Typically, small molecule drugs have well-defined structures and building blocks, are made by controllable organic syntheses, and the results can be analysed with a high degree of precision, Jan Gunnar Gustafsson, owner of life sciences consultancy firm Bio Evaluation, told delegates at last month’s Global Pharmaceutical Contract Manufacturing (GPCM) conference in London, UK.
In contrast, he continued, biopharmaceuticals are larger molecules with amino acid and DNA building blocks made by living organisms, making the process development and manufacturing a multidiscipline activity and limiting the number of potential outsourcing partners.
“Analyses and characterisation are more complex and do not have the same precision as for a small molecule,” he said, adding “the use of living organism for manufacturing cannot be a totally controlled process, and [large molecules] cannot be autoclaved or radiated for sterility .”
As such, for a firm looking for a supplier of large molecules the pool of contract manufacturing organisations (CMOs) with the relevant abilities and technologies is small when compared with makers of small molecule drugs, although there has been an increase in more complex small molecules, such as HPAPIs and cytotoxics.
Successful selection
Gustafsson’s words were mirrored by John Little, QC Manager at Cobra Biologics, a CMO specialising in the development and manufacture of mammalian and microbial proteins, plasmid DNA, and virus products for gene therapies and vaccines.
He told Biopharma-Reporter.com traditionally large molecule products were made from blood plasma but they are increasingly coming from recombinant technologies and for a biologics CMO to be successful it needs to have highly developed systems for the specific manufacturing capabilities, or be able to tool up.
Thus this is where the selection process can differentiate between CMOs, he said, as “the legal side and the contract structure is very similar whether it is for small or large molecules.”
However, both Little and Gustafsson warned about the importance of choosing a capable CMO, as from the regulator’s point of view the responsibility for the manufacture lies with the IND holder, even if all aspects of the manufacturing process have been contracted out.