Upstream and Downstream Bioprocess

What is upstream and downstream bioprocessing?

At TECNIC, we possess a deep understanding of both upstream and downstream processes, crucial for biotechnological product development. Therefore, this article aims to illustrate their differences and highlight their significance in biotechnology.

What is an upstream bioprocessing?

The upstream process in bioproduction is akin to the stage in a cell culture laboratory where optimal conditions are prepared for cell growth and multiplication.

In a laboratory, before any cell experiment can be conducted, it is crucial, therefore, to prepare a conducive environment for their growth. This involves preparing a nutritious culture medium, adjusting temperature conditions, and ensuring that the cells have the space and resources necessary to grow and multiply.

Similarly, in the upstream bioprocessing in bioproduction, the necessary raw materials, in this case, microorganisms, are prepared and cultivated. The goal is to create a conducive environment for their growth and multiplication. This bioprocess includes preparing the culture medium, inoculating with the desired microorganisms, and managing growth conditions like temperature, pH, and aeration, among others, to secure the desired product quality and yield.

Just as in the cell culture laboratory, where a controlled and favorable environment for cell growth is established, the upstream bioprocess optimizes conditions for microorganism growth and the production of desired biotechnological products. This bioprocess is crucial for ensuring the final product's desired quality and yield.

Infographic showing the upstream bioprocessing, including microorganism preparation, culture medium, aeration, temperature control and the production of recombinant proteins, monoclonal antibodies and vaccines

1. Media Preparation

2. Fermentation

3. Cell Culture

4. Monitoring and Control

What is a downstream bioprocessing?

The downstream process in bioproduction closely resembles a chemical laboratory's stage where the goal, following a series of chemical reactions, is to isolate and purify the desired compound from the mixture’s other compounds and impurities.

In chemical laboratories, after completing a reaction, techniques like filtration or distillation separate and purify the compound of interest. For example, achieving a specific chemical compound necessitates separating desired reaction products from undesired ones and impurities.

Similarly, bioproduction's downstream bioprocess entails separating, purifying, and concentrating the product microorganisms created during the upstream bioprocess. Consequently, using filtration techniques, this stage effectively isolates biotechnological products from impurities and other microbial culture components, yielding a purified, concentrated product ready for use or commercialization.

Just as achieving a pure compound is the aim in a chemical lab, the downstream bioprocess in bioproduction seeks to produce a biotechnological product of high quality, with suitable purity and concentration, thereby preparing it for its final application or further stages of processing and analysis.

Infographic showing the downstream bioprocess, where harvested culture is filtered to isolate and purify biotechnological products like recombinant proteins, monoclonal antibodies, and vaccines

1. Purification

2. Separation

3. Packaging

4. Quality Control

Conclusions

Understanding the differences between upstream and downstream processes is crucial for bioproduction excellence. At TECNIC, we are dedicated to enhancing bioprocess efficiency and product quality within the biotech industry. Consequently, we invite you to visit our website and explore our wide range of services and solutions ⇀ , all designed to meet modern bioproduction demands.

Upstream and Downstream Bioprocessing FAQ

Frequently Asked Questions (FAQ)

1. What is an upstream bioprocessing?

The upstream bioprocessing is the stage in biotechnology production where micro-organisms are prepared and cultured under optimal conditions for growth and multiplication. This includes preparation of the culture medium, inoculation with desired micro-organisms and management of growth conditions such as temperature, pH and aeration.

2. What is a downstream bioprocessing?

The downstream bioprocessing is the biotechnological production step where the desired product is separated, purified and concentrated from the micro-organisms and other impurities produced during the upstream bioprocess. Filtration, centrifugation and other techniques are used to obtain a pure and concentrated biotech product.

3. What is the difference between upstream and downstream processing?

In biotechnology, upstream processing focus on the cultivation and growth of microorganisms or cells, while downstream processes focus on the separation, purification and concentration of the final product.

4. How do the upstream and downstream processing complement each other?

The upstream and downstream processing complement each other by providing a continuous flow from the cultivation and growth of microorganisms to the production of a purified final product. Each stage is dependent on the other to ensure that the entire process is efficient and produces a high quality result.

