One of the most significant changes to be seen across discovery and development in recent years is a sector-wide tightening of timelines and increasing expectations around speed. This comes in light of the COVID-19 pandemic, which saw vaccines and therapeutics brought to market at ‘breakneck pace’, disrupting what the industry had previously thought possible.
Add to that capacity restraints: already seen pre-pandemic but exacerbated with additional demand.
All of this means having outsourcing partners lined up well in advance is becoming increasingly important.
Planning ahead
With innovators increasingly turning to compressed timelines, development methods are shifting in response. For example, phase-appropriate development – whereby an innovator seeks to advance to just the next key milestone as quickly as possible – is still seen in the marketing of the majority of CDMOs.
But a new CPhI report on 'The Future of Outsourcing' advises against this approach.
“Traditionally, outsourcing strategies were designed to help secure next stage funding, but many biotechs and small pharma companies are now entering development with more robust cash flows and the ability to plan further downstream," notes the report. "This opens the door for innovators to plan more fully a product’s roadmap from discovery to commercial launch.
"And decisions made in early development have downstream implications, and failing to plan for scale-up and commercialisation can lead to time-intensive redoes and revalidation work."
Another driver in shifting development methods is that investors are now more involved in their biotech’s development and outsourcing strategy, as this has fundamental implications for when and how they can exit. A biotech with a clearly mapped out and ready-to-scale manufacturing strategy will deliver a much better validation than another target.
“What we therefore anticipate is that early-stage investors may start to bring in CMC consultants to map out the outsourcing approach as early as pre-clinical.”
“Perhaps the most consequential learning of the report relates to the fact that innovators are making outsourcing decisions much earlier than before. Our experts were unanimous in their recommendation to develop a roadmap from the outset and stressed the importance of process development as early as the pre-clinical phase.
“Similarly, we have established that robust development planning makes biotechs significantly more attractive to investors, and we have seen a marked shift away from phase-appropriate development strategies."
One of the features of the drug R&D pipeline today is that new therapies are increasingly for orphan and rare diseases and, in fact, accelerated pathways of some kind are estimated to affect 50% of drugs in clinical trials.
"The implication for such a development timeline is that the drug sponsor needs its CDMO partner to deliver a close-to-commercial ready formulation, without slowing development. In the case of many accelerated trials, this means jumping from an early phase scale to Phase 3 and missing out on a significant amount of potential development time.”
Getting a place in the queue
Putting aside the option of in-house development, innovators must consider whether it is better to go for a two-CDMO strategy (ie one for drug substance and one for drug product), a larger full service provider, or to work with a specialist integrated development partner earlier before re-viewing their options in Phase 1 or 2. They must also make decisions on whether it's better to advance to Phase 1 faster and lose time later, or take a slow and steady approach.
“However, what is almost universally relevant to the situation biotechs encounter today is they need to make and evaluate these decisions much earlier than before, as there is no guarantee there will be capacity immediately available when they need it. With CDMOs in such record demand, particularly those with the best approval and development histories, many biotechs are reporting simply ‘getting a place in the queue’ is their single biggest challenge."
The small molecule market experienced unprecedented growth in 2020, exacerbating capacity issues. However, due to the sheer number of CDMOs that offer small molecule services, getting a place in the queue is generally easier than with other drug types.
In large molecule, the majority of development and manufacturing falls under the mammalian category, which accounted for more than 55% of overall large molecule revenue in 2021. Outsourcing is common in this market, with contract manufacturers or hybrid firms expected to control 44% of mammalian biomanufacturing capacity by 2025.
Advanced therapy medicinal products (ATMPs) such as cell and gene therapy, represent a much smaller share of CDMO activities. This is unlikely to be the case for long, however, as the FDA has authorized more than 20 cell and gene therapies since the first approval in 2017—and expects to approval 10 to 20 new therapies a year from 2025 onwards.
“Contract organizations are immensely popular in this segment, with some reports showing a higher percentage of outsourcing in cell and gene therapy than any other field. In addition to industry giants such as Lonza, Catalent, Thermo Fisher Scientific, Fujifilm Cellular Dynamics and WuXi Advanced Therapies, there are several specialty CDMOs carving out a niche in the cell and gene marketplace. One example is Helixmith, a biotech that expanded into CDMO services for early-stage CAR-T developers.”
The full report can be found here.