When does one speak of a "true" First in Human trial?

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

Early phase clinical trials have risks associated with them that require mitigation. Not only the legislation has to be followed; all  associated guidance documents, which will help in maintaining public safety and data integrity, must also be abided by. Thinking about how trials might be inspected and performing appropriate risk-assessments helps to distinguish true first in human (FIH) trials from other early phase trials. While the decision may not have an impact on the authorization decision by the MHRA Clinical Trials Unit (CTU) or approval by the ethics committee, it can have an impact on:

• how to identify and mitigate the risks associated with the clinical trial,
• how the clinical trial will be inspected by the MHRA GCP inspectors in relation to GCP and early phase guidance,
• meeting GCP requirements for trial activities, such as dose escalation,
• expectations for accredited phase 1 units maintaining their accreditation.

Therefore, the MHRA blog provides two flowcharts with some questions and answers to help in performing risk assessments and completing  IRAS (Integrated Research Application System) and CTA (Clinical Trial Application) forms:

• Flow chart 1: Is it a ‘true’ FIH trial?
  If it’s not a ‘true’ FIH trial, as the IMP has been given to humans before, other factors may be taken into account which might influence the decision as to whether it should be considered a FIH trial.
• Flow chart 2: For an IMP that has been given to humans before, do the risks identified warrant categorizing it as a FIH?
  (e.g. considering new combination therapies, new formulations, new populations)

By deciding what type and phase of trial it is, one can confidently risk-assess the clinical trial and complete the corresponding CTA and IRAS forms. This will then allow MHRA GCP inspectors to inspect the clinical trial according to the applicable legislation and guidance. It will also help inspectors and MHRA accredited phase 1 units to identify those trials appropriately for assessment against the MHRA phase 1 accreditation scheme. Additionally, according to the MHRA, the sponsor has to make the right decision about type and phase of the trial.

More useful information can be found in the EMA guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products, adopted in July 2017.

The full post, "Is it really a First in Human trial? Categorizing and assessing the risks correctly" can be found on the MHRA Inspectorate blog.