How the EMA evaluates a Marketing Authorisation Application (MAA)

by | Apr 22, 2024 | European Medicines Agency, Marketing Authorisation Application

Highlights

  • How the EMA validates your MAA
  • Step-by-step EMA MAA evaluation process
  • Start of scientific evaluation of your MAA: Day 0 to Day 120
  • List of questions and outstanding issues: Day 121 to Day 180
  • Final CHMP opinion on your MAA
  • When the European Commission adopts the CHMP opinion

We previously wrote about the important regulatory milestones you must hit to submit your marketing authorisation application (MAA) to the European Medicines Agency (EMA). This blog explains the MAA evaluation process, resulting—hopefully—in a positive opinion for a centralised marketing authorisation (MA) in the European Union (EU) and its associated member states.

What is the MAA evaluation process in Europe?

Validating your MAA dossier

Before the scientific evaluation even begins, your MAA dossier will be validated by the EMA.

If your MAA dossier passes validation, the scientific evaluation will begin. If your MAA dossier doesn’t pass validation, the EMA will request Validation Supplementary Information (VSI), and you will be given 2 months to provide this information. If you do not meet the 2-month deadline, you will be given a negative validation.1

Worth noting is that there is a paediatric component to the validation – in which the EMA will confirm compliance with an agreed paediatric investigation plan or waiver. Without either of these, the EMA will not validate the MAA and the evaluation will not start.

Timeline of the EMA's MAA evaluation timeline
EMA’s MAA evaluation timeline

EMA scientific evaluation of your MAA: Day 0 to Day 120

Initial assessment reports

The rapporteur and co-rapporteur appointed from the Committee for Medicinal Products for Human Use (CHMP) will write separate assessment reports based on the MAA dossier you submitted. If you’re developing a biologic or advanced therapy medicinal product (ATMP), the Committee for Advanced Therapies (CAT) will be involved.

Inspection

The rapporteurs may consider it necessary to conduct inspections of your manufacturing site(s), non-clinical or clinical study sites. If an inspection is required, this will fall under the remit of European Union (EU) national agencies who will appoint inspectors.

Risk management plan evaluation

The EMA will also appoint two members within the Pharmacovigilance Risk Assessment Committee (PRAC) to evaluate the risk management assessment plan (RMP) that you submitted as part of your MAA dossier.

Draft list of questions

Remember that your appointed rapporteur and co-rapporteur will create separate assessment reports. At this stage, they will share their reports and proposed list of questions with all CHMP and PRAC committee members to review and add comments. Additionally, the PRAC members appointed to evaluate your RMP will share their assessment.

The assessment reports and draft list of questions will undergo a full peer review in a dedicated peer-review meeting. This results in one consolidated assessment report.

The consolidated assessment report is then discussed in a plenary meeting held by the CHMP. Any differences of opinion and outstanding concerns will be raised during this meeting. The CHMP will then fully adopt the final assessment report, along with the final list of questions for you to address.

Day 120 clock stop

At Day 120, the final CHMP assessment report and list of questions are shared with you; the evaluation clock is stopped, and you will be given 3-6 months to address the questions.1

Further evaluation and list of outstanding issues: Day 121 to Day 180

The MAA evaluation clock resumes at Day 121, once you have submitted answers to the CHMP’s first list of questions.

Your appointed rapporteur and co-rapporteur will assess the answers you gave and include their responses in an updated assessment report. Members from PRAC will once again review and add comments, which will be further discussed in a PRAC plenary meeting.

CHMP members will once again discuss the updated assessment report at a plenary meeting, which will result in a list of outstanding issues for you to address.

Day 180 clock stop

The clock is stopped at Day 180, and you will be given 1-2 months to answer the list of outstanding issues.1

Day 181 to Day 210

At this point, an oral explanation may address lingering concerns. A point worth considering is that an oral explanation is usually requested if there are major concerns highlighted in your application.

The CHMP may also seek expertise outside of the EMA, consulting doctors and patients of scientific advisory groups.

Final CHMP opinion on your MAA

Following any oral explanation and advice from outside experts, your appointed CHMP rapporteur and co-rapporteur PRAC rapporteurs will finalise the assessment report. This will be discussed at a CHMP meeting. By Day 210 (this can also occur at Day 180 if the Day 120 questions have been satisfactorily addressed), you will receive the final opinion on your MAA application.1

The final opinion on whether your product should be granted an MA will also include an opinion on the scope of use for your product. The final opinion may also include changes to the wording of your Summary of Product Characteristics and product labelling, as well as any further data you may be required to provide through post-authorisation measures.

European Commission’s decision

If you receive a positive opinion from the EMA to grant your product marketing authorisation, the European Commission will legally adopt this within 67 days2 of the EMA’s positive opinion. Your medicinal product will then be listed in the register of medicinal products.

Summary

The entire marketing authorisation evaluation process usually takes 210 days. This includes 2 clock stops on Day 120 and Day 180.1 Within these clock stops you must answer questions and additional concerns brought to light by the CHMP, PRAC and any other committees within the EMA that are involved in evaluating your MAA dossier. If concerns persist following Day 180, you will be expected to give an oral explanation and the EMA may seek external opinions. If your MAA is successful, the EMA will adopt a positive opinion (around Day 210)1 and the European Commission will legally adopt this opinion into a marketing authorisation. You can then market your medicinal product throughout the European Union and its member states under the centralised procedure.

How Somerville Development Partners can help

We can support every aspect of your MAA filing, including the following:

  • Developing a Common Technical Document (CTD) table of contents for the submission and conducting a gap analysis to ensure that all submission components have been identified and planned.
  • Preparing key messaging and the company core data sheet.
  • Preparing regional labelling such as the Summary of Product Characteristics and US Prescribing Information.
  • Planning the data presentation, analysis and discussion in the dossier.
  • Conducting detailed reviews of the data (tables, figures and listings) shells to ensure the required analysis and outputs are planned.
  • Writing Modules 1–5 of the electronic CTD.
  • Publishing and submitting the completed submission.
  • Responding to questions from the agency during the evaluation.
  • We frequently, work as part of the global filing team for parallel submission to the US, EU and additional authorities. If possible, it is worthwhile writing a submission with common US and EU Module 2–5 components, especially the Module 2 summaries, so that multiple consistent submissions can be made to streamline regulatory agency interactions.
  • We can also provide peer review of existing projects, to stress-test the work that has been done and recommend solutions to address any gaps. Peer review may be especially useful to prepare for the MAA submission, where an additional perspective may help to highlight any potential risks.

Get in touch

We welcome the opportunity to discuss scientific advice and regulatory strategy with you!

Nicole

Author

Nicole Brooks, Regulatory Consultant / Copywriter
Nicole@somerville-partners.com

References

1: European Medicines Agency. (2024). The evaluation of medicines, step-by-step. Available at: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/evaluation-medicines-step-step

2: European Commission. (2024). Authorisation Procedure. The Centralised Procedure. Available at: https://health.ec.europa.eu/medicinal-products/legal-framework-governing-medicinal-products-human-use-eu/authorisation-procedures-centralised-procedure_en