In this interview we caught up with Hua Li (Boehringer Ingelheim Pharmaceuticals, CT, USA). In 2018 Li authored a methodology article published in Bioanalysis titled ‘Application of Mitra® microsampling for pharmacokinetic bioanalysis of monoclonal antibodies in rats.’ When we spoke to Hua, she told us about the inspiration for this research and discussed the importance of PK/PD scientists in the early phases of drug development.
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“I majored in Biotechnology in college back in China and then earned a Master’s degree in Molecular, Cellular and Developmental Biology from the University of Kansas (KS, USA). After graduation, I started my career as a research associate and laboratory manager at the Stem Cell Center of Yale University (CT, USA). My main roles included investigating the essential proteins that play a critical role in the division and differentiation of mouse testes stem cells, as well as administrative responsibilities for a laboratory of around 12 people including graduate students, post-docs and laboratory technicians. Since 2008, my career has been focusing on the quantitation of pharmacokinetics (PK) and pharmacodynamics (PD) study of protein therapeutics. Currently I am a bioanalytical research scientist in the NBE PK Group in the Biotherapeutics Discovery department at Boehringer Ingelheim Pharmaceuticals (CT, USA).”
Q What inspired your career in bioanalysis? Is there a particular reason some of your research focuses on PK/PD studies of protein therapeutics?
Over the past decade, I have witnessed a tremendous expansion of new technologies, devices and theories in the PK/PD field, all of which have helped us better serve the patient community all over the world. I was very excited to join Boehringer Ingelheim Pharmaceuticals in 2008 when my manager was establishing a new NBE PK Group for pre-clinical research projects. Since then, our group has expanded substantially in both size and functions. We are supporting multiple therapeutic indications including cardiovascular and immuno-oncology with preclinical species PK/PD bioanalysis and human PK dose prediction and modeling. My work mainly focuses on protein therapeutics PK/PD/ADA assay development, sample bioanalysis, PK analysis, as well as preparing data summary packages for the candidates that successfully pass from our hands into development. Being able to contribute to our group growth and always be learning cool science and technologies have been my inspirations. I will continue to work in this field with enthusiasm and will make every effort to contribute more in the future.
Q At the time of your Bioanalysis publication, the bulk of research concerned with volumetric absorptive microsampling (VAM) focused on small molecule PK studies. What inspired you to focus on the use of VAM for protein therapeutics?
In protein therapeutics, we require a relatively long blood sampling time course to accurately characterize monoclonal antibody PK/PD. Because the volume and frequency of blood sampling are strictly regulated in preclinical species, we were often required to compromise sampling schedules. We were evaluating various approaches to minimizing sample size and a colleague who worked on small molecule PK was trying out Mitra® microsamplers. I heard about it during coffee break, became very curious, and asked for a few to try. It worked beautifully for several of the protein therapeutics we had run previously using traditional sampling methods. Mitra® microsamplers require much less blood volume than serum or plasma sampling methods. Therefore, VAM technology like Mitra® microsamplers may allow us to increase the quantity and quality of our data while simultaneously reducing animal use.
Check out the full methodology article published in Bioanalysis.
Q In the past 2 years since your publication, we’ve seen a vast increase in biologics research. What trends (if any) have you observed in the use of VAM during this time and why do you think this might be?
I definitely see a burst of new technologies/devices/equipment related to VAMS and other small volume sample bioanalysis in the past few years. In my opinion, one major reason for this phenomenon is the challenge we face in the pharmaceutical industry nowadays: we desire more and more data sets from every sample of in vivo preclinical studies. For example, we are learning about new pathways and new biomarkers for diseases. Thus, we would like to add those evaluations in our early discovery in vivo studies. Therefore, we must find creative ways to manage the conflict between very small and limited volume of samples but an increase in the number of desired bioanalytical data sets.
Q What (if any) additional challenges do protein therapeutics present when it comes to pharmacokinetic bioanalysis and pharmacodynamic evaluation? What solutions have you found particularly effective to address them?
To accurately predict and model PK/PD of a protein therapeutic from bioanalytical raw data, we need to develop appropriate assay formats to address each individual research purpose. For instance, we may need to measure both free and total drug levels, as well as free and total target levels. That is not always easy to achieve and sometimes we just do not have the right tools in hand. In addition, due to the increasingly rapid development of new drug concepts and modalities, bioanalytical method development is getting even more challenging. Not only are we in need of the appropriate high-quality reagents for quantitating drugs, targets and biomarkers of interest, we also need higher assay sensitivity and faster throughput. However, we are confident we can overcome these challenges because we support each other in the research community and work together well as a team. This enables us to rapidly identify, evaluate and implement new technologies like Mitra® to continue to build on the knowledge of those who have gone before us.
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Q As biologics are likely to feature more and more in research, robust PK/PD evaluation is going to become increasingly important. What kind of changes do you think the field will see to maximize the chances of clinical success?
There are lots of PK/PD talents accumulated in the development and clinical stages of biologics comparing with those in early discovery or research stage. As a research PK/PD scientist, I see urgent need of PK/PD talents in the research stage to support the early prediction and modeling so there are promising candidates to work on in the next milestones. I hope to see more and more talents join research PK/PD field especially modeling experts and I definitely believe it could be a key to clinical success of the pharmaceutical industry. In addition, I could see more automation systems incorporated into PK/PD sample bioanalysis. In the process of sample bioanalysis, there are manual mundane steps, such as serial dilutions, which could be replaced by robotic systems. Implementing this type of automation would increase work efficiency by freeing scientists to work on other challenges.
Q What advice would you give to someone interested in working in such a rapidly evolving field?
On one hand, it is a very challenging field. In the current fast pace of the pharmaceutical industry, every scientist is multi-tasking and responsible for several projects at the same time. We must not only work hard, but also work smart. We are achieving more goals faster than ever, but companies are not necessarily increasing headcounts.
On the other hand, it is a very exciting and rewarding field. Many scientists who work on small molecule drugs may not see their hard work turning into marketed drugs because of the long drug discovery and development duration. While for biologics, the time course is typically much shorter. I worked on a biologic drug candidate in 2010–2012 during its research stage, and it made to the market as SKYRIZI (Risankizumab) in 2019, which was definitely the highlight of my entire career.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
The opinions expressed in this feature are those of the author and do not necessarily reflect the views of Bioanalysis Zone or Future Science Group.