CPI collaboration investigates the compatibility of biologic medicines with drug product containers


Potentially improving stability and shelf life during transportation and storage

The UK's Centre for Process Innovation (CPI) is collaborating with Arecor, a pioneer in the stabilisation of biologic molecules, on investigating ways to enhance the compatibility of biologic medicines with drug product containers and thereby potentially improve stability and shelf life during transportation and storage.

This project, which began in 2014, was the first industry partnership undertaken by CPI in association with its £38m National Biologics Manufacturing Centre, which opened in September. The investigation took place 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, and in some cases resulting in product recalls. Although this issue is widely recognised in the biopharmaceutical industry, the components that cause this and the degradation mechanisms have not been fully explained.

The project 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 reduce these effects.

The ability to stabilise therapeutic proteins using formulation as demonstrated during the project benefits the global biologics manufacturing supply chain because it can cut costs and reduce waste through increased shelf life and reduced product specification failures.

The key points arising from the collaboration are:

  • Aggregation is one of the most challenging issues for the development of therapeutic products, yet we still have much 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 reduce 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 reducing any negative effects observed. The partners demonstrated a marked effect on the stability of the test proteins in the presence of silicone oil, with substantial aggregation occurring. Subsequently, they were able to demonstrate stabilisation and almost complete inhibition of aggregation by using specific excipient combinations.

Dr Chris Dowle, Director of Biologics at CPI said: 'We are delighted to have formed this partnership with Arecor and hope this will be the first of many such projects to continue to improve the formulation of therapeutic proteins.'

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Arecor's Chief Scientific Officer Dr Jan Jezek, added: 'Rapid development in pre-filled syringes for biologics in the last decade has led to increasing occurrence of stability issues due to interactions with primary packaging materials. The collaboration with CPI allowed us to gain crucial insights into the nature of these undesirable effects and make an important step toward effective formulation strategies to mitigate them.'