Association for Human Pharmacology in the Pharmaceutical Industry conference 2022: impending change, innovations and future challenges.

The Association for Human Pharmacology in the Pharmaceutical Industry's annual meeting focused on current and impending challenges facing the United Kingdom's (UK) pharmaceutical industry and how these opportunities can inspire innovation and best practice. The UK pharmaceutical landscape is still evolving following Brexit and learnings from the coronavirus disease 2019 (COVID-19) pandemic. As such, the UK's clinical community is in a unique position to steer innovation in a meaningful direction. With the continuation of remote forms of working, further opportunities have arisen to support novel practices away from the clinic. The keynote speaker reflected on clinical development over the past 40 years and how the industry must continue to concentrate on patient welfare. The future of drug development was discussed regarding challenges associated with developing translational gene therapies, and the status of investment markets analyzed from a business strategy and consulting perspective. The patient viewpoint was a core theme throughout the conference with patient-centric blood sampling and decentralized clinical trials providing suggestions for how the industry can save costs and increase efficiency. Moreover, the patient perspective was central to a debate over whether ethics requirements should be the same for oncology patients taking part in first-in-human studies as those for healthy subjects. Discussions continued around the changing roles of the Qualified Person and Principal Investigators which underpins how sponsors may want to run future trials in the UK. Lessons learned from conducting challenge trials in healthy volunteers and patients were discussed following a presentation from the serving Chair of the COVID-19 challenge ethics committee. The current state of interactions with the Medicines and Healthcare products Regulatory Agency were also explored. It was considered how the immediate future for the UK clinical trials community is inevitably still linked with Europe; the newly implemented European Medicines Agency Clinical Trials Information System has been met with lukewarm responses, providing a promising opportunity to ensure UK Phase I units continue to play a vital role in global research.

The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting October 2019: Impending Change, Innovation, and Future Challenges.

The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on impending change, innovation, and future challenges facing early phase drug development as we move into the second decade of the 21th century. The meeting opened with discussion around the technical revolution in pharmaceutical medicine over the 4 decades since the AHPPI was founded and how transformative technologies have accompanied the introduction of processes such as physiologically based pharmacokinetic modeling. During the meeting examples were presented of how in terms of the development of new therapies, the classic phases of clinical drug development are becoming a thing of the past and the lines between the phases have begun to blur, particularly in the field of oncology. The contribution that monoclonal antibodies have made to medicine and the next chapter in their design and use was also discussed. A representative of the UK's Medicine and Healthcare Products Regulatory Agency discussed the increasing numbers of requests to approve complex innovative design trials, how novel trial designs are impacting on the traditional linear "phase" approach to drug development and the common pitfalls associated with them. Guidance was provided from a regulator's viewpoint on what was meant by the term "novel design" and how to submit successful trial applications for such complex trials. In an Oxford-style debate, the audience discussed the motion that "there is no longer a need to include placebo subjects in early clinical trials." The keynote speaker focused on delivering change in complex environments such as the field of drug development. The afternoon session included presentations on the challenges associated with drug product design, the complexities within non-oral dosage forms and proposed new methods of formulations for drug delivery. Presentations were also given on advances in mechanistic and computational pharmacokinetic modeling and how they have proved to be valuable tools to rationalize and facilitate the process of drug development.

European Federation for Exploratory Medicines Development Lyon Conference 2019: The Changing Landscape of Early Medicines Development-Be Prepared.

The second biennial conference of the European Federation for Exploratory Medicines Development (EUFEMED) was the result of a continued effort of EUFEMED to gather all stakeholders of exploratory clinical drug development to evaluate and discuss recent developments in the field. The conference focused on how the landscape around early clinical development is changing and how clinical pharmacologists might prepare for these changes. A preconference workshop gave consideration to the impact that modeling and simulation, including physiology-based pharmacokinetic strategies, is having on the practice of clinical development. A second workshop looked at the challenges introduced by biological agents. The keynote address explored the potential role of virtual trials in early medicines development with emphasis on how models can help to understand and inform the drug development process. Presentations that followed covered a broad range of subjects including the potential impact of digital support on study performance in early phase development, extending from recruitment to remote data collection, lay person summaries, data transparency, and ethical considerations for trials in healthy subjects. The second day of the conference focused on future regulatory challenges in the field of early clinical development (including Brexit) and how to prepare for changes in the landscape. Subjects covered included new approaches and designs in oncology, the introduction of more complex study designs and digital biomarkers. Presentations given by invited speakers are published at https://www.eufemed.eu/download-presentations-of-the-lyon-conference-2019/.

