What is it? Why is it important?

Findings are results of a process where audit/inspection criteria are compared against audit/inspection evidence.

Findings means that given criteria were not met. There are 3 categories with minor-, major-, and critical finding.

Audit criteria may include:

  • Study protocol, SOPs
  • GCP, ISO and regulatory requirements

Evidence include verifiable study documents, such as:

  • Essential documents in TMF/ISF
  • Signed and dated IC
  • IMP/MD handling
  • Safety reporting procedures
  • Evidence also originates from staff interviews

More

Based in the European Medicine Agency (EMA) findings that are not-met are categorised – as follows:

Critical:

  • 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

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

Minor:

  • 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?

Non-met findings must be subject to a root-cause analysis.

  • Means to correct findings must be defined in order to return to criteria compliance
  • Preventative action or processes must be defined in order to prevent reoccurrence of finding(s)
  • A CAPA report is written summarising handling of non-met findings. A timeline is included stating until when CAPAs will be processed

More

Example of a finding

Participant and Site-INV did not date and sign the IC on the same day. The participant singed the document 2 days prior to the Site-INV.

Criteria: Participant and Site-INV must jointly date and sign the IC during the visit when the participant is informed - and included in the study.

Route cause analysis: Participants receive study information including the IC document to take home for evaluation. Upon return to the clinic participants have already signed IC. The Site-INV is not aware of the requirement that the IC must be jointly signed on the same day.

Preventative action: Training of Site-INV regarding joint signing criteria. IC process was adapted. In the event the participant has pre-dated and singed the IC 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

References

ICH GCP E6(R2) – see in particular guidelines

  • 1.29 Inspection
  • 1.6 Audit
  • 5.0 Quality management

ISO 9001 – see in particular section

  • QMS Requirements (access liable to costs)

ISO 19011 – see in particular section

  • Guidelines for auditing management systems (access liable to costs)

EMA – Classification and analysis of GCP inspection findings

Swiss Law

ClinO – see in particular articles

  • Art. 46 Agency inspections
Abbreviations
  • CAPA – Corrective and Preventative Actions
  • CTU – Clinical Trials Unit
  • GCP – Good Clinical Practice
  • IC – Informed Consent
  • IMP/MD – Investigational Medicinal Product / Medicinal Device
  • Site-INV – Site-Investigator
  • SOP – Standard Operating Procedures
  • TMF/ISF – Trial Master File / Investigator Site File
Conduct ↦ Quality and Risk ↦ Regulatory Inspections ↦ Findings
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Conduct ↦ Quality and Risk ↦ Regulatory Inspections ↦ Findings

Please note: the Easy-GCS tool is currently under construction.