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.

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).

AI/ML Overview

Here’s a summary of the acceptance criteria and study details for the A1AT Genotyping Test, as extracted from the provided FDA 510(k) submission.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list "acceptance criteria" in a separate section with specific numerical thresholds for each performance metric. Instead, the study aims to demonstrate "100% concordance" with bi-directional Sanger sequencing for accuracy. The "Performance specifications" section outlines the areas tested, and the "Comparison Data" section reports the accuracy.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (Saliva Samples)
Accuracy (Concordance)	100% concordance with bi-directional Sanger sequencing	100%
Precision/Reproducibility	Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868)	Referred to K171868 - assumed acceptable
Reagent Stability	Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868)	Up to 24 months at 2-8ºC, up to 9 months after opening
Specimen Stability	Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868) and for saliva to K152464	Saliva (ORAcollect Dx model OCD-100): up to 60 days at ambient temperature
Lower Limit of Detection (LoD)	Not explicitly stated in terms of acceptance criteria, refers to previous submission (K171868)	Referred to K171868 - assumed acceptable
DNA Extraction Variability	All results correct	All results correct (12 samples tested with 3 methods by 2 operators on 3 days)
Cross-reactivity/Cross-contamination	No inhibition/interference	No inhibition observed for tested microbes. Potentially interfering variants listed with information included in assay limitations.
Interfering Substances	No inhibition of the assay	No inhibition observed for α-amylase, hemoglobin, IgA, total protein. Saliva samples should be collected at least 30 minutes after activities (eating, drinking, smoking, chewing gum, mouth washing, brushing teeth).

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Accuracy Test Set: 147 DNA samples.
- 140 archived left-over clinical genomic DNA samples obtained from human saliva (buccal swabs using ORAcollect Dx model OCD-100).
- 3 genomic DNA samples extracted from cell lines.
- 4 synthetic DNA samples.
Data Provenance: The 140 clinical samples were "archived left-over clinical genomic DNA samples," suggesting a retrospective collection of samples from clinical practice. The country of origin for the clinical samples is not specified in the provided text.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Not applicable. The ground truth was established by bi-directional Sanger sequencing, which is a laboratory method, not human expert interpretation.

4. Adjudication Method for the Test Set

Not applicable, as the ground truth was based on a laboratory method (bi-directional Sanger sequencing) rather than expert review requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is a genotyping test, not an image-based AI-assisted diagnostic tool for human readers. It provides direct genetic results.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

A standalone performance study was done for the device, where its results were compared directly against bi-directional Sanger sequencing (the ground truth). The A1AT Genotyping Test ANALYSIS SOFTWARE algorithm processes raw data to obtain the final report, effectively representing the "algorithm only" performance against the comparator.

7. The Type of Ground Truth Used

The ground truth used for the accuracy study was bi-directional Sanger sequencing.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the device itself in the context of an AI/ML algorithm. This device is a PCR and hybridization-based assay with associated analysis software. The performance data presented refers to the evaluation of this assay. If the "ANALYSIS SOFTWARE" incorporates machine learning, the training set details are not provided. However, given the nature of the device (genotyping test), it is unlikely to involve a dynamic machine learning model in the typical sense that would require a separate, distinct training set in the context of this submission. The software's algorithm converts allelic variants into associated alleles based on existing literature.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as a distinct training set (in the context of AI/ML) and its ground truth establishment are not discussed in the provided text. The "analysis software algorithm" is described as converting genotypes into alleles "based on the current literature," implying established scientific knowledge rather than a learned model from a specific training dataset.

Summary

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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

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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

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Indications for Use

510(k) Number (if known) K192858

Device Name A1AT Genotyping Test

Indications for Use (Describe)

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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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

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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:

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

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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.

