The level of contract manufacturing sector investment in antibody drug conjugates over the last two years has been remarkable, with firms like Lonza, Piramal, Novasep, Fujifilm DioSynth and – most recently – Carbogen Amcis and SAFC adding capacity.
Most observers attribute this to two things: growing regulatory acceptance of this type of hybrid drug, with Roche’s Kadcyla being the most obvious example; and growing Big Pharma interest in developing such products.
Another less recognised factor is the technical challenges involved in developing these complex medicines, says Gerry MacKay, CEO of specialist bioanalytical services firm BioOutsource.
“The issue with ADC is that the mechanism of action intracellularly is not really understood so it is often a case of trial and error to get an antibody, linker, toxin combination which works. Therefore there is a need to manufacture different molecules, which can increase the need for CMOs.”
Another factor behind the recent slew of contract manufacturing organisation (CMO) investments is the current mismatch in capacity between the two components of an ADC according to MacKay.
“Capacity for the manufacture of these highly toxic molecules is not great,” he said, adding that “The capacity for mAb production is good but the key is the toxin production and conjugation.”
This Fits with what Lonza’s Dominik Werner told Outsourcing-pharma.com.
“There are 25 clinical programs and a lot of new compounds in development. The capacity currently provided is limited and it is expected that new capacity need to come on stream in the future. To that end Lonza is expanding its ADC capacities in Visp, coming on stream by Q2 2014.”
Recent ADC investor Carbogen Amcis shares this view.
The firm – which is owned by India’s Dishman – told us that: “There are only a handful of CMOs specialized in the development and manufacture of new targeted cancer treatments…Thanks to our recent investment in ADC, we are well positioned to offer our customer superior service for ADC programmes.”
“Developing ADCs is a complex process and outsourcing to an experienced CMO offers a variety of advantages, such as access to expertise in process development and scale-up for drug conjugates to support toxicological studies and clinical trials as well as fill-&-finish capabilities to address solubility and formulation challenges during the development phase.”