End-To-End ADC Manufacturing Works Best With Active Sponsor Oversight
By Jeffrey S. Buguliskis, PhD, Deputy Chief Editor, Outsourced Pharma
ADC success is less about perfect execution and more about early signal detection, tight communication, and decisive governance
For a small biotech sprinting toward its first clinical trial, an integrated antibody–drug conjugate (ADC) manufacturing partner can feel like the most efficient path forward. One contract. One primary vendor. A program team that can coordinate everything from antibody through fill finish, so that the sponsor can stay focused on the science and the fundraising. But even in an end-to-end model, the work still needs orchestration: multiple specialized teams have to come in on cue, share the same score, and stay in tempo as the program moves from one step to the next. When it works, this kind of integration reduces vendor management friction and limits the number of higher-complexity transitions across the supply chain.
The risk is not the integrated model itself. The risk is assuming integration replaces sponsor governance. In more than one program, sponsor teams later admitted it was a mistake to assume an integrated program could run without an explicit sponsor-side governance model. Whether you select one integrated CDMO or several specialist providers, the sponsor still owns the integrated plan, the decision cadence, and the escalation paths that keep an ADC supply chain moving.
Why ADC Supply Chains Resist “Set It And Forget It”
ADCs are not just complicated biologics. They force multiple specialized manufacturing streams to run concurrently: monoclonal antibody (mAb), payload linker, conjugation, and fill-finish campaign. “ADCs are fundamentally harder than standard biologics because you are running multiple complex supply chains in parallel, and they only come together late in the game,” explained Ben Hutchins, PhD, Founder & Principal at First Principles CMC. That late-stage convergence is where small misalignments become big problems.
ADC programs run multiple complex workstreams in parallel. Coordination demands intensify at the late-stage merge, where small upstream mismatches can trigger downstream schedule pressure.
Hutchins pointed to familiar friction points: cytotoxin handling, the cultural gap between small molecule and biologics teams, and the fact that every component is “expensive and time critical.” Even strong partners miss things sometimes. “That is just reality at this level of complexity,” Hutchins said. The differentiator is not perfection. It’s how quickly the sponsor detets drifts, recognizes what is truly fixable, and then makes decisions before small issues cascade.
One-Stop Convenience, and the Limits of Integration
End-to-end CDMO offerings in ADCs are popular for a reason. Fewer vendors can mean fewer transitions, fewer contracts, and fewer opportunities to lose context. “Most fumbles happen at handoffs, so reducing the number of handoffs does reduce risk,” Hutchins noted. Integrated providers can also build more realistic internal schedules and troubleshoot faster when teams are co-located.
It also helps to be precise about what “one stop” means in practice. In ADCs, an integrated offering can mean one accountable program team coordinating work across multiple suites or sites, and sometimes across qualified partners. Sponsors should confirm what is truly in-house, what is executed elsewhere, and where the remaining handoffs sit, because those seams still determine where oversight needs to be tightest.
Most experienced ADC CDMOs execute reliably within their scope. The recurring challenge is orchestration across parallel workstreams and fixed-slot interfaces, which still requires sponsor leadership.
But “one stop” does not eliminate operational constraints. Truly end-to-end ADC manufacturing is usually delivered by large organizations with established operating models, platform approaches, and slot discipline. Sponsors may encounter long lead times and limited flexibility when a program needs to pivot. Hutchins cautioned that integration is not the same thing as flexibility. It works best when sponsors stay close enough to understand constraints early and make informed trade-offs.”
What about early integration and long-term costs, though? “Certainly in the early stages, [a one-stop model] can speed things along… you don’t have to build a whole supply chain, especially if you’re a smaller company without the expertise, so it helps you get to the clinic quicker,” explained Dante Romanini, PhD, Senior Director of Global MSAT at Gilead Sciences. “But if you rely on a third party to do a lot of the development work end to end, you’re giving up a lot of that technical knowledge that you’re not generating internally. It becomes more challenging to address problems throughout the product's lifespan, and you may not have all the information you need to support regulatory filings or answer questions from health authorities. The trade-off really is convenience, but you’re giving up a lot of the deep understanding of the product.”
That’s the trade-off to manage. A sponsor can gain speed early, then find that it needs more internal product knowledge to diagnose issues quickly, pressure-test assumptions, and assemble the narrative regulators expect.
This is one reason many sponsors invest in a lean internal CMC and technical operations core, even when manufacturing remains external. For larger organizations, this can include selectively insourcing analytical development or process knowledge generation to enable the sponsor to respond quickly when questions arise.
Handoffs Are Where Coordination Matters Most
When ADC programs slip, the root cause is often not a failure inside any single facility. It is the seam between them. “Timelines almost always break at the handoffs between providers, not inside any one operation,” Hutchins said. “Most mAb, payload linker, and conjugation teams execute their piece well. The problems start when material and information move from one site to the next, and the assumptions don’t line up.”