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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 DeviceModified A1AT Genotyping Test	Predicate DeviceA1AT Genotyping Test (K171868)
Intended Use	The Progenika A1AT genotyping kit is a qualitative, polymerasechain reaction (PCR) and hybridization-based in vitro diagnostictest to be used with the Luminex 200TM instrument (withxPONENT® software) for the simultaneous detection andidentification of 14 allelic variants and their associated alleles foundin the Alpha-1 antitrypsin (A1AT) codifying gene SERPINA1. Thetest is intended for use with genomic DNA extracted from humanwhole blood samples collected as dry blood spots (DBS) or in K2-EDTA or from human saliva samples collected as buccal swabsusing ORAcollect-Dx model OCD-100. The A1AT allelic variantgenotypes and associated allele results, when used in conjunctionwith clinical findings and other laboratory tests, are intended as anaid 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 chainreaction (PCR) and hybridization-based in vitro diagnostic test to beused with the Luminex 200TM instrument (with xPONENT® software)for the simultaneous detection and identification of 14 allelic variantsand their associated alleles found in the Alpha-1 antitrypsin (A1AT)codifying gene SERPINA1. The test is intended for use with genomicDNA extracted from human whole blood samples collected as dryblood spots (DBS) or in K2-EDTA. The A1AT allelic variant genotypesand associated allele results, when used in conjunction with clinicalfindings and other laboratory tests, are intended as an aid in thediagnosis of individuals with A1AT deficiency (A1ATD).The kit is indicated for prescription use only.
Specimen Type	Genomic DNA extracted from human whole blood samplescollected as DBS or in K2-EDTA and human saliva samplescollected as buccal swabs using ORAcollect-Dx model OCD-100.	Genomic DNA extracted from human whole blood samples collectedas DBS or in K2-EDTA.
Target	Same.	Qualitative identification of A1AT alleles (which represent thephenotypes) causing A1ATD.
Item	Candidate DeviceModified A1AT Genotyping Test	Predicate DeviceA1AT Genotyping Test (K171868)
Devicecomponents	Same.	The test is composed of four reagent components (A1AT PCR MasterMix, A1AT Beads Master Mix, SAPE and SAPE Dilution Buffer) insufficient quantity for either 48 or 192 tests and a CD containing theA1AT Genotyping Test ANALYSIS SOFTWARE.
Technology	Polymerase chain reaction (PCR) and hybridization-based in vitrodiagnostic test to be used with the Luminex 200TM instrument (withxPONENT® software).	Polymerase chain reaction (PCR) and hybridization-based in vitrodiagnostic test to be used with the Luminex 200TM instrument (withxPONENT® software).
	DNA is extracted from human whole blood samples collected asdry blood spots (DBS) or in K2-EDTA or from human salivasamples collected as buccal swabs using ORAcollect-Dx modelOCD-100, amplified and biotinylated by multiplex PCR and PCRproducts are denatured and hybridized to oligonucleotide probescoupled to color coded beads. Hybridized DNA is labeled with afluorescent conjugate and resulting signal is detected with aLuminex 200TM system. The raw data obtained is finallyprocessed with the A1AT Genotyping Test ANALYSISSOFTWARE in order to obtain the final report.	DNA is extracted from human whole blood samples collected as dryblood spots (DBS) or in K2-EDTA, amplified and biotinylated bymultiplex PCR and PCR products are denatured and hybridized tooligonucleotide probes coupled to color coded beads. Hybridized DNAis labeled with a fluorescent conjugate and resulting signal isdetected with a Luminex 200TM system. The raw data obtained isfinally processed with the A1AT Genotyping Test ANALYSISSOFTWARE in order to obtain the final report.
Performancespecifications	Lower Limit of Detection: same.Interferences: α-amylase, hemoglobin, immunoglobin A, totalprotein, microbes, eating food without beef, eating food withbeef, drinking, smoking, chewing gum, mouth washing andbrushing teeth.	Lower Limit of Detection: 0.0310 ng/µl DNA.Interferences: hemoglobin, bilirubin, triglycerides and short blooddraw.
Item	Candidate DeviceModified A1AT Genotyping Test	Predicate DeviceA1AT 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.
Intendedpopulation	Same.	Prescription use only.
DNA extractionmethod	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
SpecimenStability	- 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:

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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

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Progenika Biopharma GRIFOLS

Progenika Biopharma, S.A.

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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

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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 AssociatedAlleles	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.

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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	MostfrequentlyassociatedAllele	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 granitefalls	143	0	0	2	2	100%
c.646+1G>T	PI* Q0 west	143	0	0	2	2	100%
c.721A>T	PI* Q0bellingham	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:

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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.

Regulation Number and Section

§ 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).