Customer Requirement
A US-based biopharmaceutical company conducting early-phase clinical development encountered a regulatory hurdle when the US FDA placed a clinical hold on its Phase 2 study application for a higher dose. The hold was issued due to toxicological findings observed during preclinical studies. To move forward, the company required scientific rationale and justification to address the FDA’s concerns and seek lifting of the clinical hold.
Problem Statement
The FDA identified potential safety concerns related to higher-dose usage proposed in the Phase 2 clinical trial. These concerns stemmed from toxicology data in the preclinical studies, leading to a clinical hold. The company lacked internal toxicology regulatory expertise to develop a compelling justification package. An in-depth review of the Investigational New Drug (IND) application, along with preclinical toxicology data, was required to construct a regulatory strategy and scientific rationale acceptable to the FDA.
Key Objective
Technical Upskilling through Expert Training Support on Validation Methods
DDReg Solutions & Processes Adopted
DDReg was brought in to support the sponsor with its toxicology and regulatory strategy expertise. The approach included:
- Thorough review of the complete IND package, with a specific focus on toxicology sections.
- Detailed analysis of all preclinical toxicology study reports provided by the client.
- Identification of key safety signals, species-specific toxicological responses, and dose-justification gaps.
- Development of a comprehensive scientific justification document addressing the FDA’s concerns.
- Submission of the justification package to the FDA.
- Strategic regulatory support and participation in the formal meeting with the FDA held in September 2024.
Business Impact
Following DDReg’s intervention and submission of the justification package, the FDA granted conditional lifting of the clinical hold. The client is now authorized to initiate its Phase 2 clinical trial using the proposed higher dose, while concurrently conducting the additional studies required by the FDA. This progress enabled the sponsor to continue its clinical development without prolonged delays, preserving timelines and funding milestones critical for investor confidence.
Key Learning
A successful response to FDA clinical holds relies heavily on expert interpretation of preclinical data and the ability to translate findings into a defensible regulatory narrative. Strategic toxicology support combined with regulatory foresight plays a pivotal role in enabling clinical progress.
Read more Case Studies from DDReg’s experts: Successful Resolution of FDA 483 Inspection Gaps by Expert Pharmacovigilance Support