SOP-308
Protocol Deviations and Noncompliance
- Number
- SOP-308
- Category
- Study Conduct
- Edition
- Reference Edition 1.3
- Approx. pages
- 5
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] prevents, identifies, documents, assesses, reports and learns from protocol deviations and other noncompliance, including changes made to eliminate an immediate hazard to participants.
2. Scope
This SOP applies to all departures from the protocol, the investigational plan, GCP, applicable regulations, IRB requirements and these SOPs, in every study at [SITE NAME], whether found by site staff, the monitor, an auditor or the sponsor's data review.
Out of scope: root cause analysis and CAPA method (SOP-703); suspected research misconduct or fraud (SOP-704); unanticipated problems that are not deviations (SOP-502).
Where the protocol, sponsor or IRB sets a stricter definition or reporting time than this SOP, the stricter requirement applies.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Conducts the study per protocol and deviates only to eliminate an immediate hazard. Reviews and assesses every deviation for impact on participant safety, rights and data reliability. Decides reportability with the sponsor's and IRB's criteria. Explains important deviations and approves preventive measures. |
| Sub-Investigator (Sub-I) | Reports deviations they cause or observe. May take emergency action to protect a participant and informs the PI at once. |
| Clinical Research Coordinator (CRC) | Identifies and records deviations on F-308-01, documents details in source, and prepares reports for PI review. |
| Lead CRC | Keeps F-308-01 current for the study, reconciles it with the sponsor's deviation list, and prepares trending for the PI. |
| Regulatory Coordinator | Submits deviation reports to the IRB within the IRB's time limits and files acknowledgments in the ISF. |
| Quality Lead | Reviews deviation trends across studies, decides when CAPA is required, and tracks CAPA to closure (SOP-703). |
| All Research Staff | Report any deviation they become aware of to the CRC or PI the same day. |
4. Definitions
| Term | Definition |
|---|---|
| Protocol Deviation | Any change, divergence or departure from the study design or procedures defined in the protocol or investigational plan, whether planned or unplanned. |
| Important Protocol Deviation | A subset of protocol deviations that may significantly affect the completeness, accuracy or reliability of trial data, or a participant's rights, safety or well-being. The sponsor sets trial-specific criteria for classifying deviations as important. Some sponsors and IRBs use the term "major" deviation. |
| Noncompliance | Failure to follow the protocol, SOPs, GCP, applicable regulations or IRB requirements. |
| Serious Noncompliance | Noncompliance that, as defined by the reviewing IRB, increases risk to participants, affects their rights or welfare, or significantly affects the reliability of the data. The IRB applies its own definition. |
| Continuing Noncompliance | A pattern of noncompliance that, as defined by the reviewing IRB, suggests a likelihood that it will continue without intervention. |
| Immediate Hazard Change | A change to protocol procedures made without prior IRB approval because it is necessary to eliminate an apparent immediate hazard to a participant. |
| Planned Deviation (Protocol Waiver) | A deviation agreed in advance with the sponsor for an individual participant. Sponsors should not grant eligibility waivers, and the site does not request them. |
| CAPA | Corrective and preventive action: action to fix a problem and prevent recurrence (SOP-703). |
| QC finding grade | The critical, major or minor grade SOP-700 gives internal QC findings. It does not replace the important or not-important deviation classification in this SOP. A deviation found by QC is logged on F-308-01 and classified under this SOP. |
5. Procedure
5.1 Prevention
5.1.1
Staff follow the current IRB-approved protocol version and do not use a new protocol version until IRB approval and sponsor activation are on file (SOP-203).
5.1.2
The Lead CRC prepares visit checklists or source worksheets that list each protocol-required procedure and visit window, and staff use them at every visit.
5.1.3
Staff do not request or accept eligibility waivers. A participant who does not meet all eligibility criteria is not enrolled (SOP-303).
5.1.4
Any other planned deviation for an individual participant is made only with documented sponsor approval in advance and, where the IRB requires it, IRB approval. The approval is filed in the participant file and the event is still recorded on F-308-01.