ADC programs often run well within individual workstreams. Schedule risk tends to emerge at the interfaces, when materials, data, and assumptions move from one step to the next.
Those assumption gaps can be mundane and still schedule-threatening: the antibody arrives in a format that is technically acceptable but operationally inconvenient for the conjugation site; a payload clears QC with handling limitations that were not fully integrated into downstream planning; a minor upstream delay collides with a fixed conjugation or fill finish slot that has near-zero slack. By the time the final step flags a miss, the problem has already propagated.
Romanini emphasized the ripple effect: a delay at “one node” can erase downstream time even when every partner is trying to help the project stay on track. The earlier the sponsor identifies a slip upstream, the more options exist to prevent a cascade.
The warning signs are rarely dramatic at first. Delivery dates soften into ranges. Milestones stay “on track,” but with quiet qualifiers. Sponsors who stay engaged catch those signals and force specificity. Passive sponsors often learn about trouble only when it is almost too late. “When sponsors stay hands off, the first real sign of trouble is often a last-minute email or a red circle on a dashboard telling you a slot is about to slip,” Hutchins warned.
The Sponsor’s Real Job: Be The ADC General Contractor
If the failure mode is misalignment across workstreams, the solution is straightforward, and sometimes resource-intensive: the sponsor must integrate the workstreams. Think of the sponsor as the general contractor, coordinating specialized subcontractors. Strong vendors are essential, and sponsor-led integration is what connects their work into a single executable plan.
“A good sponsor-run model is simple and disciplined,” Hutchins noted plainly. The sponsor, not any CDMO, should own the integrated master schedule and treat it as a living document, updated as reality changes. That discipline is not administrative overhead. It is how the sponsor keeps the integrated plan aligned with real-time constraints.
Practically, this means the sponsor assigns:
- a strong internal project manager to drive cadence and coordination
- a technical lead who understands cross-stream risks (antibody, payload linker, conjugation, fill finish)
- a quality lead who can balance rigor with momentum, and who knows where requirements are non-negotiable
Then the sponsor runs frequent cross-functional reviews, weekly or biweekly, focused on dependencies and readiness, not just dates. It is not enough to hear “batch complete.” The sponsor should ask: released yet, with data package complete, shipped in the right format, with downstream testing and handling assumptions confirmed.
“It definitely is on the sponsor to maintain a lot of that oversight and the timelines,” Romanini explained. Because CDMOs typically cannot freely share detailed schedules with one another, the sponsor becomes the “clearing house” that consolidates updates, reconciles assumptions, and keeps everyone aligned. Romanini also stressed transparency and early escalation: “At the same time, you need to be really transparent about what’s going on, what your risks are, what the potential things are that could set you back. And the earlier you can do that, the better,” he noted.
In this model, communication is a core control mechanism that prevents silent drift.
A Practical Playbook To Prevent Avoidable Delays
Logistics and release readiness are often the true critical path. A single delayed shipment can erase downstream slot flexibility.
For emerging biotechs, the goal is not to build a massive internal manufacturing organization. It’s to build the minimum effective sponsor control tower that keeps the network synchronized.
- Own the integrated timeline, and keep it current
Build a master schedule that spans antibody, payload linker, conjugation, and fill finish, including release testing, shipping, and data turnarounds. Reconcile it with each partner’s constraints, then continuously update it. Don’t wait for a milestone miss to revise assumptions. - Treat logistics as a primary risk, not an afterthought
Shipping, permits, cold chain, hazardous goods requirements, and customs can become the critical path. Romanini noted that “a lot of the risk is just from the logistics, moving the material around.” Plan shipping lanes early, qualify containers, and pre-clear import export needs where possible. - Align analytical and quality expectations early
Agree on methods, release criteria, and documentation pathways up front. Where feasible, leverage partner platform methods rather than introducing unnecessary novelty that creates validation burden and delays. Ensure every site understands what “ready for next step” truly means. - Put experienced eyes on site during critical runs
Remote governance is not always enough, especially early in a program. Embedding a sponsor representative is “a very common practice… And it has saved batches,” Romanini stated. A capable on-site presence can catch subtle deviations, accelerate decisions, and prevent small issues from escalating into batch impact or rework. - Pre-decide how you will respond when trade-offs appear
Build targeted buffers at known pressure points (for example, before fixed slots), and define decision rights before a crisis. Who can approve a deviation, authorize a rush shipment, or accept a cost increase to protect a trial date? Do not leave those decisions to improvisation. “Hope is not a strategy, and risks will eventually land,” Hutchins concluded.
Active Oversight Is Essential
ADC complexity is manageable, but only when the sponsor manages it. The controls that matter are the ones that keep the network aligned, informed, and ready to act, even when reality deviates from the plan. A one-stop shop can reduce certain risks, particularly at handoffs, but it does not replace sponsor vigilance. If you want the benefits of outsourcing while maintaining control, run a sponsor-side operating cadence that keeps you connected to each milestone, each interface, and each decision point, in partnership with your CDMO team.