Five top tips for securing marketing authorization in Europe

What is the centralised procedure?

The centralised procedure is the European Medicines Agency’s (EMA) process for obtaining a single marketing authorization for a medicinal product that is applicable across all member states of the European Union (EU) as well as Norway, Liechtenstein, and Iceland. The procedure involves a thorough scientific review by various committees, including the Committee for Medicinal Products for Human Use (CHMP) or the Committee for Advanced Therapies (CAT), and supported by the Pharmacovigilance and Risk Assessment Committee (PRAC).

The centralised procedure is compulsory for new active substances to treat diseases including HIV, cancer, diabetes, neurodegenerative disease, autoimmune diseases and viral disease, as well as for medicines made by biotechnology processes and for advanced-therapy medicines such as gene therapy, somatic cell therapy and tissue-engineered medicines. It is optional for other medicines containing new active substances for indications other than those stated above, that are a significant therapeutic, scientific or technical innovation, whose authorization would be in the interest of public health at EU level.

Top tips for navigating the centralised procedure

1. Be realistic about the timelines – the centralised procedure is legislated to take up to 210 days for review. However, this timeline does not include clock stops for responding to questions and the time needed for the European Commission to ratify the CHMP’s opinion. It is not unusual to receive a large volume of questions during review, so time is needed to respond. A standard three-month clock-stop usually occurs at day 120 and another one-month clock-stop at day 180, but these can be extended under exceptional circumstances and with agreement from the CHMP. The EMA is trying to reduce clock-stop extensions to increase predictability of timelines, so this may become less prevalent in the future. In 2023, the average review time for a new active substance was 441 days, but this increased to 512 days for SMEs (EMA Annual Report, 2023). Therefore, it is advisable to plan for an average review time of around 14 to 15 months.

2. Understand accelerated assessment – accelerated assessment in Europe reduces the EMA’s review time from 210 days to 150 days, but comes with its own set of challenges. The applicant has less time to address queries with just one clock stop of one month, putting a lot more pressure on the applicant’s team as well as the agency. Therefore, accelerated assessment is only available for products that can demonstrate a major public health interest, particularly from the point of view of therapeutic innovation. In the event that the applicant can’t respond to the questions in time, the procedure reverts to a standard review, so many reviews that start on an accelerated procedure may not remain so at the time of questions.

3. Ensure your dossier is well-prepared – a well-prepared dossier is crucial for minimising the number of questions from regulators and therefore reducing the time needed during the clock stops to respond to questions. EU regulators expect a critical review of the data and doing this well can vastly reduce the time and effort needed to respond.

3. Engage with rapporteurs early on – early engagement with rapporteurs and co-rapporteurs is key. These individuals, assigned from member states, lead the review process and present assessment reports to the committee. Pre-submission meetings and meetings at key points during review with rapporteurs can help address scientific issues and align strategies, ensuring a smoother review process.

5. Recognise regional differences with global filings – when writing global submissions, there are important regional differences to be mindful of. The review process is generally considered to be different between the US and EU, with a bottom-up approach and a focus on raw data in the US and a top-down review with a focus on summaries and critical review from the EU. Global dossiers can often be written that address expectations of multiple agencies with good planning that will then reduce the time needed to adapt between regions. The EMA has also run pilots of the submission of datasets as submitted to the FDA, but this is not yet common practice. Module 1 is the key difference between regions and there are many components that are needed for EU that differ significantly from US requirements. The environmental risk assessment, orphan similarity reports (if relevant), new active substance justification, the risk management plan (RMP), the summary of product characteristics (SmPC), and legal considerations such as having an EU legal entity and qualified person for pharmacovigilance must be included and adapted to meet the requirements of the region. Establishing these elements well in advance can help to ensure compliance and avoid delays in the approval process.

Summary

Thorough preparation, effective communication with regulatory authorities, and a strategic approach to dossier submission are essential for navigating the complexities of drug development and approval in the EU. By understanding the nuances of the centralised procedure and implementing the strategies discussed, you can navigate the EU regulatory landscape more effectively, with the goal of bringing your product to market for the benefit of patients.

For further insights on this topic, check out our podcast episode: A Guide to Marketing Authorization Applications in Europe.

Experts in EU regulatory affairs

The regulatory affairs team at Boyds has leading expertise in navigating the EU regulatory landscape. We work closely with clients to understand and advise on regulatory strategy for interactions at all stages of drug development.

In addition, Boyds has SME status with the EMA and we are able to offer companies that qualify based on the EMA’s SME criteria access to the incentives for SMEs in the EU, including fee reductions for scientific advice from the CHMP.

Get in touch to find out how Boyds can help you on your drug development journey.