If your protocol doesn’t show early identification of critical-to-quality factors, inspectors will notice. Critical-to-quality factors are the starting points for GCP Risk Management. With new R3 guidelines, Sponsors should expect a deeper focus on protocol development procedures, with inspectors looking for: 

✅ Evidence of early identification of critical-to-quality factors
✅ How those factors were considered during protocol design
✅ Whether patient perspectives were incorporated 

Inspectors are now trained to identify critical-to-quality factors from the protocol itself and will compare their findings with what the Sponsor identified. If you’re using an electronic system for this, inspectors may request access to the system. 

💡 Inspectors will look for objective evidence of continuous risk assessment, since this should never be a “one and done” activity. 

💡 Be ready to defend your TMF. Ensure all essential documents are accounted for and not filed at the last minute (audit trails make that easy to spot). 

💡 Sponsors are expected to oversee all subcontractors, including those engaged by a CRO. 

Regardless of region, R3 is worthwhile to follow as it helps sponsors understand and mitigate risk early. ICH E6 (R3) Section 3.10 introduced risk-based quality management, beginning with risk identification and followed by evaluation, control, communication, periodic review, and reporting. 

Sponsors should identify risks that may impact critical-to-quality factors before trial initiation and throughout trial conduct. Risks should be assessed across all processes and systems, including computerized systems; from trial design and participant selection to informed consent, randomization, blinding, investigational product handling, data management, and service provider oversight. 

Risk management begins before the trial starts, continues throughout, and spans all systems, processes, and vendors — which is why a CRO cannot solely perform this task on a Sponsor’s behalf. 

At RegDev, our educational approach helps clients interpret and apply the new R3 guidelines in a practical, structured way. Our team works with clients to ensure that risk management principles are reflected in their SOPs, oversight processes, and overall quality framework. 

Our experts have collaborated across functionalities to develop a library of SOPs across a variety of topic areas, all updated and in alignment with R3 guidelines: 

✅Quality Management 

✅Records Quality and Records Management 

✅Regulatory Submission Documentation 

✅Investigational Product Handling 

✅Service Provider Management 

✅Clinical Trial Quality Assurance 

✅Clinical Trial Management 

✅Clinical Risk Management 

✅Data Handling and Data Lifecycle Management 

✅Safety Management and Reporting 

Get in touch to learn more about how we partner with clients to prepare them to successfully prepare for and meet the R3 guidelines.