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Upstream Bioprocessing
From Pre-clinical to Manufacturing


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Accelerate Your Process Development

Maximize Productivity

Meet Quality Requirements

Simplify Operations


Scale Up

Prevent Contaminants



Take the Right Path Upstream

Upstream ecosystem

You are developing a monoclonal antibody and a world of potential is ahead of you. However, your time to realize this potential is limited. You need to act quickly to get your biological drug to market, but have you considered the impact of your decisions as you are developing upstream? Decisions may be difficult to reverse or will require significant backtracking and resources. With our upstream ecosystem, you get your upstream development right the first time.


Lay the Groundwork for Downstream Success

Explore our upstream ecosystem and find the right path to effectively balance speed to market, product quality, process efficiency and scalability while ensuring patient safety.


Accelerate Your Process Development Maximize Productivity Scale Up
Meet Quality Requirements Simplify Operations Prevent Contaminants

The Upstream Ecosystem

Our upstream ecosystem is comprised of cell line and media platforms, cell line development, cell line and product characterization services, single-use bioreactors and mixers, process development services, and next generation processing programs. Our experts will save you precious time, optimize performance, improve feasibility and sustainability, while laying the groundwork for downstream success.





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Accelerate Your Process Development

Want to advance your molecule from the laboratory to the clinic as quickly as possible without sacrificing product quality, process efficiency, or patient safety?



Cell Line Development

Reduce your cell line development time by up to 8 weeks

Cell line platform for performance and speed to clinic

Creation of highly productive clonal cell lines is time-consuming, labor-intensive and costly. Our CHOZN® platform allows for more rapid clone selection when isolating production cell lines and can reduce development time by up to 8 weeks. Couple with the UCOE® technology and further reduce cell line development timelines.



Accelerate cell line development with our automated mini-pool approach

In the early stages of upstream development your goal is to get good quality material for pre-clinical trials, quickly. At the same time, you need to make sure all steps are done in a proper way and meet regulatory requirements.

Accelerate your cell line development with our innovative approach to automated mini-pools, where we confidently use early material from mini pools for process development.




Process Development

Expedite media development time with small volume, custom media and R&D services

Selecting the right cell culture media, feeds and supplements to support your manufacturing process can require significant time and expertise to achieve the optimum level of performance.

  • Expedite your media development timeline with our small volume imMEDIAte ADVANTAGE® services (liquid and dry powder).



Expedite qualification process of your raw materials

Material qualification and risk assessment

Ever-increasing regulatory requirements and process complexity have dramatically increased the volume of raw material information required for qualification and risk assessments. Drug manufacturers are heavily reliant on their raw material suppliers to provide this information, but typical timelines to collect it via questionnaires and separate statements run into several weeks. The Emprove® Program provides product quality information, supported by robust quality systems and processes, in structured dossiers which are available online, 24/7.


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Production

Save up to 3 weeks in your upstream process with High Cell Density, High Volume Process Intermediates

Conventional fed-batch processes begin with 1 ml of banked (frozen) cells, which are then expanded to 15,000 liters. This process takes weeks, during which time a part of the manufacturing site is blocked and not available for other projects. High cell density, high volume process intermediates allows expansion of cells and preparation of frozen seed train intermediates in bags of up to 100 ml, dramatically reducing the time required for subsequent expansion steps.



Leverage single-use bioreactor and mixer platforms to improve speed to market

Development of a MAB process from benchtop scale to 2KL production scale

Stainless steel installations are often cost prohibitive and time-consuming. In contrast, adoption of single-use or hybrid systems represents a faster, more flexible and less capital-intensive route.




Analytics and Biosafety

Accelerate cell line and product characterization testing

Explore what's next: Product characterization

Cell line characterization typically requires more than 3 months. Rapid molecular testing slashes turnaround time from 63 days to 7, significantly accelerating cell line characterization.

When it comes your biologic drug, assessing its critical quality attributes is essential. Obtaining actionable product characterization data is critical to make informed decisions that accelerate development and reduce risk throughout the product’s life cycle.


Maximize Productivity

At the earliest stages of clinical development, it may be tempting to get to the clinic as quickly as possible at the expense of process development efficiency. This strategy is likely to result in a poorly developed process that is not amenable to later stages of development when scale-up is necessary.



