Nandini Kashyap of Cambridge Healthtech Institute recently spoke with Dr. Jean-René Authelin of Sanofi about challenges in manufacturing and industrial-scale operations for high-concentration proteins formulations and where the industry is headed in coming years. Dr. Authelin is the keynote speaker at the 7th Annual High-Concentration Protein Formulations which is taking place on August 15-16, 2018 in Boston, MA where he will be delivering his talk on “Challenges in Industrial-Scale Fill & Finish Operations for High-Concentration Proteins Formulations”. This conference is being organized as part of the 10th Annual The Bioprocessing Summit which runs from August 13-17, 2018 in Boston, MA.

KEYNOTE PRESENTATION:

Challenges in Industrial-Scale Fill & Finish Operations for High-Concentration Proteins Formulations

Jean-René Authelin, PhD, Global Head of Pharmaceutical Engineering, Pharmaceutical Sciences, Sanofi France

High-concentration protein formulations are more and more required to administer proteins, especially mAbs. However, due to their high viscosity, propensity to aggregate or to form gel by drying, there are many hurdles to develop a robust commercial fill & finish process. The role of product development studies, which will be shared during this talk, is to anticipate the main difficulties and to adapt the process to the product by setting up a de-risking methodology, based on downscaled models and the use of well-designed surrogates.

SPEAKER BIOGRAPHY

Jean René Authelin has an Engineering degree in Chemical Engineering from ENSIC (Nancy France), and a PhD from The Institut National Polytechnique de Lorraine (France). He joined Rhone Poulenc in 1988 as a Chemical Engineer. In the 90’s, he founded the Physical Quality function, dedicated to the API crystallization, drying, polymorphism for which he was for 10 years Global Head in Rhone Poulenc Rorer, Aventis and finally Sanofi. In 1988, JR Authelin was nominated Global Head of Pharmaceutical Engineering. Domains of interest of JRA include: thermodynamics of hydrates, drug polymorphism, amorphous solids physics, drug stability, crystallization, nanoparticles engineering and processing, drying, milling; spray drying, fluid bed granulation, roller compaction, freeze drying. Jean René Authelin is the author or co-author of 20 publications or book chapters and the co-inventor of 9 patents.

1. Can you tell us about yourself and about your role at Sanofi?

My role is the scientific coordination of the work on Drug Product process development executed by several development teams in the company (small molecules or biotech). I’m also directly involved as a scientific expert on trouble shooting actions concerning API or DP process or physical chemistry.

2. What are major obstacles in your field of research?

In the Pharma world, production process should never delay manufacturing of the Drug product whether it is for clinical trials or commercial productions, as our patients are expecting to get these products in due time. The challenge is that the diversity of the modalities is dramatically increasing: classical mAbs, enzymes are already old stuff, but bi or tri specific antibodies, siRNA, gene therapies etc. are arriving and bring unknown difficulties. In particular, the physical chemistry and chemical/physical stability of these drug products, in combination to the process induced stresses may lead to extremely subtle and complex issues. Moreover, these unexpected problems may raise late in the development if we do not envisage all possibilities from the beginning, and sometime even if we do it because of what happens was never observed and was not part of prior knowledge.

The main difference of our process research domain to other research domains, is that in general researchers are trying to answer to well defined problems that they have decided to study, whereas in our process domain, we have to deal with extremely diverse kind of challenges that occur spontaneously.

3. What are the most effective ways to deal with the manufacturing and scale up issues posed by high viscosity?

Probably the best way is to avoid the highly viscous formulations! That is the challenge for formulators. However, it is not impossible to deal with viscous products, provided we anticipate the process development. For instance, some filling technologies are sub optimal for this kind of products. So, the methodology is to test quickly at lab scale -with a very limited amount of material or a well-designed surrogate- the product using the same technology than in the intended industrial workshop in order to evaluate how the technology fits to the product. The solution may be simply to propose a fine tuned operating procedure, if the issue is not too complex. Unfortunately, sometimes it just does not work. In such a case it is necessary either to transfer the product to another workshop already equipped with the adapted technology or to go for an investment if the required equipment is not available. Cost and time lines have to be considered in the overall project schedule. Obviously, anticipation is critical in order to achieve a smooth industrial transfer.

4. Where is the field headed in coming years and what will revolutionize this field of research?

There is no specific and unique field. The secret is probably having multi-skilled team’s knowledge as well classical engineering aspects (fluid mechanics, thermodynamics,), physical chemistry, protein science & soft matter, wetting etc. Indeed, as already said, the challenges we will have to face are really diverse and they will be impossible to solve without the coordinated efforts of many disciplines.

5. Why have you chosen to speak at The Bioprocessing Summit and what are you looking forward to at 2018 gathering?

The Bioprocessing Summit is clearly one of the best occasions to communicate and to learn, with a very large and wonderful audience; and Boston is great place to be!

6. What can audience expect from your talk?

First, I hope they will have some fun! And also, that it may trigger new ideas. Pierre Gilles de Gennes (Physics Nobel price 1991) said “the important thing is not to be always right. It is to dare propose new ideas and then to verify them.”