Issue link: https://www.e-digitaleditions.com/i/1468049
26 Pharmaceutical Technology TRENDS IN MANUFACTURING 2022 eBOOK P h a r mTe c h . c o m cycles can be developed and implemented that can be used to freeze-dry a COVID-19 mRNA vaccine. Meanwhile, Matthew Bourassa, process develop- ment manager at LSNE Contract Manufacturing, a PCI Pharma Services company, notes that, in the past 36 months, oligonucleotides and mRNAs have been among the fastest growing market segments (particu- larly for LSNE). "As the biologics market continues to mature and new products enter the clinic, LSNE's techniques for minimizing line-loss continue to gain efficiency. [The company] has seen a significant in- crease in the number of companies developing RNAi [RNA interference] or siRNA [small interfering] products, and the cost of the oligonucleotide drug substance is high as well," Bourassa says. LSNE is currently working on lipid nanoparticle (LNP) formulations, which is a common formu- lation technology used in mRNA vaccines. Tra- ditional critical quality attributes (CQAs) such as residual moisture, cycle time, and an elegant cake are important, but, additionally, because of the lipid component in the LNP, special consideration must be taken for potential reconstitution issues. LSNE is taking an iterative approach to developing a robust lyophilization cycle with optimized reconstitution characteristics, according to Bourassa. Sustainability in lyophilization Given the fact that there is a large number of new biologics and emerging biotherapeutics currently in clinical development, the sustainability of the ly- ophilization process, for such products, is coming under greater scrutiny. Some industry participants have been looking towards solutions to keeping ly- ophilization sustainable. There are potential pros and cons pertaining to the sustainability implications of lyophilization when it comes to certain aspects, such as packaging, according to Matt Hall, principal technical affairs manager, Corning. "For example, removal of water from the drug product reduces the overall weight, which can re- duce the energy required for shipping. In addition, freeze drying should significantly improve the sta- bility of the drug product, allowing for room tem- perature storage and avoiding the energy needed to maintain a cold supply chain. Another potential sustainability benefit is reduced usage of expanded polystyrene insulation materials that are bulky and difficult to recycle," Hall states. The process of lyophilization does come with some potential negative implications in terms of sustainability, Hall observes. While the energy cost of the cold chain storage is avoided, the freeze- drying process itself can be energy intensive, he explains. "In addition, sterile diluent (and its as- sociated energy costs for production and distribu- tion) is still required to reconstitute the lyophilized drug. Finally, the use of f luorinated refrigerant gases could have negative impacts on the envi- ronment and increase adverse reactions related to global warming," says Hall. Hall enumerates the innovations below that can be used to improve sustainability of lyophilization. These innovations include, but are not limited to: • New refrigerant technologies that reduce or eliminate the use of gases with a high global warming potential • Development of pretreatments and/or simul- taneous processes (e.g., infrared, microwave, etc.) that reduce the time to complete conven- tional freeze-drying cycles. • Development of process analytical technologies that accurately determine the endpoint of the Biologics