“Shadows” help prevent unpleasant surprises for CMOs says Melinta
“One of the things our founding CEO was adamant about was building a small chemistry group in-house who would shadow our discovery chemists,”Erin Duffy, Melinta's chief scientific officer, told Outsourcing-Pharma.com.
These “process” or “shadow” chemists closely follow the scientists who create Melinta’s novel antibiotics, and find ways to cut unnecessary steps early in the production process, such as purification, before a drug is handed over to a contract manufacturing organisation (CMO).
Duffy said the strategy cut lead time from drug discovery to first-in-human research and commercial manufacture, and saved money.
Investment in shadow teams pays off, she said, because “when we nominate a candidate for clinical development, that group has already done some optimisation– so [we are further ahead] when we hand over to the CMO.”
‘Reducing unpleasant surprises’
Problems with production of drug materials “can be costly to address if they are discovered late in the clinical trial process,” Duffy told us. “Common CMC [chemistry, manufacturing, and controls] challenges relate to purification of the product, number of steps required in manufacturing, and cost of reagents.”
For this reason, she said, Melinta manufactures large volumes early on in development, for study by the shadow team to “reduce unpleasant CMC surprises later on.”
“In terms of scaling-up production, Melinta’s research and development approach is unusual in that – even at the earliest stages – we produce compounds on a 50-100mg scale,” Duffy continued. The unusual amount means, if the biology team finds the compound successful, the company has a ready-made store to use in the next round of tests.
“This provides enough material to conduct the biology team’s testing, but also – should a molecule perform favourably – allows Melinta to move rapidly into successive stages of testing. It also ensures that any potential manufacturing issues are identified and addressed early on in development.
“One of the roles of the process ‘shadow’ chemist is to ensure that this scalable manufacturing is viable and cost effective.”
Outsourcing
Chemistry teams at Melinta are organized into what it calls structure-based drug design (SBDD) units, Duffy told us. These include a crystallographer, a computational chemist, four to six synthetic organic chemists and one shadow chemist.
The company is currently creating molecular scaffolds as assays for discovery of new antibiotics that target the bacterial ribosome.
“Computational chemists develop designs for new molecular scaffolds or backbones, synthetic chemists make 10-12 new compounds per week, and crystallographers confirm that they are properly binding the ribosome using X-ray crystallography,” said the chief medical officer.
“The process chemists think about how to transition new chemistry to larger-scale manufacture, to speed the movement from discovery to development, and ultimately, to commercialization.”
After Melinta’s early process work which is done in-house, drug development typically moves to working with global contract research organisations for clinical stage trials, Duffy told us.
