Collaboration Enhances Shelf Life of Biologic Medicines

This project was the first industry partnership undertaken by CPI in association with its £38m National Biologics Manufacturing Centre which is due to open in September. The project, which commenced in 2014, was performed in CPI’s laboratories at Wilton, Redcar in advance of the opening of the new facility.

The components of drug product vials and syringes have been found to have an adverse impact on the stability of some biologics, causing degradation which can render the medicine unsuitable for administration, in some cases resulting in product recalls. Although this issue is widely recognised in the biopharmaceutical industry, the actual causative components and degradation mechanisms have not been fully elucidated. This collaboration has investigated the effects of selected silicone oils and other primary packaging materials on the stability of proteins to enhance our understanding of container related causes of degradation and the use of novel formulations to mitigate these effects.

The ability to stabilise therapeutic proteins using formulation as has been demonstrated during this project can provide great benefit for the global biologics manufacturing supply chain by cutting costs and reducing waste through increased shelf life and reduced product specification failures.

Key points:

• Aggregation is one of the most challenging issues for the development of therapeutic products, yet we still have a lot to understand about how aggregation occurs and effective ways to prevent it.
• Aggregation can be a result of stresses that a protein undergoes during manufacture, storage and use, such as temperature fluctuations and agitation. Silicone oil coatings in pharmaceutical containers such as pre-filled syringes have also been implicated in therapeutic protein aggregation, and this is an important challenge in product development. Strategies to mitigate silicone oil induced aggregation of therapeutic proteins are required.
• Using a range of methods for characterising protein aggregation CPI and Arecor have investigated the effect of silicone oil on the stability of a number of proteins and the effect of formulation on mitigating any negative effects observed. We demonstrated a marked effect on the stability of the test proteins in the presence of silicone oil, with substantial aggregation occurring. Subsequently we were able to demonstrate stabilisation and almost complete inhibition of aggregation by using specific excipient combinations.