determine:

• If the site has written procedures for essential clinical functions
• If SOPs are up-to-date, approved, and version controlled
• If staff have been trained and documented on applicable SOPs
• If site SOPs align with sponsor expectations and protocol-specific activities

A site may have sufficient infrastructure and an experienced PI, but if there is no SOP for AE/SAE reporting or IP accountability, the trial is at risk of non-compliance.

2. Essential SOPs to Verify During Feasibility

Sponsors should request and review a list of active SOPs, particularly those relevant to clinical trial execution. The following SOPs are considered minimum requirements for most interventional studies:

Clinical Function	Required SOP
Informed Consent	SOP on obtaining and documenting informed consent, including re-consent procedures
IP Management	Storage, accountability, temperature monitoring, destruction/return procedures
AE/SAE Reporting	Timelines, documentation, reporting to EC/sponsor/authorities
Source Documentation	Source-to-CRF transcription, source data verification, ALCOA+ principles
Protocol Deviations	Identification, documentation, notification process
Data Entry and Query Resolution	eCRF entry timelines, data corrections, audit trail management
Monitoring Visits	Preparation, availability of documents and staff, issue resolution
Archiving	Duration, storage location, retrieval procedures, fire/flood protection

Additional SOPs may be required depending on protocol complexity (e.g., genetic sample handling, radiology imaging transfer, central lab management).

3. SOP Quality Review Criteria

Beyond the presence of SOPs, sponsors should review the quality and structure of the documents. Each SOP should meet the following criteria:

• Clearly titled and numbered per a standardized SOP index
• Includes version number, effective date, and revision history
• Approved by site management and quality representatives
• Written in a clear, step-by-step format with defined roles and responsibilities
• Reflects current regulatory expectations (FDA, EMA, ICH)
• Last review date within 24 months or earlier if protocol demands updates

Example SOP Header Review:

SOP Section	Expected Content
Title	SOP for AE and SAE Reporting
Version	v3.0
Effective Date	01-Apr-2024
Previous Versions	v1.0 (2019), v2.0 (2022)
Approval	Signed by PI and Quality Manager

4. Staff Training and SOP Compliance Documentation

SOPs are only useful if site staff are trained on them. Sponsors should request:

• Staff training logs indicating completion of relevant SOPs
• Sign-in sheets or electronic training records with dates
• Staff acknowledgment of role-specific SOPs
• Retraining plans for SOP revisions

Feasibility teams should verify that the PI, study coordinator, pharmacist, and lab staff have been trained on core SOPs applicable to their duties. For instance, a sub-investigator managing patient consent must be trained on the ICF process SOP.

5. SOP Alignment with Protocol and Sponsor Requirements

Some SOPs may be too generic to support protocol-specific requirements. Sponsors should identify gaps such as:

• Protocol requires SAE reporting within 24 hours, but site SOP states 72 hours
• Sponsor uses eConsent, but site SOP only covers paper-based processes
• Protocol requires weekly IP temperature uploads, but SOP outlines monthly review

In such cases, sponsors can request a protocol-specific work instruction or temporary process deviation with training logs. Sites with flexible SOP structures and rapid document revision workflows are generally better prepared for fast-paced studies.

6. SOPs and Regulatory Inspection Readiness

During FDA or EMA inspections, SOPs are routinely requested by auditors to evaluate GCP compliance. Common inspection findings include:

• No SOPs available at site during the visit
• SOPs signed by unauthorized personnel
• SOPs contradict sponsor instructions or protocol requirements
• Training logs incomplete or missing
• Staff unaware of content or location of SOPs

Sites should maintain SOPs in a central regulatory binder or electronic SOP system that is accessible to all staff. Version control, approval history, and archival practices must be documented and compliant with 21 CFR Part 11 or Annex 11 where applicable.

7. Best Practices for Sponsors and CROs

• Request SOP index and list during initial feasibility outreach
• Pre-review SOPs during pre-study visits (PSV) or remotely for e-feasibility
• Document findings using standardized SOP review templates
• Collaborate with site to align SOPs with protocol-specific needs
• Include SOP review as a line item in site qualification reports and TMF

Conclusion

Evaluating a site’s SOPs is an indispensable part of clinical trial feasibility and site qualification. SOPs are not only a reflection of operational quality but also form the basis of regulatory compliance and protocol adherence. Sponsors must move beyond check-the-box SOP lists and actively verify that procedures are documented, current, aligned with the trial, and embedded in staff training. A well-prepared site with robust SOP governance is far more likely to deliver quality data, meet timelines, and withstand regulatory scrutiny.