Application
Downstream Bioprocessing
Downstream processing focuses on steps after bioproducts have been produced until fill & finish of final products.
This includes:
- Harvesting (separation of cells or debris)
- Purification (by means such as chromatography, filtration, or centrifugation)
- Polishing (ensuring purity to meet required quality standards)
- Formulation and Packaging (turn purified products into a usable form)
Process optimization is essential to avoid bottlenecks and ensure product quality. Sensors designed specifically for the biopharmaceutical industry provide reliable, real-time measurements of critical process parameters.
How Hamilton Supports Your Bioprocess Downstream Workflows
In chromatography, filtration, and other downstream process steps, sensor accuracy and reliability facilitate automated control. Throughout these steps, pH and conductivity are consistently monitored by our sensors, and liquid waste is removed during centrifugation. This can minimize the risk of low process yield, reduce waste, and enable the production of high-quality products that meet regulatory requirements.
Samples can be taken at any process step for further analytical quality assessments. Furthermore, our automated liquid handling solutions can streamline analytical techniques during analytical development and quality control. Please refer to the Analytical Development and QC page for details on those solutions.
In biopharmaceutical production, the transfer of protein solutions to buffer systems that are meticulously prepared and controlled is crucial to ensure successful downstream processing. The buffer systems are meticulously formulated to provide ideal conditions for the purification of the target molecule, including preserving its stability and activity. The utilization of high quality buffer solutions is pivotal to achieving excellent purification results. To maintain the quality standard of these solutions, stringent pH and conductivity monitoring and control, facilitated by our sensors, are imperative.
In the centrifuge, cells and debris are removed in order to prepare the solution for further purification in downstream processing. In this process step, our sensors enable total cell density and oxygen saturation control.
Various techniques are employed to isolate the target molecules and perform buffer exchange during the purification process. The effectiveness and efficiency of these purification steps are highly reliant on precise management and monitoring of critical process parameters such as pH and conductivity, as even slight fluctuations can adversely impact the final product quality. Therefore, maintaining stringent process control over these parameters is indispensable in achieving the high purity and potency necessary to produce safe and efficacious biopharmaceuticals.
Before undergoing fill & finish, or other downstream processing processes, virus inactivation is required to ensure the product's safety. As this happens at a specific pH level, this is a critical process parameter in this production step and requires tight in-line control. Given that virus inactivation transpires at a particular pH level, precise management and monitoring are imperative, requiring stringent in-line control.
Explore our Downstream Bioprocessing Solutions and Applications in Detail
Choose an outcome below to see personalized product recommendations.
pH Sensors
EasyFerm Bio pH Sensors
EasyFerm Bio pH sensors offer Foodlyte biocompatible electrolyte and EHEDG Certification for pH measurement in processes where non-toxicity is mandatory.
pH Sensors
EasyFerm Plus pH Sensors
Hamilton EasyFerm Plus pH sensors are the most popular product for pharmaceutical applications where autoclave and SIP are frequently performed. They provide accurate and stable pH measurement in demanding biopharma processes.
VisiFerm Dissolved Oxygen Sensors
VisiFerm RS485-ECS
VisiFerm RS485-ECS is an advanced optical dissolved oxygen sensor for biotechnology, biopharmaceutical, and food and beverage industries, offering full measurement functionality, self-diagnostics, and simplified maintenance.
Conducell 4UxF
Conducell 4UxF Arc
The Conducell 4USF Arc is a 4-pole conductivity sensor equipped with advanced Arc technology and a VP8 connector. This sensor is designed for hygienic applications, offering features like onboard calibration storage and direct connection to control systems, simplifying integration and maintenance.
Conducell 4UxF
Conducell 4UxF VP
The Conducell 4USF VP is a 4-pole conductivity sensor with Stainless steel electrodes and a VP6 connector, designed for biopharma applications and compatible with CIP/SIP/autoclave procedures. It provides precise conductivity measurements across a broad range and requires a Hamilton H110 transmitter.
Lab Syringes
Gastight Syringes
The solution for dispensing both gases and heterogeneous liquids. Hamilton Gastight syringes are equipped with a precision-machined PTFE plunger tip to create a leak-free seal.
Lab Syringes
Microliter Syringes
Hamilton Microliter syringes are ideal for dispensing homogeneous liquid samples not prone to glass bonding or precipitation. With a hand-fitted stainless steel plunger for frictionless movement and minimal wear, these syringes are designed to last.
