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Regulatory Strategy Considerations for Working with the FDA vs the EMA, Part 2

As regulatory requirements become increasingly harmonized across the globe, the development and marketing of pharmaceutical products worldwide are also becoming more streamlined. However, global regulations are not one-size-fits-all, and sponsors aiming to market their products in multiple regions should be aware of the current standards and processes they may encounter during development. This blog series explores the regulatory strategy considerations sponsors should bear in mind when working with the FDA and the EMA, with a focus on the development of pharmaceutical products.

In Part 1, we analyzed differences in the approval processes and the formal meetings/scientific advice processes between the FDA and the EMA. In this second installment, we compare applications for conducting clinical studies, expedited programs, pediatric plans, and labeling in the US and EU markets.

Applications for the Conduct of Clinical Studies: INDs vs CTAs

The FDA’s Investigational New Drug (IND) application regulations cover all US clinical activities for drugs and biologics. An IND submission serves as a request to start clinical studies, containing a summary of information known about the drug, including nonclinical studies; chemistry, manufacturing and controls (CMC); and a proposed clinical plan. The primary goal of the initial submission is to demonstrate the product’s safety for clinical trial participants and to justify the proposed starting dose in humans.

An IND is a living dossier that a sponsor submits before the first clinical study and then expands throughout the clinical program for the given indication, with some INDs accruing upwards of 100 amendments. INDs must contain full study reports of nonclinical and clinical (if available) studies. In contrast, full study reports  are only submitted for Clinical Trial Authorizations (CTAs) in the EU upon request by the reviewing authority. The FDA does not charge fees for IND submission or maintenance, another contrast to the process in the EU member states. Fees often apply for CTA submissions both to the National Competent Authority (NCA) of each member state and to relevant Independent Ethics Committees (IECs), which are equivalent to Institutional Review Boards (IRBs) in the US.

Applicable clinical trials conducted under an IND or with one or more US sites must be registered at On the other hand, at the time of writing (September 2021), clinical trials in the EU are registered at EudraCT. However, a new Clinical Trial Regulation introduces a major change to the conduct of clinical trials in the EU that addresses several “issues” with the current system (required registration to each Concerned Member State resulting in multiple submissions for one trial, double submissions to NCAs and IECs, lack of a harmonized dossier, and limited data availability to the public). On January 31, 2022, a centralized EU portal and database for clinical trials, the Clinical Trials Information System (CTIS), will go live with the goal of increasing the safety and efficiency of EU trials and increasing the transparency of trial information. Notable changes include a single e-submission to all Concerned Member States (including NCAs and IECs), a joint assessment, and the availability of all information related to the clinical trial.

In the EU, sponsors submit CTAs regardless of the type of approval procedure pursued. There is no centralized process for obtaining approval to conduct a clinical study, so sponsors must submit CTAs to each of the individual member states where the sponsor intends to conduct a clinical trial (as opposed to submitting a single application to the EMA). Unlike an IND, which covers the entire clinical program for a given product and indication, a new CTA must be submitted for each new trial. The core of many CTAs is the Investigational Medicinal Product Dossier (IMPD), a comprehensive, high-level summary of a product’s details that contains overviews of CMC, nonclinical, and clinical (if available) data. An IMPD is brief compared to an IND, as it is revised over time and must be resubmitted with each new CTA. A separate IMPD is required for a comparator or placebo, if applicable.

Expedited Programs: Breakthrough Therapy vs PRIME

Several expedited programs/designations exist both in the US and in the EU to aid in the development of medicines for patients with unmet medical needs. In this section, we will focus on Breakthrough Therapy designation in the US and priority medicines (PRIME) in the EU.

Breakthrough Therapy designation is intended for medicines that represent a substantial improvement in safety or effectiveness (as demonstrated by preliminary clinical evidence) over available therapies for the treatment of a serious condition. When the designation is granted, the FDA offers intensive guidance on the drug development program, beginning as early as Phase 1, as well as enhanced interactions involving senior managers. Products with Breakthrough Therapy designation may also benefit from priority review, which shortens the NDA or BLA review time from 10 months to six months. Between 2012 and 2020, 190 medicines received Breakthrough Therapy designation.

The PRIME scheme was launched by the EMA in 2016 to provide increased support for the development of medicines that target an unmet medical need. PRIME offers sponsors enhanced interactions and early communication with the EMA, with the goal of optimizing development and accelerating the evaluation of a product in order to provide benefit to patients as soon as possible. Medicines that offer a major therapeutic benefit over existing therapies or that benefit patients without treatment options are considered for PRIME based on early clinical data. PRIME medicines may also be eligible for accelerated assessment, a counterpart of priority review by the FDA, which reduces the review time of a marketing authorization application (MAA) by the EMA from 210 days to 150 days. Between 2016 and June 2021, 93 medicines (25% of all applications) were granted PRIME eligibility.

Pediatric Plans: PSPs vs PIPs

In the US, the Pediatric Research Equity Act (PREA) requires sponsors to conduct pediatric studies of certain drugs or biologics (including an age-appropriate formulation) with the goal of obtaining pediatric labeling for the product. PREA instituted a requirement for pediatric study plans (PSPs), which must be submitted no more than 60 days after an End of Phase 2 (EOP2) meeting, or at least 210 days prior to NDA submission if no EOP2 meeting is held. The FDA may defer the requirements or grant partial or full waivers of studies in certain age groups based on low or no occurrence of a specific condition in pediatrics.

In the EU, pediatric investigation plans (PIPs) are analogous to PSPs; however, the submission timing for a PIP is different. A PIP must be submitted to the EMA after Phase 1 pharmacokinetic studies and before Phase 3 studies. As with the FDA, the EMA may grant partial or full waivers of studies as well as deferrals.

Labeling: PI vs SmPC

Labeling information for prescription products approved in the US can be found in the Prescribing Information (PI) and accessed in its most up-to-date form at Drugs@FDA. Labeling information for products approved in the EU is located in the Summary of Product Characteristics (SmPC), accessible via the EPAR database.

As a full-service global regulatory partner, Premier Consulting can help you craft a time- and cost-efficient development strategy that enables you to attain approval in both the US and the EU. Contact us to find out how we can support your program.


Dominika Trzilova, PhD
Regulatory Scientist