Typical Applications of Centrifuges in the Biopharmaceutical Industry

Centrifuges are a cornerstone of downstream processing in biopharmaceutical manufacturing. By harnessing centrifugal force, these machines efficiently separate biological materials based on density, enabling the clarification of broths and the harvesting of cells.

From cell culture harvesting to lysate clarification and product recovery, centrifugation plays an important role in producing high-purity biopharmaceutical products.

Modern biopharma centrifuges often operate continuously to handle large volumes (thousands of liters) of fermentation or cell culture, while maintaining sterility and product quality.

Disc-stack centrifuges in a biotech production facility accelerate the separation of cells and solids from liquid culture media. Each application comes with its own biological context and technical considerations. Below, we delve into how centrifugation is used in each scenario, the challenges, and the types of centrifuge configurations that are suitable.

The Role of Centrifuges in Pharmaceutical Manufacturing

Pharmaceutical production involves several critical steps, including drug formulation, extraction, purification, and waste treatment. Throughout these processes, centrifugal force is used to separate materials based on differences in density.

Key Functions of Centrifuges in Pharmaceutical Manufacturing:

• Separation of Active Pharmaceutical Ingredients (API): Centrifuges enable the efficient separation of API, which is a fundamental step in producing high-quality pharmaceuticals.
• Purification of Biological Samples: This includes processes such as protein separation and cell harvesting, allowing fine particles and biological materials to be separated efficiently.
• Waste Management and Solvent Recovery: Centrifuges help separate waste materials and recover solvents, reducing production costs while minimizing environmental impact.

Types of Centrifuges in the Pharmaceutical Industry

The pharmaceutical industry utilizes various types of centrifuges; the following provides an overview of these different centrifuge types.

Basket Centrifuges

Basket centrifuges feature a simple structure and high efficiency, making them widely used in batch production processes. By rotating a basket, they utilize centrifugal force to separate the solid and liquid phases within a suspension. These centrifuges have broad applications in pharmaceutical manufacturing and are frequently employed in processes such as crystallization and filtration—procedures where the separation of solid particles from the liquid phase is critical. However, Huading Separator does not offer this specific type of centrifuge.

Decanter Centrifuges

Decanter centrifuges are commonly used to process suspensions with a high solid content. Additionally, when two liquids possess different specific gravities, decanter centrifuges are often utilized to separate them. These centrifuges are typically paired with skimming tubes to remove the separated, lower-density substances.

Disc Centrifuges and Tubular Centrifuges

Disc centrifuges and tubular centrifuges are utilized for the clarification of suspensions and for high-speed separation, respectively. These centrifuges are suitable for use in specific pharmaceutical applications.

Peeler Centrifuges

Peeler centrifuges are specialized for batch processing and are applied in the production of Active Pharmaceutical Ingredients (API) as well as for impurity removal. However, Huading Separator does not offer this specific type of centrifuge.

Separation of CHO Mammalian Cell Cultures

CHO (Chinese Hamster Ovary) cells are the workhorse of biopharmaceutical production, commonly used to produce monoclonal antibodies and other therapeutic proteins.

After a fed-batch or perfusion culture reaches harvest, the cells must be separated from the valuable extracellular product (the culture supernatant). Centrifugation is a primary method for cell harvesting in this context.

A high-speed disc-stack centrifuge is typically employed to continuously clarify the cell culture broth, removing the CHO cells and cell debris while preserving the proteins in the clarified liquid.

Technical considerations for CHO cell centrifugation include the relatively large cell size (~10–20 µm) and shear sensitivity of mammalian cells. The centrifuge must provide sufficient g-force to pellet or capture cells (often 5,000–10,000+ g), but without excessive shear that could lyse cells and release contaminants.

Temperature control is also important. Harvest is often done at cool temperatures (~4–10 °C) to maintain protein stability and prevent microbial growth.

Disc-stack centrifuges designed for biopharma use, such as Huading’s BTSX series, address these needs by operating under sterile, closed conditions with CIP/SIP (clean-in-place/steam-in-place) capability. They offer features like automated periodic solids ejection to handle cell biomass.

Clarification of E. coli Lysate

coli is a widely used microbial host for producing recombinant proteins (insulin, enzymes, plasmid DNA, etc.). After fermentation, if the product is intracellular or periplasmic, the bacteria are lysed (for example, via high-pressure homogenization) to release the target product.

This results in a cell lysate containing cell debris, soluble proteins, DNA, and other components. Centrifugal clarification is a crucial step to separate the solid cell debris from the liquid containing the product.

High-speed centrifuges can rapidly remove bulk debris, dramatically reducing the load on downstream filters. In large-scale processes, continuous disc-stack centrifuges with self-cleaning (solids ejecting) bowls are preferred to handle the high solids content and viscosity of E. coli lysates.

Indeed, Huading’s steam-sterilizable disc separators are designed for such biotech applications, with capacities from 100 up to 10,000 L/hour based on E. coli feedstocks. These centrifuges operate at high g-forces to sediment the fine bacterial debris effectively.

