Introduction

The use of the device is subject to the term and conditions provided on the log-in screen, and to the ITA (Individual Tier Agreement).

Manufacturer contact details:	Product Labelling:
Nostos Genomics GmbH c/o Stresemannstrasse 123 Tenant GmbH Stresemannstrasse 123 10963 Berlin Germany

Intended Use

AION is a clinical-decision-support (CDS) in vitro diagnostic (IVD) software for the interpretation of next generation sequencing (NGS) data in the context of diagnostic testing of genetic diseases.

Product Description

The device is a Clinical Decision Support (CDS) stand-alone software (SaSW). As input data, the software requires NGS data resulting from secondary bioinformatic analysis (VCF files). In addition, patient information may be added specifying the phenotype features and symptoms if applicable (HPO terms). The output of the automated analysis is a list of variants contained within the provided file, each linked to a suggested disease, based on the combination of the genes in which a candidate pathogenic variant is contained as well as the patient's phenotype. The variants are ranked according to an algorithmic confidence score, and every variant contains annotations that a human genetics professional must critically assess to decide on the most relevant variant and the associated clinical diagnosis for the patient. If the variant is not found in the ranked list, the device also provides an overview of all variants from the original sample including all annotations and classifications, which may then be manually assessed by the human genetics professional to select the variant and identify a diagnose. Device features include also variant storage and results reporting.

Product Performance

AION’s clinical performance is successfully achieved with an average sensitivity and positive predictive values above 90% (sensitivity confidence intervals ranging from 84%-95%) for both small variants (SNVs, INDELs) and CNVs. Algorithm-based prioritization measured as rank metrics (ranking of the disease-causative variant) reflects AION’s clinical outstanding performance with values close to 1 in most of the cases tested. Of note, ranking evaluation for CNV/SV variants might be subjected to changes as optimal phenotypically characterized cohorts are limited for this type of variants, and new data sets are currently to be generated and tested. Precision evaluation based on repeatability and reproducibility yielded scores of 100%.

Indications for use

AION is a clinical-decision support IVD for genetic diseases testing. Genetic testing involves the detection and assessment of specific alleles, variants and genotypes, that are associated with heritable traits and diseases or predispositions to disease for the individual or their descendants (diagnostic, screening and predictive testing). 

AION’s indications of use relate to mendelian genetic diseases, consequently  interpretation of variants that may not follow traditional mendelian patterns (such as somatic variants implicated in cancer or pharmacogenetics) is currently excluded from the indications of use (“limitations of use or contraindications”).

Similarly, interpretation of genetic variation associated with trisomy 21, diagnosing phenylketonuria and determining HLA tissue types DR, A and B is not part of the device indications of use. 

Intended patient population includes patients of all ages (prenatal, postnatal), sex, and ancestries who might undergo NGS sequencing analysis with the aim of testing for genetic diseases.

Intended users

The device is intended to be used by human genetics professionals, geneticists, variant scientists, and healthcare practitioners with expertise in genetics.

The software is not intended to be used by lay users.

The software is intended to be used as part of the diagnostic workflow for NGS-based genetic testing.

Intended Environment

The typical use environment is an office or genetic testing laboratory.

AION runs on cloud computing.

Browser specifications to run AION are as follows. Minimum hardware requirements to run app UI, the minimal requirements would be:

• A device with 2GB of RAM or more

• A recent version of a web browser (such as Google Chrome, Firefox, Safari, or Microsoft Edge)

• A CPU with 2 cores or more

• A resolution of 1024x768 or higher

Safety Information

Please see AION-IFU section Safety Information for product safety information in English and applicable EU members' languages.