/mL and total protein at 3.18 mg/mL (composed of 0.185 mg/mL salivary α-amylase, 0.43 mg/mL IgA and 2.56 mg/mL human serum albumin). No inhibition of the assay was observed for any of the interfering substances tested.
Saliva samples from five (5) random donors (M/M except one M/F and one M/S) were collected in ORAcollect-Dx model OCD-100 prior to the activity (baseline/control sample), immediately after the activity and 30 minutes after the activity. Seven (7) activity groups were tested: eating food without beef, eating food with beef, drinking, smoking, chewing gum, mouth washing and brushing teeth. The results indicated that saliva samples collected in ORAcollect.Dx model OCD-100 should be collected at least 30 minutes after the activity which is compatible with the instructions for use of ORAcollect-Dx model OCD-100.
DNAs from human cell lines (MS, SZ, SS and MZ) were spiked with DNA of the following microbes: Staphylococcus epidermis, Streptococcus mutans, Lactobacillus casei, Actinomyces viscosus and Candida albicans. No inhibition of the assay was observed for any of the microbial interfering substances tested. Potentially interfering variants identified for the allelic variants detected by the A 1AT Genotyping Test are listed in the table below. None of the listed potentially interfering variants was tested.
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Progenika Biopharma, S.A.
ahal hidoa Edificin 504 enológico do Rizkais enika.com - www.grifols.com
| Allelic Variant | Reported Associated
Alleles | Interfering variants |
|---------------------------|--------------------------------|-------------------------------------------------------|
| RefSeq:
NM_001127701.1 | | |
| c.187C>T | PI* I | rs199422213 |
| c.194T>C | PI* M procida | rs199422213 |
| c.226_228delTTC | PI* M malton | rs199422213 |
| c.230C>T | PI* S iiyama | rs199422213 |
| c.552delC | PI* Q0 granite falls | rs148207011 |
| c.646+1G>T | PI* Q0 west | rs148207011 |
| c.721A>T | PI* Q0 bellingham | rs200634040, rs72552401 |
| c.739C>T | PI* F | rs544632177, rs577164283 |
| c.839A>T | PI* P lowell | rs1049800 |
| c.863A>T | PI* S | rs149537225 |
| c.1096G>A | PI* Z | rs143370956, rs201774333,
rs551595739, rs372571769 |
| c.1130dupT | PI* Q0 mattawa | rs148362959, rs372571769 |
| c.1158dupC | PI* Q0 clayton | rs143329723, rs121912712,
rs372571769 |
| c.1178C>T | PI* M heerlen | rs61761869, rs372571769 |
One sample homozygous for PI* Q0 amersfoort (c.552C>G) was tested and detected as homozygous for PI* Q0 granite falls (c.552delC). The information related to this interfering variant has been included in the assay limitations section of the package insert.
Comparison Data:
- h) Method Comparison:
See K171868 for Method Comparison information in whole blood samples.
12
Progenika Biopharma, S.A.
Ibaizabal bidea, Edificio 504
Parque Tecnológico de Bizkaia
48160 Derio - Bizkaia - SPAIN
Phone: +34 94 406 45 25
Fax: +34 94 406 45 26
CIF: ESA95091799
www.progenika.com - www.grifols.com
The results obtained with the A1AT Genotyping Test were compared with the results obtained from bi-directional Sanger sequencing. A total of 147 DNA samples, representing all variants interrogated by the assay, were included in the study, distributed as follows: 140 archived left-over clinical genomic DNA samples obtained from human saliva collected as buccal swabs (ORAcollect Dx model OCD-100), 3 genomic DNA samples extracted from cell lines and 4 synthetic DNA samples.
The sample panel covered all heterozygous and homozygous genotypes of each allelic variant and 12 compound heterozygous genotypes.
The comparison showed 100% concordance between A1AT Genotyping Test and bidirectional Sanger sequencing results, as it is shown in the table below.
| Allelic Variant | Most
frequently
associated
Allele | Genomic DNA, n | | | Synthetic DNA, n | | Concordance
(%) |
|-----------------|--------------------------------------------|----------------|----|----|------------------|---|--------------------|
| c.187C>T | PI* I | 130 | 13 | 0 | 1 | 1 | 100% |
| c.194T>C | PI* M procida | 138 | 5 | 0 | 1 | 1 | 100% |
| c.226_228delTTC | PI* M malton | 120 | 21 | 2 | 1 | 1 | 100% |
| c.230C>T | PI* S iiyama | 143 | 0 | 0 | 1 | 1 | 100% |
| c.552delC | PI* Q0 granite
falls | 143 | 0 | 0 | 2 | 2 | 100% |
| c.646+1G>T | PI* Q0 west | 143 | 0 | 0 | 2 | 2 | 100% |
| c.721A>T | PI* Q0
bellingham | 143 | 0 | 0 | 2 | 2 | 100% |
| c.739C>T | PI* F | 139 | 4 | 0 | 2 | 2 | 100% |
| c.839A>T | PI* P lowell | 128 | 14 | 1 | 2 | 2 | 100% |
| c.863A>T | PI* S | 93 | 35 | 15 | 2 | 2 | 100% |
| c.1096G>A | PI* Z | 93 | 35 | 15 | 2 | 2 | 100% |
| c.1130dupT | PI* Q0 mattawa | 137 | 5 | 1 | 2 | 2 | 100% |
| c.1158dupC | PI* Q0 clayton | 143 | 0 | 0 | 2 | 2 | 100% |
| c.1178C>T | PI* M heerlen | 138 | 5 | 0 | 2 | 2 | 100% |
l. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR 809.10.
J. Conclusion:
13
Progenika Biopharma, S.A. Ibaizabal bidea, Edificio 504 Parque Tecnológico de Bizkaia 48160 Derio - Bizkaia - SPAIN Phone: +34 94 406 45 25 Fax: +34 94 406 45 26 CIF . ESA95091799 www.progenika.com - www.grifols.com
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
K. Date of summary preparation:
September 30, 2019.