By: Anders Neil, Principal Consultant, PAREXEL Consulting
On 20th July , 2017, the EMA adopted an update to the EU “Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products (EMEA/CHMP/SWP/28367/07 Rev. 1)” that will come into effect on 1st February 2018.
The express purpose of this update is to ensure the safety and well-being of trial subjects, taking into account recent development, including a severe trial event since the issue of the original guidance in 2007. The focus of the new version is on reducing uncertainty in benefit/risk assessment of new products by a stepwise process to ensure that information on safety needs are integrated from many sources, and provide more detailed requirements on risk mitigation. The guideline is extended to cover both FIH and early clinical trials thus handling integrated (multi-stage/adaptive) protocol design, and also adds requirements on Quality (CMC) aspects and trial facilities not in the first version.
Based on the degree of uncertainty, risk mitigation strategies are now proposed also to consider:
- Product Quality (CMC). Measures to ensure adequate quality of the test product with respect to strength and potency determination; qualification of the material used; reliability of very small dose delivery.
- Nonclinical. Potential need for additional non-clinical data of relevance for the risk assessment as relevance of animal models (or need to use human-derived material to close gaps); secondary pharmacodynamics data; determination of systemic exposure in primary pharmacodynamics studies.
- Clinical. Demand for a scientific rationale in the selection of the starting dose, for dose escalation and when defining the maximum exposure to be achieved. Application of appropriate risk mitigating measures in the design and conduct of FIH/early trials, including detailed views on integrated protocols (SAD/MAD combinations), and decision criteria to enter next phase; stopping rules; clear demands on trials facilities and staffing for early trials.
Future applicants should note that some of the new measures extend well beyond current ICH guideline requirements on documentation for early trials, that now need to be incorporated in CMC and non-clinical development plans.
PAREXEL Consulting provides dedicated subject-matter expertise that is uniquely suited to advise biopharmaceutical companies on the development, regulation, and submission of clinical trials in EU. PAREXEL is currently supporting clients in developing regulatory strategies, CMC, pre-clinical and clinical development plans, and trial submissions in all therapeutic areas. PAREXEL also provides early and late phase clinical trials services covering the entire product life-cycle from first-in man to post-approval studies, as well as market access and reimbursement support.