Ahead of CPhI Worldwide 2015, CPhI expert panelist, Vivek Sharma, CEO of Pharma Solutions at Piramal, analyses the challenges in developing and manufacturing of Antibody-drug Conjugates (ADCs) and how the market has progressed over the past few years.
Major challenges faced by companies looking to enter the ADCs market are the availability of technologies, which are few as yet, and the complex supply chain to manage while going for the clinics. Many a time a sponsor ends up working with 4 different CMOs before the clinical supplies are available for dosing – one each for antibody, cytotoxic molecules, the ADC conjugate & the Fill/Finish. Add to it the availability of quality CMOs in the space and this becomes a major stumbling block for the ADC player.
Most high potent facilities are not suitably designed to produce biologics (i.e. environmental standards, particularly microbiological controls may be inadequate) and, similarly, most biologics facilities don’t have high potent capabilities – so it is rare to find a recognized, credible manufacturer that operates in both fields.
Hugely under resourced
As such, despite the increase in development targets for ADCs, the global contract manufacturing sector still remains hugely under resourced, with only a couple of players having the experience & necessary regulatory approvals to commercialize these products.
Piramal is one of the longest established ADC producers (beginning in 2004) and the main challenge when they transitioned was moving from the high potent field to biologics and combining the two practices for successful conjugation. For many CMOs entering this space now, the real issue is building a facility with high containment in mind. Furthermore, having the desired skillsets to work efficiently with ADCs is crucial, as each new ADC requires specialist adoption and a track record of prior experience is understandably what all pharma companies are searching for in a partner.
ADC manufacturing involves a complex supply chain and it is a major concern for pharma clients, as they seek to de-risk the process as much as possible. So, our view is that you will see pharma consolidating a majority of their projects with a few specialized players.
Linker chemistry improvements
Looking at the industry as a whole, over the past few years, we have definitely seen improvement over the aggregation of proteins. In the past, first generation drug linkers would produce 20-30% aggregation of proteins, which is a big problem as it gives a low yield. However, through linker chemistry improvements this has now dropped to 1-2% of aggregation, which is a giant step forward. The next stage is a consolidation amongst specialists.
The complexity of the supply chain and market demand for looking at projects more in their entirety, from production of mAb all the way through to fill/finish; the more parts of these that can be aligned, the easier it is for all parties. There is definitely a distinct benefit for the client, particularly if the different supply chain areas are across the same company – with shared project management, established point of contacts, and using the same quality and release systems.
Some of the industry’s most active producers of antibody-drug conjugates – Almac, Calalent, Lonza and Piramal – will be in attendance at CPhI Worldwide 2015.