5. What is the importance of upstream and downstream processing in biotechnology?

Upstream and downstream processing are crucial to ensure the desired quality and yield of the final product in biotechnology. These processes optimise conditions for microbial growth and production of biotech products, and then purify and prepare these products for final application or further processing and analytical steps

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Cassette

We understand the importance of flexibility and efficiency in laboratory processes. That's why our equipment is designed to be compatible with Cassette filters, an advanced solution for a variety of filtration applications. Although we do not manufacture the filters directly, our systems are optimized to take full advantage of the benefits that Cassette filters offer.

Cassette filters are known for their high filtration capacity and efficiency in separation, making them ideal for ultrafiltration, microfiltration, and nanofiltration applications. By integrating these filters into our equipment, we facilitate faster and more effective processes, ensuring high-quality results.

Our equipment, being compatible with Cassette filters, offers greater versatility and adaptability. This means you can choose the filter that best suits your specific needs, ensuring that each experiment or production process is carried out with maximum efficiency and precision.

Moreover, our equipment stands out for its 100% automation capabilities. Utilizing advanced proportional valves, we ensure precise control over differential pressure, transmembrane pressure, and flow rate. This automation not only enhances the efficiency and accuracy of the filtration process but also significantly reduces manual intervention, making our systems highly reliable and user-friendly.

Hollow Fiber

We recognize the crucial role of flexibility and efficiency in laboratory processes. That's why our equipment is meticulously designed to be compatible with Hollow Fiber filters, providing an advanced solution for a broad spectrum of filtration applications. While we don't directly manufacture these filters, our systems are finely tuned to harness the full potential of Hollow Fiber filters.

Hollow Fiber filters are renowned for their exceptional performance in terms of filtration efficiency and capacity. They are particularly effective for applications requiring gentle handling of samples, such as in cell culture and sensitive biomolecular processes. By integrating these filters with our equipment, we enable more efficient, faster, and higher-quality filtration processes.

What sets our equipment apart is its 100% automation capability. Through the use of sophisticated proportional valves, our systems achieve meticulous control over differential pressure, transmembrane pressure, and flow rate. This level of automation not only boosts the efficiency and precision of the filtration process but also significantly diminishes the need for manual oversight, rendering our systems exceptionally reliable and user-friendly.

Contact General

Cellular configuration

The cellular configuration of the eLab Advanced is equipped with a pitched-blade impeller designed to support efficient mixing for cell culture processes in both laboratory development and early scale-up. The blade geometry promotes mainly axial flow, helping to distribute gases, nutrients and pH control agents uniformly throughout the vessel while keeping shear stress at a moderate level. This makes it suitable for mammalian, insect and other shear-sensitive cell lines when operated with appropriate agitation and aeration settings. In combination with the vessel aspect ratio and baffle design, the pitched blade supports stable foaming behavior and reproducible oxygen transfer, which is essential when comparing batches or transferring processes between working volumes.

Operators can fine-tune agitation speed to balance oxygen demand and mixing time without excessively increasing mechanical stress on the culture. 

Cellular configuration

The cellular configuration of the eLab Advanced is equipped with a pitched-blade impeller designed to support efficient mixing for cell culture processes in both laboratory development and early scale-up. The blade geometry promotes mainly axial flow, helping to distribute gases, nutrients and pH control agents uniformly throughout the vessel while keeping shear stress at a moderate level. This makes it suitable for mammalian, insect and other shear-sensitive cell lines when operated with appropriate agitation and aeration settings. In combination with the vessel aspect ratio and baffle design, the pitched blade supports stable foaming behavior and reproducible oxygen transfer, which is essential when comparing batches or transferring processes between working volumes.

Operators can fine-tune agitation speed to balance oxygen demand and mixing time without excessively increasing mechanical stress on the culture. 

