An Interview with Patrick Ahl, Assistant Principal Scientist, Merck

Patrick Ahl

We sat down over a virtual cup of coffee in November 2020 to interview Patrick Ahl, Assistant Principal Scientist, Merck. Patrick's current research at Merck focuses on fostering innovation to accelerate and improve vaccine formulation development. Innovation efforts include liquid handling robotics, differential scanning fluorometry, dynamic light scattering, automated western gel electrophoresis, and FTIR spectroscopy. Prior to joining Merck, Patrick developed liposome-based drug delivery at The Liposome Company in Princeton, NJ. Learned FTIR spectroscopy from Dr. Kenneth Rothchild as a Post-Doc at Boston University and MIT. A Ph.D. graduate of the Thomas C. Jenkins Department of Biophysics at Johns Hopkins University under Dr. Richard Cone. Penn State undergraduate.

Editor:
Why did you focus on the potential impact of antigen unfolding and aggregation in vaccine formulations as your area of study?

Patrick Ahl:
Antigen unfolding and aggregation is probably the most common reason for vaccine potency loss. In addition, unfolding and aggregation are thermally driven, i.e. higher temperatures typically lead to more unfolding and aggregation. Thermal stress is unavoidable during vaccine production and storage. Designing vaccine formulations where the antigen is stable at the highest possible temperature will make vaccine transportation and storage much easier. This potentially has the public health benefit of making the vaccine available to more people.

Editor:
What have been the biggest challenges the protein characterization sector has faced over the past few years

Patrick Ahl:
Characterization of proteins in solution at relatively low concentrations is, even today, quite difficult. There are several indirect and highly specific methods to measure the biological activity of a protein in solution. Immuno-assays are also useful. Spectroscopic methods are available to determine protein size by light-scattering and low-grade structural information by intrinsic protein fluorescence and circular dichroism. However, there are no easy methods to characterize protein secondary structure in solution.

Editor:
How do you think these will be addressed/solved?

Patrick Ahl:
I believe Microfluidic Modulation Spectroscopy (MMS) has the potential to play a major role in addressing this problem.

Editor:
What have been the technological challenges faced by biophysical characterization scientists? How are these now being addressed?

Patrick Ahl:
The greatest challenge has been automating new characterization technologies with high throughput sample handling and sophisticated data analysis. Biophysical characterization scientists need better data management systems to collate data from multiple characterization technologies into useful databases.

Editor:
The techniques available for detection and application in formulation studies is a particular area of interest of yours. What are the shortcomings of existing biophysical techniques?

Patrick Ahl:
The technology for high throughput characterization of vaccine formulations has become more available and powerful in recent years, e.g. MMS. This has made the preparation of vaccine formulations one of the most time-consuming part of the vaccines development process. Although laboratory automation for preparing vaccine formulation does exist. The development of this automation process is often too time consuming to meet the unique challenges of different vaccine formulations. The integration of vaccine formulation automation technology with the high throughput characterization technology needs improvement.

Editor:
How have things changed since you started working in the industry? How do you think the industry will develop technologically?

Patrick Ahl:
Miniaturization of biophysical characterization of proteins has dramatically reduced the amount of sample material required to characterize formulations and significantly increased the amount of data generated by a single instrument. I anticipate that in the future companies will develop better software tools to combine large amounts of orthogonal biophysical data directly from different instruments into a single database to facilitate better visualization and interpretation of data.

Editor:
What role do you think MMS will play in the industry?

Patrick Ahl:
I believe MMS will become a standard technology for monitoring the thermal stability of protein vaccine drug substances in the 1 to 10 mg /mL concentration range. Importantly this technique can quickly provide quantitative secondary structure information, particularly aggregation associated β-sheet formation.

What does MMS' increase in data quality and automation mean to vaccine development?
It will now be possible to quantitatively measure the thermal stability of vaccine protein secondary structure at 1 to 10 mg/mL protein with relative ease. Frankly, this was not possible before.

Thank you Patrick, for your great insights.

Learn more about how Patrick is using the AQS3pro in this on-demand webinar