What is it? Why is it important?
Findings mean that given audit/inspection criteria were not met. Findings occur as a result of a process and/or system deficiency, where audit/inspection evidence do not comply with audit/inspection criteria.
In studies, typical audit/inspection criteria include:
- The EC approved study protocol
- Study relevant SOPs
- ICH GCP, ISO Guidelines (e.g. ISO 14155)
- The law (e.g. Swiss law)
In studies, typical evidence include:
- Essential documents in TMF/ISF
- Signed and dated ICF
- IMP/IMD handling
- Safety reporting procedures
- Evidence can also originate from staff interviews
Findings are categorised based on the severity of non-compliance and include the 3 categories, namely minor, major, and critical according to EMA`s grading of inspection findings. Main focus is any non-compliance that jeopardizes the safety of study participants and the quality of study data.
Based in the European Medicine Agency (EMA) findings that are not-met are categorised – as follows:
- Condition, practices or processes that adversely affect the rights, safety or well-being of the subjects and/or the quality and integrity of data
- Critical observations are considered totally unacceptable
- Possible consequences: rejection of data and/or legal action required
- Observations classified as critical may include a pattern of deviations classified as major
- Condition, practices or processes that might adversely affect the rights, safety or well-being of the subjects and/or the quality and integrity of data
- Major observations are severe deficiencies and are direct violations of GCP principles
- Possible consequences: data may be rejected and/or legal action required
- Observation classified as major may include a pattern of deviations and/or numerous minor observations
- Condition, practices or processes that would not be expected to adversely affect the rights, safety or well-being of the subjects and/or the quality and integrity of data.
- Possible consequences: observations classified as minor indicate the need for improvement of conditions, practices and processes.
- Many minor observations may indicate poor quality and the sum might be equal to a major finding with its consequences.
What do I need to do?
Findings must be subject to a root-cause analysis. This mean that:
- Findings must be corrected in order to return to criteria compliance
- Corrective actions must be defined in order to prevent the reoccurrence of finding(s) (e.g. risk management)
- The SP-INV submits a CAPA plan to inspectors that describes the management of findings, including a timeline for their resolution. A priority should be given to critical or major findings.
Based on the outcome of the inspection, the SP-INV is responsible to submit a CAPA plan to the inspectors and ensure the CAPA plan is implemented according to defined timelines.
Example of a finding
Criteria: Participant and Site-INV must jointly date and sign the ICF during the visit when the participant is informed - and included in the study.
Route cause analysis: Participants receive study information including the ICF document to take home for evaluation. Upon return to the clinic participants have already signed the ICF. The Site-INV is not aware of the requirement that the ICF must be jointly signed on the same day.
Preventive action: Training of Site-INV regarding joint signing criteria. ICF process was adapted. In the event the participant has pre-dated and signed the ICF he/she will re-sign on the day of study inclusion together with the Site-INV.
Where can I get help?
Your local CTU↧ can support you with experienced staff regarding this topic
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.usz.ch
ICH GCP E6(R2) – see in particular guidelines
- 1.29 Inspection
- 1.6 Audit
- 5.0 Quality management
ISO 9001 (access liable to costs) – see in particular section
- QMS Requirements
ISO 19011 (access liable to costs) – see in particular section
- Guidelines for auditing management systems
EMA – see in particular document
Procedure for reporting of GCP inspections requested by the committee for Medical Products for Human Use (CHMP)
- Appendix 5: Grading of inspection findings
ClinO – see in particular articles
- Art. 46 Agency inspections