Fermentation Expertise FAQs

Microbial fermentation is a metabolic process that uses microorganisms, such as bacteria, yeast, or fungi to convert
raw materials (carbon sources like glucose) into high-value products. These “cellular factories” can produce proteins,
enzymes, small molecules, and primary or secondary metabolites. Unlike chemical synthesis, it relies on the biological
machinery of the cell to build complex molecules.

Beyond its ancient roots in food and beverage, industrial fermentation is now the backbone of several high-tech
sectors, including but not limited to:

• Pharmaceuticals: Production of recombinant proteins (e.g., insulin), vaccines, antibiotics, and plasmid DNA for gene therapy.
• Specialty Chemicals: Organic acids, amino acids, and high-purity solvents.
• Nutraceuticals: Vitamins (B12, Riboflavin), omega-3 fatty acids, and probiotics.
• Agriculture: Bio-pesticides and growth stimulants.

While both involve biology, they are distinct operational strategies:

• Fermentation (De Novo Synthesis): The microorganism is alive and growing. It consumes a substrate (sugar) and uses its entire metabolic pathway to build a product from scratch. It is recommended for complex molecules that require many steps to build.
• Biocatalysis (Biotransformation): This uses specific enzymes (either isolated or within a “resting” cell) as a catalyst for a specific chemical reaction. You start with a precursor molecule and “transform” it into the final product. A common use case is achieving extreme precision (e.g., specific chirality) in a chemical synthesis route.

Fermentation and biocatalysis are pillars of sustainable manufacturing. They offer:

• Mild Conditions: Reactions occur at ambient temperature and pressure in aqueous (water-based) environments, drastically reducing energy consumption compared to high-heat chemical reactors.
• Waste Reduction: Biocatalysts are highly selective, meaning fewer side reactions and less toxic byproduct waste.
• Step Economy: Biocatalysis can often combine three or four traditional chemical steps into a single “one-pot” enzymatic reaction.

Transitioning to biological processes introduces unique compliance requirements:

• Strain Characterization: Regulators (FDA/EMA) require data on the genetic stability of the production strain to ensure consistent product quality across batches.
• Impurity Profiling: Removing “host cell proteins” (HCPs) and DNA to parts-per-million levels is critical, particularly for injectable drugs.
• Process Validation: Biological systems are “living” and variable, requiring rigorous “Quality by Design” (QbD) to control parameters like dissolved oxygen and nutrient feed rates.
• Regulatory Refiling: Switching an existing chemical process to a bio-based one often requires a “Type II” variation or a new filing, which can delay market implementation.

The market is currently experiencing “hyper-growth” driven by the biologics boom. It is currently valued at
approximately $4.5 – $5.2 billion (2024/2025) and projected to reach over $12 billion by 2033 (12.5% CAGR). Moreover,
industrial enzymes (biocatalysis) are growing at ~6.4% CAGR, expected to hit nearly $1 billion by 2030. There is a clear
outsourcing trend. Over 44% of manufacturing is now handled by CDMOs as companies seek to avoid the high CAPEX
of building their own bioreactor suites.

• Precision Fermentation: Using CRISPR to program microbes for animal-free proteins (e.g., collagen, dairy).
• Continuous Manufacturing: Switching from “batch” to continuous flow to increase yield and reduce footprint.
• AI & Digital Twins: Using machine learning to predict large-scale (10,000L+) performance before leaving the lab.
• Cell-Free Synthesis: Eliminating the cell entirely to use enzymatic “machinery” in a soup, bypassing toxicity limits of living organisms.

Scaling from a 2L benchtop to a 5,000L+ industrial fermenter is capital-intensive and technically risky. Curia
provides the specialized scale-up expertise, GMP compliance, and downstream purification (DSP) infrastructure that
most companies cannot maintain in-house.

Curia runs fermentation at three sites. León and San Cristóbal in Spain cover strain development and cell banking, process development in 5 to 10 L and 20 to 30 L fermenters, and scale-up from 600 L to 15,000 L, with San Cristóbal providing downstream processing, including ATEX-rated equipment for organic solvent filtrations and centrifugations. Rozzano in Italy is the GMP manufacturing site, with fermenters from 200 L to 40,000 L and intermediate sizes available.

Downstream capabilities across the network include tangential flow filtration, filter press, centrifugation, chromatography and distillation, with glass reactors from 2 L to 80 L and stainless steel reactors from 15 L to 500 L for downstream work.

GMP fermentation runs at Curia’s Rozzano, Italy site, which has been inspected by the FDA, AIFA, PMDA and ANVISA. León and San Cristóbal support strain development, process development, pilot scale and downstream processing, so a program can be developed in Spain and manufactured under GMP in Italy within the same network.

Yes. Curia covers strain development and cell banks, including GMO strains and strain improvement programs, process development, scale-up and GMP manufacturing, together with downstream processing and analytical services. Fermentation and biocatalysis are integrated with chemical synthesis in the same network, so a fermentation-derived intermediate can move into chemical steps, purification by industrial chromatography and final API manufacture without a transfer to another supplier.

Curia works with a broad range of common engineered hosts as well as native producers, and has published strain improvement and scale-up work in peer-reviewed literature, including a Streptomyces roseosporus program for daptomycin and the scale-up of phytosterol bioconversion to androstenedione.