SESSION RECAPS AND PRESENTATIONS
October 2, 2013
Day One of the workshop began with a presentation on recent progress in drug development and CPTR’s goals for the future by Dr. Debra Hanna, Executive Director of CPTR at the Critical Path Institute. This was followed by the keynote presentation by Dr. Mario Raviglione, Director, WHO Global TB Programme, who focused on the adoption of new drugs, including the prequalification medicines program (PQP) and WHO’s approach to integrating soon to be available new drugs into its TB treatment and control policies and guidelines.
Afternoon sessions provided an opportunity for participants to engage in practical working group discussions around regulatory science – including biomarkers and clinical endpoints, preclinical and clinical sciences, modeling and simulation, and data standards and integration. Research resources workgroups reviewed current initiatives on regulatory pathways and clinical trial infrastructure support.
The day concluded with multiple regulatory perspectives on new TB drugs and regimens, and was followed by a roundtable discussion with a panel of regulators from around the world.
Jan Ghuens, Bill & Melinda Gates Foundation, welcomed participants to the workshop. See Jan Ghuens’ video.
CPTR Roadmap: Accomplishments and Future Direction
In the opening presentation, Dr. Debra Hanna, Executive Director of CPTR at the Critical Path Institute, shared progress on novel drug regimen testing and challenges facing the field, including how to balance single drug development with regimens, and the currently fragile TB pipeline. She also gave an overview of CPTR’s recent accomplishments, including formation of the Rapid DST consortium and recent activities of the Research Resources and Regulatory Science working groups. See Debra Hanna’s Roadmap presentation and video.
Keynote: TB Elimination and TB drugs: Can We Make It?
In his keynote address, Dr. Raviglione, Director, WHO Global TB Programme, reviewed the global burden of TB and asked, “Is elimination possible in our lifetime?” He provided data on what is needed to accelerate incidence decline, an update on the current drug pipeline, and challenges to the TB community to prioritize research, supportive policies, and patient-centred care and prevention. See Mario Raviglione’s presentation and video. See the Q&A video.
WHO Role in Adopting New Drugs
Moderator: Martha Brumfield, President & CEO, Critical Path Institute (C-Path)
Presenters: Matthias Stahl, Head of Assessments, Prequalification of Medicines Programme (PMP), and Christian Lienhardt, Senior Scientist, Stop TB Partnership, WHO
This session provided participants with an overview of the WHO’s approach towards new TB drugs, with Matthias Stahl giving an overview of the Prequalification of Medicines Programme. He shared updates and resources on a number of finished pharmaceutical products (FPPs), including the 70 currently approved for TB and 44 FPPs in the pipeline. See Matthias Stahl’s presentation andvideo.
Christian Lienhardt presented WHO’s strategic plan for rational introduction of new TB drugs and regimens in countries, approaches for the introduction and delivery of new drugs and regimens, and then shared the WHO’s Policy Implementation Package, which assists countries in implementing new TB drugs or drug regimens. See Christian Lienhardt’s presentation and video.
See the WHO Role in Adopting New Drugs Q&A video.
Regulatory Science Workgroups – Plenary Session
The regulatory science plenary session provided an overview of a number of modeling initiatives being undertaken by CPTR partners. These included clinical trials simulation, Hollow Fiber, an integrated model for MTB, a physiologically based pharmacokinetic model and a liquid culture model.
Research Resources Workgroups
The Clinical Trials Infrastructure Workgroup examined the status of current projects, including a clinical trials database, which would serve as an information-sharing portal for TB drug developers and investigators. The eventual database could allow those developing clinical trials for TB to more efficiently gain and share information about upcoming trials. The group also discussed an ongoing project to provide standards for mycobacterial labs for TB clinical trials.
The Global Regulatory Pathways Workgroup received an update on the ethics review and clinical trial authorization process review recently conducted by the Global Health Regulatory Team, which explores issues around ethics committee review and clinical trial application approval in greater depth.
Regulatory Science Workgroups –Breakout Sessions
The Biomarkers and Clinical Endpoints Workgroup examined both the validity and feasibility of symptom studies and PROs (Patient Reported Outcomes) for TB trials, including discussion of a questionnaire to be used by Janssen and TB Alliance in upcoming trials. The group also discussed the use of liquid cultures in Phase 3 trials and a plan to help establish it as a standard tool for evaluation by the FDA as drug development efforts move forward. The session closed with discussion of future tools for identifying and measuring biomarkers and endpoints, as well as the feasibility for implementation.
The Modeling and Simulation Workgroup focused on a new expansion of CPTR’s modeling work, which will focus on achieving more efficient translation and decision making at each stage of TB drug development through a variety of models. Several of those tools were examined within the following categories: Hollow Fiber, physiologically based PK, and clinical trials simulation tools.
The Preclinical and Clinical Sciences Workgroup reviewed further updates and details on the in vitro Hollow Fiber for TB modeling work, including discussion on its potential and challenges. The group also reviewed plans for a potential upcoming workshop on PK/PD models.
The Data Standards and Integration Workgroup examined data standards for pediatric TB and existing standards set by the US and international registry.
Regulators’ Perspectives: Expediting New TB Treatments
Moderator: Mark Goldberger, AbbVie. See the video of Mark Goldberger’s comments.
Bob Clay, Regulatory Affairs from AstraZeneca, profiled recent regulatory developments in TB drug and regimen development as well as some of the regulatory challenges specific to high burden countries, including examples from Kenya, Thailand and Brazil. See Bob Clay’s presentation and video.
Ed Cox, Director of the Office of Antimicrobial Products at the FDA, provided an overview of the FDA’s process for approval of antimycobacterial drug development, background on EMA-FDA parallel advice, the FDA’s GAIN program and the relevance of the Tropical Disease Priority Review Voucher process for TB drugs. He also shared various online resources, including guidance documents and information on the FDA advisory committee and product labeling. See Ed Cox’s presentation and video.
Eric Prelfrene, European Medicines Agency, examined the EMA’s regulatory tools currently in place, focusing on “Article 58”, orphan medicinal product designations and other tools in place for TB drugs and regimen regulation. He also provided a review of EMA initiatives, including confirmatory studies on various TB types. See Eric Prelfrene’s presentation and video.
These presentations were followed by a Q&A session on global regulatory perspectives. Presenters were joined for this discussion by regulators from around the world, including Joe Toerner, FDA; Stephen Kimatu, Kenya; Prapassorn Thanaphollert, Thailand; Dr. Barbano, ANVISA-Brasil; and Matthias Stahl, WHO. See the Q&A Session video.