Gaining a deeper understanding of your API

Early identification of potential formulation challenges in complex molecules and APIs

February 02, 2023 by Vincenza Pironti (5 minute read)

Category | Small Molecule

As active pharmaceutical ingredients (APIs) become increasingly complex, they pose potential formulation problems that can extend timelines and explode budgets. Certain physiochemical characteristics, such as melting points, density, flowability, and compressibility, may be manageable at a smaller scale, but production at greater volumes can present a completely different story. The last thing any developer should have to do is repeat early-development stages when many of these challenges can be anticipated and mitigated with proper expertise and understanding of the formulation space.

Early efforts to fully understand the API prevent challenges later

Mature chemist examining chemicals for her scientific research in laboratory.

Complex molecules react more sensitively to changes in conditions and can have a greater variety of side reactions than simpler APIs. To anticipate these circumstances, API and drug product development teams can work together during phase I and phase II trials to understand critical physical properties and determine the target characteristics of the API at scale-up. These characteristics should be adopted as the formal specification for future production. Some tools to support this approach include:

  • A systematic risk and critical attribute assessment
  • Online in process control to monitor filling process
  • Models of technical process and plant parameters to include identification of aggregation, production of by-products, absorption to contact materials, etc


Mature chemist examining chemicals for her scientific research in laboratory.

Innovation in formulation development

Every day, our teams work to improve existing tools or develop new strategies to address formulation challenges. Some areas of formulation innovation that Thermo Fisher finds particularly exciting include:

  • Innovations in spray-drying techniques
  • Subcutaneous injection for highly concentrated biologics
  • Reduction of viscosity in excipients for highly concentrated biologics without protein destabilizationv
  • Formulation developmentbased on fluid suspension for highly concentrated biologics
  • New approaches to long-acting injectables
  • Use of machine learning and predictive modeling to accelerate biopharmaceutical formulation design

Trends such as these bring great promise for new treatment options and subsequent improvements in patients’ health care overall.

The importance of early collaboration among development teams

As molecule complexity continues to increase and options for formulations continue to expand, the importance of early collaboration between API and drug product development teams becomes even more critical. These early conversations between groups require minimal resources from companies, especially in contrast to the immense costs of encountering formulation challenges at scale-up. Early investments to more deeply understand the critical attributes of the API can yield great savings throughout the development process.

To learn more about how Thermo Fisher Scientific addresses formulation challenges, see our recent case study here.