The safety of vaccines and other biological products is a critical goal for industry and regulatory agencies. This is particularly critical for live vaccines, gene therapy viral vectors, and cell therapy medicinal products, since their production does not include downstream adventitious virus elimination steps. Extensive tests are performed using various in vitro and in vivo assays. Some recent detection of virus in biological materials have highlighted some limitations of the assays and the need for exploring new virus detection technologies. Next Generation Sequencing (NGS) is a nucleic acid-based technology that makes no a priori assumptions regarding viruses to be detected, since it identifies all viral nucleic acid sequences found in a sample. NGS can also be used to investigate eukaryotic DNA and this may be of particular interest for the study of novel cells and other biological materials. However, NGS is a complex technology, and, for safety evaluation of biologics, its regulatory implication is complex, and its implementation should be supported by adequate standardization and qualification of the method. Due to its complexity, appropriate performance of the various steps of the method, including upstream handling and processing steps prior of the sequencing, should be considered, including the different sequencing platforms and bioinformatics pipelines available. Various conferences and discussions have been done from the beginning of the decade leading, in 2014, to the formation of the Advanced Virus Detection Technologies Interest Group (AVDTIG), gathering together Regulatory and Government agencies, Industry, Service providers, Technology developers, and Academics from all over the world. The interest is also growing up in Europe and the European Pharmacopoeia has recently acknowledged NGS as a methodology to be investigated and implemented. Therefore, a deep discussion among all the stakeholders should occur in order to improve experimental projects for an accurate standardization of all the steps involved in NGS and biologicals control.