Therapeutic Proteins & Peptides Upstream Cell Culture Process Development

Upstream cell culture processes are a core part of biopharmaceutical process development. High-yield, robust cell culture process development is the focus of upstream process development for therapeutic proteins and peptides. Relying on advanced cell culture technology, CD Formulation has built an excellent upstream process development platform that focuses on developing stable, high-yield, easy-to-scale high-quality products and scalable processes. Our independent upstream process development services include the identification of preferred cell banks and clones, culture medium screening, process development and characterization, optimization of processes and key quality attributes, etc.

Introduction to the Upstream Cell Culture Process

The production of protein/peptide drugs mainly involves three main production units: cell culture, separation and purification, and formulation filling. The cell culture process is complex and has many influencing factors, which play a key role in the expression and quality of proteins. A complete upstream cell culture process involves cell line development, media optimization, seed trains, and bioreactor operation. Among them, media optimization is one of the key steps in the upstream process, which directly affects the yield and quality of the final product. The ideal culture medium must contain the necessary nutrients, vitamins, and growth factors to support cell growth and protein production. Bioreactor operation is another key factor affecting the cell culture process. Bioreactor conditions, including parameters such as pH, dissolved oxygen, temperature, and stirring rate, must be strictly controlled to ensure optimal growth and protein expression.

Fig. 1 Cell culture process operating parameters affect process performance and product quality. (Li F, et al., 2010)

Explore Our Therapeutic Proteins & Peptides Cell Culture Process Development Services

With decades of deep cell culture experience for different types of protein biomacromolecules, including monoclonal antibodies, Fc fusion proteins, bispecific antibodies, growth factors, enzymes, etc. CD Formulation's process development team provides global customers with unparalleled cell culture process development, characterization, validation, and process scale-up and transfer services to achieve successful cGMP clinical and commercial manufacturing.

Our cell culture process development activities cover the entire development cycle, from supporting early discovery work, and small-scale protein production, to fully integrated comprehensive process development programs, to cGMP manufacturing, process characterization, and scale-down validation studies.

Our goal is to use our team's rich process development experience, high-standard experimental facilities, and reasonable experimental design to establish a robust, efficient, and low-cost cell culture process that meets every stage of your therapeutic protein and peptide development.

Our cell culture process development services include:

• Applying quality by design (QbD) principles throughout the development process.
• Clone screening.
• Basic/customized media screening.
• Optimization and screening of bioreactor fed-batch culture systems.
• Evaluation, optimization, and establishment of control strategies for key cell culture process parameters.
• Process optimization based on the improvement of product key quality attributes (glycoforms, charge heterogeneity, protein aggregates and fragments, etc.).
• Cell culture scale-up process development and optimization.
• Process parameter research for quality control.
• Perfusion process development.
• Process transfer and scale-up.
• The process scale can be expanded from laboratory scale to 10,000L.
• Process characterization, process optimization, and process validation for late-stage clinical projects.

Our Cell Culture Process Development Process

Fig. 2 Cell culture process development flow. (CD Formulation)

Material Preparation and Cell Pool Evaluation

• Reactor culture preparation of research materials.
• Evaluation of Top Cell Pool at shake flask level.

Monoclonal Evaluation and Culture Medium Screening

• Basic and feed screening.
• Quality attribute optimization.

Laboratory (3L) Scale Reaction Process Optimization

• Feed strategy optimization.
• Process strategy optimization.

Pilot (15L) Scale Process Development

• Process scale-up study.
• Process confirmation.
• Cell culture process development report.

Process Scale-up and Transfer

• From laboratory scale to 10,000L.
• Process characterization, process optimization, and process validation for late-stage clinical projects.
• Cell culture process transfer.

Our Expertise in Cell Culture

Cell Culture Capabilities

• Our cell culture process development team has worked on protein production processes at all scales, from bench scale, pilot scale, and clinical scale to commercial scale up to 20000L.
• We have characterized mixing conditions in bioreactors from 15 to 20000L scale. A deep understanding of the impact of agitation, aeration, and working volume at each scale enables successful technology transfer across a wide range of processes.

Fig. 3 Our cell culture capabilities. (CD Formulation)

Product Quality Optimization

Product quality optimization is an important part of any bioprocess development process. We incorporate cutting-edge analytical technologies into our protein/peptide process development pipeline, using high-throughput micro bioreactors and the related analysis to optimize processes and characterize upstream processes for intensification, as well as targeted optimization of product quality attributes.

• Multimerization control.
• Charge isoform control.
• Glycosylation optimization.
• Bioactivity optimization.
• Degradation product analysis.
• Identification of incorrect modifications.

Why Choose Us for Therapeutic Proteins & Peptides Upstream Cell Culture Process Development?

• We have experience in culturing a variety of therapeutic proteins, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, fusion proteins, and recombinant proteins.
• Our advanced cell culture development laboratory is equipped with a series of first-class cell culture systems and testing equipment, including disposable bioreactors from 3L, 15L, 25L, 200L to 500L, wave bioreactors, cell culture analysis instruments, and culture medium preparation systems.
• We use DoE experimental design for targeted optimization to improve charge isomers, glycosylation modification, protein purity, etc.
• We provide a variety of cell culture mode options, including fed-batch culture, continuous perfusion, high-density inoculation culture, concentrated batch feeding culture, etc.
• We define the design space by establishing mathematical models of process parameters and key quality attributes to ensure the consistency and robustness of the cell culture process.
• We provide flexible experimental options to meet the needs of different customers.

Publication

CD Formulation cell culture process development team has established a first-class cell culture platform process that can quickly lock and scale up the process at 3L, 5L, and 25L reactor scales, while the upstream process development platform can be robustly scaled up to 200,00L. Please don't hesitate to contact us if you are interested in our services. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.