How New Drugs Are Evaluated in the EU

All new medical products seeking entry to European market must undergo the stringent review process overseen by the European Medicines Agency (EMA). The EMA's primary role is to evaluate whether medical advances are safe, effective, and meet quality standards before approval. In this role, the agency aims to conduct thorough assessments through defined procedures while also providing guidance to support innovation. Ultimately, the EMA strives to balance comprehensive scientific review with helping expedite therapies for patients, all while safeguarding public health across Europe.

The key principle guiding a medicine's assessment is whether its anticipated benefits to patients outweigh any potential risks based on a full analysis of submitted clinical evidence. The EMA review pathway involves multiple stages from a drug's initial submission through final determination of approval or rejection. Through its sequential steps and emphasis on open dialogue, the agency seeks to ensure only treatments demonstrating adequate safety, efficacy, and quality gain authorization.

The European regulatory review process is initiated upon formal submission of a marketing authorization application by the sponsor. To carry out a scientific assessment, a rapporteur is appointed from the Committee for Medicinal Products for Human Use (CHMP) based on relevant expertise to conduct the scientific assessment and prepare a report. The rapporteur may be supported by a co-rapporteur for certain major applications and procedures. The rapporteur selects an assessment team of experts to assist in the evaluation.

In its assessment, the CHMP coordinates with multiple EMA committees that provide specialized expertise. The Committee for Advanced Therapies (CAT) oversees the assessment of advanced therapy medicines, such as those involving gene, cell, or tissue components. Safety and risk management aspects are handled by the Pharmacovigilance and Risk Assessment Committee (PRAC). The Paediatric Committee (PDCO) focuses on issues related to a medicine's potential use in children. Meanwhile, the Committee for Orphan Medicinal Products (COMP) contributes to the review of therapies designated for rare diseases. By collaborating cross-functionally, the EMA leverages the distinct knowledge and perspectives of these separate committees to conduct a thorough multi-faceted analysis of new medical products.

Once the initial analyses are complete, the rapporteurs share their reports with the entire CHMP as well as PRAC members. They will also present a consolidated list of questions seeking clarification from the sponsor.

The assessment of an application for a new medicine takes up to 210 ‘active’ days. This time is interrupted by one or two ‘clock-stops’ during which the applicant prepares the answers to any questions raised by the CHMP. After 120 days, known as the first "clock stop," the process pauses to give the sponsor time to thoroughly address each question raised. They usually have 3-6 months to provide written responses and an updated risk management plan for consideration.

When answers are received, the rapporteurs thoroughly re-examine the application and write updated assessment reports. These go through another rigorous peer review process by other EMA member state experts who may suggest additional questions.

If unresolved issues remain after peer review, they are compiled into an official list of "outstanding issues." The clock stops again, typically for 1-2 months, to allow responses. For very complex applications, the EMA may schedule an oral explanation meeting for live discussion. External scientific groups can also provide specialized input during this stage.

The EMA review culminates in a final opinion voted on by the CHMP. By day 210 of the process at the latest, the CHMP will recommend one of three outcomes:

• Approval - If the application demonstrates a positive benefit-risk profile based on the rigorous evaluation of safety, efficacy and quality data. Approved drugs may have conditions or requirements for certain populations.
• Rejection - If critical issues remain unresolved and the evidence fails to show adequate medical need is met. Deficiencies in data quality or integrity could also lead to rejection.
• Conditional approval - For certain categories like orphan drugs treating rare diseases, interim approval may be granted with specific obligations and time-bound requirements still to be fulfilled post-market.

The CHMP provides scientific reasoning for its non-binding opinion to help guide the final step. The European Commission then reviews this analysis and makes a legally binding EU-wide decision within 67 days. In rare cases where new concerns arise, independent assessment may be sought before authorization is granted.

Applicants can request re-examination by separate EMA rapporteurs if dissatisfied. Manufacturers have 15 days to appeal and trigger re-evaluation by new rapporteurs, leading to a binding final decision.

The multi-stage EMA review process facilitates a rigorous evaluation of new medical products. Through initial assessment, questions to sponsors, and addressing outstanding issues, the EMA thoroughly appraises submitted clinical evidence. While real-world use may later uncover issues, the step-by-step approach and dialogue between regulators and applicants seeks to make well-informed decisions. It provides a framework for companies to demonstrate a treatment's benefits outweigh its risks for European patients. For patients and healthcare systems, this systematic process evaluates therapies to facilitate access to valuable innovations that withstand scrutiny throughout the review.