Bringing a monoclonal antibody from bench to commercial launch is a rare achievement. But staying there, with consistent quality and regulatory confidence, is where the real engineering begins.
Between the controlled chaos of early clinical supply and the unforgiving rigor of commercial production lies the often underappreciated core of CMC strategy: process characterization and risk mitigation. These activities are the backbone of sustainable biologics manufacturing.
And they separate the programs that fly through licensure from the ones that buckle under their own variability.
The Biological Realities of Scaling Up
Scaling a mAb process isn’t like scaling a recipe. The process changes in complex ways. Cell metabolism shifts. Nutrient gradients behave unpredictably. Oxygen transfer becomes a critical engineering constraint. Glycosylation patterns, the subtle chemical signatures that define a molecule’s function, half-life, and immunogenicity, are suddenly at risk.
This is where process characterization earns its reputation. The goal is to demonstrate that the process performs reliably at scale. Success must be shown statistically, mechanistically, and reproducibly, across equipment trains, geographies, and years of production. Characterization takes the unknowns from clinical-scale development and subjects them to the kind of scrutiny that holds up under BLA review, post-approval changes, and global expansion.
It means executing design of experiments (DoEs) that link process parameters to critical quality attributes (CQAs). This involves identifying the subtle interactions that can shift charge variants, increase aggregates, or degrade binding potency. Most importantly, it establishes your control strategy for both product launch and long-term lifecycle management.
Without it, you’re not in control of your product. You’re just lucky.
The Structural Nature of CMC Risk
Process characterization doesn’t begin with a blank slate. Decisions made during discovery and early-phase development often carry forward, creating constraints that can be difficult to unwind.
Maybe you locked in a high-yielding cell line with an unstable glycosylation profile. Or you chose a chromatography resin without thinking about reuse at scale. Or your potency assay hasn’t evolved past “good enough for Phase 1.” These early compromises become hard risks as you approach commercial readiness.
CMC risk mitigation involves recognizing potential points of failure and taking deliberate steps to build resilience. This includes mapping every dependency: raw material variability, supply chain redundancy, analytical method maturity, and operator training at your commercial site. Effective mitigation requires managing both quality and complexity to avoid critical breakdowns during regulatory milestones such as BLA submission.
This is particularly true for tech transfers. Shifting from development to manufacturing—especially across CDMOs or global sites—can introduce invisible risks: changes in water systems, differences in equipment control logic, or deviations in column packing methods. If you haven’t characterized your process deeply enough to absorb these variables, every transfer carries a significant comparability risk.
The Real Product Is the Process
In biologics, the phrase “the process is the product” gets repeated like a mantra. In the case of monoclonal antibodies, this idea reflects a critical truth: success depends on maintaining control of the process itself.
A well-characterized process and a proactive CMC risk strategy provide the foundation for long-term regulatory success. They help preserve the molecular identity of your therapy as it moves from early development into global production. They also support your ability to manage raw material disruptions, post-approval manufacturing changes, and market expansions while maintaining compliance.
Done right, these practices turn your mAb platform into a true engine for commercial growth. Done poorly, they leave you vulnerable to variability, inspection findings, and costly remediation.
The industry doesn’t need more emergency CAPAs or post-licensure rescue projects. It needs biologics programs built on deep technical understanding, operational discipline, and the humility to admit that biology doesn’t scale unless it’s intentionally designed to.
So the next time someone tells you their mAb is “almost ready for commercial,” ask them this: Have you truly characterized your process, or have you simply survived it?
QxP Vice President Christine Feaster is a 20+ year veteran in pharma quality assurance. Prior to joining QxP, Christine was a vice president of U.S. Pharmacopeia.
