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ICH E6 – Summary of Changes

ICH E6 Good Clinical Practice

ICH E6 Good Clinical Practice is an international scientific and ethical quality standard for conducting, designing, recording and reporting trials involving human participation. It provides the public with assurance that all rights and safety of trial subjects are protected and consistent with the principles that originate in the Declaration of Helsinki and clinical data. ICH E6 GCP Guidelines were developed to provide unified standards for Japan, United States, European Union, Australia, Canada and the World Health Organization. Involvement of modern technology in clinical trials made the process of data processing more complex, the last update to these guidelines was June 1996. Hence, amendments were required in original ICH E6 (R1) text.

Principles of ICH GCP

Clinical trials should be conducted per ethical principles and before it is initiated, risks and inconveniences should be considered and weighted against the anticipate benefits. They should be scientifically sound, conducted in compliance with the protocol and the rights and well-being of the trial subjects should be the most important consideration. Anyone involved in the process should be qualified and experienced. In the latest release of E6 GCP the following principals were added:

  1. Principles of ICH E6 applies to all records and media used;
  2. Systems need to be focused on human subject protection.

Updated Investigator Requirements

Adequate Resources

The GCP guidelines have elaborated the responsibilities of investigators to include:

  1. Investigator is responsible for delegated trial-related duties and functions at site;
  2. Investigator is responsible for ensuring that staff is qualified to complete activities;
  3. Investigator needs to implementing procedures and process ensuring the integrity of the trial.

Records and Reports

The guideline elaborated on the responsibilities regarding adequate and accurate source documents. Source documents should be attributable, legible, contemporaneous, original, accurate and complete. Any changes to source documents should include the following:

  1. Original entry;
  2. Who made the change;
  3. Reason for change.

Updated Sponsor Requirements

Quality Management

GCP guidelines outlined the need for sponsors to maintain a quality management system. The quality management system should oversee all stages of the clinical trial process. This system should focus on activities that ensure human protection and reliable trial results. The quality system should be flexible and adjust to the level of risk to human protection or data integrity. A risk based approach should include the following:

  1. Critical process and data identification;
  2. Risk identification;
  3. Risk evaluation;
  4. Risk control;
  5. Risk communication;
  6. Risk review;
  7. Risk reporting.

CRO Oversight

The sponsor may continue to transfer trial-related duties and functions, but all the responsibilities for integrity and quality trial data reside with the sponsor. However, the sponsor should ensure oversight of all activities carried out on its behalf.

Trial Management, Data Handling and Record Keeping

ICH expanded on the expectations when validating clinical system, the sponsor should ensure it conforms to the requirements for accuracy, reliability, consistent performance and completeness. The following addendums where added to E6:

  1. Sponsor should use risk based approach when validating system, consideration include intended use and potential impact on human protection and trial results;
  2. Maintain SOPs of using these systems;
  3. SOPs should cover set up, installation and on-going use.
  4. Ensure the integrity of the especially when making changes to computerized systems, such as software upgrades or migration of data.

Risk Based Monitoring

Sponsors are expected to ensure the well-being of human subjects and maintain data integrity throughout the life of the trial. The guidelines defined a risk based approach to monitoring that includes a centralize monitoring component when managing a clinical trial. Here are some of the additional highlights:

  1. A flexible approach to monitoring that include onsite, centralize, or a combination of both;
  2. Sponsors are expected to maintain monitoring plans that includes the rationale of monitoring strategy;
  3. Monitoring plans should include the following:
  4. Missing/inconsistent data reviews;
  5. Review trends within and across sites;
  6. Evaluation of systematic or data collection errors within and across sites;
  7. Performance metrics;
  8. Process for targeted on-site monitoring.
  9. Sponsors should maintain onsite and /or centralize monitoring reports.


Noncompliance with the protocol, GCP or applicable regulatory requirements by the institution/investigator or sponsor staff should lead to prompt action by the sponsor to secure compliance. If it has significant effects on human subjects or the trial results, the sponsor should analyze and implement appropriate collective and preventive actions or should terminate the institution/investigator participation in the trial.


In conclusion, the updates to the ICH E6 Guidelines (http://www.ich.org) is to provide clarity on the use of electronic records and clinical systems since the last updated in 1996. Additionally, ICH continued to provide guidance on expectations for risk based monitoring and quality management processes.

Emanate is passionate about supporting small to midsize biotech and medical device companies get their products approved. Our clients have access to experienced industry professionals and subject matter experts for their clinical IT needs. Our expertise keeps sponsors compliant with government regulations, exercising good clinical practices and improving data quality in a cost-effective manner.

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