When developing a biologic, great science does not always translate into a great product. Doing the rights studies, the right way, is paramount to realizing the product’s potential. Knowing which studies to conduct, when to conduct them and interpreting the data in the context of the product’s development, can make the difference between success and failure.
For Biologics, “The Product is the Process”
Biological medicines, including therapeutic proteins, DNA vaccines, monoclonal antibodies, and fusion proteins are large, complex molecules that cannot be fully defined by physicochemical analytical methods. They are manufactured from genetically modified living cells using processes that are usually complex. Biological medicines are often 200 to 1,000 times the size of small molecule drugs, and because of the biological nature of the starting materials, the manufacturing processes have inherent variability and product heterogeneity.
For biologics “the product is the process,” as the properties of the biologic often depend directly on the nature of the manufacturing process. Manufacturers must ensure product consistency, quality, and purity by ensuring that the manufacturing process remains substantially the same over time. When process changes occur, manufacturers need to demonstrate comparability–that the process changes have not changed the quality of the molecule, and therefore, the safety and efficacy profile. To this end, understanding which of the biological medicine’s quality attributes are important, as they are critical in determining whether additional in vitro or in vivo studies are needed to ensure the generated data is supportive for the product’s future development.
Large-Molecule Development Pitfalls Can Be Avoided and Risks Mitigated
Early decisions in the large-molecule development process can significantly impact the time to the clinic, progression to the market, development costs, and the overall technical product development risk. If product development aspects are not considered early enough, key studies may need to be repeated, and/or unexpected results explained, both of which can add significant delays and costs.
Sponsors can accelerate their product’s development and minimize costs by avoiding common pitfalls of large-molecule drug development.
- Understand the physicochemical properties of the biological medicine product: Understanding the attributes of the product early in development is essential for the appropriate design of non-clinical and clinical studies, and then interpretation of the data in the context of the overall development goals and target product profile. Simple studies, such as basic formulation development studies, enable assurance of the quality and quantity of the product to be administered. If you don’t know what you have administered, then how can you interpret the data?
- Ensure that the manufacturing development strategy is defined early: This enables the manufacturing changes, which are often made during development, to be managed in a proactive way, with potential consequences on the product prospectively considered. The biological medicine material used in the non-clinical studies needs to be representative of what will be administered in the clinic to assure patient safety and enable the interpretation of results.
- Remember your Target Product Profile and clinical goals: Start with the end in mind. Studies conducted in the pre-clinical phase have a direct impact on your goals for Phase I and beyond. For instance, it’s critical to know your intended patient population and disease setting, and define the appropriate starting clinical dose.
Biologic Development Requires a Unique Mindset and Expertise
Given the nature and complexity of biological medicine development, choosing a development partner with proven expertise in biologics is critical to market success. In fact, choosing the right partner with the right experience can help streamline development processes and timelines and reduce your development costs.
Overall, planning early and considering the end goal throughout the development process is critical to realizing the potential value of the biological medicines you are developing and bringing innovative medicines to patients.