Drug Safety 2007; 30 (10): 919-990 0114-5916/07/0010-0919/$44.95/0
ABSTRACTS
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Oral Presentations O.15 Review of New Challenges for the Development of Early Phase Biologic Compounds in the Wake of the TGN1412 Clinical Trial A.J. Mackey, C.J. Wadsworth AstraZeneca, Macclesfield, UK Objectives: Identify challenges in Biologics development post TGN141. Methods: Search of scientific and regulatory literature for the period March 2006 - May 2007 identifying new recommendations for the development of Biologic agents. An internal consultation on the challenges faced post TGN1412 clinical trial. Comparison of the Guidelines for Phase 1 Clinical Trials 4th Edition, The Report of the Working Party on Statistical Issues in First in Man, Expert Scientific Group on Phase 1 Clinical Trials Final Report, Volume 9a of the Rules Governing Medicinal Products in the European Union and the EMEA guidance. Results: The MHRA has authorised 842 so-called chemical trials and 66 Biologic trials from September 2004 to approximately December 2006 in healthy volunteers.[1] Many companies e.g. AstraZeneca are actively pursuing an expanding Biologics portfolio. Pharmacovigilance challenges; including the mandatory reporting of transmissible elements in medicinal products as SAEs in draft 9A; the expedited reporting of SUSARs to include those concerned with placebo according to the ABPI guidelines,[2] risk mitigation in dosing schedule, input in site selection. Regulatory challenges; new draft guidelines produced by the ABPI, the EMEA and the MHRA are detailed in the poster. Among the new challenges discussed are the establishment of an extra review step for so called “high risk compounds”, the recommendation of the MABEL approach for calculation of first dose exposure etc. Clinical Pharmacology; despite multiple confounding factors the impression of an AstraZeneca Clinical Pharmacology Unit that specialises in FTIM clinical trials is that volunteering has decreased. The advertising spend to generate approx 300 entrants to the potential group has almost doubled from £250,000 in 2005 to £500,000 predicted for 2007. Occupancy rates have decreased as fewer volunteers dosed per day. Increased running costs/length of study. Discussion: Many of the regulatory and the academic papers are guidelines however it is apparent that these will be adopted as requirements and will also from the basis of binding regulation outside Europe. Conclusion: It seems inevitable that greater regulatory, public and political scrutiny will come on early phase development of Biologic agents. Furthermore it seems that Biologic agents are set to expand in importance as potential new medicines. The impact will be to substantially increase the safety requirements to bring a new Biologic agent to later phase development. As the changes are driven by the will to increase the safety of individual healthy volunteers it is a challenge to be embraced by the industry. References 1. Appendix H “Duff report”. 2. Guidelines for phase 1 clinical trials. 4th edition
