The drug development process is a long and complex journey, requiring years of research, rigorous testing, and regulatory approvals before a new treatment reaches patients. Discover this intricate pathway, stage by stage, exploring the challenges and triumphs along the way.
Understanding the Drug Development Process
Depending on the type of drug, the development process may look different. There are some fast-track regulatory pathways (COVID-19, orphan drugs) that allow products to come to market faster with high public need. For biologics, however, there are common stages that each drug must go through.
Statistics show that for every 10,000 molecules tested in the discovery phase, only 10-20 compounds make it to the development phase . The first after the discovery phase – that is, evaluating molecules for their therapeutic profile – is to conduct nonclinical studies to assess the toxicity and activity of the drug candidate on human cells (in vitro) and on model animals (in vivo). To get to this point, a biologic drug needs to be synthesized, with biotechnology leading the way.
The foundation of biologic drug development begins with cell line development, where host cells, such as Chinese Hamster Ovary (CHO) cells, are genetically engineered to express the therapeutic protein. Screening and selection processes identify high-yielding clones with desirable growth characteristics and protein expression stability . The goal is to establish a robust, scalable, and regulatory-compliant cell line that maintains product consistency throughout manufacturing. Key methodologies include transfection, clone selection, stability studies, and media optimization.
The cell line prepared in this way, effectively producing the desired protein, goes to the next stage. Upstream bioprocessing involves process intensification strategies, such as fed-batch or perfusion culture systems, to enhance productivity. Critical parameters include bioreactor conditions (pH, dissolved oxygen, temperature), nutrient feeding strategies, and process monitoring using advanced sensor technologies.
Following upstream bioproduction, the harvested cell culture undergoes downstream processing to isolate and purify the target biologic molecule while maintaining structural integrity and bioactivity. This stage includes primary recovery (cell separation via centrifugation or filtration), chromatography-based purification (affinity, ion-exchange, and size-exclusion techniques), and formulation development.
Biologics Development and Process Optimization
There are many methods to optimize the drug development process. At the technology platforms scale, matching USPs and DSPs to the needs of a specific project turns out to be crucial.
Once a stable cell line is established, upstream bioprocessing should focus on optimizing cell culture conditions to maximize cell viability and protein expression. This is accomplished through computational fluid dynamics modeling to refine bioreactor parameters, real-time process analytical technology (PAT) for continuous monitoring, and dynamic feeding strategies to maintain optimal cell metabolism .
Downstream processing benefits from multi-column chromatography for enhanced purification efficiency, high-throughput screening of resins to optimize selectivity, in-line diafiltration to streamline buffer exchanges, and precipitation-based impurity removal to enhance purity profiles [3].
Challenges and Strategies in Bioprocess Scaleup
There are many challenges in scaling up a bioprocess. During optimization, there is a risk of changes in toxicity, therapeutic potential or structural modifications of the molecule. Variability in cell culture performance, shear stress sensitivity, and nutrient distribution require precise optimization to ensure reproducibility. After development and testing performed at lab scale, it is necessary to adapt the process to new equipment before clinical production.
Throughout biologic drug development, analytical support provides critical insights into product characterization, stability, and quality control. High-resolution analytical techniques, such as mass spectrometry, cell-based assay, posttranslational modifications profile assasement and bioassays, are employed to evaluate structure, identity, potency, purity, and safety attributes. Analytical methods are validated to meet regulatory requirements, ensuring batch-to-batch consistency and early detection of process deviations. The implementation of real-time release testing and in-line monitoring enhances process control, minimizing risks associated with variability .
Bioprocess scale-up presents significant challenges in maintaining process consistency, yield, and regulatory compliance when transitioning from lab scale to commercial scale manufacturing. In the upstream platform stage, integrating computational modeling and process analytics is essential for predicting bioreactor performance and minimizing scale-related deviations. Yield optimization, impurity removal strategies, and strict adherence to GMP guidelines further support process scalability, ensuring that biologics manufacturing remains efficient, compliant, and capable of meeting commercial demand.
Future Trends and Innovations in Drug Development
Seven of the top ten selling biopharmaceutical products in 2024 are new modalities, underscoring their significant market impact. Large biopharma companies have invested nearly $200 billion in new drug modalities since 2022 [5]. The industry is witnessing rapid growth of antibody-drug conjugates, gene and cell therapies market. These innovations are transforming therapeutic approaches and expanding treatment options for various diseases. Driven by the success of ADCs and GLP-1 agonists $168 billion in projected pipeline value for 2024 [5].
The shift from a one-size-fits-all approach to personalized medicine is accelerating, driven by advancements in genomics, biomarker discovery, and targeted therapies. Regulatory agencies are adapting approval pathways to accommodate these innovations, fostering a new era where treatments are not only more effective but also reduce adverse effects and healthcare costs. The next decade will see an increasing convergence of biologics, AI-driven analytics, and real-world data to refine precision medicine strategies.
References
- Torjesen I. Drug development: the journey of a medicine from lab to shelf. The Pharmaceutical Journal, 2015.
- Singh N., Vayer P., Tanwar S., Poyet J.L., Tsaioun K., Villoutreix B.O. Drug discovery and development: introduction to the general public and patient groups. Frontiers in Drug Discovery, 2023, 3: 1201419.
- Gronemeyer, P., Ditz, R., Strube, J. Trends in Upstream and Downstream Process Development for Antibody Manufacturing. Bioengineering, 2014, 1: 188-212.
- Pietruszkiewicz A., Stapleton N., Henehan M., Bednarek M., Bartusik-Czubek E., Czubatka-Bienkowska A., Malecka A., Dobrowolski M., Toboła P. From Tech Transfer To Validation: One CDMO’s Client-Centric Approach To Development. Bioprocess Online, 2024.
- Chen L., Bush B., Brochu M., King G. New Drug Modalities 2024. Boston Consulting Group, 2024.