Laboratory Considerations for Clinical Trials

This podcast from Q² Solutions looks at factors sponsors should consider when preparing for clinical trials.

In this episode, Dr. Robert Bailer, Senior Director for Vaccines at Q2 Solutions, describes the processes for testing vaccines against the novel coronavirus, SARS-CoV-2. He covers both ELISA and virus neutralization assays.

Q2 Solutions has developed an ELISA assay to evaluate multiple different antigens at the same time. Looking primarily at the spike protein, it is dissected into different parts: S1, S2, S1 plus S2, and  the receptor binding domain. The nucleocapsid protein is being evaluated as well.

We are taking a 2 pronged approach to the viral neutralization assays, working in collaborations with academic institutions to deliver a cutting edge approach.

The first, in collaboration with the laboratory Dr. Pei-Yong Shi at the University of Texas Medical Branch in Galveston, involves viral-like particles (VLPs) where the structural genes of wild type SARS-CoV-2 virus are removed and replaced with a reporter gene. In this particular case, it's a GFP or green fluorescent protein gene along with a neomycin resistance gene.

The second approach is a SARS Co-V 2 surrogate neutralization assay used under a license agreement with the Albert Einstein College of Medicine. This is the vesicular stomatitis pseudovirion process, commonly used for viral neutralization assays. It’s a different way of expressing an artificial virus. It involves taking the vesicular stomatitis virus genome, replacing some of the genes for VSV by inserting the SARS-CoV-2 spike genes, plus a reporter gene. Expressing that produces a virus-like particle or a pseudovirion that can be utilized. This approach has been used over the years in a wide variety of different applications at Q2 Solutions for example in Ebola.

The vaccine operation at Q2 Solutions has the infrastructure, the capabilities and support to have a three shift operation. We anticipate doing this 24/7, which is exactly what’s needed in the context of a pandemic. Further, our center for vaccine excellence located in Beijing, China will evaluate clinical trial samples coming to us there with the same repertoire of assays that are available in San Juan Capistrano, California. The Q2 Solutions model is that we provide answers globally and with high throughput.

Learn more at

In this episode, Drs. Steven Lowes and Barry Jones discuss hybrid assays, combining immuno-affinity with liquid chromatography-mass spectrometry (LC-MS). This is a growing area of opportunity for protein bioanalysis.

Topics covered include:

  • What is meant by hybrid assay
  • Reasons to choose a hybrid assay
  • Top down vs bottom up
  • Specific challenges
  • Assay design considerations
  • Future potential for this type of bioanalysis

...I think that fundamental point about more sensitivity, and associated with that is more selectivity, is going to be part of the future adoption of these hybrid assays. We have needs already, we can see needs for looking at quantifying proteins in very small samples, say tissue biopsies. - Steven Lowes

Learn more at

Protein Biomarker Quantification by Immunoaffinity Liquid Chromatography–Tandem Mass Spectrometry: Current State and Future Vision (Article in Clinical Chemistry)

ADME testing (Absorption, Distribution, Metabolism and Excretion) is an essential part of early stage drug development.  In this episode, Dr. Matt Hutzler, Director of ADME Services at Q2 Solutions, describes the common paradigm of ADME testing and why short turnaround times are important.


Because speed is so important, outsourcing testing overseas may not make as much economic sense as it might have in the past, given shipping costs and the possibilities for delays (at customs for example.)


Dr. Hutzler explains the factors that contribute to the success of high-throughput ADME testing and what advances and innovations we might expect in the future.

A liquid biopsy is a minimally invasive alternative to a more traditional surgical solid tumor biopsy.

In this episode, Dr. Stephanie Hastings, genomics product lead at Q Squared Solutions, lays out the considerations for liquid biopsy collection and the type of information that can be gathered from circulating free DNA (cfDNA).

The main approaches comprise for evaluating cfDNA are:

  1. specific mutation detection to help support targeted therapies
  2. broader sequencing technologies to enable biomarker evaluations
  3. custom sequencing panels to support clinical trial assay development

She describes the typical panels for each of the approaches, the sample collection requirements and how these analyses are implemented on a global scale.

In this episode, Dr. Wayne Hogrefe and Dr. Pat Hurban discuss the use of NGS in the development and assessment of new vaccines against the influenza virus.

Topics covered include:

  • What health organizations are looking for that drives the selection of the next season's vaccine strains
  • How sequence data is used to evaluate the effectiveness of a vaccine while providing insight into the evolution of the virus
  • How the sequence data can inform the development of new types of vaccines and therapeutics
  • The prospects for a vaccine that is effective across multiple strains and multiple seasons
  • How NGS data differs from traditional Sanger sequencing data and what can be learned from that

You can learn more about this topic at

In this episode, Victor Weigman, Director of Translational Genomics at Q Squared Solutions and Mark Stewart, Vice President of Science Policy at Friends of Cancer Research (FOCR) joined to talk about standardization of TMB measurements by alignment to reference standards.

