Trehalose, sucrose, and amino acids are key components of biopharma formulations. Dr Christian Lotz, General Manager EMEA, Pfanstiehl, discussed how the applications of these molecules are related to their functionalities. He also gave examples of sucrose and trehalose in COVID-19-related formulation applications.
Pfanstiel’s products are used by the top ten biotech companies in the world. Lotz emphasised that his company is a market leader in terms of manufacturing capabilities and capacity, as well as the quality of their trehalose and sucrose, specifically designed for use in biologics.
A comparative analysis between sucrose and trehalose found that trehalose is chemically more stable than sucrose due to its alpha-alpha 1-1 glycosidic bond, making it resistant to hydrolysis and less likely to produce free glucose. Furthermore, trehalose has a higher glass transition temperature and lower solubility than sucrose, which makes it more appropriate for stabilising proteins, particularly in frozen or lyophilised formulations.
From a crystallisation standpoint, trehalose is prone to crystallisation under specific frozen conditions, which could lead to protein aggregation. However, Lotz mentioned that this can be mitigated by optimising the trehalose-to-protein ratio and adjusting the freezing conditions. Another key edge trehalose holds over sucrose is the fact that there are no impurities like beta-glucans in trehalose. Beta-glucans are concomitant components of cellulose containing plants, which can cause a false positive response to endotoxin testing. Alongside this, beta-glucans can also induce unwanted immune responses.
Lotz then highlighted the applications of trehalose and sucrose as stabilisers in mRNA vaccines, including the Pfizer-BioNTech and Moderna vaccines. He also acknowledged that buffer selection is also vital in determining mRNA stability during freeze and thaw cycles. Lotz briefly compared Tris-HCl and phosphate buffer. Finally, he stressed that all excipients intended for use should be free from RNases to enhance RNA stability.
With a regulatory perspective in mind, Pfanstiehl’s products align with pharmacopeial standards and have been rigorously tested for impurities, endotoxins, and nanoparticles. Overall, their excipients are consistently low in impurities and highly characterised. This quality assurance guarantees the safety and stability of drug formulations.