Cell Line Development

Select the right cell line, the first time

Demonstration of cell Line clonality during the process of cell Line development

Key considerations when choosing a cell line as the expression platform include:

  • Selecting a single-cell clone that can produce the biologic of interest.
  • Generating a clone from that cell line that can produce the biologic at high productivity/titer and high protein quality.
  • Ensuring successful scale-up with a robust cell line.



Process Development

Increase productivity with an optimized media and feed strategy (Fed-batch)

The best feeding strategy is crucial to achieve high cellular growth while maintaining high specific productivity. Optimization of feed volumes and timing of feed administration should be empirically determined on a process- and cell-line specific basis to maximize performance.



Screen, select, and optimize the right media

The quest for a viable industrial biotechnology process generally starts with the generation of a cell line expressing the protein of interest, and the selection and optimization of the right cell culture media & feed.

Media screening, media optimization, and nutrient testing can help you find and optimize the right media and feed for your cell line. Leverage high throughput (HTP) and Design of Experiment (DOE) approaches by partnering with experts from our R&D team and expedite simultaneous screenings.




Production

Achieve higher productivity with perfusion processing

Tech Talks - Voice of the Expert: Perfusion and intensified fed-batch

Use of perfusion mode of operation is becoming more widely adopted in bioprocessing. A perfused seed train can save time, reduces bioreactor size and reduces footprint in the seed train. Production perfusion processing delivers higher protein yields when compared with fed-batch and requires specifically-designed type of medium to facilitate high productivity at low perfusion rates. EX-CELL® Advanced HD Perfusion Medium meets such manufacturing requirements.



Overcome issues with insoluble or unstable amino acids

Simplification of fed-batch processes using modified amino acids

The essential amino acids tyrosine and cysteine are a challenge when used in upstream processing due to low solubility (tyrosine) and low stability (cysteine) at neutral pH. To simplify fed batch processes and enable high available concentrations of both amino acids, we offer chemically-modified tyrosine and cysteine, enabling a single feed strategy at neutral pH.



Ensure lot-to-lot consistency

Lack of consistency in raw materials can create significant variation in upstream processes, causing unexpected loss of cell density and viability, and ultimately, loss of yield. A better understanding of your raw materials increases your ability to control process variabilities.


Meet Quality Requirements

With a focus on the established critical quality attributes, product quality should be data-mined as early as possible prior to development of the first clinical batch, and then monitored closely after the first injection into patients during the clinical trial.



Cell Line Development

Produce high quality cell banks for the development and manufacture of your therapeutic

To produce a high-quality Master Cell Bank (MCB) from the original therapeutic-producing cell line, cells must be passaged regularly, while in culture. However, this increases the chance of genetic alteration, contamination, and loss of expression constructs. Thus, it is critical to passage the cells as few times as possible. To prevent alteration, they can be cryopreserved and stored in a stable condition at ultra-low temperatures. At later stages of development and manufacturing, a Working Cell Bank (WCB) is required. A WCB is produced from a single vial of the MCB that has been grown for several passages and cryopreserved.




Production

Know your raw materials

Tech Talks - Voice of the Experts: Material qualification and risk assessment

Current regulatory and industry guidelines do not define clear standards for chemicals used in upstream bioprocessing. In the absence of standards, what is the best approach for efficiently and effectively sourcing raw materials? Our raw material characterization and Emprove® programs can help bring clarity.



Ensure quality, robustness and regulatory acceptance of your single-use systems

For single-use products and systems to meet high quality standards, there must be a mature quality control system in place. The system needs to manage the entire life-cycle, from component selection, testing and qualification, to assembly manufacturing, in-process testing and final product release.




Biological Product

Measure the quality of a biological product

Explore what's next: Product characterization

The complexities of biological manufacturing along with product heterogeneity introduced by cellular expression systems present significant challenges when measuring the quality of a biologic drug. Newer, high-resolution analytical techniques for product characterization addresses this challenge.


Simplify Operations

Improve your operators’ experience and the productivity of your operations. Select technologies that are simple to use and flexible in their application.



Media Preparation

Make shipping and storage simple with dry powder cell culture media

Comparison of cell culture media solubility: Dry powder vs. compacted feed formulations

Dry powder cell culture media formulations provide many advantages for shipping and storage. To leverage these benefits, dry powder media formulations need to be highly soluble, homogeneous and convenient to handle. These properties can be achieved by the combination of optimized milling procedures and suitable formulation technologies.