5.2 Changes to Eliminate an Immediate Hazard
5.2.1
An investigator may depart from the protocol without prior IRB approval when necessary to eliminate an apparent immediate hazard to a participant (21 CFR 312.66; 21 CFR 56.108(a)(4)). Staff do not delay emergency care to obtain approval.
5.2.2
The investigator records in source what was done, when, and why it was needed to protect the participant.
5.2.3
For drug and biologic studies, the investigator informs the sponsor within [DEFAULT: 1 business day] of the change, or the protocol or sponsor time if shorter, and reports the hazard, the change and any proposed amendment to the IRB within the IRB's reporting time.
5.2.4
For device studies, the investigator notifies the sponsor and the reviewing IRB of any deviation from the investigational plan made to protect the life or physical well-being of a participant in an emergency as soon as possible and no later than 5 working days after the emergency (21 CFR 812.150(a)(4)). Outside an emergency, device deviations need prior sponsor approval, and where they may affect scientific soundness or participant rights, safety or welfare, FDA and IRB approval as well.
5.2.5
The event is recorded on F-308-01 and handled under the rest of this SOP.
5.3 Identification and Documentation
5.3.1
Any staff member who finds a deviation reports it to the CRC or PI the same day. Deviations may be found at visits, during data entry, by monitors, through EDC or IRT checks, by sponsor central review, or during internal QC.
5.3.2
The CRC records the deviation on F-308-01 [DEFAULT: within 5 business days of discovery], including:
- study, participant ID (if applicable), date of occurrence and date of discovery
- description of what happened and which protocol section or requirement was not followed
- who found it and how
- immediate action taken
- preliminary classification against the sponsor's criteria
5.3.3
The CRC also records the facts in the participant's source record where the deviation concerns a participant. The source entry states what happened; it does not recreate missing data.
5.3.4
Deviations communicated by the sponsor (for example from monitoring reports or central data review) are added to F-308-01 if not already recorded. The Lead CRC reconciles F-308-01 with the sponsor's deviation list at each monitoring visit.
5.3.5
Deviations that affect the whole study rather than one participant (for example use of an unapproved consent form version, expired calibration, temperature log gaps) are recorded on F-308-01 without a participant ID, or with all affected participant IDs.
5.4 PI Assessment
5.4.1
The PI reviews each deviation [DEFAULT: within 5 business days of it being recorded] and records on F-308-01:
- impact on participant safety, rights and well-being
- impact on data reliability and on the participant's continued participation
- classification as important (major) or not, using the sponsor's criteria
- whether it meets the IRB's reporting criteria, including possible serious or continuing noncompliance
- any action needed for the participant (for example safety follow-up, re-consent, sponsor consultation)
5.4.1.1
Where a deviation may fall in an IRB prompt-reporting category (SOP-502 5.3), including any consent error, the person who finds it routes it to the PI and the Regulatory Coordinator the same day, without waiting for the F-308-01 entry or the PI review in 5.4.1. The Regulatory Coordinator opens F-502-01 with the discovery date as the awareness date (SOP-502 5.4). The PI completes the assessment on F-502-01 in time for the report to be submitted within the IRB's window.
5.4.2
Where a deviation may affect participant safety, the PI assesses the participant the same day and records the assessment and action in source.
5.4.3
Where the deviation involves consent (for example a procedure done before consent, or an outdated consent version), the PI follows SOP-301 for re-consent and IRB reporting.
5.4.4
Where a deviation is also an adverse event, an SAE, an IP excursion or unblinding, the related SOP is followed in addition (SOP-304, SOP-305, SOP-500, SOP-501).
5.5 Reporting
5.5.1
The CRC reports deviations to the sponsor as the protocol and sponsor require (for example in EDC, on a deviation log or by notification), and records the report date on F-308-01.
