Bringing a new therapy into the clinic requires clinical, nonclinical, regulatory, and CMC activities to advance in parallel. In early development, getting drug in hand often sits on the critical path to toxicology studies and clinical trials, creating an understandable incentive to engage a CDMO and begin CMC work as early as possible.
But starting early and committing early are not the same thing.
Clinical, nonclinical, and CMC strategies are closely interconnected. Decisions about indication, dose, formulation, route of administration, nonclinical studies, and clinical trial design can influence what is ultimately required from the CMC program. When these workstreams are planned separately against an idealized timeline, CMC decisions can get ahead of the evidence needed to support them.
The result can be rework that costs both time and money.
When moving quickly creates work that has to be repeated
One development program shows how quickly those early assumptions can change.
A biotech company developing a poorly soluble API worked with its CDMO to address the solubility challenge, moving quickly to produce an engineering batch using a solubility-enhancement approach.
The work, however, was based on a preliminary target product profile and was completed before pharmacokinetic (PK) and toxicology studies were finalized.
Those studies changed the picture. The nonclinical results indicated that much lower doses, without solubility enhancement, would allow the company to evaluate safety and tolerability, characterize the PK profile in Phase I, and better inform the strategy and product attributes for Phase II.
The CMC work therefore had to be repeated using a non-solubilized approach. Rather than accelerating the program, the early formulation decision added cost and delayed both the IND filing and the start of the clinical trial.
The lesson is not that the company engaged its CDMO too early. It is that a product decision was advanced before the evidence needed to support it was available.
Engage early, but know what needs to remain flexible
Early CDMO engagement can be valuable, particularly when it helps development teams understand technical requirements, dependencies, timelines, and potential risks. But engaging early does not mean every element of the CMC strategy needs to be defined at the outset.
Drug substance development, for example, can often move forward while some drug product decisions remain open. This is particularly important when a program is considering multiple indications, since the indication ultimately pursued can affect dosing regimens, routes of administration, and other product requirements.
In one recent program, a biotech company developing an injectable API took a phase-appropriate approach to product supply for its first-in-human study. Rather than advancing process and scale development before longer-term nonclinical studies were complete, the team moved forward with fit-for-purpose clinical supply. This supported an earlier IND submission and trial start while allowing emerging nonclinical and clinical data to inform later development decisions. Once safety and tolerability were established, the team could advance process and scale development for resupply with greater confidence.
The goal is not to wait until every uncertainty has been resolved. It is to distinguish between activities that can move forward with confidence and decisions that depend on clinical or nonclinical evidence still being generated. Maintaining flexibility around those decisions can help avoid committing time and resources to work that may need to change as the development strategy takes shape.
Optimize the development plan, not one workstream
That flexibility matters because the goal is not to optimize CMC in isolation, but to keep CMC aligned with the needs of the broader development program.
A CDMO can play an important role in that process, helping translate laboratory processes into scalable drug substance and drug product strategies, define CMC scope and budgets, and plan for clinical supply. But those plans need to evolve alongside the clinical and nonclinical strategy as new data refine or challenge early assumptions.
That requires ongoing communication across CMC, clinical, nonclinical, and regulatory teams so that decisions made in one area continue to reflect what is being learned in others.
The objective is not to advance every CMC activity as quickly as possible. It is to advance the right activities at the right time, while preserving flexibility where important development questions remain unresolved.
A faster CMC timeline does not accelerate development if new evidence ultimately requires the work to be done again.