TMB differs from other biomarkers such as PDL1 in that:

"...we're leveraging next generation sequencing to generate a composite score from tens of thousands or in some cases millions of bases of sequence. So really you're summarizing this collection of mutations in a singular value versus a more qualitative range of expression levels done by looking at proteins in a microscope. - Victor Weigman

One challenge is that as treatments are being developed, the thresholds for the diagnostics are out of sync. Friends of Cancer Research understands the difficulty of harmonizing assays to a standard after FDA approval. For that reason, there is strong interest in harmonizing the results of different assays to a standard reference set.



Mark Edinger is the Scientific Advisor for Flow Cytometry at Q2 Solutions. In this episode, he describes recent advances in flow cytometry and what that means for immuno-oncology trials.

New instruments, reagents and software are enabling researchers to monitor 30-some markers simultaneously to get a better picture of the tumor micro-environment and the interactions taking place.

For example, there's a whole list of new checkpoint inhibitors, like PD-1, CTLA-4, CD-1-52 and a multitude of other CD-47 that have been described, and their ligands on T cells and immune cells, not just T cells, that allows the tumor to actively turn off the host response to the tumor that prevent the tumor from being killed by the immune system. We weren't aware of these, many of these, until we had the tools that allow us to look at many more markers simultaneously. For instance markers of T cell activation have been around for a long time, but that list has expanded remarkably now, and the lists of markers of T cell exhaustion have really expanded as well, and some of those were not discovered until relatively recently, in the last 5 or 6 years.

Mark explained how flow cytometry is being used to determine whether a therapeutic is efficacious or not and the benefits that flow to the patient.

He stressed, as others in this series have, the importance of early engagement between sponsors and their clinical trials partners. Regular phone calls and direct conversations between scientists help refine the assays to produce the desired result in terms of the information collected from a panel.


In this episode, he describes strategies for mitigating risk in the development of companion diagnostics (CDx) for immuno-oncology.

Depending on the bio-marker, there might be difficulties in developing an assay that correctly characterizes that bio-marker. There are also, there could be reduced ability to enter into markets due to the accessibility of that particular technology used to identify that bio-marker or test that bio-marker globally. For example, it's common throughout hospitals to have IHC or pathology review of particular of bio-markers but next-gen sequencing is a new and more expensive type of technology, so they might not be able to go after that as a particular companion diagnostic.

But, that being said, the trade-off or what they gain from getting a companion diagnostic, they have a greater chance of reaching the correct population of patients that will see the greatest benefit of their therapeutic.

The podcast conversation discusses an alternative to the traditional three-way partnership of a drug developer, an IVD manufacturer and a CRO. Single-site, pre-market approval can reduce the front-loaded investment needed for an IVD. It also can align better for the management of the project timeline. 


Genomics has come a long way from the days of being primarily a discovery tool.

It used be that essentially all of the genomic data that was being produced as part of clinical trials was purely exploratory in nature. We're doing a great deal of that now, there's no doubt about that. However, now we're actually translating those into real uses. So for example, we might have specific markers that we're using for patient selection. We might have specific markers that are candidates for eventual development companion diagnostic and so we are taking them into clinical trials, characterizing them further.

Dr. Hurban discusses the use of broad genomic features such as microsatellite instability and tumor mutational burden as biomarkers in addition to specific point mutations that have been in use for some time. 

He envisions a future where a multidisciplinary approach leads to a companion therapeutic strategy as opposed to a companion diagnostic strategy. In this approach, a single test could direct a patient into any of a number of therapies rather than testing the possibility of one therapy at a time.


Mike Brown is the Senior Director of Immuno-analytical and the Bioanalytical Site Lead at Q2 Solutions. In this episode, he describes the considerations for pharmacokinetic and immunogenicity assays in the development of biologics.

He lays out the types of analysis that are needed along with the associated challenges, such as detecting the concentration of a specific antibody therapeutic present at 100 picograms/ml in an antibody background of up to 20 billion picograms/ml. He suggests that sponsors think about the reagents that will be essential for the assays that need to be performed. An analyst will ask:

"Are you going to help put some tools in our toolbox to be able to see that needle in a haystack?" And what the sponsors need to be able to do is to really have good lines of communication within their company, to make sure during the drug development program, that they actually are beginning to invest in those specific materials.

And having disease state matrix during method development, also, in my opinion, it's critical to ensuring that once we get into that patient population, we reduce the risk those are going to be big surprises for working in that biological matrix that's going to interfere with that assay selectivity. The lead times can be significant as can the price, but it really does mitigate risk.

Dr Brown also recommends engaging the FDA early to reduce any risk to your timelines. No one wants to get to the point of submission to find out that the approach was unacceptable and lose precious time.


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