Scope for biodegradable API molecules
One solution put forward to reducing the burden of pharmaceuticals in the environment (PIE) is to design and market totally biodegradable API molecules. Vaccines, therapeutic enzymes, hormones and biological therapies (termed ‘biologics’) like monoclonal antibodies are not subject to ERA, or to as much scrutiny post-patient as small molecule APIs, as they are deemed to be ‘natural’ and rapidly breakdown in the patient and environment to form small non-toxic materials like amino acids.
This may not always be the case with ‘hybrid molecules’ such as PEGylated antibodies and antibody drug conjugates. While the number of biological medicines (biologics) in use has risen over the past 10 years, small molecule APIs are still heavily prevalent for treating many diseases, which suggests that biologics are unlikely to replace small molecules in the near future.
Most pharmaceutical drug candidates fail at the R&D stage (93-96% failure rate), as shown in Figure 1. Early development failure arises from a range of factors such as inadequate pharmacokinetics, bioavailability and unacceptable toxicology profiles, in addition to lack of efficacy in man. Candidate drug properties, a consequence of chemistry design, are key to the success or failure of a proposed molecule. Hence an additional barrier in the form of designing biodegradable drugs would impact further still on what is already a very high attrition rate.
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