Before initiating a first-in-human clinical trial, thorough preparation is critical to reduce risks, align stakeholders, and ensure regulatory readiness. This checklist outlines the six key steps that should be completed upstream to structure a robust and coherent development program, from defining the clinical strategy to engaging with regulatory authorities.
It is designed as a practical guide to support teams in securing a solid foundation before moving into human studies.
1. Clarify the development strategy
The first step is not about study design. It is about clarity of intent. Before any protocol work begins, the strategic foundation must be set.
Strategy checklist
- Definition of the target indication
- Identification of the expected benefits and the associated measurement parameters
- Comparative analysis versus existing products: mechanism of action, route and frequency of administration, adverse effects
- Drafting of the Target Product Profile (TPP), including indication, route of administration, target population, dosing regimen
- Development of an overall clinical development plan, at a minimum from Phase I through proof of concept (end of Phase II)
This strategic clarity is also what investors look for when you pitch your clinical program. A well-defined TPP and CDP are the foundation of both internal execution and external credibility.
2. Design a robust study synopsis
Once the strategy is clear, the study design can be built. A robust synopsis will anticipate regulatory questions and operational challenges.
Synopsis checklist
- Definition of the study design: SAD / MAD, inclusion of placebo, stopping rules, safety committee, duration, number of subjects
- Calculation of the starting dose based on the preclinical NOAEL, with an appropriate safety factor
- Definition of the dose-escalation scheme
- Identification of safety criteria and pharmacokinetic (PK) parameters
- Review of the synopsis by preclinical and CMC teams to ensure overall program consistency
3. Build a complete preclinical package
The preclinical package is your foundation for regulatory approval. Any gap here will become a blocker later.
Preclinical checklist
- Verification that the preclinical package is complete and compliant with applicable regulatory requirements (pharmacology, PK, toxicology, biodistribution, genotoxicity)
- Review of the dossier by a preclinical expert
4. Ensure CMC (Chemistry, Manufacturing & Controls) readiness
Clinical timelines are often broken by CMC issues. Anticipate, do not react.
CMC checklist
- Confirmation that the clinical batch is under manufacture or already available
- Clear understanding of batch availability timelines and quantities produced
- Documentation of the stability plan and quality control strategy
- Anticipation of transport and storage conditions up to the clinical sites
5. Select the right partners
Partner selection is a major strategic decision. Poor CRO or vendor choices can delay a trial by months. For a deeper dive on this specific step, see the dedicated guide on how to select the right CRO for your FIH trial.
Partner selection checklist
- Identification of potential CROs, bioanalytical laboratories, and clinical sites (multiple options recommended for comparison)
- Preparation and submission of Requests for Proposal (RFPs) based on the synopsis and development plan
- Receipt, review, and comparison of proposals, including budgets and timelines
- Preparation and planning of qualification audits for critical service providers
- Drafting of master service agreements (MSAs) and work orders, including legal and budget reviews (often lengthy to finalize)
6. Interact with regulatory authorities
Regulatory engagement is not a formality. It is an opportunity to validate your strategy and uncover any gaps before they become submission issues.
Regulatory checklist
- Identification of the relevant regulatory region (FDA, EMA, MHRA)
- Preparation of the briefing package
- Definition of key questions to be submitted for validation of the development plan
- Integration of regulatory authority feedback into the overall clinical strategy
Thorough upstream preparation is what separates a trial that runs smoothly from one that stumbles through avoidable delays.
Completing these six steps before entering human trials is not optional. It is the difference between a first-in-human program that advances on schedule and one that loses months (and credibility) to preventable issues. If you need senior support to structure your FIH preparation, this is precisely where fractional clinical leadership adds the most value.