Easily handle cell culture media

EZ BioPac™ and right sized weighing for safer, faster processing

EZ BioPac® dry powder bags with Right Sized Weighing connect directly to your hydration tank, minimizing product contamination risk, while safeguarding employees and facilities. Antistatic properties of the bags ensure 99.9% product transfer from bag to hydration tank, while eliminating the need for costly weigh room operations.



Achieve media dissolution fast and efficiently

Mobius® Power Mix 2000

Mixing of media, especially at high volume, presents substantial challenges in getting good dispersion and dissolution of particles.

The Mobius® Power MIX 2000 has proven wetting out and effective dispersion of powder in under 35 minutes.




Bioreactor

Easily manage single-use bioreactors at any scale

Our bioreactor platform has been designed to ensure ease-of-use and operational flexibility at small scale can be translated to full-scale production.


Scale Up

During the earliest stages of process development, you need to ensure the process is efficient and viable in terms of tech transfer at later stages of clinical development. The process needs to be reproducible and meet expected robustness and economic goals.



Cell Line Development

Produce high quality cell banks for the development and manufacture of your therapeutic

To produce a high-quality Master Cell Bank (MCB) from the original therapeutic-producing cell line, cells must be passaged regularly, while in culture. However, this increases the chance of genetic alteration, contamination, and loss of expression constructs. Thus, it is critical to passage the cells as few times as possible. To prevent alteration, they can be cryopreserved and stored in a stable condition at ultra-low temperatures. At later stages of development and manufacturing, a Working Cell Bank (WCB) is required. A WCB is produced from a single vial of the MCB that has been grown for several passages and cryopreserved.




Production

Mix your most challenging cell culture media efficiently, at any scale

Mobius® Power MIX single-use systems provide an effective mixing platform in a range of sizes including 100, 200, 500, 1000, 2000, 2500, 3000 L. Each size has been characterized, providing a comprehensive understanding of liquid-liquid mixing and mixing of both sinking powders (buffers) and floating powders (media).



Achieve consistent process performance from flasks through 50 L bioreactor

Variability in cell lines, plus the need to optimize media formulations, add to the number of studies required to obtain a stable, productive and scalable upstream process. We can accelerate and simplify your upstream process development with a robust, turnkey platform including DNA vectors, modified cell lines, chemically defined cell culture media and single-use bioreactors.



Demonstrate equivalent performance of your bioreactor platform across scales

To successfully implement a large-scale single-use bioreactor platform, equivalent performance, or scalability with smaller sized bioreactors across the platform, must be demonstrated. Characterization of key engineering parameters, including power input per volume, mixing time, oxygen transfer capabilities and temperature mapping across all scales are required. Our Mobius® bioreactor portfolio enables you to achieve equivalent performance.




Scale Up & Tech Transfer Services

Manage process scale-up and tech transfer

Converting from pilot to process scale and transferring technology requires precise and seamless organization, communication and documentation. A well-developed technology transfer package:

  • Provides a clear understanding of the process and technologies
  • Determines the appropriate path to achieve goals of the project
  • Aligns with the pharmaceutical quality management system as outlined in ICH Q10

Prevent Contaminants

Regulatory agencies and international organizations provide a framework to assure the safety of biologics through prevention of contamination from microorganisms. New scientific advances and technical innovations continue to enhance biosafety initiatives.



Cell Line Development

Ensure continued stability and safety of cell lines

Establishing master and working cell banks is critical to supporting clinical development through commercial supply. Safeguarding precious cells under cGMP conditions is paramount.

Cell line characterization is required by regulatory agencies to confirm the species origin and history of the cell line and test identity, stability, and purity. Characterization includes phenotypic or genotypic identity testing and a broad range of adventitious agents testing.




No Viruses Allowed

Tech Talks - Voice of the Experts: Virus contamination prevention in upstream processes

A major component of a viral safety strategy is preventing viruses from entering upstream cell culture processes. This is supposed by careful selection of cell lines and raw materials and implementation of new virus inactivation or barrier technologies designed to prevent viral contaminants from entering upstream processes.