CPHI report: Get ready sooner

A new CPHI report highlights a significant shift in the pharma outsourcing market

A significant shift is under way in global outsourcing strategies, with innovators now mapping a product’s full life-cycle development as the early as pre-clinical stage, according to a new CPHI report that has been released ahead of CPHI Frankfurt on 1-3 November. A key finding of the report is that innovators across the industry are planning ‘pharma-ready’ synthetic routes much earlier in the development process. 'Phase-appropriate development’ is increasingly seen as outdated and particularly inappropriate for accelerated pathways.

As a result, the report predicts, innovators will need to choose either a single end-to-end provider or take a multi-provider model. CDMOs will thus need to rethink their approach both to development as well as to how they market their services to innovators and biotechs.

“The type of outsourcing strategy presented by CDMOs helps customers to identify their most suitable potential partners,” the authors say. “As a result most CDMOs will focus on marketing to specific types of customer rather than the entire market.  This shift reflects the different risk tolerance and collaborative capabilities of biotechs, small pharma or large pharma organisations.”

According to the report’s experts, innovators are now looking for an outsourcing approach which gets them rapidly through the Investigational New Drug to reach Phase IIB and beyond as fast as possible. The impact of this trend is being felt not only on development timelines but also on investors. ‘Pharma process readiness’ will have a fundamental impact on when and how investors can exit.

At Phase II, when a biotech with a promising molecule is most likely to be acquired by a pharma company ready to fund it through the later stages, a company with a clear plan and ready-to-scale manufacturing strategy will deliver a better validation than a promising target in need of ‘fine tuning’. Early-stage investors, it is predicted, will therefore increasingly use CMC consultants and ‘process specialist’ CROs and CDMOs to help ensure a smooth scale-up process.

The CPHI experts are warning innovators against adopting an exclusive ‘phase-appropriate’ approach, which runs the risk of building in severe delays to later stages of the development process. Bikash Chatterjee, CEO of Pharmatech Associates, comments: “There are lots of strong chemistry houses out there that can get you to IND, if that’s your goal. But an IND is where you lay the foundational CMC, quality and clinical arguments for your ultimate submission.

“Developing an IND strategy with the end submission in mind is how a drug sponsor shrinks their time to market and lowers programme risk. For drug sponsors relying upon their CDMO partner for programme insight, an early-stage specialist may not be the best way to realise overall programme acceleration.”

Drug sponsors will need to decide whether to use two or more CDMOs (i.e. one for drug substance and one for drug product), a larger-full service provider, or work with a specialist integrated development partner earlier before re-reviewing options in Phase I or II.   Brian Scanlan, operating partner – life sciences at Edgewater Capital and a former senior executive at what is now Alcami says: “Mid-sized outsource partners may be a better fit for highly nimble biotechs who are willing to accept the added complexity of working with multiple vendors as a trade-off for quality and cultural alignment”.

Meanwhile, Valdas Jurkauskas, senior vice president at Pardes Biosciences, advises that it is not only synthetic routes that need to be optimised, but also data packages. “The ‘redoes’ are the killers of program timelines, and we see that very often in the oncology space, he says.

“For example, Phase I studies are short with very few subjects, allowing the company to expand into Phase II, and the quality presentation requirements, both in the US and the EU, are much more demanding than for Phase I. So it may be that quality is in place, however, the quality presentation is not ready for Phase II pivotal studies.”

For accelerated pathways, the report advises that innovators will need both a ‘pharma-ready’ process in early development and to be fully prepared for a post approval change order. Stephanie Gaulding, managing director at Pharmatech Associates, adds: “Typically, I would say within the first year or so the majority of those that are going through accelerated pathways do see some level of change associated with the manufacturing process. In my experience, it’s hard to get the process fully optimised from the get-go. In this case, a pharma-ready formulation is still needed to get through approval, but innovators must also plan for post approval manufacturing improvements."