Based on a presentation by Rob Forbes (university of Bradford, UK).

Last year, the UK’s National Institute for Health and Clinical Excellence (NICE) decided that a new biopharmaceutical cancer drug costing £3000 per month, which could extend a patient’s life by 6 months, was not value for money and would not be prescribed in the UK. Manufacturers are, therefore, faced with a big challenge to be more efficient and effective in their production processes so that the cost to the patient is appropriate.

We only need to make incremental changes in efficiency and production processes to achieve big cost savings. For instance, for a company with $20 billion in annual revenues, a 1% reduction in manufacturing cost will translate into savings of $50 million per year. This should hopefully lead to cheaper products, as well as more of us being kept in our jobs!

One of the major hurdles in biopharmaceutical manufacture is protein aggregation. In the wrong conditions, proteins tend to group together — sometimes in inappropriate configurations. In the solution state, we may see unwanted clusters, aggregation and dimers. At best, these may make a drug ineffective, but in the worst case scenario these aggregations may have untoward effects. Therefore, it is important to understand cluster properties — how they form, what we can do to prevent them, and how to qualify and quantify them.

To help alleviate the problem of aggregation and achieve batch-to-batch consistency, we have formed a consortium to develop a novel analytical instrument that can detect aggregation in biopharmaceutical processes. The consortium comprises end-user groups (Avecia Biologics Ltd, Eli Lilly and Co. Ltd and Lonza Biologics plc), as well as three other institutes: the University of Bradford (UK), Paraytec (a spin-out company from the university) and Intertek ASG (UK).

This consortium will hopefully aid the identification and design of optimal biopharmaceuticals and biologics that do not aggregate. The techniques may also give us more in-depth understanding in certain pivotal areas, such as colloidal behaviour, conformational stability and surface/interfacial stress, as to why and how aggregates form. The ultimate goal is to develop an interactive ‘switching’ system; when we’re processing or trying to separate dimers or aggregates on a large scale from the monomer, we can use the switch at the right time to maximise yield and minimise the input from unwanted dimers and aggregates.

Apart from the cost and effort that goes into monitoring and minimising aggregation, patient safety is a key issue. We don’t know for sure whether aggregation causes immunogenic reactions — there is ongoing debate about this issue — but if we can manufacture products that we know aren’t going to aggregate, or that will be less prone to aggregate, then this will help to minimise the problem.