Spotlight Interview with Dipanwita (Dipa) Batabyal, PhD; Senior Scientist, Process Development at Amgen

We sat down over a virtual cup of coffee to interview Dipa Batabyal, Ph.D. and Process Development Senior Scientist in the Attribute Sciences group at Amgen, Inc. of Thousand Oaks, California. Dr. Batabyal is a subject matter expert on various spectroscopic techniques including FTIR, CD, intrinsic fluorescence, and Microfluidic Modulation Spectroscopy (MMS) for product characterization and technology development initiatives. The main focus of the HOS group within Amgen is biophysical product characterization by means of secondary structure, tertiary structure, thermostability, and size distribution analyses.






Dr. Batabyal received her Ph.D. from Albert Einstein College of Medicine, NY in biophysics and molecular biology. Her research focused on structural and functional characterization of heme dioxygenases using enzymology and resonance Raman spectroscopy. Prior to joining Amgen, she was a project scientist/postdoctoral fellow at UC Irvine, where her research focused on structural and functional characterization of cytochrome P450s using crystallography, enzymology, and spectroscopy.

For a deeper dive into this topic, read these peer-reviewed article by Dr. Batabyal and her colleagues: Shaping IR Spectroscopy into a Powerful Tool for Biopharma Characterizations and Advancing secondary structure characterization of monoclonal antibodies using Microfluidic Modulation Spectroscopy

Q: Why is determining higher-order structure (HOS) of biopharmaceutical molecules important in drug development?  

A: Determining the higher-order structure (HOS) of biopharmaceuticals is critical for biological and pharmacological function. Slight changes in HOS can impact the efficacy and quality of the drug, and therefore it is important to be characterized. Hence, the successful development of biopharmaceuticals involves the study of their higher-order structure to ensure a therapeutically active molecule in appropriate formulation conditions.


Q: What techniques do you use currently for HOS analysis?  

  1. Near-UV CD and intrinsic fluorescence for tertiary structure analysis
  2. Far-UV CD and traditional FTIR for secondary structure analysis
  3. DSC, nano-DSF for thermal stability
  4. SE-HPLC/LS, SV-AUC for size distribution
  5. NMR for HOS analysis
  6. MMS for secondary structure analysis (newer technique in our toolkit specially for low formulation concentrations)

More details of our HOS work can be found in A Comparison Between Emerging and Current Biophysical Methods for the Assessment of Higher-Order Structure of Biopharmaceuticals.


Q: What have been the main challenges you have faced with these techniques?

Currently, the biopharmaceutical landscape is going through a transition from the traditional mAbs to the BiTE® molecules that show relatively high potency and hence significantly low product concentrations which poses a major challenge in higher-order structure characterization. Some challenges commonly faced include high sample concentration requirements, interference from formulation buffers containing chromophores, labor-intensive methods, and lack of automation.


Q: Why and how have you incorporated MMS to overcome your analytical challenges in these areas?

A: We have incorporated MMS for secondary structure characterization of biotherapeutic proteins mainly due to its high sensitivity, high repeatability, and automation along with consistent HOS analysis over a wide concentration range. Using MMS, we are now able to characterize secondary structure of BiTE® molecules using IR spectroscopy and run samples over a wide concentration range without having to worry about interference from chromophores in formulation buffer or instrument background drifts. We have successfully run samples with concentrations ranging from 0.5 mg/mL to 100 mg/mL and published our results in peer reviewed journals.


Q: What have been the main benefits of its incorporation?

A: To us, the most important benefit is sensitivity with high reproducibility in data for low product concentrations, especially in the range of 1 mg/mL to 0.5 mg/mL. The other benefits include automation, continuous buffer subtraction with auto-referencing and removal of background instrument drift (a common problem in traditional FTIR), a powerful laser (no additional requirement for detector cooling using liquid nitrogen), robust HOS analysis software that calculates spectral similarity scores on the second derivative and tells us about the contributions of different secondary structural elements in a given molecule. An additional benefit is that it calculates the final concentration of the samples during the experimental runs.


Q: Do you have any recommendations for scientists considering adding MMS to their bioanalytical toolkit?

A: MMS is a powerful new technique for the assessment of secondary structure using IR spectroscopy for proteins. It offers certain advantages over the conventional FTIR and far-UV CD for secondary structure characterization over a wide concentration range without requiring dilution or concentrating samples. With a simple workflow, automated platform, and robust software for data analysis, MMS makes it possible to use IR spectroscopy for assessing secondary structure for screening purposes in early stages, in addition to product characterization during the later stages.


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