Final ICH E8(R1) Guideline on General Considerations for Clinical Trials

The final ICH E8(R1) guideline reached Step 4 of the ICH Process. The modernization of E8 is the first step towards the Renovation of Good Clinical Practice (GCP) initiated in 2017. Earlier this year, updated principles of ICH E6(R3) including revised and expanded principles regarding GMP for IMPs have already been released. According to ICH, the E8(R1) guideline provides "guidance on the clinical development lifecycle, including designing quality into clinical studies, considering the broad range of clinical study designs and data sources used".

Background

In 2017, the International Council on Harmonization (ICH) decided to undertake a general revision of the GCP principles. This also includes the revision of all ICH guidance documents that pertain to this area. One of the core documents is ICH E8 "General Considerations for Clinical Trials." The ICH E8(R1) draft guideline reached Step 2b of the ICH Process in May 2019 and included three annexes. However, the final E8(R1) guidance contains only one annex on types of clinical studies (i.e. tolerance & safety, exploratory, confirmatory, post-approval studies). The next step in the ICH process is to implement the Guidance in ICH member countries. The Guideline E8(R1) has, for example, already been published as EMA Guidance (Step 5 of the ICH process) and has thus been incorporated into the European regulatory framework (date for coming into effect: 14 April 2022).

Quality of Investigational Medicinal Products (IMPs)

Ensuring adequate quality of IMPs is addressed in ICH and regional GMP guidelines (e.g. Annex 13 of the EU GMP Guide). According to the ICH, more extensive characterization may be required for complex or biological products. In addition, formulations should be well characterized, including information on bioavailability, and should be appropriate for the stage of drug development and the targeted patient population (e.g. age-appropriate formulations for paediatric populations). Evaluation of the drug quality may be extended to devices required for administration. Changes in a product during development should be supported by comparability data to ensure the ability to interpret study results (e.g. establishing links between formulations through bioequivalence studies).

Further information can be found on the ICH E8(R1) webpage.