The Truth About Scaling Biologics: It’s Not the Science That Slows You Down

Sarah Sink
Oct 16
3 min read

At first glance, protein-based biologics seem like the crown jewel of modern medicine: complex, precise, and capable of treating diseases that small molecules never could.

But behind every promising molecule is a reality few like to talk about. Scaling a protein-based biologic is one of the most challenging feats in drug development.

And it’s not always science that causes the biggest headaches; it’s what happens between the teams trying to get it done.

When “Almost Ready” Isn’t Ready Enough

Biotech teams often approach manufacturing thinking their process is mostly defined. After all, the early data looks solid, yields are predictable, and the molecule behaves.

Then scale-up begins, and suddenly it doesn’t.

The same protein that expressed beautifully at 2L acts differently at 200L.

Aggregation shows up. Purification yield drops. A formulation that looked stable for six months starts showing particles at nine.

That’s the reality of scaling something alive. Proteins are sensitive to conditions like shear, temperature, and pH, and those conditions don’t always scale linearly.

Even when the process science is sound, a missed discussion or misalignment between development, manufacturing, and quality can bring everything to a halt.

The Real Bottleneck: Communication, Not Capability

Here’s where business development professionals often see the breakdown first.A biotech sponsor might assume their CDMO can “just scale it up.” The CDMO, on the other hand, assumes the process knowledge transfer is complete.

Somewhere in between, details about mixing speeds, hold times, or analytical comparability get lost.

That’s when timelines slip, yields drop, and trust takes a hit.

Scaling isn’t only about stainless steel or single-use systems; it’s about how teams coordinate risk, document assumptions, and share real-time feedback.

The most successful programs I’ve seen are the ones where both sides communicate like partners, not vendors and clients.

Early Alignment Saves Months (and Millions)

Before scaling begins, ask the tough questions:

What assumptions are we carrying from small-scale that haven’t been proven at pilot or GMP scale?
Are our analytical methods robust enough to detect meaningful differences?
Have we discussed what “success” looks like at the first GMP batch?

What is their historical track record of successful GMP batches?

Too often, those conversations happen reactively after a deviation or failed lot.

But when biotech teams set expectations upfront, they can identify risks before they snowball.

Think of it like a relay race. If the handoff between development and manufacturing isn’t clean, the baton drops, and everyone loses time.

BD’s Role in the Middle of the Storm

From a business development perspective, this stage is where credibility is built or lost. Scaling issues aren’t unique to any one company; they’re part of biologics reality. But how you communicate through them defines your partnership.

For biotech teams, that means choosing CDMOs who don’t just “talk tech” but actually help you de-risk it. Ask about their scale-up track record, how they manage comparability, and whether they have integrated development and analytical support. Those are signs you’re not just buying capacity. You’re buying confidence.

For CDMOs, it means being upfront when something is uncertain.

Biotech partners respect honesty far more than blind optimism.

Why This Matters

Scaling protein-based biologics isn’t a linear path. It’s a series of adjustments, validations, and conversations that can make or break your launch timeline.

The sooner both sides acknowledge that complexity, the smoother the path becomes.

The lesson?

Great partnerships are built before the first batch ever hits the reactor.

Final Thoughts

If your biotech team is approaching scale-up or comparing CDMOs for biologic manufacturing, don’t just focus on cost or timelines. Focus on how a potential partner communicates, escalates issues, and collaborates under pressure.

My downloadable guide, “How to Compare CDMO Quotes: 10 Factors Beyond Cost,” walks you through the questions that reveal true capability and how to interpret what’s not written in the proposal. It’s one of the best ways to evaluate technical, cultural, and risk alignment before you sign.

Because in biologics, success isn’t just about having the right process. It’s about having the right partner.

For more insights and personalized support in navigating the biotech-CDMO landscape, visit www.yourpharmagirl.com and follow Your Pharma Girl on LinkedIn. Whether you need strategic guidance, tailored BD solutions, or expert advice on building lasting partnerships, I'm here to help you and your team succeed at every stage of development.