Rise in antibacterial resistance coupled with a stagnating development pipeline continues to be an urgent public health concern. As the regulatory authority responsible for ensuring that available antibacterial therapies are safe and effective and facilitating their development, FDA’s Center for Drug Evaluation and Research (CDER) recognized that it plays an important role in addressing this issue. Therefore, a dedicated effort was launched to utilize the experience and expertise of CDER scientists to play their role in addressing this public health crisis.
In September 2012, CDER announced the establishment of a multidisciplinary task force focused on antibacterial drug development. Upon its inception, the task force sought to promote antibacterial drug development through the use of novel approaches. The task force leverages not only the expertise of Agency scientists, but also promotes collaboration of the many stakeholder groups involved with the clinical development enterprise. The task force provides guidance related to antibacterial drug development, stimulates and facilitates drug development through communication and outreach, and identifies ways to advance the underlying science needed for drug development.
Regulatory Flexibility – Clarification of Clinical Development Pathways
A major part of the task force’s work is devoted to the review and revision of existing guidances, as well as the development of new guidances related to antibacterial drug development. With its broad representation across CDER, the task force assists in the review and issuance of multiple guidances on key topics, such as development of antibacterial drugs for patients with unmet medical needs, Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP), Community-Acquired Bacterial Pneumonia (CABP), Uncomplicated Gonorrhea, and Acute Bacterial Skin and Skin Structure Infection (ABSSSI). Development of guidances not only provides clarification to drug developers on potential clinical pathways to be utilized in development, but also provides predictability, as it documents the Agency’s current thinking on these topics. Furthermore, these guidances illustrate how CDER plans to utilize regulatory flexibility to facilitate antibacterial drug development. For example, these guidances explain how supportive information can be leveraged to augment trial data in providing evidence of safety or effectiveness when a traditional development program (i.e., two large, phase III trials) may not be feasible and describe approaches to addressing enrollment challenges, such as patients receiving prior antibacterial therapy. In addition, the guidances indicate the Agency’s willingness to discuss with sponsors alternative approaches to satisfying certain requirements. Continued support of guidance development continues to be a focus of the ongoing task force activities aimed at providing regulatory flexibility in the field of antibacterial drug development.
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Communication and Outreach – Collaboration across stakeholders
The task force has been directly involved in a number of meetings and workshops to incorporate input from key stakeholders, including drug developers, academics, and patients, into its activities. Through such activities, the task force collaborates with a cross section of parties involved in the clinical development enterprise with the goal of promoting efficient antibacterial drug development. Meetings and workshops have focused on topics such as the use of innovative statistical approaches to the design and analysis of clinical trials in antibacterial drug development, development of clinical design approaches to address unmet medical needs in antibacterial drug development, priorities and issues related to feasible design features of HABP/VABP clinical trials, and alternative pathways for approval for drugs addressing unmet medical needs for antibacterial treatments. The task force recognizes that it alone cannot tackle the list of challenges impeding development of new therapies or preserving the utility of existing ones, and plans to continue the communication and outreach efforts to work collectively to address this important public health issue.
Regulatory Science Advancement – Identification of novel approaches
Alongside efforts on clarifying development pathways and facilitating communication and outreach, the task force has also sought ways to advance regulatory science and identify potential novel solutions to the various challenges impeding development of needed therapies. A major commodity of the task force is the wealth of knowledge possessed by its members. CDER has leveraged that knowledge asset to improve efficiencies within the antibacterial clinical trial enterprise, while still ensuring the information generated from antibacterial trials stands up to the rigor needed to establish safety and effectiveness. In particular, the task force is working with outside public private partnerships, such as the Foundations for the National Institutes of Health Biomarkers Consortium and the Clinical Trials Transformation Initiative (CTTI) to further expedite antibacterial drug development. Work has focused on activities related to appropriate endpoint selection, application of Quality-by-Design approaches, and streamlining clinical trial protocols for HABP/VABP.
Next Steps – Drug Discovery and Attacking Resistance
The large undertaking the task force was given in helping to regenerate interest in clinical development in this field has taken tremendous time and resources, and gaps still need to be addressed. While much of the focus has been made on regulatory flexibility and more efficient approaches to drug development, a continuing supply of new therapies will have an important impact on addressing the public health concern of a diminishing pipeline coinciding with rising antibacterial resistance. To date, the activities of the task force have helped provide a framework for future drug development. As that framework starts to mature, the task force intends to broaden its communication and outreach efforts by holding meetings and workshops to foster the discovery and development of innovative therapies to combat increasingly difficult to treat pathogens.
While these efforts address new antibacterial drug development, additional approaches are needed to break the cycle of emergent resistance when new antibacterial drugs are approved and used in clinical practice. The task force will put increasing emphasis on communication and outreach efforts in areas of drug discovery designed to preempt or reduce emergent resistance. The task force will put increasing emphasis on communication and outreach efforts in areas of drug discovery designed to preempt or reduce emergent resistance and to identify new bacterial targets to preserve the activity of antibacterial drugs.