Building the Plane While Flying It: How Biopharma Leaders Can Drive Transformation Without Stopping the Business
There is a paradox at the heart of biopharma transformation that does not get discussed plainly enough: the organizations that most urgently need to change are the ones that can least afford to stop.
A company running a Phase 3 program cannot pause submissions to redesign the process. A commercial team preparing for launch cannot halt operations to overhaul the systems it depends on. A regulatory function navigating simultaneous multi-indication filings cannot go offline for six months to build something better. And yet — if they do not transform, they will fall behind competitors who did.
This is what I think of as building the plane while flying it. And it is one of the most underestimated leadership challenges in biopharma today.
The Stakes Are Not Abstract
The numbers make this undeniable. According to McKinsey & Company, 67% of drug launches miss their first-year sales targets. Of those that underperform in year one, 70% continue to underperform three years later — meaning the gap rarely self-corrects. Perhaps most sobering: McKinsey found that launch performance determines 81% of a drug's peak sales potential. These are not margin-of-error misses. They represent billions of dollars in value that never materializes — and in many cases, patients who wait longer than necessary for treatments that could change or save their lives.
Credit to Larry Mickelberg of Axonal.ai for surfacing these numbers in a recent presentation. His framing reinforced something I have observed across many biopharma engagements: the gap between organizations with efficient, scalable commercial and R&D operations and those without is not closing — it is widening.
Why Transformation Cannot Wait
The pace of change in biopharma has accelerated to the point where operational excellence is no longer a background function — it is a competitive weapon. Across oncology, rare disease, immunology, metabolic disease, and beyond, the race to market has never been more consequential.
At the same time, the complexity of what organizations must manage has increased dramatically: multi-indication global programs, AI-accelerated discovery pipelines requiring faster downstream execution, and regulatory agencies demanding higher-quality, more structured submissions. The old ways of working — siloed, sequential, document-heavy — simply cannot keep pace.
The Core Problem: There Is No Pause Button
In manufacturing, a company can take a production line offline, retool it, and restart it. The cost is measurable and the timeline is contained. In biopharma — particularly in regulatory submissions and clinical development — there is no equivalent.
Submissions are live. Timelines are committed. Patients are enrolled. Investors, regulators, and partners are watching. Every month of delay in a major program represents not just a cost, but lost market position that is extraordinarily difficult to recover.
This means transformation programs in biopharma must be designed differently from the start. They cannot be sequential — design the future state, then implement it. They must be concurrent: improving the process while the process is running, without disrupting the outcomes it is producing.
That is a fundamentally different kind of leadership challenge. It requires people who understand both the strategic change agenda and the operational reality on the ground. People who can protect the running business while designing the future one.
What Makes This Different From Other Transformations
Most transformation programs operate in environments where short-term disruption is manageable. A delayed quarterly report. A slower customer service cycle.
In biopharma, the stakes are asymmetric. The cost of getting transformation wrong — or of letting it slow the core work — is not measured in inconvenience. It is measured in regulatory delays, competitive market share, and patients who wait longer for treatments that could change their lives.
This changes the calculus entirely. The transformation leader must carry two things simultaneously: the strategic vision of where the organization needs to go, and an almost granular sensitivity to the operational reality of getting there without breaking what already works.
Success cannot be defined too narrowly. "Did the process change?" is the wrong question. The right questions are: Did the change hold under live-fire conditions? Did the team perform better — not just differently? Did the business outcomes improve, not just the metrics on a transformation dashboard?
What It Actually Takes
Based on my experience leading complex, high-stakes transformation programs across commercial and R&D functions in biopharma, a few principles separate successful in-flight transformation from well-intentioned change that stalls or causes harm.
Start with alignment, not process. In ambiguous, high-pressure environments, the first failure point is almost always stakeholder alignment, not process design. Getting alignment before anything else — through structured working sessions, clear problem definition, and explicit agreement on what success looks like — is the prerequisite for everything else.
Define success before you design the solution. This sounds obvious and is consistently skipped. When success is not defined, transformation drifts toward what is familiar rather than what is needed.
Protect the critical path. Whatever represents the highest-stakes ongoing work — the submission due in ninety days, the trial that cannot be paused — is untouchable. Transformation must route around it, not through it. This constraint, properly understood, is what makes good design possible.
Build for permanence, not just performance. Enduring transformation requires that the people inside the organization understand and own the new ways of working — not merely execute them while a consultant is in the room.
The Opportunity
The organizations that figure out how to transform under pressure — to build the plane while flying it without losing altitude — will have an enormous structural advantage in the years ahead. They will move faster, respond more effectively to regulatory complexity, and execute launches with a precision that organizations still running on legacy processes simply cannot match.
This is not a theoretical challenge. It is happening right now, at scale, across some of the most important programs in the industry.
The leaders who understand it — and who have the discipline, the methods, and the experience to navigate it — are exactly what biopharma needs most.