Precise Conductivity Measurement for Downstream Applications
The new FlowCell COND sensor provides accurate conductivity and optional pH measurement across a wide conductivity range, making it well-suited for critical downstream applications such as chromatography, filtration, and formulation.
Featuring a four-electrode platinum design, it ensures excellent linearity and accuracy, while a fast temperature response and CIP/SIP compatibility support reliable operation in hygienic environments. With integrated Arc technology, the sensor simplifies communication and data handling without the need for external transmitters.
Good to Know About Downstream Bioprocessing
Useful Links:
This insightful article dives into the power of in-line monitoring and Process Analytical Technology (PAT) – often overlooked in DSP – to dramatically boost efficiency and ensure top-tier biopharmaceutical products. Learn how cutting-edge sensor technology, exemplified by real-world applications in buffer management, chromatography, and filtration, is overcoming traditional DSP limitations. Discover the lessons learned from the pandemic and the compelling advantages of real-time control for yield, quality, and preventing costly failures.
| Technological Innovations Enhancing Downstream Productivity and Their Critical Process Parameters for Real-Time Control | Read Article |
Solutions for top 3 Challenges of Downstream Bioprocessing
Downstream biopharmaceutical processing faces several challenges that impact productivity, cost, and regulatory compliance. These include maintaining process analytical technology (PAT) performance under harsh conditions, transitioning from traditional analog sensors, and ensuring efficient documentation for stringent regulatory requirements.
Maintaining sensor functionality during harsh Cleaning-in-Place (CIP) and Sterilization-in-Place (SIP) procedures
Challenge: CIP and SIP are demanding on sensors. Sensor durability and reliability under these conditions are crucial. Cleaning cycles are also part of single-use skids. Although less harsh than those applied for reusable equipment, they are present and challenge the functionality of single-use sensors, too. For example, sanitization with NaOH 1M during the same batch can occur.
Solution: This challenge can be overcome with Hamilton's proven single-use sensor robustness, such as the OneFerm pH sensor. Hamilton's sensors are designed specifically for the biopharmaceutical industry to provide reliable, real-time measurements of critical process parameters (CPPs) in various downstream steps like chromatography and filtration.
Overcoming the limitations of traditional analog sensors for efficient and reliable measurements
Challenge: Analog sensors present limitations compared to intelligent sensors, impacting maintenance, data integrity, and process optimization.
Solution: Hamilton's expertise lies in providing in-line sensors and accessories that facilitate real-time measurement of critical process parameters (CPPs) such as pH, conductivity, and dissolved oxygen, eliminating the need for manual off-line sampling and helping to maintain consistency and reliability throughout the process. These in-line sensors provide real-time data of process-critical events and parameters. Improved batch-to-batch reproducibility and better data continuity from R&D to production are achievable through the adoption of intelligent sensor technologies.
Ensuring efficient documentation and meeting stringent regulatory requirements
Challenge: Manual documentation in biopharmaceutical downstream processing is challenging for FDA and GMP compliance.
Solution: Hamilton's in-line control minimizes non-conformity risks during inspections and batch release, ensuring safety and reducing waste by preventing the scrapping of intermediates and final products. Their innovative sensors enable optimal control of critical process parameters like pH and conductivity across all downstream steps, from centrifugation to fill & finish.
What Is Upstream vs. Downstream Bioprocessing?
Upstream and downstream bioprocessing represent the two primary phases involved in the production of biopharmaceutical products.
Upstream Bioprocessing: This initial stage focuses on biologically producing the target molecule through steps like culture media preparation, cell line development, cell expansion, and precisely controlled cultivation of cells (mammalian or microbial) in bioreactors or fermenters, with the primary goal of maximizing cell growth and product expression.
Downstream Bioprocessing: Following upstream processing, it focuses on isolating, purifying, and concentrating the target biopharmaceutical molecule from the complex mixture produced by the cells. This crucial phase includes a sequence of unit operations like cell separation, chromatography, filtration, and ultrafiltration/diafiltration to achieve the necessary purity and concentration for a safe and efficacious drug substance that meets strict regulatory standards.
In summary, upstream bioprocessing is concerned with the biological production of the target molecule, while downstream bioprocessing is dedicated to its subsequent purification and refinement.
Other Bioprocess Downstream Resources
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Backed by world-class service and support.
For over 75 years, the Hamilton name has been recognized globally for its unwavering commitment to quality. That pledge extends to creating long-term customer partnerships. We're proud to offer in-depth training courses, on-site field support, custom product builds, and so much more.
Let's Talk
Connect with a Hamilton expert to discuss solutions for your workflow. We are here to enable your success.
Request Type: