Welcome to the Molecular Diagnostic Revolution

How far has the field of molecular diagnostics come?

PCR technology essentially established the molecular diagnostic field as we define it today. PCR has been – and still is – a phenomenal research technique, but if you consider how the technology evolved in the laboratory medicine space, much of the innovation focused on automation of the PCR component. Unfortunately, the risk of contamination, among other issues, means that every lab needs dedicated PCR infrastructure, trained technicians, specialized equipment, and so on. The result? PCR technology has not penetrated the space as much as other clinical diagnostic systems, such as biochemistry, hematology, and
protein detection.

But every challenge is also an opportunity, which is why a number of companies realized that the next step in pushing this great technology into clinical practice was to take a fresh, holistic approach and taking the entire sample-to-result workflow into consideration. Another key hurdle that needed to be addressed was the need to measure a growing number of biomarkers in a single clinical sample and develop so-called ‘multiplexed assay’ solutions.

Multiplexed analyses are the way forward?

Mother Nature shows us that it’s feasible to simultaneously carry out multiple reactions in a single reaction environment – as long as the system and its components are well designed. Although these multiplexed technologies still have some way to go, the field has in fact made a lot of progress both in terms of system designs and molecular techniques. Advances in next generation sequencing, microarray analysis and multiplex PCR have all contributed to achieving performances incomparable to those of a decade ago. And we’re getting better all the time.

But techniques such as multiplexed PCR are just the analytical components of the total solution. As diagnostic technology developers, we must always keep focusing on true diagnostic needs of the physician and patient. The prime diagnostic objective is to provide accurate, reproducible results in close space and time proximity to where patients and physicians interact and first-time-right therapeutic decisions need to be made. This requires new, flexible systems that can process even complex clinical samples directly with minimal manual interventions and without requiring any specific laboratory infrastructure.

Do you feel that innovation has been restricted?

Yes. Molecular diagnosis has traditionally been a technique requiring specialized infrastructure and operators and, as a result, the service has been thus far mostly centralized in high-volume reference labs. In line with that trend, manufacturers built automated solutions for higher volume testing. The flexibility to step away from the traditional batch-based workflows is only a recent development. The challenge of fully automating sample preparation and creating an uninterrupted workflow to analysis has long been underestimated. Sample preparation was traditionally done as a separate, mostly manual operation necessarily carried out in a laboratory environment. It is well known that manual procedures can be the source of variation and errors in the final results, even with excellent analytical equipment.

How has the lack of innovation stunted growth in personalized medicine?

In most oncology practices, molecular diagnostic results from tumor tissues may take two to three weeks to be returned. These delays, also requiring access to specialized laboratories, not only prolong the anxiety period for patients, but also are an impediment for wider and global adoption of personalized medicine. The true objective of the diagnostic industry should be to develop solutions that can be scaled up on a global level. We need compact, high-performing, high-precision, technical solutions that do not require specialized infrastructure or trained people. Is that enough? Probably not. I think technology is a key enabler of this revolution but there are other factors. For instance, I am often surprised to hear the debate about the price of diagnostics. Though the high value is – and should be – reflected in the prices of personalized drugs, payers should take a holistic view and also recognize the intrinsic value of the diagnostic solution when considering pricing. In vitro diagnostics (IVD) manufacturers and labs should be sufficiently incentivized and rewarded.

It’s important to recognize that laboratories, especially the CLIA (clinical laboratory improvement amendments) reference laboratories, play an important role because they can rapidly develop new biomarkers and make them available. I think we should applaud collaborations between labs that can rapidly develop biomarkers and IVD companies that develop the diagnostic solutions, and recognize the value they bring to personalized medicine.

How can new molecular technologies be made attractive to small volume labs?

It all comes down to the current and future needs of the patient, which are complex and often don’t involve a single set of symptoms. In this light, the importance of multiplexing capabilities in the platform become more obvious.

Clearly, we also need to develop solutions that are flexible for use in both big laboratories and smaller, point-of-care settings.

How challenging is this approach?

It’s a big undertaking. For example, when working on biomarkers that will help stratify your patients for a specific drug, the development of an IVD is expensive and time-consuming. The ideal solution – and the challenge that we have as manufacturers – is to develop fully flexible platforms that use the same basic technology and are amenable to both point-of-care and bigger lab settings. It would lead to a single IVD development of a new assay that can be run in multiple assay volume settings.

Finally, the technology must also be efficient, cater to varying throughputs and skillsets, and be easy to use. No easy task.

Communication and connectivity are also extremely important. When using molecular diagnostic techniques, a lot of very valuable information is collected but is not always fully utilized. As with many other aspects of our life, when things become interconnected it is useful to capture as much information as possible – and in the best way.

I’ve been very much inspired by Apple and other consumer technologies in terms of developing a flexible molecular diagnostic platform that is designed for a potentially wide range of applications. I therefore want to challenge the older dogma that diagnostic systems need to be designed for specific purposes. If we want high-precision medicine, we will need high-precision diagnostics yielding clinical actionable results irrespective of where or how or by whom the test is performed. From a patient and physician perspective, these technologies are essential.

Can the dream be turned into reality?

It’s our raison d‘être at Biocartis. And it’s absolutely why I created the company in 2007. We have invested heavily in developing a new molecular diagnostic system that goes from sample to results.

However, I think the role of diagnostics is still underestimated. After my years of research in HIV diagnostics and next-generation therapeutics, I moved into industry because I really wanted to make an impact. As an industry, we have high ambition – and I believe we are well on our way.

Rudi Pauwels founded Biocartis in 2007, where he is CEO. He (co)founded several biotech companies, including Tibotec, Virco and Galapagos Genomics. For more than two decades, he focused on the search and development of anti-HIV drugs – a number of which have been approved and introduced on the market – and the development of diagnostic tools to allow personalized HIV treatment.