Optimizing Upstream Process Development in Biotechnology

The race towards innovation and the development of groundbreaking therapeutics and products is more competitive than ever. A pivotal component of this journey is upstream process development, a phase that can significantly influence the efficiency, cost-effectiveness, and eventual success of novel biotherapeutics.

This blog provides a broad overview of upstream process development in biomanufacturing and how Wheeler Bio’s innovative approach is well-positioned to create a faster, more streamlined, and cost-effective path to first-in-human trials.

The Importance of Upstream Process Development in Biotechnology

For monoclonal antibodies (mAbs) and other antibody-like therapeutics, an optimized upstream process plays a pivotal role, influencing every facet of the product lifecycle from quality and efficiency to commercial viability and regulatory approval. This overarching process can directly impact the purity, consistency, and therapeutic efficacy of mAbs, ensuring they meet stringent safety standards.

By optimizing the conditions under which cells are cultured – such as the culture medium, temperature, pH, and oxygen levels – innovators can significantly increase the yield of these vital therapeutic agents. Robust process development implementation can reduce production costs and enhance the accessibility of treatments, making a profound difference in patient care.

Forethought for Scalability

The scalability of upstream processes is essential for transitioning from laboratory-scale development to clinical and eventual large-scale commercial production. A well-designed process enables manufacturers to increase production volumes without compromising the quality of the mAbs, ensuring that the demand is met efficiently. This scalability is critical for a product’s commercial success and is closely scrutinized by regulatory bodies.

Agencies like the FDA demand adherence to strict production standards that guarantee the safety, purity, and efficacy of biopharmaceutical products. Therefore, rigorous upstream process development is indispensable for meeting these regulatory requirements, securing IND approval, and ensuring eventual commercial viability.

Ensuring a Competitive Financial Edge

Moreover, the increasingly competitive biopharma landscape encourages therapeutic developers to seek innovative production methods and product improvements through upstream process development. Such innovations can enhance product features, including increased stability or potency, offering a competitive advantage and attractive product differentiation.

Early identification and mitigation of production risks through meticulous process development can save significant resources and prevent delays, ensuring a smoother path to clinical trials and fostering investor confidence in a biotech’s future profitability. Investing early in optimizing these processes for Phase I trials lays a solid foundation for success that can support the product life cycle at later stages when it comes time for commercial supply and regulatory filings.

Upstream process development for mAb production is not just a technical necessity, but a strategic endeavor that influences the entire lifecycle of a therapeutic product, from concept to clinic through to commercialization. Its importance extends beyond mere production efficiency, encompassing quality assurance, regulatory compliance, market competitiveness, and sustainability, underpinning the success of mAb therapies in improving patient outcomes.

Accounting for the Entire Upstream Lifecycle

Upstream process development and optimization are multifaceted processes that encompass a variety of critical components, each playing a vital role in the seamless progression from concept to clinic: selection of cell line and expression technology, screening of basal and feed media, and understanding nutrient consumption and byproduct generation profiles. These factors will have a dramatic influence on productivity and product quality attributes (i.e. therapeutic efficacy).

Antibody Expression and Production

During the earlier stages of the antibody development cycle — between the late discovery phases and the beginning of preclinical development — developers must begin expressing and producing mAb candidates. Initially, this process involves identifying potential antibody candidates that can specifically and efficiently bind to target antigens. Once identified, these candidates are cloned into recombinant expression systems, typically mammalian cells. This early expression is vital for screening and optimizing the antibodies for desired traits like specificity, affinity, and therapeutic efficacy, enabling evaluation of their potential as therapeutic agents.

Efficient expression systems and optimized production processes using stable cell expression systems are crucial for achieving high titers of functionally specific antibodies, essential for therapeutic efficacy and safety. Implementing robust upstream processes minimizes variability and boosts scalability, thus enabling cost-effective production of mAbs in quantities sufficient for clinical needs later in development. Therefore, developing effective antibody expression and production strategies is foundational for advancing mAb therapies, ensuring they meet regulatory standards and are available to patients with consistent quality and affordability.

Process Development and Process Characterization

Process characterization is an indispensable portion building on the foundation of initial upstream process development and focusing on understanding and defining the operating parameters and conditions that affect the biomanufacturing process. By conducting a series of experiments, critical process parameters and quality attributes that directly impact the therapeutic product’s quality, purity, and yield can be elucidated.

