From Cell Line Development to Drug Approval, Exploring the CDMO Drug Development Process

Biopharmaceutical drug development involves discovering and developing therapeutics produced using living cells. These include drug products such as monoclonal antibodies and antibody-drug conjugates, both of which have transformed therapeutic strategies for numerous diseases, notably cancer and autoimmune disorders. Curious? Read on for a comprehensive overview of the process, from cell line development to drug approval and manufacturing, highlighting the critical stages involved and the role of contract development and manufacturing organizations (CDMOs).

Understanding the Basics: Biologic Drugs

Biologic drugs differ from traditional small-molecule drugs in that they’re derived from cells and utilize biological structures such as proteins, mRNA, and enzymes. 

Monoclonal antibodies, for instance, are engineered to target specific antigens, such as those found on cancer cells. Antibody-drug conjugates are more sophisticated, combining an antibody's targeting capabilities with a potent cytotoxic drug, delivering this lethal cargo directly to cancer cells while sparing healthy tissue. Other biologic drugs include mRNA vaccines, such as those that are used to prevent COVID-19 infection, as well as cell and gene therapies. 

Advancements in technologies such as CRISPR Cas-9 gene editing and high-throughput screening for cell line development have made the design of these drugs more effective and easy to produce, resulting in biologics increasingly occupying a large percentage of total drug development projects and drug sales.

The Journey Begins: Drug Discovery

The development process starts with drug discovery, a phase where researchers identify potential targets for new drugs and develop initial molecules or biological entities to interact with these targets. Techniques such as high-throughput screening, computational biology, and structure-based drug design play pivotal roles. This phase can be both time-consuming and resource-intensive, requiring a deep understanding of the disease biology and the mechanisms by which potential drugs can exert their effects. 

However, advancements in automation and artificial intelligence have enabled researchers to analyze vast amounts of data on subjects like genetic composition and therapeutic potential in much shorter time frames, and to identify patterns that would typically escape human analysis.

“The biopharmaceutical industry now has enough drug development data incorporated into an AI system that predicts chemical reactions and alerts which genetic modification could alter drug response,” said Joon Yoon, a senior data scientist at CDMO Samsung Biologics, in a recent roundtable for Drug Development & Delivery. “The AI-based drugs, or at least the drugs that were screened using AI, will soon become the norm in the near future.”

Laying the Foundation: Cell Line Development

For biologic drugs, cell line development is a foundational step. It involves creating and selecting a specific cell line — most commonly Chinese hamster ovary cells — that can produce the biologic drug in sufficient quantities. This stage is critical for ensuring the quality, safety, and efficacy of the drug. The selected cell line must be stable, capable of producing the drug consistently, and scalable for commercial production.

CDMOs play an indispensable role in this stage of biopharmaceutical development. Their expertise and resources are critical in navigating the complex technical and regulatory challenges associated with cell line development. Initially, CDMOs engage in cell line engineering, utilizing advanced genetic engineering techniques to insert the gene of interest, which codes for the therapeutic protein, into the chosen host cells. This genetic modification enables the cells to produce the target biologic.

Navigating Regulatory Pathways: IND Approval

Before a drug can be tested in humans, developers must obtain investigational new drug approval from regulatory bodies such as the U.S. Food and Drug Administration. The IND application includes data from preclinical studies, information on the drug's manufacturing process, and a plan for clinical trials. This step ensures that the proposed studies won’t expose participants to unreasonable risks. 

Scaling Up: Manufacturing

Once IND approval is secured, the focus shifts to scaling up manufacturing. This is another phase in which CDMOs often play a crucial role, offering expertise in bioprocessing to produce large quantities of the biologic under stringent quality standards. Scaling involves not just increasing the volume of production, but also ensuring that the drug's quality remains consistent across batches. This step requires sophisticated bioreactors and purification systems, along with rigorous quality control measures.

Fill-finish services are the final steps in the manufacturing process. The drug is filled into vials or syringes, then finished with labeling and packaging. This stage is critical for maintaining the drug's sterility and stability up to the point of delivery to patients. It requires precision and adherence to aseptic techniques, as contamination at this stage could render the entire batch unusable.

The progression from cell line development to drug approval is a testament to the collaboration among scientists, regulatory agencies, and CDMOs. While it can be a lengthy process and require substantial investment, biopharmaceutical development is constantly becoming more efficient, and the potential for these drugs to treat previously intractable diseases or to improve significantly on existing treatments makes it a worthwhile endeavor.