Whether you are developing a therapeutic or an enabling technology, you know that ambiguity can be one of the biggest hurdles to overcome in early development and can slow down or even stall decision making. One way to reduce ambiguity, and therefore risk, is to consult with regulators on your planned development activities. Companies may engage with Health Canada, U.S. Food and Drug Administration (FDA), European Medicines Association (EMA) or other global regulators as part of this process.
This blog post will provide insights into effectively engaging with regulators so that you can move your development program forward.
When to engage?
The usual advice, regardless of project type, is to engage early and often. Early is important because it will help you to make better and timely decisions, but also because it is usually less expensive and easier to make changes in early development than it would be later. For example, if you need to make any significant process changes to meet regulatory requirements, doing so late in development would usually require additional preclinical or even clinical data to support it, whereas if you do so before you even initiate your preclinical animal studies, this type of change can be made with a much smaller and easier to collect dataset.
It is also important to engage often throughout your development program. For example, you may wish to engage in very early development to ensure you are on the right path with your preclinical plans. You may then want to engage again right before filing your first clinical trial application to ensure acceptability of your clinical protocol, your finalized manufacturing process, and the preclinical data that supports both of those. It’s also common for companies to engage with their regulators at key milestones, such as at the end of their early stage clinical trials, before finalizing their late stage or pivotal studies. Similarly, if you need to make changes to significant aspects of your product, such as the manufacturing process or target patient population, these are triggers for engaging with your regulator. The aim is always to ensure that any potential issues are identified and addressed prior to any regulatory submission to reduce risk to your timelines and increase your likelihood of success.
Fig. Health Canada engagement types and example topics discussed at each stage
How to engage?
Meetings with regulators are yours to direct and so it’s up to you to get the most out of them. The ultimate purpose of these types of engagements is to help you make a decision and to move your program forward, so it’s important to be clear about the expected outcomes of the meeting(s), both internally and in your correspondence with your regulator.
The best way to achieve this is to ensure you are well prepared. Develop a clear, data-supported plan to present to the regulator, making sure to identify potential gaps or risks and how you intend to mitigate or manage them. Regulators will provide feedback, including suggesting alternative or additional measures if appropriate, and always with the intent to ensure quality, safety and efficacy is demonstrated for the stage of development. Regulators will not design your experiments for you or choose between various options for you, so keep this in mind when developing your proposal to present to them. Remember that you are the expert in your product or process; therefore, it’s up to you to make these key decisions, with their input along the way.
Presenting large amounts of novel data or concepts to any audience can be challenging. To streamline the process, we have created a list of tips to consider while you prepare your documentation.
Tips for preparing documentation for regulators
- Tell the story: explain why you generated the data you did, including how you made the decisions you made, and link that to precedent, literature, or preferably existing regulatory guidance. In early development, it’s also important to remember to highlight the expected clinical relevance of the data you’re generating.
- Keep it non-promotional and evidence-based: regulators are primarily concerned with patient safety, so presenting the potential market opportunity is not appropriate here; instead, consider highlighting the number of patients likely to be exposed or the impact on the standard of care for those patients. Additionally, as mentioned above, make sure to address gaps in data or data points that weren’t quite what you hoped they would be; this gives you the opportunity to demonstrate how you plan to mitigate or manage any risk and gives the regulator confidence that you fully understand the potential level of risk.
- Use regulatory guidance to support your decision making: regulatory guidance from all major jurisdictions is freely available online and should be referenced wherever possible, particularly to support your decision-making. Consider also looking beyond your borders at other major jurisdictions’ information as well as above-country guidance documents such as those agreed to by all members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).
It’s a good idea to do a quick internal debrief immediately after your engagement. This helps to ensure all the members of your team interpreted key details in the same way and allows you to discuss next steps. You will need to document minutes of meetings, so this is a good time to share your notes with whomever you have nominated to do that. Finally, consider sharing some of the high-level outcomes with important stakeholders such as investors, partner organizations or key advisors. The engagement should have helped you better identify your next steps from a development perspective, and those key stakeholders will likely be as keen to hear the outcomes as you were.
Also, please read the free download called “Are you ready to engage with Health Canada,” available at the link above, to learn more. Although this resource discusses engagements with Health Canada, the key takeaways can be applied to interactions with other global regulators.
For expert regulatory advice on your product, contact us here.