Processing
An IDT GMP customer, IncellDx is a unique molecular diagnostics company. They incorporate high throughput cellular analysis into technologies and assays that can simultaneously identify specific protein, RNA, and DNA species within intact cells. ISO 9001 and 13485 certified, IncellDx designs products for unique clinical applications and focuses on taking these products through the regulatory processes required to supply the clinical marketplace. They are currently one of the few companies to do so.
Integrating technologies towards providing 3-dimensional imagery
In the late 1980s and early 1990s, attempts to identify cellular reservoirs for HIV and characterize the mechanism of HIV-mediated immune destruction were unsuccessful. Those difficulties led Dr Bruce Patterson, IncellDx (IncellDx.com) CEO and founder, to redirect his early research strategy from a molecular approach to a more cellular one. Today, IncellDx scientists combine a proprietary, state-of-the-art in situ probe hybridization technology called SUSHI (Simultaneous Ultrasensitive Signal-amplified Hybridization in situ) with a cell-based, flow cytometer instrument capable of quantifying molecular biomarkers within intact cells. Fixation Permeabilization Solution, developed by IncellDx, supports complex molecular testing without DNA extraction or amplification. The reagent facilitates hybridization of labeled oligonucleotides to mRNAs, providing 3-dimensional imagery of biomarkers within cells while still preserving structural relationships. Dr Patterson remarked, “Our proprietary diagnostic method yields specific molecular details about each and every cell. This technology is capable of revolutionizing the field of molecular diagnostics, one cell at a time.”
Companion diagnostics for serious viral diseases
The company currently focuses its assays on life-threatening viral diseases, including HIV/AIDS, HPV/cervical cancer, hepatitis, organ transplant infections, and breast cancer. The technology is fast, inexpensive, and highly reproducible. Figure 1 shows an example of the type of cellular information IncellDx tests produce. These assays serve as reflex testing and companion diagnostics to reference labs and large diagnostic and pharmaceutical companies.
Identifying an appropriate GMP supplier
Previously served by a different oligonucleotide supplier, IncellDx was shopping for an alternate oligo supplier due to fluctuations in oligo purity and performance. “Since our clients are large companion diagnostic and pharmaceutical companies, it was critical to us that our new oligo supplier, now IDT, has GMP services. If we were a life sciences company producing RUOs, we could consider synthesizing our own oligos. However, “the bar” for quality and quality systems required by GMP is set much higher, and IDT has been able to deliver that,” commented Dr Patterson. “When we began looking for a GMP oligonucleotide manufacturer, we evaluated several companies. From day 1, we were very impressed with what IDT could provide us—IDT has a very large GMP facility, mature GMP processes, and great technical expertise, all of which superseded those of the other partners we were considering.”
Marion Bonneu, IncellDx’s technical operations manager, was also impressed with IDT following her first visit. She noted the meticulous follow through on GMP processes and documentation, as well as the consistent product quality and thorough batch traceability. IncellDx initially ordered a few different lots of a product from IDT and always observed consistent performance.
Testing R&D batches and small synthesis scales is important in the development of diagnostic products. Not only can IDT provide these small batches for evaluation, but we can also then take these RUO-grade product samples and transfer them to GMP. Then, IDT’s GMP customers don’t have work through this complicated transfer process with 2 separate suppliers. Bonneu notes, “This flexibility has been extremely helpful.”
IncellDx Senior Scientist Amanda Chargin also commended the technical expertise and responsiveness that IDT’s GMP team provides. As an example, she recalled, “When IDT was manufacturing our first test lot, there was a problem with the synthesis of 2 oligos. IDT immediately brought it to our attention and proposed methods to improve the synthesis of these oligos—and they worked. IDT has always been very responsive to our needs and concerns, and has given us great technical support. For instance, IDT has helped IncellDx bring QC metrics in house, and has provided guidance on how to improve our own internal QC.”
Continued progress
IncellDx continues to advance their technology. Currently, their researchers are able to perform cell surface staining with 6 or more intracellular and cell surface antibodies, in situ hybridization, and now DNA cell cycle analysis, all simultaneously. The company’s integration of these methods results in protein and gene expression measurements by distinct cell type, providing a comprehensive molecular picture of biomarker expression that aids in both diagnosis and disease localization.
Dr Patterson acknowledged that, “During this journey, what is particularly exciting about having IDT as a partner is that we feel comfortable approaching them with creative ideas, and we are met with good collaborative discussion. They have helped us design newer and better strategies around our novel applications.”
