An Interview with Dr. John Carpenter

Dr. John Carpenter

We sat down over a virtual cup of coffee in September 2020 to interview Dr. John Carpenter, Professor in the Department of Pharmaceutical Sciences in the Skaggs School of Pharmacy at the University of Colorado Anschutz Medical Campus. His research interests include mechanisms for protein degradation and stabilization in pharmaceutical formulations, during bioprocessing and in delivery systems. He has published more than 300 peer-reviewed papers and is an inventor on 35 issued patents. He is Editor for Reviews and Commentaries for Journal of Pharmaceutical Sciences. He serves on the Editorial Advisory Boards for Pharmaceutical Research, The AAPS Journal, Journal of Pharmaceutical Sciences, Molecular Pharmaceutics and BioPharm International.

Editor:
Dr Carpenter, thank you so much for chatting with us today. Firstly, why did you focus on protein characterization as your area of study?

John Carpenter:
My labs work on all types of protein studies. You need good analytical tools to study protein formulation, stabilization and degradation. Having good analytical methods helps you understand protein structure and degradation products better, hence my interest in characterization techniques.

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

John Carpenter:
Particle characterization, because we know that particles are important quality attributes and might create adverse effects in drugs. We need good methods to assess protein and foreign particles in therapeutic protein products.

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

John Carpenter:
Several different companies are developing new instruments to look at micron and submicron particles, and researchers are working with these instruments to see how they work most effectively and collaborating with instrument companies to develop improvements in current instruments and new instruments.

There are also software and AI products that are being created to improve characterization and quantification of particles with important different morphologies; such as silicone oil vs. protein particles.

Editor:
In your role as Editor for Reviews and Commentaries for Journal of Pharmaceutical Sciences, you recently published a paper by Pfizer on using automated, high-throughput infrared spectroscopy for secondary structure analysis of protein biopharmaceuticals. Why do you believe this topic is important for your readers?

John Carpenter:
This is a very popular topic!
Many instruments are not easy to use, posing a real challenge daily in the lab. For example IR spectroscopy, historically, was a challenge for obtaining high quality spectral data of protein samples in water. And often relatively high protein concentrations (e.g,. > 20 mg/ml) were needed for this analysis. With the instrument used in the Pfizer paper [the AQS3pro], those challenges were overcome. The technology was shown to be user friendly. We like to include these types of papers as an important resource for our readers so they know there are instruments out there that might solve their analytical problems.

We published another study by Brent Kendrick at KBI Biopharma. It was really good because it showed the difference between the AQS3pro, FTIR and CD spectroscopies,in terms of sensitivity to differences in structure of protein samples. Such assessment is important, for example, for characterizing a protein product after a manufacturing change.

Typically with IR spectroscopy, it is difficult to extract the information required, such as high quality spectra, but Brent demonstrated it is possible with MMS [the technology in the AQS3pro].

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

John Carpenter:
In addition to what I just mentioned (that the use of the instrument can sometimes be an art form), it can be really challenging to get proper data from traditional instruments. Other challenges include finding a technique that works across a wide range of Protein concentrations. In addition, finding proper biophysical training for scientists and other lab personnel can also be an issue.

Instruments like RedshiftBio’s AQS3pro are helping to alleviate some of these problems. An example is if five analysts ran the same test, they should get the same result, within instrument error. Most times that isn't the case, but with the RedshiftBio technology, reproducibility is significantly increased.

Editor:
How have things changed since you started working with FTIR spectroscopy on protein characterization? How do you think the industry will develop technologically?

John Carpenter:
It has changed tremendously. We've gone through instruments that were barely usable for proteins, to instruments that are routine now. Old instruments were challenging unless you had really high protein concentrations or a highly specialized scientist. Now we can use lower
protein concentrations, and just about anyone can use the instruments.

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

John Carpenter:
I think it will allow people to start using IR spectroscopy routinely for more work. Improvements such as temperature control will allow for more useful studies. It will open the door to simpler biophysical characterization and formulation screening with easy-to-use instruments. The results should be much more reproducible and impactful. Data processing is easier, and the results are much more accurate. I think this technique will become more routine in most labs. And as a bonus, customers will get to interact with Matt McGann, which is worth the price of buying a new instrument or two.

Read the Pfizer paper here