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A report from the Landscape Analysis Sub-Group of the Medical Device Innovation Consortium (MDIC), Somatic Variant Reference Samples for NGS, Landscape of Available Reference Samples, compiles all the currently available somatic reference samples identified in a comprehensive search and verification process. “We have basically taken information that is available and compiled it in one uniform format. We have done the vetting of going back to the source of the information, showing them what we’re going to present, and asking them for necessary edits or additions, to verify that what we are presenting is correct,” said Barbara Zehnbauer, PhD, FACMG, FACB, adjunct professor of pathology at Emory School of Medicine and editor in chief of the Journal of Molecular Diagnostics, in an interview with MD+DI. Information in the tables in the report explain what types of validation methods have been used to characterize the materials, she said.
“The unique factor of this project is that we’ve really engaged in a multi-stakeholder approach,” said Carolyn Hiller, clinical diagnostics program director of MDIC in the same interview. “It’s a challenging problem and project that we’ve set out to undertake,” she continued. “We’ve recruited individuals from industry, both in IVD or next generation sequencing (NGS) manufacturers on the diagnostics side, and we also have pharmaceutical companies involved. We have FDA involved—not only CDRH, but also CDER—and we have academic medical centers, CMS, biorepository, and professional societies. All of these [entities] are coming together to work collectively to create these reference samples.”
Zehnbauer said that the report could be useful to anyone who is actively in a laboratory using NGS technology, “whether they’re in a research laboratory, whether they’re in a diagnostics laboratory, whether they’re in a test development environment—they can all benefit in knowing what reference samples are out there,” she said.
She went on to explain that there are many types of somatic reference samples available, but they are not all equivalent, and noted that this report groups them according to sample type. “Some are synthetic DNA, some of them are isolated purified DNA, some of them are human cell lines,” Zehnbauer said. “They each have different roles to play in terms of development and test quality control. What many clinical diagnostics labs, and I think manufacturers of IVDs, are looking for are samples that most closely represent an actual patient specimen, because what you get in the complexity of a specimen right out of a patient is very, very different than if you had an isolated verified piece of DNA,” she continued. “The performance that you get with the latter may not be what you experience in the field, and that is actually the end use that you hope these diagnostic assays can be employed for.”
There are hundreds of genes and variants represented, but Zehnbauer said that there is a rapid pace of discovery, with many new ones coming up. “Oncologists have to have confidence in the accuracy of what these labs are providing and reference samples are necessary quality components of that performance.”
Zehnbauer noted that regulatory agencies would also be interested in the information in this report. “NGS, with the capability to look at all the genes, really doesn’t fit the traditional FDA model of looking at submissions on one gene or a handful of genes or even a gene panel,” she said. “They’re looking to these new types of reference samples as perhaps a way to streamline the review of submitted products and submitted materials.”
The report is freely available as a pdf, with no commercial advertisements or claims.