Standing up a new NGS assay from scratch is no easy feat, and Velsera is here to help laboratories regardless of which assay they are looking to start doing. One of the biggest challenges clients have regarding standing up for a new NGS research use only (RUO) assay from scratch is by far the amount of time it takes. The average validation can take anywhere from 6 months to 2 years to complete including training, wet lab work, and full analytical and clinical data analysis. This is dependent on assay type, run failure rate, along with numerous other factors. Adding to that time is the amount of time needed for the standard MolDx* approval. From submission of the technical assessment, it takes 60 days to get a response back from MolDx. If they return with questions, as they often do, it is an additional 60 days for another response. All these factors combined make standing up a new NGS assay and getting reimbursement a lengthy process.
IVD assays are a new development that has dramatically changed the picture for standing up NGS assays. These include PGDx Elio Tissue Complete and TSO Comprehensive, among others in development. Instead of validation, these require verifications. The average verification is 6 runs plus two training runs. If the pace is two runs a week the wet work can be completed in about a month rather than 6+ months. This is a dramatic shift forward for labs looking to start up new NGS assays without the time and financial investment that is required for RUO assays. In addition, the approval process for reimbursement is substantially reduced.
I personally have experienced the process of standing up new NGS testing for laboratories for both RUO and IVD assays over a dozen times. I have done NGS testing on the wet bench personally and have managed numerous full laboratories stand up projects from initiation to final completion with full reimbursement success. I have seen the promises and struggles that come with these projects and what it takes for them to be successful.
FDA Final Rule
IVD assays have the additional benefit of not being impacted by the FDA Final Rule, which requires new LDT assays to be FDA approved by the facilities providing them by 2028. The FDA approval process is lengthy and very expensive. Where this is a requirement for new LDT assays not grandfathered in, it is not a requirement for IVD as these assays are already FDA approved. Laboratories need not be concerned with an IVD assay having to be stopped and going through FDA approval.
The FDA LDT final rule has been overturned in court recently. However, there is still uncertainty on the regulations around testing. In addition, IVD assays still offer many benefits over LDT assays such as faster timelines and less upfront work with obtaining Z-codes and MolDx TA approval. Where LDTs (Laboratory Developed Tests) require full Technical Assessment (TA) packet preparation including several forms and validation reports, IVD assays only require Z-code application or Z-code sharing. Typically for LDTs when the TA is submitted it takes 60 days to get a response, and often questions come back resulting in additional 60-day review periods. For Z-code applications and sharing, that time is slashed to 2 weeks or less and doesn’t involve review that can be returned with questions.
Reimbursement
Reimbursement is another area that has dramatically sped up with IVD assays. Instead of applying for a Z–code, waiting two weeks, then submitting a full technical assessment and waiting 60 days for a response, the only item required here is a Z code. With some assays like TSO Comprehensive this is a shared Z code. Overall, the process for IVD reimbursement is about 2 weeks as opposed to the entire 60 day wait period.
IVD Issues and Pitfalls
This is not to say IVD assays don’t have their pitfalls. There are certainly struggles with NGS as a whole and the complexity of tests for labs that may be less experienced with sequencing. The biggest hurdles for IVD assays are in the wet lab, as runs rarely complete 100% to schedule without some issue. Most common issues seen in the laboratory work revolve around the bead normalization and pipetting, even very slight errors here have a major impact on sequencing quality. These issues, however, can typically be overcome with time and practice. Velsera also offers a wealth of expertise for both LDT and IVD assays in terms of troubleshooting with the company that offers the assay. This assistance can reduce troubleshooting time dramatically compared to laboratories trying to determine wet lab assay issues on their own.
IVD assays will continue to grow from here, with additions in the works for Illumina and PGDx offerings. This landscape is only going to expand. For new labs looking to get into clinical patient sequencing, IVD assays have transformed a very long process of validation to a process that can be completed in 90 days or less. Having seen many validations over the last few years, this is an absolute game changer for healthcare providers looking to offer the most up to date testing for their patient populations.
IVD assays have dramatically changed the landscape compared to even a year or two ago. Where assays were multi-year processes to get stood up before, IVD assays allow a lab to go-live accepting patient samples in as little as 3 months. With the right circumstances we have assisted in even very ambitious timelines for go-live (60 days) with successful outcomes. Whether it is an RUO assay like TruSight Oncology 500, Archer VariantPlex, or TruSight Hereditary Cancer or an IVD (in vitro diagnostic) assay, Velsera has expertise in guiding laboratories through the complexity of adding new tests. From lab layout to validation/verification all the way through reimbursement we have experts on hand and services available to assist your lab in success.
Please reach out if you have any questions regarding IVDs and the FDA Final Rule.
*MolDx is the approval body governing reimbursement of individual laboratories for testing in the United States. The approval of MolDx is a requirement for many states, numerous insurance companies, and Medicare in many regions of the country. Z-codes are the billing codes assigned for tests according to their specifications.