New GCP addendum E6 R2

Since the GCP (E6 R1) was first released in 1996, clinical trials have evolved substantially in complexity, technological capabilities, and costs.

ICH E6(R1) has been amended to encourage implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording, and reporting while continuing to ensure human subject protection and reliability of trial results. The amendment resulted in E6R2 which was released in Nov 2016.

The changes are summarised as below:

Investigator Delegation:

  • Supervise individuals or parties to whom trial-related duties and functions are delegated (section 4.2.5).
  • Ensure individuals and parties are qualified and implement procedures to ensure integrity of study tasks and data (4.2.6).

Source Document:

  • Maintain adequate and accurate source documents and trial records (4.9.0).
  • Source data should be attributable, legible, contemporaneous, original, accurate, and complete.

Quality Management (section 5.0).

  • Implement a system to manage quality throughout all stages of the trial process.
  • Focus on trial activities essential to ensuring human subject protection and the reliability of trial results.
  • Use methods to assure and control the quality of the trial that are proportionate to the risks.
  • Avoid unnecessary complexity, procedures, and data collection.
  • Use a risk-based approach to the quality management system.
  • Identify critical processes and data (section 5.0.1)
  • Identify risks to critical trial processes and data (5.0.2)
  • Evaluate risks (5.0.3)
  • Control risks (5.0.4)
  • Communicate risks (5.0.5)
  • Review risks (5.0.6)
  • Report risks (5.0.7)


  • Oversee trial-related duties and functions, including those that are subcontracted by Contract Research Organizations (CROs) (section 5.2.2).

Electronic Systems

  • When using computerised systems, base the validation approach on a risk assessment, maintain standard operating procedures, and ensure data integrity (5.5.3(a) and 5.5.3(h)).

Risk-based Monitoring

  • Monitoring (sections 5.18.3, 5.18.6(e), and 5.18.7)
  • Develop a systematic, prioritised, risk-based approach.
  • Develop a monitoring plan tailored to the human subject protection and data integrity risks of the trial.
  • May use varied approaches to monitoring (for example, combination of on-site and centralized monitoring) to improve effectiveness and efficiency.
  • Document the rationale for the monitoring strategy.
  • Document results of monitoring activities.


  • Follow-up of non-compliance that has or may significantly affect human subject protection or reliability of trial results, by performing a root cause analysis and implementing corrective and preventive actions (5.20.1).

Essential Documents (section 8.1):

  • Sponsor and investigator should maintain a record of the location(s) of their respective essential documents. Storage system should provide for document identification, version history, search, and retrieval.
  • Essential documents for a specific trial should be supplemented or may be reduced as appropriate.
  • Sponsor should ensure that the investigator has control of and continuous access to the case report form data.
  • When a copy is used to replace an original document, it should fulfil the requirements for certified copies.
  • Investigator should have control of all essential documents and records generated by the investigator before, during, and after the trial.

Mobius Medical can assist you to learn more about the new GCP addendum and how you can implement the new changes.