Key technical challenges in clarifying bacterial lysates include the small particle size of E. coli fragments (often <1 µm) and the potential for viscosity increase due to released DNA.

Disc centrifuges provide a large equivalent filtration area (thanks to their conical disc stacks) but may not remove the very finest particles below ~0.5–1 µm. Thus, a centrifuge typically achieves the bulk clarification, and a subsequent depth filtration step polishes the supernatant to remove fine particulates.

Temperature control is important here as well – lysate clarification is often done cold (4 °C) to preserve protein stability and reduce foaming.

For very high cell density cultures, nozzle-type disc centrifuges (which continuously discharge concentrated solids through peripheral nozzles) can be used to handle the heavy solids load without frequent stopping. A clarification centrifuge configured in this way ensures robust, scalable processing of E. coli lysates.

Isolation of Saccharomyces cerevisiae (Baker’s Yeast)

Saccharomyces cerevisiae, or baker’s yeast, is used not only in brewing and baking but also in biotechnology for producing vaccines (e.g. Hepatitis B vaccine) and recombinant proteins.

In bioprocesses involving yeast fermentation, centrifuges are commonly employed to separate yeast cells from the culture broth. Yeast cells are larger (5–10 µm) and more robust than mammalian cells, which generally makes them easier to sediment.

In fact, the brewing industry heavily relies on disc-stack centrifuges to rapidly remove yeast and clarify beer after fermentation. Similarly, in a biopharmaceutical context, a centrifuge can harvest yeast biomass either to collect the cells or to clarify the supernatant if the product is extracellular.

The isolation of yeast via centrifugation must account for high cell densities and often high viscosity in fermentation broths. Disc-stack centrifuges with self-cleaning bowls are effective, as they can continuously process large volumes and periodically eject the dense yeast solids.

Throughputs of tens of thousands of liters per hour are achievable with industrial yeast separators. Yeast are less shear-sensitive than animal cells, but gentle handling is still beneficial if the goal is to keep cells viable.

In some cases, decanter centrifuges are also used for yeast separation, especially if a very high solids content slurry is being dewatered.

Decanters excel at producing a concentrated yeast paste, whereas disc centrifuges excel at producing a clear liquid. For most upstream fermentation harvests, however, a disc centrifuge is preferred for its clarity and continuous operation.

Centrifugal Collection of Probiotics

Probiotics, such as Lactobacillus and Bifidobacterium species, are cultivated at industrial scale to produce dietary supplements and functional foods. Once a probiotic culture has grown to the desired density, the bacterial cells need to be collected (harvested) from the fermentation medium, typically to be concentrated and dried into a powder.

Centrifugation is a common method for separating and collecting probiotic bacterial cells from culture medium. Compared to filtration, centrifuges offer faster separation, higher efficiency, and a closed, hygienic process that is well-suited for large-scale operations.

Importantly, continuous centrifugation can be achieved, allowing ongoing harvesting of probiotics from a production fermentor. When collecting probiotics, several technical considerations arise.

Cell viability is crucial since these bacteria are intended to be alive when administered to consumers. Thus, the separation process should minimize cell damage: gentle acceleration, avoidance of excessive heat, and short residence times in the centrifuge all help maintain viability.

Many industrial probiotic processes utilize disk-stack centrifuges because they rapidly separate cells while operating in a sealed environment that protects against contamination.

The disc stack’s large settling area yields a good separation effect even for relatively small bacterial cells. Often, the centrifuge is run at chilled temperatures (e.g. <10 °C) to keep the probiotics stable.

After centrifugation, the concentrated probiotic cell paste can be further processed (washed, resuspended, and then freeze-dried or spray-dried). Huading’s disc separators are widely used in the probiotic industry, illustrating their reliability.

The feed is introduced through a central pipe and flows through many thin disc gaps; solids (probiotic cells) slide outwards and collect, while clarified broth exits via overflow.

This design dramatically increases the effective settling area and shortens settling distance, achieving excellent separation. By leveraging such centrifuge technology, manufacturers can efficiently produce high-potency probiotic products.

The proven performance and reliability of Huading’s separators in probiotic production plants have earned trust in the industry, highlighting centrifugation as the go-to solution for probiotic separation.

Clarification of Chicken Embryo Allantoic Fluid (Vaccine Production)

Egg-based vaccine production (for example, for influenza vaccines) involves inoculating fertilized chicken eggs with virus and allowing it to replicate in the allantoic fluid of the embryo. After incubation, the allantoic fluid – now rich in viral particles – is harvested from the eggs.

This raw harvest contains not only the target virus but also egg proteins, cell debris, and other impurities. Centrifugation is traditionally used to clarify allantoic fluid, removing unwanted solids and coarse debris as a first purification step.

Typically, a continuous disk-stack centrifuge (operated at moderate speeds to avoid fracturing virions) will separate cellular debris, eggshell fragments, and other particulates, yielding a clarified viral-containing supernatant.

This clarified allantoic fluid can then undergo further filtration and downstream processing (such as ultrafiltration and chromatography) to purify the vaccine antigen. One of the main challenges in clarifying allantoic fluid is handling the heterogeneous mixture of solids while maintaining a sterile process.