5.5.2
The Regulatory Coordinator reports to the IRB those deviations that meet the IRB's reporting policy, within the IRB's time limit, and files the submission and acknowledgment. Central IRBs generally require prompt reporting of deviations that harmed or increased risk to participants, affected their rights or welfare, or affected data integrity, and changes made to eliminate an immediate hazard; other deviations are often reported only at continuing review or study closure, or not at all. The Regulatory Coordinator confirms the current policy of [CENTRAL IRB NAME] for each study.
5.5.2.1
Each deviation reported to the IRB is also recorded on F-502-01, and F-308-01 and F-502-01 cross-reference each other.
5.5.3
When the IRB determines that an event is serious or continuing noncompliance, the PI follows the IRB's required actions. The IRB has its own obligation to report serious or continuing noncompliance to FDA (21 CFR 56.108(b)(2)) and, for federally funded research, to OHRP.
5.5.4
Deviations that also meet the definition of an unanticipated problem are reported under SOP-502.
5.6 Root Cause and CAPA
5.6.1
For each important deviation, the PI and CRC identify the cause and record on F-308-01 the measures taken to prevent recurrence.
5.6.2
The Quality Lead opens a CAPA on F-703-01 (SOP-703) when:
- a deviation is important (major) or harmed a participant
- the IRB finds serious or continuing noncompliance
- the same type of deviation recurs [DEFAULT: 3 or more times in a study, or across studies, in a rolling 6 months]
- a sponsor, auditor or FDA requests a CAPA
5.6.3
Retraining given as a corrective action is recorded on F-103-01.
5.7 Trending and Review
5.7.1
The Lead CRC reviews F-308-01 for each active study at least [DEFAULT: quarterly] and before each monitoring visit, looking for repeated types, causes or staff.
5.7.2
The Quality Lead reviews deviations across all studies [DEFAULT: quarterly] and reports trends and open CAPAs to the Site Director and PIs.
5.7.3
F-308-01 is filed in the ISF and kept for the study retention period (SOP-402).
6. Related Forms and SOPs
- F-308-01 Protocol Deviation Log
- F-502-01 Reportable New Information Assessment
- F-703-01 CAPA Record
- F-103-01 Staff Training Log
- F-903-01 Member Site Performance and Quality Scorecard (Model N only)
- SOP-203 IRB Submissions, Approval and Continuing Oversight
- SOP-301 Informed Consent Process and Documentation
- SOP-303 Screening, Eligibility Verification and Enrollment
- SOP-304 Investigational Product Management
- SOP-305 Randomization, Blinding and Emergency Unblinding
- SOP-306 Source Documentation and Data Integrity (ALCOA+)
- SOP-500 Adverse Event Identification, Assessment and Recording
- SOP-501 Serious Adverse Event and Expedited Safety Reporting
- SOP-502 Unanticipated Problems and Reportable New Information
- SOP-600 Sponsor Monitoring Visits
- SOP-703 Corrective and Preventive Action (CAPA)
- SOP-704 Research Misconduct and Fraud Reporting
- SOP-903 Network Oversight of Member Sites (Metrics, Central QA, Escalation) (Model N only)
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| 21 CFR 312.60 | General responsibilities of investigators |
| 21 CFR 312.66 | Assurance of IRB review |
| 21 CFR 56.108 | IRB functions and operations |
| 21 CFR 812.150(a)(4) | Investigator reports: deviations from the investigational plan |
| 21 CFR 812.35(a) | Supplemental applications: changes in investigational plan |
| 45 CFR 46.108 | IRB functions and operations (federally funded research only) |
| ICH E6(R3) Annex 1, 2.5 | Compliance with Protocol |
| ICH E6(R3) Annex 1, 3.9.3 | Sponsor Oversight: important protocol deviations |
| ICH E6(R3) Annex 1, 3.12 | Noncompliance |
| FDA Guidance (2009) | Investigator Responsibilities: Protecting the Rights, Safety, and Welfare of Study Subjects |
Independent Site SOP Library. Licensed CC BY-NC 4.0 by the American Institute for Medical Research (AIMR), with added permission for any site's internal use (license terms). Not legal advice: each adopting site confirms state law, IRB and sponsor requirements with its own counsel and owns every step it approves.