Cellular configuration

The cellular configuration of the eLab Advanced is equipped with a pitched-blade impeller designed to support efficient mixing for cell culture processes in both laboratory development and early scale-up. The blade geometry promotes mainly axial flow, helping to distribute gases, nutrients and pH control agents uniformly throughout the vessel while keeping shear stress at a moderate level. This makes it suitable for mammalian, insect and other shear-sensitive cell lines when operated with appropriate agitation and aeration settings. In combination with the vessel aspect ratio and baffle design, the pitched blade supports stable foaming behavior and reproducible oxygen transfer, which is essential when comparing batches or transferring processes between working volumes.

Operators can fine-tune agitation speed to balance oxygen demand and mixing time without excessively increasing mechanical stress on the culture. 

Microbial configuration

The microbial configuration of the eLab Advanced is equipped with a Rushton turbine specifically designed for high-oxygen-demand processes such as bacterial and yeast fermentations. The radial-flow impeller generates strong mixing and intense gas dispersion, promoting high oxygen transfer rates and fast homogenization of nutrients, antifoam and pH control agents throughout the vessel. This makes it particularly suitable for robust microbial strains operating at elevated agitation speeds and aeration rates.

Operators can adjust agitation and gas flow to reach the required kLa while maintaining consistent mixing times, even at high cell densities. This configuration is an excellent option for users who need a powerful, reliable platform to develop and optimize microbial processes before transferring them to pilot or production scales.

Cellular configuration

The cellular configuration of the eLab Advanced is equipped with a pitched-blade impeller designed to support efficient mixing for cell culture processes in both laboratory development and early scale-up. The blade geometry promotes mainly axial flow, helping to distribute gases, nutrients and pH control agents uniformly throughout the vessel while keeping shear stress at a moderate level. This makes it suitable for mammalian, insect and other shear-sensitive cell lines when operated with appropriate agitation and aeration settings. In combination with the vessel aspect ratio and baffle design, the pitched blade supports stable foaming behavior and reproducible oxygen transfer, which is essential when comparing batches or transferring processes between working volumes.

Operators can fine-tune agitation speed to balance oxygen demand and mixing time without excessively increasing mechanical stress on the culture. 

Technical specifications

Materials and finishes

Typical
  • Product-contact parts: AISI 316L (1.4404), typical Ra < 0.4 µm (16 µin)
  • Non-contact parts/skid: AISI 304/304L
  • Seals/elastomers: platinum-cured silicone, EPDM and/or PTFE (material set depends on selection)
  • Elastomers compliance (depending on selected materials): FDA 21 CFR 177.2600 and USP Class VI
  • Surface treatments: degreasing, pickling and passivation (ASTM A380 and ASTM A968)
  • Roughness control on product-contact surfaces

Design conditions

Pressure & temperature

Defined considering non-hazardous process fluids (PED group 2) and jacket steam/superheated water (PED group 5), depending on configuration and project scope.

Reference design envelope
ModeElementWorking pressure (bar[g])Working pressure (psi[g])T max (°C / °F)
ProcessVessel0 / +2.50 / +36.3+90 / 194
ProcessJacket0 / +3.80 / +55.1+90 / 194
SterilisationVessel0 / +2.50 / +36.3+130 / 266
SterilisationJacket0 / +3.80 / +55.1+150 / 302
Jacket working pressure may also be specified as 0 / +4 bar(g) (0 / +58.0 psi[g]) depending on design selection; final values are confirmed per project.

Pressure control and safeguards

Typical
  • Designed to maintain a vessel pressure set-point typically in the range 0 to 2.5 bar(g)
  • Aseptic operation commonly around 0.2 to 0.5 bar(g) to keep the vessel slightly pressurised
  • Overpressure/underpressure safeguards included per configuration and regulations
  • Pressure safety device (e.g., rupture disc and/or safety valve) included according to configuration

Agitation

Reference ranges
Working volumeMU (Cell culture), referenceMB (Microbial), reference
10 L0 to 300 rpm0 to 1000 rpm
20 L0 to 250 rpm0 to 1000 rpm
30 L0 to 200 rpm0 to 1000 rpm
50 L0 to 180 rpm0 to 1000 rpm

Integrated peristaltic pumps (additions)

Typical

The equipment typically includes 4 integrated variable-speed peristaltic pumps for sterile additions (acid/base/antifoam/feeds). Actual flow depends on selected tubing and calibration.

