As therapies become more advanced and personalized, it’s crucial that diagnostic tools keep pace. For some diseases, such as dementia, improving diagnostic tools means developing tests that are less invasive and more accessible.
For diseases like cancer, diagnostic progress can be made by identifying disease biomarkers that enable more precise, targeted therapies. In pursuit of this goal, billions of dollars are invested each year across many different disease states to advanced diagnostic tools. But without careful planning, these assays may falter as they transition out of the lab and into clinics.
In this article, we’ll discuss how diagnostic developers can equip themselves for long-term success with the right supplier and take a close look at an evolution in antibody production that is enabling diagnostic progress in both labs and clinics.
A Range of Reagents
Many assays that perform well in research settings encounter unexpected challenges when moving towards clinical validation and real-world deployment. This transition brings new expectations around reproducibility, documentation, quality control, and regulatory standards that can be difficult to manage. All too often, developers and researchers find that their reagent supplier is not well equipped to scale with them. The result is assays that begin to deviate between lots, operators, and lab settings, requiring significant rework to bring products back into alignment with quality and regulatory standards. Fortunately, these risks can be significantly mitigated with the proper foresight.
Small and early-stage teams often face pressure to develop diagnostic tests in a rapid and cost-effective manner. As teams focus on maintaining a slim budget and delivering results, the challenges of clinical translation may be underestimated or ignored. Short-term success seen in this context often results in long-term headaches. One crucial step that companies should take to set themselves up for success is to evaluate research grade reagent suppliers for their ability to scale with the product. Early use of research grade reagents can be an effective way to save money, but without a supplier with an equivalent GMP-grade product, diagnostic developers risk introducing inconsistencies as they transition to clinical grade assays.
A good reagent supplier will not only have a range of research and GMP products, they will also have the expertise necessary to guide companies to through the transition in a well-documented and compliant manner. Working with suppliers committed to comprehensive characterization and consistent performance of reagents is also vital for long-term success. The ideal vendor should have a rigorous and reproducible manufacturing protocol and be able to provide multiple lots for evaluation.
Another frequent bottleneck occurs when there is a lack of supply continuity as production scales. Developers will benefit from suppliers prepared to produce critical reagents at multiple sites around the globe, with quality control systems in place to ensure minimal variation between lots. Furthermore, geopolitical or climate events can introduce supply chain challenges without warning. It’s crucial that companies have supplier representatives in nearby time zone who are prepared to quickly address hurdles and limit the impact of supply chain disruptions as much as possible. By investing the time to thoroughly vet suppliers upfront, companies give diagnostic advances the best chance of reaching the patients that need them.
Hybridomas: A Limiting Approach
Suppliers should also be evaluated on their production technologies. For example, antibodies form the backbone of many diagnostic assays. Their ability to bind antigens in a highly specific manner, as well as the ability of secondary antibodies to amplify signals, makes antibodies an ideal reagent for detection of important biomarkers. In the past, biomanufacturers have primarily relied on hybridoma-based production, where antibody producing B cells are combined with immortalized myeloma cells to generate monoclonal antibodies (mAbs).
However, a 2018 paper published by Bradbury et al. showed that roughly 30% of the hybridoma-produced antibodies they analyzed were not truly monoclonal in nature. Sequenced antibodies were found to have additional heavy or light chains, which can impact the specificity and binding performance of mAbs. Production difficulties can also be introduced by genetic drift or contamination issues that can occur within cell cultures. These limitations can affect mAb performance in both research and clinical settings, and scientists have begun exploring alternative methods of mAb production. For many diagnostic developers, recombinant antibodies are becoming the new gold standard.
Enhanced Experimentation with Recombinant Antibodies
Recombinant antibodies are produced by placing the desired antibody sequence on an appropriate vector and expressing these proteins in the biomanufacturer’s preferred cell line. The reliance on a defined genetic sequence results in increased mAb consistency between batches and eliminates concerns of genetic drift. While the initial shift to recombinant antibodies may require developers to adjust their regulatory strategy, recombinant mAbs offer more regulatory simplicity in the long run when compared to hybridoma-derived mAbs.
Recombinant antibodies are also a more malleable reagent for diagnostic development. Hybridomas rely on harvesting cells from immunized animals, and creating new cell lines can take weeks. In comparison, the genetic sequence of recombinant antibodies can be editing with relative ease and speed, allowing developers to fine-tune binding affinities, binding sites, specificity, and even change isotypes as they develop diagnostics. This flexibility lends itself well to the fast-paced experimentation required during early diagnostic development, allowing researchers to refine diagnostic assays to meet rigorous quality standards. Additionally, because recombinant antibodies can be engineered with great precision, developers are more equipped to create diagnostic tools tailored for performance in specific sample types or assay formats.
In addition, recombinant mAbs better support the transition from research to commercialization by generating more reliable, scalable, and high-performing mAbs than hybridoma-based techniques. For example, recombinant antibodies can be formatted to enhance stability, ensuring reliable performance at higher temperatures, within complex matrices, or in other demanding diagnostic conditions. Recombinant antibodies also tend to be more sensitive than their hybridoma counterparts, meaning that important signals can be detected at lower concentrations. These advantages open the door for more diagnostic innovation, whether that’s designing tests for high-throughput laboratory systems, creating less invasive detection tools, or increasing accessibility to point-of-care tests in resource-limited regions.
Delivering Diagnostic Excellence to Patients
Advances in diagnostic research are helping us understand how to detect, track, and even treat diseases with more precision than ever before. Recombinant antibodies are poised to propel these evolved diagnostic tools, and patients and researchers alike deserve to see these discoveries translated into real-world benefits. But the road from lab to clinic can be a rocky one. Fortunately, diagnostic developers don’t have to travel it alone. With the right supplier, diagnostic developers can map out a commercialization strategy that will give their diagnostic innovations the best shot of reaching the care teams and patients who need them.
About the author
Catherine Bladen, PhD, is Chief Scientific Officer, at Vector Laboratories. Catherine leads the technical development and innovation team at Vector Laboratories, Inc. She has more than 25 years of experience in biochemistry research (specifically protein identification, purification, and characterization), both in the UK and the U.S. She completed her PhD in 2001 in the Cancer Research Unit at Newcastle University, studying novel proteins involved in p53-independent cancer pathways.