What are critical parameters in the downstream process?

The critical parameters in the downstream process are pH, conductivity, and dissolved oxygen, and they are monitored and controlled throughout the process to ensure the quality and safety of the final product.

Biopharma Downstream Processing

Q: What is the downstream process?

The downstream process is the part of biopharmaceutical manufacturing that follows cell culture. It is responsible for purifying and concentrating the product of interest, such as a monoclonal antibody or vaccine. The downstream process typically involves a series of steps, such as cell separation, clarification, filtration, and polishing.

Biopharma downstream processing is dedicated to isolating and purifying biopharmaceuticals before fill & finish. Process optimization is vital to solve process bottlenecks. Designed specifically for the biopharmaceutical industry, Hamilton's sensors provide reliable, real-time measurements of the most critical process parameters (CPPs). Whether in chromatography, filtration, or other downstream process steps, the accuracy and reliability of our sensors help you get automated control. As a result, you can minimize the risk of low process yield, reduce waste, and produce high-quality products that meet regulatory requirements. Unlock the full potential of your drug production process with our in-line sensors today!

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Sensors and Accessories for Critical Process Parameters in Downstream Processing

At Hamilton, we recognize the significance of accurate process control at every stage of the downstream process to guarantee the end product's best possible quality and safety. Therefore, our 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. This eliminates the requirement for manual off-line sampling and helps maintain consistency and reliability throughout the process. In addition, our sensors are designed to work seamlessly with our flow cells, which are compatible with a broad range of systems, offering versatility and flexibility to biopharmaceutical manufacturers.

Take a look at the different downstream skids below and discover what measuring solutions Hamilton has to offer:

Solutions for the Centrifuge

In the centrifuge, cells and debris are removed in order to prepare the solution for further purification in downstream processing. In this process step, the total cell density and the oxygen saturation should be controlled tightly. Hamilton has a specific solution to measure both CPP's in-line and in real-time:

Dissolved Oxygen Sensors:

VisiFerm RS485


Dissolved Oxygen Sensors:
VisiFerm RS485

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 top-notch buffer solutions is pivotal to achieving excellent purification results. To maintain the high quality of these solutions, stringent pH and conductivity control are imperative. We offer a comprehensive range of sensing solutions for buffer preparation that can assist in achieving optimal process outcomes:

pH Sensors
Sensor Output	Single-Use	Reusable
Traditional (analog)	OneFerm Traditional	EasyFerm Bio Traditional (Foodlyte Electrolyte)
Digital (Memosens)	n/a	EasyFerm Bio Memosens (Foodlyte Electrolyte)
Intelligent (Arc)	OneFerm Arc	EasyFerm Bio Arc (Foodlyte Electrolyte)

Conductivity Sensors
Sensor Output	Single-Use	Reusable
Traditional (Analog)	n/a	Conducell 4UxF Traditional
Intelligent (Arc)	Conducell SU	Conducell 4UxF Arc

Liquid Solutions
pH Buffers	Conductivity Standards

Various techniques are employed to isolate the target molecules from other cellular components during the purification process. The effectiveness and efficiency of these purification steps are highly reliant on precise management and monitoring of critical process parameters (CPPs). Among these CPPs, pH, and conductivity are paramount, 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.

pH Sensors
Sensor Output	Single-Use	Reusable
Traditional (analog)	OneFerm Traditional	EasyFerm Bio Traditional (Foodlyte Electrolyte)
Digital (Memosens)	n/a	EasyFerm Bio Memosens (Foodlyte Electrolyte)
Intelligent (Arc)	OneFerm Arc	EasyFerm Bio Arc (Foodlyte Electrolyte)

Conductivity Sensors
Sensor Output	Single-Use	Reusable
Traditional (Analog)	n/a	Conducell 4UxF Traditional
Intelligent (Arc)	Conducell SU	Conducell 4UxF Arc

Flow Cells	Liquid Solutions
Stainless Flow Cell	pH Buffers	Conductivity Standards

In biopharmaceutical production, protein solutions are transferred to buffer systems appropriate for further downstream processing. Before undergoing fill & finish, or other downstream processing (DSP) 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 of this critical process parameter during this production step are imperative, and it requires stringent in-line control.

pH Sensors
Sensor Output	Single-Use	Reusable
Traditional (analog)	OneFerm Traditional	EasyFerm Bio Traditional (Foodlyte Electrolyte)
Digital (Memosens)	n/a	EasyFerm Bio Memosens (Foodlyte Electrolyte)
Intelligent (Arc)	OneFerm Arc	EasyFerm Bio Arc (Foodlyte Electrolyte)

Liquid Solutions
pH Buffers

Benefits of Using In-line Sensors

Real-Time Data

Real-time monitoring and of process critical events and parameters.

