Successfully Managing the Transition from Research to Development

The journey from research to development is one of the most critical phases in drug development. At this point, the focus shifts from exploration and discovery to ensuring the product's safety, efficacy, and readiness for human clinical trials via preclinical animal models. Navigating this transition successfully requires an understanding of the regulatory requirements, a clear strategy and plan, and execution led by subject matter experts (SMEs) with domain expertise. Below, we outline the essential steps and considerations to manage this process effectively.

Before moving a drug candidate into human clinical trials, the FDA requires the following elements:

Integrated preclinical data that includes:

• Pharmacology – data on the drug’s mechanism of action (MoA) and efficacy in relevant animal models
• Toxicology – safety data generated from single and repeat dose toxicology studies as well as reproductive, developmental and genotoxic studies
• Pharmacokinetics – absorption, distribution, metabolism and excretion of the drug in animal models
• Drug Formulation – composition, stability and methods of manufacture

Chemistry, Manufacturing and Controls (CMC) data that includes:

• Good Manufacturing Practice (CGMP) information for drug substances and drug products evaluating the product's strength, identity, safety, purity, and quality (SISPQ).

Proposed clinical study that:

• Leverages preclinical data to support the starting dose in humans and identifies potential adverse effects and target organs of toxicity that need to be monitored

Includes objectives, methodology, statistical and operational details as well as the intended population, inclusion and exclusion criteria and endpoints to be measured.

Developing an Integrated Development Plan

To effectively meet the FDAs requirements and advance your development in an efficient and cost-efficient manner, a robust Integrated Development Plan needs to be created. This plan defines the path and actions and ensures alignment across all functional areas. It must include:

• Target Product Profile (TPP): Defining the desired product specifications and outcomes.
• Regulatory: Requirements, timelines, costs, and risks.
• Clinical: Study designs, timelines, costs, and risks.
• CMC: Chemistry, Manufacturing, and Controls requirements.
• Preclinical: Efficacy, safety, toxicology, pharmacokinetic (PK) and pharmacodynamic (PD) studies, with associated timelines and costs.
• Assumptions, Risks, and Opportunities: Across all areas to mitigate delays or issues.

Common Pre-clinical Issues:

• Choosing the right species and product for pharm/tox studies.
• Allowing time to modify study designs after FDA feedback.
• Avoiding incorrect assumptions that could lead to delays or clinical holds.

Preparing for FDA Interactions

FDA feedback is invaluable in shaping your pre-clinical and clinical plans. A pre-IND meeting is a critical and beneficial method to gain feedback to support your first-in-human and early clinical development studies. A pre-IND meeting provides a sponsor the opportunity to obtain information and guidance from the FDA that includes feedback on preclinical data, identification of potential issues, discussion of clinical study designs, clarification of regulatory requirements, guidance on development plans and advice on specific scientific questions.

However, companies often fall into common pitfalls, such as:

• “Our work is published in Science; the FDA will find everything they need in our papers.”
• “Let’s hold off on more studies until we hear from the FDA.”
• “We don’t need a pre-IND meeting; we know what we need to do.”

To avoid these mistakes, companies must ask: Am I ready for the pre-IND or INTERACT meeting?

Navigating Organizational Change

The research phase is driven by innovation, exploration, and a tolerance for risk. It is a time for taking chances, learning from failures, and celebrating surprises. However, transitioning to development where regulations guide and direct data generation and supporting activities requires a more structured and strategic mindset.,

The transition from research to development often requires organizational shifts. Different roles and domain expertise are required, team structures will change, and data will need to be seamlessly transitioned, leaders will need to adapt and keep teams focused on the end goal and program management support will be key to ensuring execution in this highly cross-functional environment.

Key Takeaways for Success

Successfully transitioning from research to development and advancing your asset effectively to early human studies require strategic focus and strong execution. Here are the key takeaways:

• Understand FDA expectations and requirements
• Create an Integrated Development Plan to define your path and ensure cross-functional alignment on execution and timing
• Engage the FDA to seek guidance and gain alignment on requirements, data and plans
• Build your development team of SMEs and domain experts, seamlessly transition team members and data and direct the focus on IND enabling work

By proactively addressing these elements, you set the foundation for a smoother transition into development, ensuring your drug candidate is ready for human trials and eventual market approval.

Final Thoughts

The shift from research to development is a defining moment in drug development. By aligning teams, refining processes, and maintaining a sharp focus on safety and efficacy, you increase your chances of success. Plan strategically, seek expert guidance, and always keep the end goal in sight: delivering a safe and effective product to patients who need it.