Managing Outsourcing For Complex Formulations

A well-established technology transfer, process development, scale-up, and formulation is key to positioning a successful clinical trial preparation. While technology transfers can be a challenge with any drug product, even greater vigilance is needed with more complex formulations such as lipid nanoparticle-based (LNP) drugs. These complex formulations have structural similarities to naturally occurring biological vehicles; consequently, they are generally well tolerated by the body. As a result, LNPs are increasingly being used to deliver highly specialized therapeutic molecules, such as oligonucleotides, which are likewise seeing increased attention in drug development due to their ability to tackle disease on the genetic level. These formulations are inherently complex and require a more comprehensive manufacturing and testing approach.

Despite the growing body of research and scientific knowledge, perhaps the biggest challenge with LNP formulation is the journey into the unknown. The stability profile of the finished formulation is very dependent on lipid selection and the manufacturing process. Many involve novel payloads or APIs, and interactions between the various compendial raw materials are not fully understood. The supply chain requires careful and collaborative scheduling, and as such, a successful tech transfer will often rely on parallel transfer and development efforts at raw material suppliers. The development of an LNP-formulated drug product can be a daunting task unless one has preliminary data to work with or previous experience with lipids.

Getting the final drug product to the clinic — and eventually over the finish line of final approval — is very much a team effort. Experts from PCI Pharma Services explored the necessary components of a smooth tech transfer for LNP-based drugs, including the variables that impact LNP formulation and the outsourcing strategies needed to avoid common pitfalls. PCI Pharma Services' technical experts, have answered some questions relating to PCI’s work and expertise.