Effective risk mitigation for process design & scalability of HPAPIs
Juliette Martin of Seqens overviews strategies to overcome the challenges of HPAPI production
High-potency APIs( HPAPIs) are active ingredients that are highly effective even in small doses, offering significant advantages over traditional APIs. They are widely used in treating diseases including cancers, respiratory disorders and hormonal imbalances. Thanks to their selective action, they make it possible to reduce the frequency of administration and side effects.
Cytotoxic drugs, a category of HPAPIs, are particularly useful in cancer treatment and other disorders like rheumatoid arthritis and multiple sclerosis. They target rapidly growing cells, such as cancer cells.
Oncology is a major driver behind the development of HPAPIs, with many anti-cancer compounds being cytotoxic and cytostatic. Other HPAPIs include steroids, hormones, peptides, beta-lactam compounds and prostaglandins.
Evolution of HPAPI manufacturing
The global HPAPI sector is one of the fastest-growing areas in the pharmaceutical industry. Global demand for HPAPIs is growing at a compound annual growth rate( CAGR) of 6.0 %, reaching approximately $ 35.5 billion by 2031.1
This is being driven by patent expiry of blockbuster drugs, trends in pharmaceutical outsourcing and by the patent expiration of various drugs globally. The trend is likely to continue as the anti-cancer market will sustain the growth of HPAPIs and cytotoxics.
Chemistry-based therapeutic developments are enjoying a renaissance, based on several factors. While the main mode of action for small molecules was inhibition, researchers have expanded their toolbox and can now develop covalent binding or proximity induction.
New modalities have been discovered, making it possible to extend the opportunities to target specific proteins or RNAs using small molecule therapeutics or even polymer-drug conjugates. Even for biotherapeutics, hybrid drugs are emerging.
For example, novel drug delivery systems, like antibody-drug conjugates( ADCs), combine monoclonal antibodies with biologically active drugs. 2 Fatty acid-derivatised peptides( such as GLP-1 agonists against diabetes and obesity) and tailored lipids and polymers for mRNA therapeutics all depend on chemistry.
Furthermore, improved modelling tools and artificial intelligence also accelerate drug discovery and make it possible to address more ambitious targeted therapies. 3 45 % of all drug discovery start-ups that use or develop specialised AI tools are focused on small molecules, compared to 24 % focused on biologics. Figure 1 shows the R & D landscape of active R & D projects in oncology. Most therapeutics under development are still small molecules.
Risk-based strategy
The lack of data on the novel pharmacological actions of compounds potentially designated as HPAPIs and the transformation of process intermediates to meet acceptable occupational exposure levels( OELs) poses a significant challenge. To address this in early drug discovery, a riskbased approach is recommended,
22 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981