Regulating and Authorizing Medicines: A Comparison of the FDA and EMA

Jurisdiction and Authority

While the FDA and EMA are often compared as equal regulatory counterparts, it is essential to note many differences. At baseline, the two organizations have different jurisdictions and regulatory authorities.

The FDA is the principal governing agency in the United States responsible for regulating medications, medical devices, veterinary medicines and food, tobacco products, animal products, cosmetics, most human foods, and other miscellaneous items. The organization covers a broad range of products for which it can make regulatory decisions.

Comparatively, the EMA evaluates human and veterinary medicines in the European Union, Iceland, Norway, and Liechtenstein. One important caveat is that after Brexit — the United Kingdom’s exit from the EU — medications in the UK are no longer regulated by the EMA.

Rather than enforcing regulations on these medicines, the EMA is responsible for evaluating clinical data and providing drug recommendations based on efficacy and safety information. Unlike the FDA, the EMA cannot authorize or approve certain medications. Instead, the organization offers suggestions, and the European Commission (EC) provides the final regulatory decision.

New Drug Regulations

According to a publication in JACC Basic to Translational Science, the review processes for new medications in the US and EU are relatively similar. While the intricacies of each operation may differ, the general steps follow the same pattern, including pre-authorization, clinical trials, and approval or recommendation.

Preauthorization

Across both locations, new medicines must receive pre-authorization before conducting clinical trials to develop a treatment. Preauthorization aims to confirm that clinical research is necessary and rooted in scientific evidence. Additionally, preauthorization and review attempt to minimize potentially adverse outcomes in clinical trials. The FDA states, “the process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials.”

In the US, the FDA grants researchers and manufacturers approval to conduct clinical trials based on pre-clinical data. Drug developers — sometimes called sponsors — are required to submit an Investigational New Drug (IND) application.

The FDA website states that an IND should include preclinical data from animal trials and toxicity data, information on manufacturing processes for the medication, clinical trial plans and protocols, any available or previous human data, and information on the investigator of the study and their educational or research background.

After receiving an IND, the FDA will take 30 days to review and assess the application before approving or denying it. The organization can deny or place a clinical hold on an investigation to delay or stop it if the trial poses an unreasonable risk to trial participants, the leaders are underqualified, the application information is insufficient, or the trial misleads volunteer participants.

While the FDA preauthorization process is centralized for the entire nation, preauthorization in the European Union is left to the union’s member states. Each state or location has a regulatory body that approves or denies clinical trials in their jurisdictions. Clinical trials in the EU and other associated countries are tracked in the European Clinical Trials Database (EudraCT), similar to ClinicalTrials.gov.

Clinical Trials

After preauthorization, clinical trials can begin for medications in each location. The clinical trial outline is relatively similar across both countries, starting with small-scale Phase 0 and 1 studies to test the drug’s safety in humans and clarify the dosage range. Usually, early-phase clinical trials have under 100 participants.

Phase 2 clinical trials recruit several hundred patients with the condition the medicine is supposed to treat. This phase primarily collects medication efficacy information and determines the dose–response relationship.

Finally, phase 3 studies can recruit thousands of participants to show a larger-scale analysis of the safety and efficacy of the treatment or therapy. Phase 4 trials may also be conducted after a medication is approved to confirm results and monitor long-term effects.

Research Review and Evaluation

Aside from emergency, orphan drugs, or expedited approval processes in the US, the FDA uses two pathways to approve medications: small and biologics or biosimilars.

The approval pathway is called the New Drug Application (NDA) pathway for small-molecule drugs. The FDA has used NDAs since 1983 to weigh the risks and benefits of small-molecule medicines in the US. The NDA is also intended to evaluate the labeling of the medication and the manufacturing methods and practices. Similarly, the Biologic License Application (BLA) is used to assess the risks and benefits of biologics and biosimilars.

The FDA Center for Drug Evaluation and Research (CDER) gets recommendations for approvals from its advisory committees.

In comparison, the EMA has four approval pathways for new drugs: centralized, national, mutual recognition, and decentralized. Premier Consulting notes that the appropriate EMA process may depend on the type of medicine being evaluated; however, some cases allow the manufacturer or applicant to decide which pathway to pursue.

According to JACC Basic to Translational Science, the EMA manages the centralized process (CP). CP is often used for biotechnology or technological products. Additional approvals under this category are advanced therapy medications and medications that treat HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune or immune diseases, viral illnesses, and rare diseases. 

After review, the EMA provides an approval recommendation for all member states in the EU and other jurisdictions that are associated with the EMA. The European Commission (EC) considers the advice and decides on market approval.

National processes allow the medicine to be approved by one of the EU states using its own drug approval processes. Drugs not mandated to go through the centralized process may be supported through national processes.

Once a drug has been approved through a national process in one of the member states, it can get mutual recognition approval in other states, allowing market authorization in the state in question.

Finally, JACC Basic to Translational Science states, “Manufacturers can apply for simultaneous approval in more than 1 EU state for products that have not yet been authorized in any EU state and do not fall under the mandatory centralized process.” The study states that this is one of the most common approval processes, getting most applications in the EU.

Once the recommendations have been made for each approval pathway, the EC uses the data collected to approve or deny the medication in question.

Post-Approval Monitoring

Both organizations — the FDA and EMA — acknowledge some limitations to making regulatory decisions based on clinical trials. While these trials are thoroughly evaluated, they are only conducted on a portion of the population for a limited time, meaning errors and adverse reactions may arise after market approval.

Based on that understanding, the FDA and EMA conduct post-market authorization evaluations on approved drugs. In the US, the FDA monitors each medication's adverse reactions or errors. MedWatch is a technology that individuals can use to report adverse reactions. The data collected may inform the FDA’s decision to alter regulations or suggest a recall.

In Europe, the EMA and EC monitor any adverse reactions or severe concerns in approved medications. According to the EMA website, “Once a medicine has been authorized for use in the EU, EMA and the EU Member States continuously monitor its safety and take action if new information indicates that the medicine is no longer as safe and effective as previously thought.”

Interagency Collaboration

Despite the differences in regulation between the two agencies, they collaborate and communicate in multiple ways to share information for drug approvals to standardize approvals globally. According to the EMA, since 2003, the EMA and FDA have shared confidential information regarding scientific evidence, research plans, adverse drug reactions, drug guidance, good manufacturing practices, and good clinical practices.

Beyond sharing confidential information, the agencies communicate regularly in what they call cluster activities, virtual meetings between regulatory agencies to discuss topics that require additional information sharing and collaboration.

Finally, the two agencies have a mutual recognition agreement that allows them to standardize the understanding of good manufacturing practices and rely on each other’s inspections. Additionally, the two agencies can waive batch testing for some products and communicate quality defects to one another.