The New First-in-Human EMA Guideline: Disruptive or Constructive? Outcomes From the First EUFEMED Discussion Forum.

The European Federation for Exploratory Medicines Development (EUFEMED) organized a meeting in Leuven, Belgium entitled 'The new FIH EMA guideline: Disruptive or constructive?' to provide a forum for stakeholders to discuss the guideline's operational impact. The revised EMA Guideline on strategies to identify and mitigate risks for first-in-human (FIH) and early clinical trials with investigational products was published on 20 July 2017. The revision gave guidance on sentinel dosing/staggering of subjects within a multiple-ascending dose (MAD) clinical trial, permissible maximum exposure/investigation of supra-therapeutic doses and dose escalations above the no-observed adverse effect level. As the guidelines came into operation on 1 February, 2018 it was assumed that by the date of the meeting many early phase stakeholders had gathered sufficient first-hand experience of working within the guideline to discuss their thoughts on its impact. The concluding part of the meeting focused on the possible differences between European countries in handling the revised FIH guideline and ways of achieving harmonization. Information on current industry practice was gathered by online polling during the meeting, where perception of the revised guideline as either 'disruptive' or 'constructive' was explored at the start and at the end of the Forum along with recommendations on reducing future regulatory discordance. It was generally agreed that the necessary changes encompassed by new guidelines included both constructive and disruptive aspects. The final vote on whether the new FIH guideline is disruptive or constructive was taken by 69 delegates: 51% stated that it was both constructive and disruptive, 48% decided on constructive, none on disruptive and 1% were still undecided. It was generally accepted that stakeholders need to continue in a process of stakeholder engagement and discussion, particularly on critical safety issues. Such an approach allows partners to adopt a proactive approach to sharing best practice. For example, attendees agreed that a 'Question and Answer' document harmonized between the European agencies is required for the sentinel approach and for the selection of supratherapeutic doses.

The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting 2018: Brexit and Other Challenges in Early Phase Drug Development.

The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on the changing face of early phase drug development and opened with a keynote speech concerning the revolution in pharmaceutical medicine over the last 30 years and the impact this has had on the way patients are treated. Examples were presented of how translational pharmaceutics is being used to tackle the high drug candidate failure rate and is improving productivity when moving drug candidates from the laboratory through to clinical proof of concept. The European Medicines Agency revised 2007 Risk Mitigation guideline on first in human (FIH) clinical trials was discussed. The focus of the revised guideline, which came into force in February 2018, is on risk mitigation and promotion of safety and will assist drug sponsors with the design and performance of early clinical studies. The use of integrated adaptive protocol designs in early clinical development was discussed in relation to the challenges involved when running early phase clinical trials in patients. The Health Regulatory Authority presented its strategies to ensure that following Brexit, the United Kingdom remains an attractive place to conduct Phase I clinical trials. The Medicines and Healthcare products Regulatory Agency confirmed that in the event of a "no deal" Brexit, it is well placed to implement and influence many provisions of the new EU CTR. The meeting provided an opportunity to discuss the changing regulatory environment and the opportunities and challenges facing the United Kingdom following Brexit with invited speakers from a range of disciplines including drug development, clinical trials and research organizations, government science policy and regulatory agencies.

EUFEMED London Conference 2017: Exploratory Medicines Development: Innovation and Risk Management.

The first formal conference of the EUropean Federation for Exploratory MEdicines Development (EUFEMED) held in London was the result of a collaborative effort of its founding associations: the Association for Applied Human Pharmacology (AGAH; Germany), the Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI; UK), the Belgian Association of Phase-I Units (BAPU; Belgium), and Club Phase-I (France). The conference focused on innovation and risk management in early clinical drug development. Among other innovations, immunotherapy in oncology and inflammatory diseases were discussed as well as the importance of adaptive trial designs in early clinical drug development. Consideration was given to assessing and mitigating risk in early clinical drug development, and included a preconference workshop. Different measures to minimize risks in healthy volunteers and patients in first-in-human trials were discussed in addition to the importance of non-clinical data, the need for reliable biomarkers, improved communication on adverse events (AEs) and well-trained study sites with ready access to intensive care units and clinical specialists. The need for a European-wide system for prevention of over-volunteering was also discussed. The conference provided opportunity to discuss these developments and concerns and the changing regulatory environment with stakeholders from academia, industry, and regulatory agencies including the European Medicines Agency (EMA). Presentations given by invited speakers are published on http://www.eufemed.eu/london-conference-2017/.