Module 9 2021

19/03/2021

Phase 3 Studies

Therapeutic confirmatory studies are governed by ICH and CHMP specific-therapeutic area guidelines ● Well controlled, randomised studies ● Placebo or active comparator-controlled Possible to consider an adaptive design of seamless Phase 2 to Phase 3 Immunogenicity is a key area for investigation ● Potential impact on PK, efficacy or safety must all be considered – Increased clearance, neutralising ADAs, infusion-related reactions, hypersensitivity (Type I and III), cross-reacting antibodies

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Safety and Risk Management

ICH requirements for level of safety exposure ● Biopharmaceuticals are usually developed for long-term use – Long-term controlled studies are usually 1-2 years in duration – Long-term open-label extension studies Need to understand the safety profile of the IMP and develop a risk management plan (RMP) ● Any identified or potential risk will be described along with any measures that can be taken to mitigate against these risks (risk minimisation measures) Post Approval efforts can include ● Long-term open-label extension reporting for safety and/or efficacy ● Post-authorisation safety or efficacy studies (PASS or PAES) – Usually observational or registry type studies focusing on general safety under normal conditions of use, potential important risks, effectiveness of any risk minimisation measures (e.g. patient and healthcare provide alert cards)

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