Kelly Gelinne, our Associate Director of Marketing, sat down with Nuventra’s Associate Director of Pharmacokinetics, Venkateswari (Eswari) Muthukrishnan, Ph.D., to learn more about her life as a consultant, her advice for how non-clinical studies can support clinical development, and her predictions on how COVID-19 will impact the future of drug development. Listen to Kelly’s interview with Eswari above or read the transcript below.
Eswari joined Nuventra in 2019. She has 19 years of broad experience in various stages of drug development with a focus in DMPK, PK/PD modeling and simulations, IVIVC model development, and clinical pharmacology. She has contributed to 2 approved drugs and to 2 clinical development programs entering Phase 3 studies. She has authored several PK/TK (GLP) study reports for first-in-class INDs and has contributed to nonclinical and clinical sections of various international regulatory submissions. She also has extensive experience as a trainer for PK/PD modeling software.
Kelly: Welcome, Eswari. We’re happy to have you today.
Eswari: Glad to be here too, Kelly!
Kelly: Alright, let’s get to our first question
Can you describe some of your favorite projects you’ve worked on at Nuventra so far and why you’ve enjoyed them?
Eswari: I worked on a drug device inhalation product for the treatment of pulmonary arterial hypertension. The formulation was developed with the latest technologies, then delivered using a smaller hand-held device to target the drug to the intended location in the lung. The client filed a regulatory submission for the approval under 505(b)(2).
Also, I worked on IVIVC models to support the development of complex drug products. Understanding the relationships between in vitro dissolution data and in vivo dissolution data—that is clinical data—early on is the key for the success of the drug product. So far, there were no approved generic versions for complex drug products just due to challenges from the excipients, characterization, and conduct of bioequivalence studies. For these complex products, smaller changes in the product can result in larger changes in the clinical efficacy.
Can you talk about something that requires consideration by Sponsors conducting non-clinical studies to support clinical development?
Eswari: It is very important to do dose-range finding studies before initiating regulatory GLP toxicology studies because these dose-range finding studies provide concentrations for future studies and also let you select optimal PK/TK time points, and give you some idea about what type of metabolite exposure you would expect.
This information helps to validate the bioanalytical method with the appropriate standard curve ranges and also to include metabolite as a part of measurements, if required. It is also wise to start GLP toxicology studies only after completing the bioanalytical method validations under conditions that you expect to conduct studies and store samples. Sometimes, if you initiate studies at risk, you may end up voiding the whole study because, either you do not have enough stability data to cover the sample storage or you did not have good understanding of the study conditions.
In addition to that, you would want to collect some sparse samples in your pharmacology models to come up with a good early PK/PD modeling data. In addition to that, you can start doing allometric scaling, either using MABEL or compartmental approaches to come up with first-in-human doses based on in vitro data and animal PK/PD data.
Kelly: That’s great. That’s really helpful advice, thank you. On a personal note…
What do you enjoy about life as a consultant?
Eswari: So, I started my first job in a consulting company and it was a great experience and I had the opportunity to learn quickly in diverse areas under the guidance. After about 19 years, I am back to the consulting side and now, I have an opportunity to contribute to more and mentor the other scientists in a wide variety of projects that involves cutting edge science and technologies.
In the past, I had strong discovery experience in small molecules, large molecules, and biosimilars. Now, I get to use my experience in my current role, as well as the opportunity to get into the latest drug development trends such as gene therapy. In addition, I have expertise in IVIVC modeling which, again, is another key aspect that most companies tend to overlook during drug development because it involves a lot of upfront investment, in general, to generate this type of IVIVC model.
For me, these IVIVC models are worth the investment and these are like insurance for the product life cycle management for future events such as small changes in the manufacturing process, equipment, or supplier. You do not have to conduct expensive bioequivalence studies again to prove that these changes are not impacting the quality or clinical efficacy of the product if you have the IVIVC model available.
Is there a therapeutic area you’re particularly passionate about working on?
Eswari: No, I am not very therapeutic area focused. I get excited about new ways of delivering treatments with better compliance, less side effects, and possibly a cure for the disease. I also get passionate about treatments to treat and manage diseases affecting children. Examples are life-saving treatments like CAR-T cell therapy for ALL (Leukemia) or gene therapy for Spinal Muscular Dystrophy for children younger than 2 years. Unfortunately, these costly options are yet to be available to the wider population. However, we do see some very technology-oriented products coming in.
Another example on that front is, recently we have seen approval of Game-Based Digital Therapeutic for the treatment of ADHD in children. I think the federal regulations regarding pediatric clinical studies helped to conduct more pediatric clinical studies and resulting in expanded use rather than off-label use.
Some products I always get fascinated about—combination products that involve drug delivery—are Glucagon and midazolam nasal sprays. Glucagon and GLP-1 autoinjectors, which are approved for children above 12 years of age, give access to really needed therapies for the children. Currently, we have glucose monitoring device and insulin pumps to deliver the drug as two separate products, but we still have to wait for the day when the devices automatically adjust the amount of insulin to be delivered. I am really hopeful and would like to see this type of device, so that children can manage their diabetes, especially juvenile diabetes.
Kelly: What an interesting answer. I have not heard of some of these technologies yet, so it’s really exciting to hear about that for the future. Speaking of the future, our final question today…
How do you think COVID-19 will impact the future of drug development?
Eswari: I think it changes in different ways. So, the COVID-19 drug development is pressure testing all the companies to become very efficient with respect to great science, collaboration, and rapid execution. I also see that competing companies are collaborating. Another thing is, because we just don’t have the time of 10 years to bring a drug to the market, we need to learn how to kill the drug candidates if they fail. So, maybe, we learn a new skill set because of this pandemic.
I also wanted to see whether these unprecedented times will let us get over the resistance of embracing the new digital technologies during the conduct of clinical studies. I know we do have some resistance from both regulatory side and company side due to privacy, but I am hopeful that this situation might let us avoid that resistance. In the near future, vaccines may dominate, but I still hope that the drug development trends focusing on cures, rare diseases, novel methods of drug deliveries, using real-life data with Artificial Intelligence, and finally personalizing medicine for better outcomes—I really hope that all these things will continue in the near future.
Finally, we are really looking very seriously at repurposing the existing/dropped drugs for COVID-19 treatment. Perhaps, these efforts will help us in the future to efficiently repurpose drugs for other indications too, because we are going to learn all these things during this process. Lastly, I would say, perhaps we will become more self-reliant with respect to health care products in the US based on what we have learned through this experience.
Kelly: Yes, we can only hope that something positive comes out of our current situation.
Kelly: Well, thank you so much. I’d love to ask one more bonus question to get to know you better on a personal level. What is your favorite hobby and what do you do in your free time?
Eswari: I believe in doing my part in taking care of mother earth. We have rain-water harvesting and compost unit in my house, and I love gardening. I planted a lot of native species to support local pollinators and I enjoy watching wild animals and birds in my backyard.
Kelly: Well, that is that perfect hobby for the pandemic during quarantine. I’m sure you have plenty of time to garden and take care of your backyard right now.
Eswari: Sure. Thank you, Kelly.
Kelly: Thank you so much for joining us today, Eswari. If you have any questions for Eswari or for any of our other consultants, please don’t hesitate to contact us.