This in-depth knowledge allows for the establishment of a robust, scalable manufacturing process with predictable outcomes, ensuring high product quality and consistency. Wheeler Bio leverages a quality-by-design (QbD) approach in this phase, employing advanced statistical models and simulation techniques to map the design space, optimize processes, and set meaningful control strategies, ultimately enhancing process reliability and regulatory compliance.

The Process Development Journey with Wheeler Bio

Wheeler Bio’s process development strategy is tailor-made for clients seeking to optimize and de-risk their antibody therapeutic program before their IND filing, improving the likelihood of success as they approach clinical trials. Our state-of-the-art Process Development Lab – located within the University of Oklahoma’s Research Park in the OKC Innovation District – offers a comprehensive suite of advanced biotech development services from cell line development through preclinical material supply and testing, including:

• Basal and Feed Media Screening and Optimization for enhancing process performance and productivity
• Process Intensification in Fed-batch or Perfusion modes for optimizing cell growth and productivity
• Chromatographic and Filtration Unit Operation Development and optimization for the efficient purification and separation of target molecules
• Process Characterization based on a QbD approach for identifying critical process parameters and their associated acceptable operating ranges to ensure robust and consistent performance
• Development of Liquid Formulations for optimizing stability and ensuring long-term product integrity

Advantages of Partnering with Wheeler Bio

Whether utilizing Wheeler Bio’s Portable CMC^® platform or contracting bespoke standalone services, choosing Wheeler Bio as a partner for a program’s process and analytical development offers unprecedented benefits for early-stage biotech firms:

• Accelerated Development Timelines: Wheeler’s ability to get a head start on process development during a candidate’s R&D, paired with Portable CMC’s pool-based workflows, reduces development timelines.
• Enhanced Yields and Product Quality: Wheeler Bio helps clients achieve robust yields and superior product quality critical for clinical success through meticulous optimization of process parameters and conditions.
• Regulatory Compliance Assurance: With deep regulatory expertise, Wheeler Bio ensures that all aspects of upstream process development comply with global regulatory standards, facilitating smoother and faster regulatory approvals.
• Flexible Workflows and Reduced Risk: Wheeler Bio’s open-source Portable CMC^® platform is purpose-built for flexibility, ensuring innovators are not locked in for the entire CMC lifecycle while retaining process ownership, de-risking scale-up, and tech transfer.
• Cost-Effective Processes: By optimizing process efficiency and scalability, Wheeler Bio reduces production costs, making the path to market more financially viable for early-stage firms.

Choosing Wheeler Bio as a partner for process and analytical development transcends conventional CDMOs, presenting a strategic advantage for early-stage biotechs. Our unique combination of accelerated development timelines, enhanced yields and product quality, regulatory expertise, flexible workflows with reduced risk, and cost-effective processes delivers a critical edge for clinical success. This comprehensive support system can transform ambitious biotherapeutic visions into tangible, life-saving therapies with efficiency and speed.

Conclusion

Optimizing upstream process development is a cornerstone of therapeutic development success. It underpins the efficient and cost-effective production of biological products. It is crucial in ensuring regulatory compliance and speeding up the journey from the laboratory to the clinic and beyond. Wheeler Bio’s commitment to providing tailored process development solutions offers early-stage biotechs a distinct advantage, enabling them to navigate the challenges of bioprocess optimization with greater ease and confidence.

Wheeler Bio’s process development capabilities are purpose-built to bridge the gap between discovery phases and early clinical trials. Building upon this, our process characterization capabilities demonstrate a profound understanding of the journey towards commercial approval. Boasting a robust strategy developed by seasoned experts, our team excels in designing and implementing process characterization.

Process characterization involves meticulously examining upstream and downstream process variables, understanding and defining operating parameters, and optimizing production to ensure the highest quality, safety, and consistency standards. Leveraging a Design of Experiments (DoE) methodology and high-throughput systems, we can ensure programs meet and exceed FDA standards, paving the way for clinical and commercial success.

In sum, Wheeler Bio is an optimal partner for biotechs looking to develop and optimize their upstream process. Through comprehensive support and expertise, we can accelerate development timelines and ensure the success of biotherapeutic programs. We are dedicated to empowering the next wave of biotech innovation, ensuring partners can confidently and efficiently navigate the path from concept to clinical trials.

Reach out to discover how Wheeler Bio can support your next biotech program. Contact us.