An Interview with Sandeep Kondaveeti, Research and Development Scientist at Teva Pharmaceuticals

Sandeep Kondaveeti

We sat down over a virtual cup of coffee to interview Sandeep Kondaveeti, Research and Development Scientist at Teva Pharmaceuticals. His research expertise is in synthesis and characterization of inorganic / organic compounds, nano-materials, and protein complexes.

Editor:
I understand you currently work in the area of biological drug product development and formulation; can you tell us more about your primary area of research, what are your primary goals in formulation of biotherapeutics?

Sandeep Kondaveeti:
As part of the drug product development and operations team, we develop biopharmaceutical formulations and manufacturing processes to deliver high quality drug products to the patients. More specifically, we are focused on fundamental and mechanistic understanding of the chemical interactions within biopharmaceutical formulations. Ultimately, our goal is to develop formulation strategies to achieve long-term protein stability and minimize the risk of drug product quality throughout the process development cycle.

Editor:
How has the industry changed in recent years, and what is the impact of new technologies on your research?

Sandeep Kondaveeti:
My experience in formulation development is relatively new and based on present work formulation development of monoclonal antibodies incorporates many standard analytical biochemical and biophysical methods traditionally applied for protein characterization. Originally, many of these methods were developed in a relatively low-throughput format to be used on samples containing high amounts of protein, but effective screening of multiple formulation conditions requires methods that can generate information fast using low amounts of protein available without significantly sacrificing accuracy, precision, and specificity. We have seen significant advances in new technologies in recent years where biophysical characterization is possible with small amounts of protein (microliters) in high throughput fashion with complete automation from data acquisition to data analysis.

Editor:
What are some of the primary analytical challenges you face in developing new drug products?

Sandeep Kondaveeti:
As mentioned earlier, early phase development of a protein formulation requires extensive screening of formulation conditions and possesses challenges due to material constraints and faster timelines. To overcome these challenges, we are developing a high throughput formulation platform where we are employing statistical study design and automation workflows to perform sample preparation and buffer exchange steps which are most labor intensive and can dramatically speed up the development process. Also, critical to this platform development are availability of high throughput analytical methods that can provide fast, accurate results with good precision and resolution. We are currently focused on addressing these issues and continuously adopting new technologies for accurate characterization of biopharmaceutical products.

Editor:
What toolbox of technologies do you use to characterize proteins?

Sandeep Kondaveeti:
We use several different overlapping and orthogonal technologies to analyze proteins because we are interested in all aspects of protein stability and function. To successfully use antibody-based biologic therapeutics, it is necessary to maintain conformational, chemical, and colloidal integrity during all steps of the development, manufacturing, and commercialization processes. So it is critical to have information on multidimensional properties of protein and their dependence on both formulation and stress factors since different conditions can affect different aspects of protein stability. For example, we use size exclusion chromatography to analyze purity and assess soluble aggregates, differential scanning calorimetry to assess thermal stability, dynamic light scattering tools to investigate colloidal stability, Infrared and circular dichroism spectroscopy to understand secondary and tertiary structure. We also perform particle analysis to understand interfacial stability.

Editor:
How important is the measurement and understanding of protein secondary structure on the formulation of biopharmaceutical?

Sandeep Kondaveeti:
During formulation screening various stress conditions such as elevated temperature, shear stress, chemical agents and surface or interface interactions are employed which can lead to structural changes and may have significant consequences on the stability and function of biotherapeutics. It is important to understand and monitor the secondary structure as they are relatively easy to perform and are good indicators of protein conformational stability and aggregation.

Editor:
How are you deploying MMS in your research and what benefits would it provide?

Sandeep Kondaveeti:
We are incorporating MMS technology to our current high throughput formulation platform to study high order structural changes and monitor stability of different formulation samples. We are very excited since we can now develop 96-well plate workflow to screen multiple formulation conditions with complete automation including data analysis. More importantly, this was the first time that we could analyze these samples directly in the different buffers and at various concentrations particularly when sample amounts are limited which is very challenging to perform using traditional FTIR technique.