Early Regulatory Strategy Is Critical for Immunotherapy Development

Immunotherapy products present unique regulatory challenges because they often combine complex biology, evolving mechanisms of action, emerging biomarkers and manufacturing processes that are central to product identity. In a recent thought leadership panel on regulatory development and approval pathways for immunotherapy products, experts highlighted the importance of building regulatory confidence early while maintaining flexibility as the product, process and clinical strategy mature.

The session was moderated by Dr Livija Deban, Chief Scientific Officer at Prokarium, and featured expert panellists Dr Callum Scott, Senior Vice President, Development at Scancell, and Dr Margareth Jorvid, Senior Partner at LSM Group / Life Science Management.

Opening the discussion, Deban noted that immunotherapy development requires companies to strike a careful balance between evidence generation and adaptability. As she explained: “Companies need enough evidence to build regulatory confidence quite early on, but they also need to preserve some flexibility as the product process and clinical strategy mature.”

A key theme was the need for sponsors to establish a strong biological rationale from the outset. Jorvid emphasised that regulatory confidence depends on several core areas, including mechanism of action, translational strategy, biomarkers, dose rationale and safety risk anticipation. She highlighted the importance of “a clear mechanism of action, and the credible link between the modulation and an expected clinical benefit.”

The panel also stressed that preclinical development should be risk-based. For many immunotherapy products, animal models may not fully represent human immunology. In these cases, sponsors should build a broader evidence package using in vitro, ex vivo and, where appropriate, animal studies to support safety, target engagement and biological plausibility. Jorvid underlined that “regulators do understand that there is not one model that will work for these products,” adding that sponsors often need to build confidence through a broader “palette of data.”

Early agency engagement was strongly encouraged. Rather than asking regulators what to do, companies should come prepared with a clear development plan, specific questions and a scientifically justified position. Scott advised that sponsors should drive the conversation: “Don’t go to regulators and say, what should we do? You drive the discussion, because you’re the subject matter experts.”

Scott also challenged the perception that regulators should be avoided, stating: “They want to facilitate drug development. They’re not on the earth to tell you no.” The discussion highlighted that early dialogue can help sponsors test assumptions, identify gaps and gain confidence before major investment decisions are made.

CMC was identified as one of the most important — and often underestimated — areas in early development. Sponsors need to understand critical quality attributes, formulation stability, manufacturability, potency strategy and comparability. Scott put this plainly: “There is no drug if you cannot make it.”

He also stressed the need to think about quality early, explaining that “what you use in the research environment is not necessarily the same quality or the required quality you get in the clinic.” For complex immunotherapies, this means sponsors must consider traceability of materials, manufacturability, formulation stability and the relationship between product quality, safety and efficacy. 

Potency testing remains a particular challenge for complex immunotherapies. While regulators may allow flexibility in early phases, sponsors still need a clear plan for demonstrating product consistency and biological activity. Scott noted that sponsors should map out their “potency assurance strategy early on,” particularly where cell-based assays or surrogate potency tests may be required.

The discussion also reinforced the importance of thinking ahead to later development and eventual approval. Jorvid advised companies to “start thinking about the end as early as possible,” including patient population, dose optimisation, biomarkers, endpoints and potential regulatory pathways.

The panel closed with practical advice for early-stage developers: engage regulators early, prepare thoroughly, define questions carefully and do not underestimate formulation, vendor selection or manufacturing strategy. Jorvid summarised the message clearly: “Do come early, do have those interactions early, do come prepared.”

Early decisions in CMC, non-clinical design and regulatory planning can significantly reduce downstream risk and support a smoother path into clinical development.