Short-changed

Counting the cost of pharma’s unsustainable change management burden

Post-approval life cycle change management is one of pharmaceutical operations’ most consequential yet most neglected disciplines.

As change volumes soar and experienced teams thin out, Megha Sinha of Kamet Consulting Group illustrates why systematic action is imperative now.

Every product in a marketed pharmaceutical portfolio exists in a state of continuous post-approval change.

Corporate structures alter, manufacturing sites move, suppliers change and formulations evolve, necessitating a range of regulatory updates and changes to product labelling internationally.

The post-approval life cycle change management challenge is substantial and growing. A large pharma company might easily have to assess several thousand changes each year, at least half of which will require regulatory submissions, with extensive implications for country-level filings worldwide.

A single site transfer could involve regulatory affairs, supply chain, quality, manufacturing, labelling, commercial, legal, pharmacovigilance and IT. Where scores of countries are affected, each with different submission categories and review timelines, a full global approval for a single change might take as long as three–five years.

That is assuming everything is still coordinated, as is commonly the case, via spreadsheets, email and weekly status calls. The systems most companies rely on to manage such changes have barely evolved in two decades.

That inefficient life cycle change management presents as friction rather than a crisis should not detract from the urgency to address it.

Although missed deadlines can be absorbed, budget overruns rationalised and supply gaps patched via expedited shipments and the heroics of stretched affiliate teams, collectively these situations erode operational performance and consume resources.

They can also create costly risk that may not be apparent until much further down the line.

There are a number of reasons why current practices are both unsustainable and untenable now.

Levels of M&A activity, divestitures and portfolio reshaping in recent years have given rise to years of downstream work, transferring marketing authorisations, switching sites, rebranding products and updating labelling across up to 100 countries, which is still tying up regulatory operations today.

In parallel, supply chain restructuring is accelerating as companies nearshore and reshore manufacturing in response to geopolitical risk and the US BIOSECURE Act.

Each facility move, CDMO switch or new production line triggers a fresh cascade of post-approval changes. A single API site transfer might generate three–five separate submission categories per country.

Each industry sub-sector brings its own challenges. In biologics, any manufacturing process change, whether a scale-up, a supplier switch or a modification to upstream cell culture, triggers comparability obligations that do not apply for small molecules.

Demonstrating equivalence in efficacy, safety and quality attributes takes months. If testing surfaces unexpected differences, a standard variation can escalate into a major filing requiring clinical bridging data, adding one to two years to the approval timeline across every affected market.

Cell and gene therapies face the most acute version of this challenge. For autologous CAR-T products, the manufacturing process is, in effect, the patient, a personalised chain of custody where any process change carries risks beyond those associated with conventional drugs.

Puzzlingly, many life cycle changes are initiated without any clear assessment of whether they make financial sense, because of a lack of end-to-end visibility of the wider ramifications.

Manufacturing might propose a cost-saving initiative, such as a supplier switch, process optimisation or site consolidation, with projected savings that look compelling on paper.

Yet once regulatory fees across scores of countries, artwork updates, dual production runs, stock write-offs and two–three years of execution time are factored in, the actual cost may cancel out or exceed the intended savings.

In effect, cost-saving projects that would not survive a fully informed business case are given the green light.

The problems only emerge later. In the case of one large-scale site transfer across more than 50 markets, a missed grace-period deadline in a single strict market created a supply gap lasting weeks, with revenue at risk in the millions, despite the submission having been approved on time.

The failure was one of coordination. The supply chain and regulatory teams were working from different timelines, so no-one spotted the gap until buffer stock could no longer be rebuilt.

In another case, involving a divestiture, the transfer of MAH status across more than 80 countries, without a unified view of country-level requirements, led to inconsistent filings, rejected submissions and a remediation programme that took more than two years and cost millions to resolve.

The issue in both cases was that no single person or system had the full operational picture.

There are well-established reasons why life cycle change management has not been systematically addressed up to now, including the fact that the process falls between functions, with the result that no single leader is accountable end to end.

The undertaking is difficult to standardise too, because every change is different and the complexity across product types, countries and regulatory pathways is considerable. It has not helped that the relevant expertise has resided with individuals rather than in formal systems.

Senior regulatory operations professionals ‘just know’, for example, that certain health authorities will not accept a new variation while a prior one remains under review, or that some markets require double-legalisation adding weeks to any timeline.

When those people retire, as is happening increasingly now, that knowledge is lost.

Companies need to guard against these risks now by looking to the role that the latest technology can play. AI tools are available that can encode practitioner expertise, compute cross-functional dependencies, flag risks before they materialise and provide an aggregate view across concurrent change programmes.

This makes it possible to instantly identify where the same product is affected by multiple simultaneous changes, where submissions can be bundled, where timelines conflict and, crucially, where total implementation cost is likely to exceed projected savings.

Without a smarter approach, the life cycle change management problem will not resolve itself. This is about acting systematically, building structured regulatory intelligence, establishing genuine cross-functional governance and connecting planning to execution in a single unified view.

The companies that do this will find that they are able to execute changes more swiftly, spend less and protect supply continuity more reliably.

Life cycle change management may not seem strategically exciting, but it underpins the commercial life of every marketed product in every portfolio, making it one of pharma’s most consequential, not to mention most directly addressable, operational challenges today.

Megha Sinha is founder and CEO at Kamet Consulting Group