Ensuring protein drugs are stable is a complex challenge. To be successful, formulation developers need to think beyond the molecule and also consider how the finished product will be handled after it leaves the factory.

Protein-based medicines are sensitive environmental damage and must be handled carefully, says Ahmad Sediq, PhD, senior group leader, formulation development and drug product services, at CDMO Lonza.

“Transportation of protein drug products from one location to another can lead to mechanical stress—shaking, dropping, etc.—or exposures to light and heat. These exposures are ‘stressful’ to the proteins and may result in a deteriorated product quality,” he explains.

Many manufacturers try to account for such stresses by preparing concentrated solutions that can be diluted to therapeutically-relevant strengths later on, but this approach is far from straightforward, notes Sediq.

“How the product is diluted, what diluent is used, in which final container the diluted product is collected are all factors that may negatively affect the stability of the protein and, in turn, result in a deteriorated product quality,” he continues. “The therapeutic efficiency of any drug product can only be achieved when the product quality is not put at risk. Instability of the protein may lead to inefficient therapeutic effect and/or even adverse reactions.”

Real-world handling

To give formulators another approach Lonza has teamed up with firms from the pharma, biotech, and nutrition industries for RealHOPE, the Real-World Handling of Protein Drugs-Exploration, Evaluation and Education Project.

This initiative, which is backed by the Innovative Medicines Initiative and European Federation of Pharmaceutical Industries and Associations (EFPIA), will look at how handling practices can inform formulation production.

For Lonza the initial focus will be modelling real-world handling practices used after products have been shipped. according to Sediq.

“The project will bring more light into the end-user handling of protein-based drugs once a batch of the drug leaves the manufacturing site,” he points out. “This will be achieved by mapping out the handling procedures outside of the manufacturer’s reach, by monitoring, through chips, different environmental conditions that a drug encounters during its life cycle after manufacturing and release of the batch for use in humans.”

The plan then is to feed these findings back into formulation development and manufacturing to help customers make products that are stable enough to pass through the supply chain.

“Lonza, as a CDMO, needs to apply state-of-the-art simulation studies and analytical technologies to help our customers develop their products in the best way possible,” he explains.

Lonza and the other organizations involved in the project say conclusions from the project will be presented at conferences and published in scientific journals.

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