ParameterTypical valueNotes
Quantity4 units (integrated)In control tower; assignment defined by configuration
Speed0-300 rpmVariable control from eSCADA
Minimum flow0-10 mL/minExample with 0.8 mm ID tubing; depends on tubing and calibration
Maximum flowUp to ~366 mL/minExample with 4.8 mm ID tubing; actual flow depends on calibration
Operating modesOFF / AUTO / MANUAL / PROFILEAUTO typically associated to pH/DO/foam loops or recipe
FunctionsPURGE, calibration, totaliser, PWMPWM available for low flow setpoints below minimum operating level

Gas flow control (microbial reference capacity)

Reference

For microbial culture (MB), gas flow controllers (MFC) are typically sized based on VVM targets. Typical reference VVM range: 0.5-1.5 (to be confirmed by process).

Working volume (L)VVM minVVM maxAir (L/min)O2 (10%) (L/min)CO2 (20%) (L/min)N2 (10%) (L/min)
100.51.55-150.5-1.51-30.5-1.5
200.51.510-301-32-61-3
300.51.515-451.5-4.53-91.5-4.5
500.51.525-752.5-7.55-152.5-7.5
O2/CO2/N2 values are shown as reference capacities for typical gas blending strategies (10% O2, 20% CO2, 10% N2). Final gas list and ranges depend on process and configuration.

Instrumentation and sensors

Typical

Instrumentation is configurable. The following list describes typical sensors integrated in standard configurations, plus common optional PAT sensors.

Variable / functionTypical technology / interfaceStatus (STD/OPT)
Temperature (process/jacket)Pt100 class A RTDSTD
Pressure (vessel/lines)Pressure transmitter (4-20 mA / digital)STD
Level (working volume)Adjustable probeSTD
pHDigital pH sensor (ARC or equivalent)STD
DO (pO2)Digital optical DO sensor (ARC or equivalent)STD
FoamConductive/capacitive foam sensorSTD
Weight / mass balanceLoad cell (integrated in skid)STD
pCO2Digital pCO2 sensor (ARC or equivalent)OPT
Biomass (permittivity)In-line or in-vessel sensorOPT
VCD / TCDIn-situ cell density sensorsOPT (MU)
Off-gas (O2/CO2)Gas analyser for OUR/CEROPT
ORP / RedoxDigital ORPOPT
Glucose / LactatePAT sensorOPT

Automation, software and connectivity

Typical

The platform incorporates TECNIC eSCADA (typically eSCADA Advanced for ePILOT) to operate actuators and control loops, execute recipes and manage process data.

Main software functions
  • Main overview screen with process parameters and trends
  • Alarm management (real-time alarms and historical log) with acknowledgement and comment option
  • Manual/automatic modes for actuators and control loops
  • Recipe management with phases and transitions; parameter profiles (multi-step) for pumps and setpoints
  • Data logging with configurable period and export to CSV; PDF report generation
Common control loops
  • Temperature control (jacket heating/cooling)
  • Pressure control (headspace) with associated valve management
  • pH control via acid/base addition pumps and optional CO2 strategy
  • DO control with cascade strategies (agitation, air, O2, N2) depending on package and configuration
  • Foam control (foam sensor and automatic antifoam addition)
Data integrity and 21 CFR Part 11

Support for 21 CFR Part 11 / EU GMP Annex 11 is configuration- and project-dependent and requires customer procedures and validation (CSV).

Utilities

Reference

Utilities depend on final configuration (e.g., AutoSIP vs External SIP) and destination market (EU vs North America). The following values are typical reference points.

