Delivering consistent, stable ADCs presents manufacturers with a unique set of challenges. Preparation and optimisation of processes, characterisation techniques, facility design and analytical transfers are just a few of the key considerations that need to be taken into account.
Jens Lohrmann, Technical Project Leader at Novartis, has faced many of these challenges in his career, particularly in ADC CMC development & outsourcing, and for him, one of the most important decisions is ‘buying vs. making’. As he explains, “for ADCs and highly active compounds you might not have ready access to facilities with the production capabilities.”
Building new facilities is obviously a time consuming and costly undertaking, and therefore, Lohrmann suggests an alternative solution:
“By leveraging the know-how of CMOs that are very active in this field, you can avoid the financial risk of building your own facilities. Equally, it can also help you build in business continuity if you want to back-up your own facilities.”
However, whilst such relationships can make some aspects of production easier, they also present their own difficulties. “The key challenge is ease of communication, especially with drug developer and CMO in different time zones, and working with novel technologies, which come with a lot of challenges themselves. You need to be very sure such a relationship is going to be successful, as well as how to actually render a collaboration successfully” Lohrmann adds.
For those who choose to go down the route of developing their own manufacturing facilities for ADC production, there are the obvious technical complications, but Lohrmann also emphasises the importance of focusing on the analytical capabilities, “spanning from process control to release testing”. In this respect, one piece of advice stands out for him: “Depending on the supply chain your product may be from one CMO or several CMOs, but one of the key aspects is that you want to have just one release site.”
As is typical for the bioprocessing industry as a whole, Lohrmann sees big changes in the ADC field in the next five to ten years that “will inevitably bring further novel challenges for manufacturing”. In particular, he highlights: “There is a huge trend to the next wave of conjugation technologies; moving away from randomized conjugation (to e.g. any accessible Lysine residue), to site-directed drug attachment allowing to achieve homogenous, tailored drug antibody ratio.”
Jens Lohrmann will be leading a session at the ADC Chemistry, Production and Manufacturing focus day on 14th April 2016 at BioProcess International Europe. He will be covering the ‘Challenges & Lessons Learned in ADC CMC Development & Outsourcing’:
- Buy vs. make: Considerations & critical success factors
- Scale up and site transfer of a conjugation process with impact on key product quality attributes: A case study
- Analytical transfers: considerations & lessons learned from a challenging assay transfers