by Diane Seimetz
The transition from R&D to clinical stage is an important phase in biopharmaceutical product development. The conventional clinical development paradigm consisting of phase 1, phase 2 and phase 3 clinical studies may no longer apply to all programs. The enhanced use of biomarker and adaptive clinical trial designs have led to a more streamlined development with combined clinical phases, such as phase 1/2 or phase 2/3 study designs. For some product categories, such as ATMPs or orphan products, the first study could already lead into a pivotal study, depending on the effect size and safety profile. The acceleration of clinical development – though highly desirable - has substantial implications on the manufacturing and quality control strategy (CMC) and the overall development approach.
For a smooth transition to clinical development stage, careful and intertwined upfront planning across important drug development disciplines is essential. This includes for example smart selection of the lead candidate, a tailored nonclinical program, a well thought out manufacturing and control strategy, and a diligent plan towards the first in human study including risk mitigation strategy. Involvement of regulatory agencies at defined milestones should be considered as well to increase the success rate. The set-up of an integrated development and regulatory plan is a valuable approach towards structured drug development. The discussion in a multidisciplinary team ensures that no essential element is missed.
An overview of the key steps for transition from research to development is shown in Figure 1.
Based on our experience, even mature research teams and start-up companies often underestimate the challenge to progress their product candidates as well as their teams from the R-stage (Research) to the D-stage (Development). Research is a solid foundation for drug development. The focus is more towards understanding pathways, exploring multiple options in a less regulated environment and identification potential drug candidates. An important focus of researchers is publication of results. Development, however, requires are more focused approach towards moving product candidates effectively and efficiently forward in a highly regulated environment. Rather than publications, well-written reports are essential, not only to fulfill regulatory requirements but also to attack potential partner for further investment. Overall, both disciplines require different capabilities and experience.
Recently, Parrish M. C. et al. (2018) shared experiences on translational challenges from a US academic perspective. They have identified in interviews that academic projects face numerous challenges in reaching the clinic, including limited funding, lack of training, skills and know-how. In addition, the lack of regional drug development ecosystems was an identified issue.
Our recommendation towards addressing translational challenges and preparing for smooth transition to clinical stage are summarized in Figure 2.
Diane was recently invited by the German Stem Cell Network to present on the topic “What is needed for smooth transition from R&D to clinical development stage”.
Interested to learn more about how YOU can efficiently translate your product candidates from research to clinical development? Get in contact with us.
Parrish MC, Tan YJ, Grimes KV, Mochly-Rosen D: Surviving in the Valley of Death: Opportunities and Challenges in Translating Academic Drug Discoveries. Annu Rev Pharmacol Toxicol. 2018 Sep 12.