Pharma’s Silent Operational Killer: Lifecycle Change Management

Every marketed pharmaceutical product exists in a state of continuous change. Manufacturing sites move, suppliers switch, formulations evolve, packaging text updates and companies restructure — not as occasional disruptions, but as the operating reality of each product on the market. And yet the systems most companies use to manage these changes have not meaningfully evolved in two decades.

According to publicly available benchmarking data, a large pharmaceutical company assesses roughly 6,000 post-approval changes every year. Around 3,300 of those require regulatory submissions — and because each must be filed separately across multiple markets, that figure expands to an estimated 90,000 country-level filings across more than 140 health authorities worldwide.^1,2 A single manufacturing site transfer can involve regulatory affairs, supply chain, quality, manufacturing, labeling, commercial, legal, pharmacovigilance and IT — 10 or more functions, each with its own timeline, deliverables and dependencies. This might be multiplied across 50 to 100 countries, each with different submission categories, review timelines and implementation grace periods. As things stand, it can take 3-5 years to achieve full global approval for a single change, because most of this complexity is coordinated through spreadsheets, email and weekly status calls. Regulations often change during that time too, requiring constant replanning.

The fact that this does not present as a “crisis” is part of the problem. Inefficient lifecycle change management is seen as a friction rather than a failure. Missed deadlines can be absorbed, budget overruns are explained away and supply gaps are often patched with expedited shipments and heroics — often by small in-country affiliate teams already juggling multiple other priorities. Individually, each situation is manageable. Collectively, they erode operational performance, consume resources and create risk that leadership often cannot see until it has already materialized.

Why Will the Pressure Get Significantly Worse?

The forces now converging on affected teams make an already strained baseline considerably harder to manage. Recent waves of M&A activity, divestitures and portfolio reshaping across the industry have been extraordinary in scale. When a major acquisition or spin-off closes, there are typically years of operational execution ahead — in transferring marketing authorizations, switching manufacturing sites, rebranding products and updating labeling across every market, often for dozens of products across what could be 80+ countries. Much of the M&A activity of the past five years is still being worked through in regulatory operations teams today.

In parallel, supply chain restructuring is accelerating, as companies nearshore and reshore manufacturing in response to geopolitical risk, the BIOSECURE Act (now signed into law) and the hard lessons of COVID-era supply disruptions. Each facility move, CDMO switch or new production line triggers a cascade of post-approval changes across every market where that product is registered. A single API site transfer might generate 3-5 separate submission categories per country.

Meanwhile, regulatory expectations across 156 countries continue to diverge rather than harmonize — and the experienced regulatory operations professionals who historically held all of this complexity in their heads are steadily retiring, taking irreplaceable institutional knowledge with them. All the while, the same-sized teams are being asked to manage 2-3 times the change volume with the same manual tools they have always used.

The Real Cost is Hiding in Plain Sight

There is a more fundamental business problem inherent in all of this, which is that many lifecycle changes are initiated without a clear understanding of whether they make financial sense in the first place. Manufacturing might propose a cost-saving project, for instance — a supplier switch, process optimization or site consolidation — with projected savings that look compelling on paper. Yet, once regulatory fees across 50 or more countries, artwork updates, dual production runs, stock write-offs, resource hours and 2-3 years of execution time are factored in, the actual cost of implementing that change could cancel out or even exceed the intended savings. Because change planning is fragmented across functions, there is no single point where the total cost of execution is calculated against the projected benefit, with the result being that a cost-savings project will not have all the data points to enable an informed business decision.

The consequences when execution derails are substantial and concrete. I have seen a large-scale manufacturing site transfer across 50+ markets where a single missed grace period deadline in one strict market (where no product could be sold from the old site once the deadline had passed) created a supply gap that lasted weeks, with revenue at risk in the millions. The root cause was not a regulatory failure; the submission had been approved on time. Rather, it was a coordination failure between the supply chain team planning the manufacturing cutover, and the regulatory team tracking grace-period trigger dates. Those respectively responsible were working from different timelines, with the result being that no one spotted the gap until it was too late to build buffer stock.

In another situation, a company executing a post-merger rebrand discovered midway through that its artwork pipeline was not aligned with the regulatory submission waves. As a result, artwork was produced for markets that had not yet received approval, while approved markets were left waiting for updated packaging. The impact included a four-month delay to market entry in several countries, unplanned dual production runs and around $200,000 in packaging write-offs.

A further case involved a divestiture requiring the transfer of marketing authorization holder status across more than 80 countries. Without a unified view of requirements, the company was subject to inconsistent filings, rejected submissions and a regulatory remediation program that took over two years and cost several million dollars to resolve.

None of these situations was exceptional. The common thread linking them was that no single person or system had the full operational picture.

Why Does this Age-Old Problem Persist, and Why is it Now Unsustainable?

There are a number of reasons why the lifecycle change management problem hasn’t yet been solved, the most glaring one being that no designated individual owns it. The discipline lives in the white space between functions, with no single leader accountable end to end. It is also genuinely hard to systematize. This is because every change is different, and the sheer complexity across product types, countries, and regulatory pathways is enormous. Added to that, the associated expertise has historically lived in people’s heads rather than in systems, e.g., the senior regulatory operations professionals who simply “know” that certain health authorities will not accept a new variation while a prior one is still under review, or that some markets require double-legalization processes that add weeks to any timeline. In most companies, this knowledge has never been formally captured. When experienced individuals retire or move on, those insights are lost forever.

This needn’t, and shouldn’t, be the case now. This is an era in which AI is more than capable of encoding practitioner expertise, computing cross-functional dependencies, flagging risks before they materialize and giving companies an aggregate view across concurrent change programs they have never had before. That offers an ability to instantly identify where the same product is impacted by multiple simultaneous changes, where submissions can be bundled, where timelines conflict and — crucially — where the total cost of implementation is likely to exceed the projected savings. Indeed, the probability of AI delivering real, near-term operational returns in lifecycle change management is significantly higher than in many of the areas currently attracting the most investment and attention, despite this being almost entirely unrecognized as an opportunity.

For CQOs and COOs, the lifecycle change management challenge is time-sensitive and something that will not resolve itself. Moreover, the window to address it before it becomes a board-level risk is narrowing as change volumes rise and experienced people leave. The companies that address this systematically — building structured regulatory intelligence, establishing genuine cross-functional governance and connecting planning to execution in a single, unified view — will find that they are able to execute faster, spend less and protect supply continuity more reliably than those organizations that continue to rely on the same fragmented manual approaches.

Lifecycle change management is unglamorous and rarely features in investor presentations, and yet it underpins the commercial life of every marketed product in every portfolio. This makes it one of the most strategically consequential and addressable operational challenges in pharmaceutical operations today.

Megha Sinha is the founder and CEO of Kamet Consulting Group.

References

1. Harris R. et al., An Evaluation of Postapproval CMC Change Timelines, ISPE's Pharmaceutical Engineering journal, September/October 2023. Available at: https://ispe.org/pharmaceutical-engineering/september-october-2023/evaluation-postapproval-cmc-change-timelines
2. Vinther A. et al., Approaches to Design an Efficient, Predictable Global Post-approval Change Management System, Therapeutic Innovation & Regulatory Science, 2024. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11043098/