Ensure Safety

In-line control prevents the risk of non-conformity during the inspection/release phases.

Reproducibility

Better batch-to-batch reproducibility and increased consistency from R&D to production.

Lower Costs

In-line control minimizes the risk of scraping intermediates and final batches. It helps to reduce the waste of expensive buffers all along the downstream process.

Take Control of your Downstream Processes with Hamilton Sensors

Hamilton products are characterized by proven quality and outstanding performance, backed by decades of engineering and manufacturing expertise in innovative design. Our innovative sensor solutions for downstream processes support the optimal control of critical process parameters such as pH and conductivity in every step of downstream processes from the centrifuge, buffer preparation and purification to virus inactivation and fill & finish. Start a conversation with us today and see how we can best support your process.

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What is the Downstream Process?

Downstream processing (DSP) in biopharmaceutical manufacturing encompasses a suite of unit operations essential for the separation, purification, and concentration of therapeutic proteins and other active pharmaceutical ingredients (APIs). This intricate process transforms biologically synthesized entities, originating from upstream processes, into formulations ready for the final fill-and-finish stages, ultimately leading to patient administration. Specifically, in monoclonal antibody (mAb) production, DSP is critical for extricating these antibodies from impurities such as DNA, RNA fragments, and various other contaminants. The overarching objectives of DSP are twofold: to maintain the molecular integrity of the product, thereby preserving its therapeutic potency, and to ascertain the absence of contaminants, ensuring the product's safety for clinical trials and subsequent patient application.

DSP involves several key unit operations, including chromatography, ultrafiltration/diafiltration, viral inactivation, and, as necessitated, procedures like centrifugation and protein refolding. Each operation is governed by specific critical process parameters (CPPs), such as pH and conductivity. The meticulous monitoring of these parameters, facilitated by advanced analytical process sensors, is imperative for securing the desired product quality attributes. Additionally, DSP leverages both reusable and single-use technologies, each presenting unique benefits and relevant applications in the biopharmaceutical manufacturing landscape.

Ready to Unlock the Secrets of Efficient Biopharma Downstream Processes?

Download our comprehensive white paper and gain valuable insights into the critical process parameters and advance sensor technologies that can revolutionize your Biopharma Downstream Process (DSP). Discover strategies and techniques to optimize efficiency, improve product quality, and ensure the safety and efficacy of your biopharmaceutical products. Are you ready to take your downstream process to the next level? Get your copy and unlock the secrets for success.

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What our customers are saying

Hamilton’s 4UxF Arc Conductivity Sensors became an integral part of our processes.

Hamilton’s 4UxF Arc Conductivity Sensors has become an integral part of our processes, seamlessly performing in downstream applications. The sensors are ±3% to ±5% accurate, provide consistent and repeatable measurements over a wide range (1 µS/cm to 300 mS/cm) of conductivity values. The conductivity sensors have helped us to improve our product quality, reduce our production costs, and ensure the consistency of our products.

Marko Scharfe, Teva Pharma

Versatility and ease of integration of Hamilton sensors.

In our QbD-centered PAT ecosystem, which requires frequent adaptation to different bioprocess modes and R&D setups, we especially value the versatility and ease of integration of the Dencytee Arc system.

Lukas Neutsch, ZHAW - Zürcher Hochschule für Angewandte Wissenschaften

Process Improvement.

VLB Berlin e.V. (VBL) conduct analysis, education, research, and consulting at the highest level. In order to support and improve their processes, VLB rely on in-line sensors from Hamilton.

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Florian Schrickel, Research Associate at VLB Berlin

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Hamilton's sales, customer service, and technical support staff are available for questions and additional information about all products and services.

Solutions for Biopharma Downstream

Sensors and Accessories for Critical Process Parameters in Downstream Processing

Solutions for the Centrifuge

Solutions for Buffer Preparation

Solutions for Purification / Concentration (Protein A / Ion Chromatography, TFF-/Diafiltration)

Solutions for Virus Inactivation

Benefits of Using In-line Sensors

Real-Time Data

Ensure Safety

Reproducibility

Lower Costs

Take Control of your Downstream Processes with Hamilton Sensors

What is the Downstream Process?

Ready to Unlock the Secrets of Efficient Biopharma Downstream Processes?

Download Related Brochures & our Product Catalog

Biopharma Brochure

Arc Intelligent Sensors Brochure

Process Analytics Catalog

Conductivity Sensors Brochure