Excipient Variability Sets Continuous Manufacturing Limits

Priya Raman

At CPHI Milan 2026, Pauline van der Wijst-Janssen, PhD, DFE Pharma’s product development manager and global technical lead, won the CPHI Award for Future Leader. In an interview with PharmTech, she focused on a less visible manufacturing variable: whether excipients retain predictable behavior as a formulation moves from laboratory batches to commercial throughput.

What makes a laboratory excipient choice risky?

Formulation risk often begins when developers choose an excipient for familiarity, availability, or success in a laboratory batch. A single good batch establishes feasibility but says little about robustness when material properties, equipment, or operating conditions change, Wijst-Janssen said.

During scale-up, small differences in particle size or density can become significant. At commercial scale, she said, variability can reduce output, interrupt connected operations, and create out-of-specification batches. Those costs, she argued, can far exceed the purchase price of the excipient.

She called excipient variability “inevitable but not a sign that a process is out of control.” Her explanation separates material variability from process control, while still recognizing that two batches can comply with pharmacopeia requirements and perform differently.

She advised developers to identify the excipient characteristics that matter for a given application, establish acceptable ranges, and question suppliers about typical variability while the formulation still permits changes.

What changes when production becomes continuous?

“Continuous manufacturing does not automatically require different excipients,” she said. What changes is the route by which material enters the process and the way disturbances travel through connected operations.

Feeding depends on the powder, the feeder, and the operating rate. Success in a batch plant therefore does not guarantee consistent feeding in a continuous system. Wijst-Janssen called the transition-as-equipment-swap approach a common mistake because it leaves underlying material assumptions unchanged.

DFE Pharma has introduced continuous-manufacturing variants of its excipients, according to the company. Their specifications reflect actual variability, but the source supplies no batch counts, measured distributions, feeder rates, or comparative performance data.

That recommendation aligns with the International Council for Harmonisation’s Q13 focus on raw-material variability. Developers must therefore evaluate material behavior within the intended process, rather than transfer a successful batch formulation without rechecking its tolerance.

For portfolio managers, the immediate implication is narrower than the award headline: DFE Pharma’s variants create options for continuous formulations, but the source identifies no qualified products, specific excipients, or operating ranges. Selection should follow application-specific material data rather than a general claim that continuous processing needs new ingredients.

Wijst-Janssen has a background in physical chemistry and powder technology. As DFE Pharma’s product development manager and global technical lead, she leads product developers creating science-based pharmaceutical solutions, sets development priorities, and supports team growth focused on continuous improvement and project delivery.

Her work also connects fundamental science with customer needs. She develops excipient application knowledge, shares findings through peer-reviewed publications and technical materials, and works with customers and partners worldwide to guide innovation and address formulation challenges. The Future Leader award recognized her scientific contributions and leadership in pharmaceutical excipient innovation.

Who owns nitrite risk?

The marketing authorization holder owns the product-specific nitrite risk assessment, Wijst-Janssen said, but the assessment requires collaboration. Suppliers cannot assess finished products alone, yet they can reduce and control nitrite levels and provide reliable analytical and stability data.

She said that evidence can support market entry or reduce routine finished-product testing, depending on the region. The source does not identify the regions, regulatory decisions, nitrite limits, stability intervals, or documented testing savings, so these remain potential benefits rather than measured outcomes.

What should teams settle before scale-up?

For R&D and procurement teams, her advice translates into four checks before a formulation leaves development:

• Identify which excipient characteristics affect the intended application, rather than relying on familiarity with a material.
• Set acceptable ranges for those characteristics and compare them with the typical variability suppliers report.
• Review feeder behavior, operating rate, and material assumptions together, because continuous operations transfer disturbances between connected units.
• Request evidence that suppliers reduce and control nitrite levels, along with reliable analytical and stability data, before the holder sets its product-specific risk strategy.

These steps determine whether a scale-up program buys a robust process or merely reproduces a successful laboratory result. A low excipient price offers little budget protection if variability reduces throughput, stops operations, or triggers an out-of-specification batch, according to Wijst-Janssen.

The account provides no independent trial, customer case, sample-size analysis, or separate funding disclosure; DFE Pharma’s commercial role and its employee’s expertise frame the claims. Its output-loss, downtime, testing-relief, and cost statements should therefore guide questions for qualification trials, not substitute for them.

For development teams, the forward step is to qualify excipient ranges, supplier variability, and nitrite-control evidence before scale-up, so continuous output rests on measured robustness rather than laboratory feasibility.