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10 Pharmaceutical Technology ® Trends in Formulation eBook September 2024 PharmTech.com BIOLOGICS Solving technical considerations Finally, what technical considerations remain to be solved that can conceivably facilitate a breakthrough to realistically realize temperature-stable biomolecules that no longer require stringent cold-chain handling? Cao answers the question by pointing out that de- veloping advanced stabilizers and excipients, as well as improving lyophilization and spray drying tech- niques, can aid in maintaining biological molecule stability without compromising efficacy or safety. Such advancements would allow biological mole- cules to be less dependent on stringent storage and transportation conditions. "Don't be afraid of lyophilization," stresses Ailhas. "It can significantly help solve this problem, and it is not so difficult to manage, at least for mAbs. For mRNA vaccines formed with LNPs, the breakthrough will involve finding a way to remove water from the inner par t of LNPs during lyophilization without damaging the LNP structure and ensuring they can return to their original form during reconstitution." Meanwhile, Chrimes says that the solutions are going to look different based on the modality, mech- anism of action, mode of delivery, and more. Across the board, however, progress always starts with un- derstanding what is causing the instabilities in a given biotherapeutic. "From there, we can work … to optimize not just for temperature stability, but shelf- life and other critical parameters that can impact commercial success. For the most part, it's an ongoing process of optimization and refinement." Chrimes adds that innovations in predictive modeling and machine learning could accelerate the development of unique excipients and formulation development. "The key focus during the process development or clinical trial stages is to minimize the risk of fail- ure," adds Lim, who notes that, to minimize risk, a pre-molecular developability assessment is crucial. "Through this evaluation process, scientists can find any potential issues, such as lack of thermal stability, which can bring out exclusion or implementation of risk mitigation strategies for further development," he says. "This assessment can help researchers optimize strat- egies for thermal stability, including lyophilization as part of the formulation development process. Not only can this reduce the risk of failure but also save time during the development timeline," Lim concludes. ■ Delving into Biopharmaceutical Development and Manufacturing In this exclusive Drug Digest video interview, Felicity Thomas, associate editorial director, Pharmaceutical Technology Group, interviews experts from Biosynth and the University of Maryland, who go into detail about the evolution of biopharmaceutical development, highlighting challenges and potential future trends. Drug Digest is a tech talk video series with the Pharmaceutical Technology® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products. Anupreet Kaur Post Doctoral Associate, Dr. Robert Brinson Research Group, Institute for Bioscience & Biotechnology Research (IBBR), National In- stitute for Standards and Technology (NIST), University of Maryland. Hans de Backer Head of the Peptide Division, Biosynth Peter Timmerman Head of Peptide Science, Biosynth