The feed may contain fine feather or eggshell particles and even semi-solid clots, making filtration alone difficult without clogging. A centrifuge excels here by spinning out these solids efficiently. Because vaccine manufacturing demands strict sterility and containment, the centrifuge system must be fully sealed and steam-sterilizable.

Centrifuges used for allantoic fluid typically have foam-free discharge systems (e.g. centripetal pumps) to gently transfer the clarified virus-containing fluid without foaming or shear.

By employing these specialized clarification centrifuges for vaccine harvests, manufacturers can achieve high throughput processing of thousands of eggs worth of allantoic fluid with consistent clarity and yield.

Plasma Separation in Blood Processing

Blood plasma is a starting material for many therapeutics, including immunoglobulins, albumin, clotting factor concentrates, and other plasma-derived medicines. In blood banks and plasma fractionation facilities, centrifuges are extensively used to separate plasma from cellular blood components.

Whole blood, when spun in a centrifuge, separates into layers: the dense red blood cells pack at the bottom, a thin “buffy coat” of white cells and platelets forms in the middle, and the top layer is the straw-colored plasma.

Industrial-scale plasma collection may use either batch centrifugation or continuous flow apheresis centrifuges to process large volumes of blood. As demand for plasma-derived therapies grows, so does the need for effective centrifugation equipment to maximize yield and purity.

In practice, this means centrifuges that can reliably separate plasma with minimal cell damage and minimal cross-contamination. Key considerations for plasma separation include gentle handling (to avoid hemolysis of red cells) and maintaining a cold chain (plasma is often kept at cold temperatures to preserve labile proteins).

Continuous centrifuge systems in plasmapheresis operate at controlled speeds, removing plasma and returning red cells to donors in real time. In manufacturing facilities, after plasma is pooled and thawed, centrifuges may again be used to fractionate precipitated proteins (for example, cryoprecipitation of Factor VIII).

The centrifuges used for plasma/blood are typically specialized disk centrifuges or chamber bowl centrifuges designed for bio-safety and sterility, often with single-use tubing or closed inserts to eliminate the risk of blood-borne contamination between batches.

Huading’s range of biopharma centrifuges also encompasses solutions for blood product processing – their CIP-capable disc separators can be used for plasma centrifugation and other blood-derived products. These machines ensure that plasma can be separated efficiently while meeting the stringent regulatory standards.

Collection of Peptide Crystals

Some biopharmaceutical processes involve a crystallization step to purify or formulate the product. Notable examples include the crystallization of insulin (a peptide hormone) and certain other peptide or protein drugs to achieve high purity and stability.

After crystals form in a solution, they must be separated from the mother liquor and collected for drying. Centrifuges are often used in such crystallization processes to isolate the solid crystals from liquids.

In pharmaceutical manufacturing, this is traditionally done with vertical basket centrifuges or peeler centrifuges in batch mode, which can spin out the liquid and then mechanically discharge the crystal cake. For instance, insulin crystals can be harvested using a batch centrifuge, washed in the centrifuge bowl, and then sent for drying.

In other cases, a decanter centrifuge may be employed for continuous crystal separation, especially if the process is a continuous crystallization. The choice depends on scale and crystal properties.

Technical factors in peptide crystal centrifugation include the particle size of crystals (which affects filtration vs centrifugation choice), the need for washing (to remove residual mother liquor or solvent from the crystals), and temperature control (some crystals might need low temperatures to avoid dissolution or degradation).

Centrifugation offers the advantage of being a closed method, reducing exposure of the product to the environment and can be faster than gravity filtration for large volumes.

It’s worth noting that crystallizing a biopharmaceutical can yield a highly concentrated product, so the centrifuge may handle a dense slurry of crystals.

How to Select the Right Centrifuge for Pharmaceutical Processes?

Pharmaceutical companies should consider a variety of factors when selecting a centrifuge. The centrifuges manufactured by Huading are designed to meet diverse requirements and offer the following customization options:

• Separation Requirements: Specifically engineered to handle particular suspensions and particle sizes.
• Production Scale: Scalable to accommodate both small-batch and high-throughput operations.
• Maintenance Efficiency: Features an easy-to-maintain design that minimizes downtime and extends equipment service life.

Conclusion

Centrifuge technology proves its value across the biopharmaceutical manufacturing spectrum. They enable continuous operations for efficiency, replacing or complementing filtration in many cases to handle biomass and solids more effectively.

Equally important, Huading biopharma Separators are engineered with the pharmaceutical environment in mind – offering features such as CIP/SIP for cleanliness, automated controls for consistency, and enclosed designs for bio-safety.

To explore state-of-the-art solutions tailored to your specific bioprocess needs, consider looking into Huading Separator’s range of biopharma centrifuges – from disc-stack clarifiers to decanter centrifuges.

With decades of experience in centrifugal separation technology, Huading offers equipment and expertise to help optimize cell separation, clarification, and product recovery in any biopharmaceutical application.