Small molecules have well-defined chemical structures manufactured by chemical synthesis. After decades of pharmaceutical development, applicable requirements are quite well known from the experience gained in bringing numerous small molecules to the market in a broad range of therapeutic areas.
Despite the rise of biological pharmaceuticals, small molecule drug pipelines remain strong. With an attractive price tag, small molecules continue to be regarded as robust, versatile and easier to make.
Besides new molecular entities, opportunities are also found in drug repositioning – the repurposing of existing, often off-patent drugs to new indications. With an abridged development, low risks of adverse toxicology and shorter time-to-market, drug repositioning is rapidly making its way to mainstream use in global markets.
Key challenges encompass:
- Quality-by-Design (QbD) and quality risk management
- Quality control and analytical methodology development
- Sourcing of API’s and related GMP compliance
- Potential genotoxicity of API’s and related impurities
- Relevance of animal models
- Nonclinical data to support First-in-Human clinical studies
- Joint regulator-payer dialogue
- Drug repositioning