By: Sarah Bly and Aman Khera, Regulatory Science and Innovation
The journey of bringing a new therapeutic agent from the laboratory to the marketplace is fraught with challenges, not least of which is navigating the complexities of regulatory feedback, which do not always converge but can diverge. For clinical research professionals, this journey often involves reconciling differing feedback from regulatory agencies, each with unique standards, priorities, and expectations. This process can be daunting, but understanding how to manage feedback effectively is crucial for developing and ultimately gaining approval for new therapies, especially in oncology clinical trials.
The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has made strides in standardizing technical requirements to streamline pharmaceutical development on a global scale. The clinical trials sector prompted a recent modernization of ICH E8 and a subsequent renovation of ICH E6 to provide updated guidance that is appropriate and flexible enough to address the increasing diversity of clinical trial designs and data sources employed to support regulatory and other health policy decisions. Despite these efforts, variations between regulatory agencies remain, often resulting in divergent feedback that can complicate clinical development strategies. Below, we offer guidance on important concerns regarding divergent regulatory feedback with opportunities to harmonize, ensuring your development program aligns with international standards while efficiently anticipating and proactively addressing potential variations.
Take Advantage of Study and Clinical Development Precedents and Existing Guidance to Streamline Discovery
A practical first step in anticipating and addressing regulatory variations is to analyze recent advice, guidance, and other feedback on similar oncology products. Information on how other sponsors have successfully navigated similar variations helps to craft a clinical development plan that is mindful of existing regulatory sentiments. Consider researching previous development journeys within the same or similar indication to better anticipate variations, as they are more likely to have encountered similar issues. Researching these precedents, regulatory intelligence trends, and region-specific guidance will take work up front but ultimately save effort and increase the chances of approval with minimal back and forth. Your CRO can also play a crucial role in helping you to understand existing precedents and how they apply to your study and overall development journey.
Early and Ongoing Engagement Will Save Effort During Your Oncology Clinical Trial
Early and ongoing engagement with regulatory agencies is invaluable; initiating dialogue early in the development process facilitates a clearer understanding of regulatory requirements and expectations and builds a relationship with regulators. Maintaining open lines of communication helps address issues as they arise, allowing for real-time clarification and adjustments. Beyond the speed of addressing variations, early and ongoing engagement fosters confidence and trust from the regulatory agencies. This confidence will make discussions about optimizing study designs easier, with fewer revisions or modifications required. We cannot emphasize enough the value of candid bidirectional communication to help cut unnecessary costs and optimize the timeline to study completion.
Partnering with a CRO like Worldwide, experienced in regulatory agency engagement, can help facilitate these conversations because we can leverage our expertise and previously established relationships with regulatory agencies. Our experts can help you navigate early and continual engagement opportunities to receive optimal regulatory feedback. This support includes taking advantage of valuable guidance and direction from regulators, primarily in scientific advice, to support study design that generates robust information on how well a medicine works and how safe it is. An illustrative example of harmonization between agencies exists via the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) Parallel Scientific Advice procedure, which aims to increase dialogue between the two agencies and sponsor companies. This is a mechanism for experts to concurrently engage in scientific discourse with sponsors on key issues during the development phase of new medicinal products.
Check out our recent webinar for a more comprehensive dive into early and ongoing regulatory engagement and how it drives program and commercial success.
Comprehensive, Harmonized Regulatory Strategies Increase Efficiency and Reduce Hold-ups
Another critical step is developing a comprehensive, harmonized regulatory strategy plan anticipating potential issues. This involves regulatory mapping and scenario planning to identify and mitigate risks early on. Taking the time upfront to understand the different regulatory agencies’ policies and working to ensure the trial can meet them contributes to a faster timeline with fewer unforeseen interruptions. A well-crafted strategy outlines the path to compliance and provides clear justifications for trial design decisions, endpoints, and other crucial elements of the clinical trial.
Such thorough preparation underscores the importance of a holistic approach to regulatory planning, one that is aware of the potential for divergent feedback and is flexible and ready to address it. Additionally, consider the locations of your trial; if it is multiregional, you can start planning for your overall product approval strategy. Each nation has varying definitions of what qualifies as a pivotal study. Searching for overlap might allow the investigational product to have a more rapid marketing authorization in multiple regions. For example, there are accelerated pathways for oncology drug approval in the U.S., E.U., Japan, and China. Project Orbis also provides a framework for concurrent submission and review of oncology products among international partners in Australia, Brazil, Canada, Israel, Singapore, Switzerland, the U.K., and the U.S.
Conduct Your Oncology Clinical Trial with Confidence
Navigating the regulatory landscape of oncology trials, particularly in the face of varying feedback, is an undoubted challenge. Yet, it becomes a manageable aspect of drug development with careful planning, strategic engagement, and flexible problem-solving. By employing the strategies outlined above, you can address these challenges more effectively and expect higher chances of streamlined success in your development journey.
Ultimately, our goal is to bring safe and effective new therapies to patients. Working with experienced partners, such as Worldwide’s highly experienced, agile regulatory experts, to help make the optimal agency engagements and study submissions, we can provide the expertise and insight needed to overcome hurdles specific to your study needs. As we look towards future developments in oncology and beyond, the importance of strategic regulatory planning and execution cannot be overstated.
If you’re facing regulatory challenges or simply looking for guidance on your clinical development strategy, meet us at the upcoming ASCO conference. Our team is ready to support you through the complexities of regulatory agency engagement, helping you to bring your innovative treatments to those who need them most.
You can also find us at the Outsourcing Clinical Trial conference, where our experts will discuss navigating the complex regulatory landscape for oncology trials with a focus on the European Union.
