Expert perspective: Navigating the complex biologics manufacturing process

What does the biologics journey from preclinical development to clinical manufacturing look like?

The process begins with discovery, where scientists identify a therapeutic target and design a biologic molecule to interact with it. Preclinical testing in cell cultures and animal models evaluates safety and efficacy, leading to the identification of a promising candidate. At this point, the focus shifts to process development, optimizing production for scalability and consistency by selecting the right cell line and refining upstream (cell culture) and downstream (purification) processes.

As the biologic progresses to clinical trials, the manufacturing process must adhere to Good Manufacturing Practices (GMP) standards. This involves producing clinical-grade material with rigorous quality control measures to ensure compliance. Successful clinical trials then pave the way for scaling up to commercial production, all while maintaining the highest standards of quality and regulatory compliance.

What are some of the key challenges in the transition from preclinical development to clinical manufacturing?

Scaling production without compromising quality is one of the most significant challenges. Early decisions, such as selecting a cell line that balances productivity, stability, and scalability, are critical. Investing in process optimization during the early stages—refining culture conditions, media formulations, and purification techniques—can significantly reduce costs and delays later in development.

Another challenge is aligning with regulatory requirements from the outset. Detailed documentation, robust quality control, and proactive risk management are essential to avoid delays. Addressing risks such as contamination or supply chain disruptions is key to ensuring smooth transitions between development phases.

How are innovations and emerging trends shaping biologics manufacturing?

Single-use technologies, such as disposable bioreactors, have revolutionized biologics manufacturing by reducing cross-contamination risks, lowering cleaning costs, and enhancing production flexibility. While initially used for small-scale clinical manufacturing, these technologies now support commercial-scale production volumes of up to 5,000 liters.

Continuous manufacturing is another emerging trend with the potential to improve efficiency, product quality, and scalability. Although still in its early stages for biologics, it represents a significant shift in manufacturing approaches. These innovations, combined with a focus on process consistency and efficiency, are helping manufacturers navigate the evolving demands of the industry.

What advice would you give to teams embarking on biologics development?

Teams should prioritize early investments in process optimization, select cell lines carefully, and ensure alignment with regulatory requirements to avoid delays and unexpected costs. Collaboration across multidisciplinary teams and proactive risk management are equally vital to navigating the complexities of biologics development. By addressing challenges early and maintaining a focus on quality and efficiency, biopharma companies can accelerate development timelines and deliver life-saving therapies more effectively.