The Preclinical to Clinical Transition: What It Really Takes
Transitioning a promising preclinical project into a safe, scalable, and compliant clinical product is an exciting milestone. The preclinical to clinical transition, or clinical translation, is where R&D must move toward manufacturability while considering new regulatory constraints.
Pharma and cell and gene therapy (CGT) companies must shift from academic operations into a cGMP-compliant environment for Phase I and Phase II. This organizational transformation can be challenging so hopefully this article provides some guidance. First the phases are outlined, then it continues by sharing some common challenges, how they can be avoided, and then a proposed pathway to move forward.
Key Phases of Clinical Translation
- Preclinical Research
Early laboratory and animal studies evaluate a product’s safety, biological activity, and how it behaves in the body (absorption, distribution, metabolism, and excretion). The data from these foundational studies support regulatory submissions and help justify moving into human trials. - Technology Optimization
During this phase, product formulations, manufacturing processes, and analytical methods are all refined. The goal is to ensure a reliable and consistent treatment can scale, laying the groundwork for an eventual GMP environment. - Regulatory Pathway Planning
Here is where planning begins for an Investigational New Drug (IND) application to the FDA, or the equivalent with global regulators like the EMA (Europe) or MHRA (UK). This includes compiling preclinical data, developing clinical trial protocols, and preparing other necessary regulatory documentation. - GMP Readiness
Before clinical trials can begin, full current Good Manufacturing Practices (cGMP) compliance must be achieved. This may involve upgrading facilities, implementing robust quality management systems (QMS), validating processes, qualifying critical equipment, and developing GMP documentation and training programs. This phase ensures that manufacturing will meet regulatory requirements during trials. - Clinical Trials (Phase I–III)
Manufacturing during this time must follow cGMP with strict quality controls, validated processes and methods, qualified equipment, and regulatory oversight to ensure the safety and consistency of the products while still in clinical trials. - Approval & Commercialization
Once clinical trials are successfully completed, companies will seek product approval through formal submissions such as NDA, BLA, or MAA. At the same time, they prepare for scaled up manufacturing, which includes such things as supply chain controls, global regulatory filings, and market launch strategies.
Solving Common GMP Transition Challenges
Facility Fit for GMP
Issue: Most R&D labs aren’t designed for GMP compliance.
Solution: Labs are reconfigured to meet cleanroom requirements, create process segregation, and control contamination.
Documentation Discipline
Issue: Informal or inconsistent documentation practices won’t meet cGMP standards and can compromise traceability, accountability, and compliance.
Solution: Well defined documentation systems, which includes master batch records and acceptance specifications, are put in place to ensure data integrity.
Supply Chain and Scale-Up
Issue: Without a supplier approval program, material variability and traceability can derail manufacturing scale-up and compliance.
Solution: Clinical and commercial readiness is established through a supplier approval program, incoming material specifications, material disposition, and supporting SOPs.
Aseptic Risk Mitigation in CGT
Issue: Cell and gene therapies are especially vulnerable to contamination due to their use of live cells and viral vectors, which require more stringent controls.
Solution: Aseptic controls are specifically designed for CGT, with procedures that address the specific risks of handling sensitive biological materials and personalized treatments.
GMP Culture Shift
Issue: Transitioning to a GMP-regulated environment is more than writing SOPs, it requires a mindset change. Teams must move toward a culture of accountability, traceability, and compliance.
Solution: Organizations must build awareness of regulations like 21 CFR Parts 210, 211, and/or 1271. This includes consistently training teams on all elements of data integrity, documentation discipline, and how safety can be impacted by their daily actions or inactions.
Our Approach to GMP Transition
At cGMP Consulting, we have the breadth and depth of services to provide a customized roadmap to guide your cGMP transition. We ensure alignment with regulations and assist by getting your team and operations ready for every step of the process.
1. Regulatory Pathway Consulting and Assistance with Filing
We help you define a compliant and efficient roadmap for your clinical development.
2. Gap Assessment and Readiness Review
We benchmark your current operations against GMP requirements, identifying gaps early to avoid costly rework or other setbacks.
3. Quality Management System (QMS) Development
We design or upgrade your QMS tailored to your product and process to ensure you are ready for inspection. For cell and gene therapies, aseptic-focused controls including media fills, gowning procedures, HVAC zoning, etc. will be necessary.
4. Facility, Utility and Equipment Qualification
We manage IQ/OQ/PQ for cleanrooms, utilities, WFI systems, and all critical equipment.
5. Training and Continuing Support
We prepare your team with an in-depth dive into the CFRs so they understand and practice cGMP for consistent and long-term compliance.
Ready to Transition from Preclinical to Clinicals?
Let’s talk. At cGMP Consulting, we can help emerging biotech and established life sciences companies successfully complete the preclinical-to-clinical transformation. We bring the technical depth and regulatory clarity you need to get you to market faster.
Contact us today to ensure your organization is ready for the next step.
