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Achieving Simultaneous New Drug Document Submission for the FDA and EMA

International Conference on Harmonization (ICH) guidance makes it feasible to construct a new drug submission dossier that can be used for applications to multiple countries. Two of the largest markets with the most evolved regulatory landscapes, the U.S. and Europe, have similar documentation requirements, but with important considerations to recognise that need special attention.

By planning for simultaneous document submissions, drug developers can minimise rework, maximise efficiencies, compile optimal data packages, and create the most direct path to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval. Many other countries follow FDA or EMA approvals, further extending the benefits of a combined approach.

While Module 1 of the ICH Common Technical Document contains regional information and will therefore present significant differences between FDA and EMA submissions, Modules 2, 3, 4, and 5 are similar in comparison. However, terminology and seemingly small grammatical distinctions can loom large if overlooked. Careful planning is crucial if not pivotal. A submission team can greatly accelerate global document submission by first creating and reviewing a checklist of differences, agreeing on the best approach to address each difference, planning the summary documents based on these decisions, and collaborating closely in pursuit of a successful outcome.

With any submission dossier, some aspects are under the developer’s control, and some are not. Timing, authoring differences, and regulatory requirements can be accounted for in the planning phase, whereas the standard of care and unmet need, regulatory interactions and agreements, and marketing and product regional differences may have to be addressed on the fly. Regardless, the first step is to consider simultaneous document submission up front.

Most drug developers seek new drug approvals in both the U.S. and Europe. They are two of the largest markets, with the most evolved regulatory landscapes and the highest uptake of new medicines. Approvals in the U.S. and Europe also provide a gateway to other countries that follow FDA or EMA guidelines.

Historically, submission teams have viewed and managed the two document submissions separately. After all, the U.S. and Europe are an ocean apart, with different policies and their own regulatory bodies in the FDA and EMA, respectively. Meanwhile, the number of people involved in any submission dossier can create complexities and – let’s face it – inefficiencies in the crucial phases of document preparation. Add in comparing, contrasting, and completing FDA and EMA submissions, and those inefficiencies become doubled and magnified.

Is there a better way? The question always breeds critical thinking and often leads to new solutions. This discussion, can entirely rewrite the approach, and relieve many of, the common pitfalls experienced during dossier development for the U.S. and Europe. Before plunging headlong into submission preparation, consider your whole global submission plan and the feasibility of simultaneous document submission to optimise the process. It takes more planning and deliberation up front but streamlines each step thereafter.

Why It’s Possible

The traditional two-lane mindset served its purpose when the U.S. and Europe truly represented two completely different regulatory environments with little to no crossover. That changed in 2000 with the finalisation and adoption of ICH guidance facilitating mutual acceptance of clinical data between the regulatory bodies of the U.S., European Union (EU), and Japan to make new drug registration less resource intensive.

“ICH’s mission is to achieve greater harmonisation worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner,” ICH says on its website. “Harmonisation is achieved through the development of ICH Guidelines via a process of scientific consensus with regulatory and industry experts working side-by-side.

ICH’s leading Article of Association hinges on “the interpretation and application of technical guidelines and requirements for pharmaceutical product registration and the maintenance of such registrations.” While licensing, joint ventures and globalisation were previously softening the borders of clinical data, ICH was the turning point enabling simultaneous document submission, particularly to the FDA and EMA.

All drug developers are familiar with ICH guidance from a regulatory perspective, and most have been pursuing simultaneous submissions for the past 15 to 20 years. However, that harmonisation has been drifting apart for the past several years. Dossiers for the FDA and EMA can still be merged to start and managed as one for the bulk of the work before later being adjusted as necessary to suit the final submissions, but a few addresses up front what is required from a tactical standpoint to do so efficiently.