UtilityTypical service / configurationPressureFlow / powerNotes
ElectricalEU base: 400 VAC / 50 Hz (3~)N/AAutoSIP: 12 kW; External SIP: 5 kWNA option: 480 VAC / 60 Hz; cabinet/wiring per NEC/NFPA 70; UL/CSA as required
Process gasesAir / O2 / CO2 / N2Up to 2.5 bar(g) (36.3 psi)According to setpointTypical OD10 pneumatic connections; final list depends on package
Instrument airPneumatic valvesUp to 6 bar(g) (87.0 psi)N/ADry/filtered air recommended
Cooling waterJacket cooling water2 bar(g) (29.0 psi)25 L/min (6.6 gpm)6-10 °C (43-50 °F) typical
Cooling waterCondenser cooling water2 bar(g) (29.0 psi)1 L/min (0.26 gpm)6-10 °C (43-50 °F) typical
Steam (External SIP)Industrial steam2-3 bar(g) (29.0-43.5 psi)30 kg/h (66 lb/h)For SIP sequences
Steam (External SIP)Clean steam1.5 bar(g) (21.8 psi)8 kg/h (18 lb/h)Depending on plant strategy

Compliance and deliverables

Typical

Depending on destination and project scope, the regulatory basis may include European Directives (CE) and/or North American codes. The exact list is confirmed per project and stated in the Declaration(s) of Conformity when applicable.

ScopeEU (typical references)North America (typical references)
Pressure equipmentPED 2014/68/EUASME BPVC Section VIII (where applicable)
Hygienic designHygienic design good practicesASME BPE (reference for bioprocessing)
Machine safetyMachinery: 2006/42/EC (until 13/01/2027) / (EU) 2023/1230OSHA expectations; NFPA 79 (industrial machinery) - project dependent
Electrical / EMCLVD 2014/35/EU; EMC 2014/30/EUNEC/NFPA 70; UL/CSA components and marking as required
Materials contactEC 1935/2004 + EC 2023/2006 (GMP for materials) where applicableFDA 21 CFR (e.g., 177.2600 for elastomers) - materials compliance
Software / CSVEU GMP Annex 11 (if applicable)21 CFR Part 11 (if applicable)
Standard documentation package
  • User manual and basic operating instructions
  • P&ID / layout drawings as per project scope
  • Material certificates and finish/treatment certificates (scope dependent)
  • FAT report (if included in contract)
Optional qualification and commissioning services
  • SAT (Site Acceptance Test)
  • IQ / OQ documentation and/or execution (scope agreed with customer)
  • CSV support package for regulated environments (ALCOA+ considerations, backups, time synchronisation, etc.)

Ordering and configuration

Project-based

ePILOT BR is configured per project. To define the right MU/MB package, volumes and options (utilities, sensors, software and compliance), please contact TECNIC with your URS or request the configuration questionnaire.

The information provided above is for general reference only and may be modified, updated or discontinued at any time without prior notice. Values and specifications are indicative and may vary depending on project scope, configuration and applicable requirements. This content does not constitute a binding offer, warranty, or contractual commitment. Any final specifications, deliverables and acceptance criteria will be confirmed in the corresponding quotation, technical documentation and/or contract documents.

Cellular configuration

The cellular configuration of the eLab Advanced is equipped with a pitched-blade impeller designed to support efficient mixing for cell culture processes in both laboratory development and early scale-up. The blade geometry promotes mainly axial flow, helping to distribute gases, nutrients and pH control agents uniformly throughout the vessel while keeping shear stress at a moderate level. This makes it suitable for mammalian, insect and other shear-sensitive cell lines when operated with appropriate agitation and aeration settings. In combination with the vessel aspect ratio and baffle design, the pitched blade supports stable foaming behavior and reproducible oxygen transfer, which is essential when comparing batches or transferring processes between working volumes.

Operators can fine-tune agitation speed to balance oxygen demand and mixing time without excessively increasing mechanical stress on the culture. 

Technical specifications

    ePILOT BR configuration questionnaire









    Project details



















    FAT:

    Shipment:

    Installation:

    SAT:

    IQ/OQ:


    Process and automation requirements























    MU only (cell culture)


    MB only (microbial)


    Utilities and infrastructure



    North America specific















    Connections, consumables and compliance












    EU specific




    North America specific


    Software / CSV (GMP)


    Validation, testing and documentation










    GMP / CSV


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