Microbial vs Mammalian Systems: Choosing the Right CDMO Partner for Your Biopharmaceutical Development

When embarking on a project in the pharmaceutical industry, choosing the right Contract Development and Manufacturing Organization (CDMO) partner is a decision that can be paramount to the success of your project. As part of this decision, you will likely need to consider which system will be optimal for your project: microbial or mammalian?

Here at SEKISUI, we pride ourselves on being experts in microbial fermentation. We understand the unique requirements of microbial expression systems and will serve you with the most appropriate equipment for your project, no matter how big or small. Our approach is entirely flexible and customizable to your needs – our project managers will schedule review meetings to track progression and deliver updates as often as needed.

With over 40 years of manufacturing expertise in the UK, you can be assured your microbial projects will be expertly handled by our dedicated team.

Here’s a helpful guide on the differences between microbial and mammalian systems, and their benefits and drawbacks, to help you make the best decision for your needs.

Microbial Systems: A Rapid & Scalable Solution

Microbial expression systems, such as yeast, fungal and bacterial systems, are a staple in the biopharmaceutical industry.

While they may not be suitable for every project (for example, when proteins require additional post-translational modifications), they are an ideal choice for any project requiring high yield without the need for complex protein modifications. Bacterial systems, for example, can supply high-quality materials for a variety of applications, including proteins and peptides such as enzymes, antibody fragments and ligands for biotherapeutics, and more.

Let’s explore the benefits of microbial expression systems in more depth…

Advantages: Highly Adaptable & Scalable

• Cost-effectiveness: Microbial systems often come at a lower cost than mammalian systems
• High yield: Bacterial systems, such as coli, and yeast expression systems produce high yields, which helps ensure the desired substance is produced with less time and manual effort than mammalian systems
• Rapid growth: Typically, both yeast and bacterial microbial expression systems offer rapid expression and replication compared to mammalian systems, meaning production and process development times are lower, and your project can run quickly and smoothly
• Scalability: Due to their rapid growth and high cell density, bacterial systems such as e.coli are particularly advantageous for projects requiring large protein quantities
  
  

Challenges: Further Processing Possible

• Limited post-translational modifications: Following biosynthesis, some systems may need to undergo further post-translational modifications involving enzymes for functionality of some proteins. However, microbial systems often lack the required machinery for this, so they may not be suitable for all products, but are still highly versatile for protein, peptide, and enzyme production, to name a few examples
• Inclusion body formation and extracellular expression: Some bacterial expression systems may form inclusion bodies during production. The good news is that these can be removed through additional processing in the form of refolding and purification to recover the protein. However, these steps may lead to additional time and costs during the life cycle of your project. An experienced CDMO may have the capability to engineer a strain that expresses proteins extracellularly.

Mammalian Systems

Mammalian expression systems, such as Chinese hamster ovary (CHO) cells, are often chosen for producing monoclonal antibodies due to their capacity to produce more complex, modified proteins.

While these systems come with many benefits, just like microbial expression systems, they also have some drawbacks, particularly due to their high specificity, which we have outlined below.

Advantages of Mammalian Systems

• Human-like post-translational modifications: Mammalian cells can execute complex post-translational modifications, which can ensure that the produced proteins closely resemble those produced in the human body
• Folding and functionality: Proteins in mammalian expression systems are more likely to fold correctly and exhibit the desired biological activity
  
  

Challenges of Mammalian Systems

• Higher costs: Mammalian expression systems often require longer production timelines than microbial expression systems, as well as elevated media, reagents and culture costs
• Complex scale-up: Scaling up production using mammalian systems can be more challenging than when using microbial systems
• Additional materials: For antibodies and other large, complex proteins, two or more plasmids are often required for the upstream manufacturing process, and stable cell lines may need to be generated for efficient expression. This greatly adds to the raw materials required and overall cost of the project

Making an Informed Choice

Now that you know the advantages and challenges of both microbial and mammalian systems, check out the reasons below for why SEKISUI could be the right choice for microbial systems:

• Nature of the biopharmaceutical: If your end product doesn’t require complicated post-translational modifications, or you need a quick turnaround, microbial systems can offer speed and flexibility in ways that mammalian systems cannot, in addition to being budget-friendly. At SEKISUI, we’re experts in microbial fermentation, so you know you can count on us
• Flexibility and customization: Bigger companies don’t always equal better! Smaller CMDO can offer greater flexibility and personalization to meet your needs, and our team can scale projects and timelines to suit your requirements
• Expertise and track record: With decades of experience in microbial fermentation, you can be assured we have all the resources needed to undertake microbial-based projects

Microbial Systems Can Offer Speed and Flexibility in Ways that Mammalian Systems Cannot

Need more guidance on choosing a CDMO? Explore our previous blog post on ‘How to choose your perfect biologics CDMO partner' for an in-depth exploration of all the factors to consider when taking this important step.

Selecting the right CDMO partner requires finding balance between speed, scalability, and the ability to deliver a high-quality product, as well as careful evaluation of the advantages and challenges associated with microbial and mammalian CDMOs.

BioProduction by SEKISUI

Now you understand more about microbial and mammalian systems, why not explore what BioProduction by SEKISUI has to offer?

BioProduction by SEKISUI is a CDMO service with expertise in microbial fermentation and downstream purification. We understand the unique requirements of projects using microbial expression systems, and will serve you with the most appropriate equipment for your project, no matter how big or small. Our microbial project portfolio covers yeast, fungi, and a variety of bacteria, so you can be assured we’ve got you covered, no matter the microorganism you choose.

With more than 100 products manufactured across plasmids, enzymes, antibody fragments, and protein complexes, and over 40 years of manufacturing expertise in the UK, why not have the SEKISUI advantage? Download our services brochure here.