In a recent article in European Pharmaceutical Review, Mareia Frost, Scientific Leader at Abzena, explores how understanding the characteristics of protein‑based drugs, and applying the right techniques means even the most complex biologics can be effectively separated from potentially harmful impurities.
The removal/separation of impurities and ensuring the purity of biologics is essential to the safety and quality of the therapeutic. Not only can impurities lead to adverse effects in patients, but they can also introduce product variability. The risks linked to contamination have led regulatory bodies, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to implement strict requirements on process characterisation and validation.
To deliver a product of high quality and purity using processes that abide by regulatory guidelines, a robust downstream processing (DSP) strategy is needed.
An ideal downstream process will achieve three aims:
In actuality, balancing purity, recovery and cost is not a simple task. Choosing methods best able to achieve these goals requires a thorough understanding of the characteristics and properties of the molecule.
Exploiting molecular properties to simplify separation and purification
If the molecule is small, compared with known impurities, filters could be used in order to retain the impurities and allow the smaller target molecule to be collected in the filtrate”
The techniques used to specifically separate and recover the target molecule (drug) from impurities and contaminants in the material resulting from upstream processes depend on the properties of the former. For example, if the molecule is small, compared with known impurities, filters could be used in order to retain the impurities and allow the smaller target molecule to be collected in the filtrate.
Although size-dependent separation methods are commonly used in the DSP of antibody-based therapeutics (eg, centrifugation, size exclusion chromatography, filtration) these will often be used in series with other techniques. Most commonly, these tandem methods will separate the molecule based on its charge.
By understanding the protein charge properties of the molecule, a wide array of tools could be used to separate it from impurities that do not share the same properties.
