Our first blog post for 2017 focuses on the ICH GCP E6 (R2) Addendum which was published in December 2016 and will become effective on the 14 June 2017. ICH GCP is the gold standard for the conduct of clinical trials. This update is an important milestone in driving adoption of Quality-by-Design and Quality Risk Management principles and methodologies in clinical development.
This is the first revision since (R1) which was published in 1996. The fundamentals of ICH have not changed but reforms to the process and organisation were needed to adapt to changes in how medicines are developed and regulated and also the advancements in technology over the last twenty years . It also takes into consideration the findings of GCP regulatory inspections in the various regions over the years. The main updates are in section 5 and relate to the implementation of quality systems and sponsor and investigator responsibilities.
Some of the key changes are as follows:
Quality Management Systems
- Sponsor should implement a system to manage quality throughout the design, conduct, recording, evaluation, reporting and archiving of clinical trials and that Sponsors should focus on trial activities essential to ensuring human subject protection and the reliability of trial results. This includes the efficient design of protocols, data collection tools and procedures and the collection of information that is essential to decision making. The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected.
- Sponsor should ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures and data collection.
- Sponsor must employ a risk-based approach to monitor the clinical trial and employ risk mitigation strategies. Quality tolerance limits are also proposed and the risk assessments need to be reviewed periodically to ensure that the implemented Quality management system is effective and relevant.
- Records and reports – investigator must maintain adequate and accurate source documents and records. This includes all pertinent observations on each of the trial subjects and documents for critical processes. The revision describes how all information should be ALCOAC (Attributable, Legible, Contemporaneous, Original, Accurate and Complete).
- The investigator should assure that there is a suitable plan in place to supervise the different individuals and parties engaged in the study. This includes staff who may not be in his/her direct employ.
- Trial management, data handling and record keeping. The sponsor is obligated to have written procedures in place for all electronic systems used in the trial and an SOP should be in place for the validation and functionality testing, data collection and handling, systems maintenance, system security measures, change control data backup, recovery, contingency planning and decommissioning.
- Sponsor oversight of Vendors (5.2.1. & 5.2.2.) The sponsor should ensure oversight of any trial related duties and functions carried out on its behalf. The sponsor should document approval for any subcontracting of trial-related duties and functions by the CRO.
- Non-compliance to protocol, GCP and written procedures are the sponsor’s responsibility. When noncompliance occurs, the sponsor should perform a root cause analysis and implement a corrective and preventative action plan. Grave violations must be reported to the regulatory authorities.
- Monitoring plans are now included explicitly in the Addendum and monitoring activities should be documented in sufficient detail to allow verification of the monitoring plan.
- In addition to the implementation of risk based monitoring mentioned above, the addendum also requires that the outcomes of any centralised monitoring should also be reported and that the monitoring plan should be tailored to the specific human subject protection and data integrity risks of the trial (5.18.7).
Ultimately the purpose of this revision is to encourage the implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording, and reporting, while ensuring that human subject protection and data integrity are maintained. This can only be viewed as a positive step and a progressive time for all research professionals. A key action now for all concerned is to ensure that all personnel actively involved in clinical research receive the necessary training and operating procedures are adapted accordingly on time for the June deadline.
You can find out more about the updates here.