How to get a drug approved by the European Medicines Agency

by | Apr 8, 2024 | European Medicines Agency, Marketing Authorisation Application

Highlights

  • What is a marketing authorization application (MAA)?
  • What are the MAA pre-authorization requirements?
  • What are the legal bases for an MAA?
  • Are you eligible for evaluation through the centralised procedure?
  • What is a letter of intent? 
  • How are the rapporteurs appointed?
  • What are the product (trade) name requirements?
  • EMA pre-submission interactions for an MAA
  • Timelines to follow when preparing your MAA

When to start preparing your marketing authorisation application (MAA)?

The MAA is the total sum of years of drug development, culminating in a monstrous dossier that you submit to the European Medicines Agency (EMA). Preparing and submitting your MAA is a significant undertaking, involving a team of 20–30 people preparing the Common Technical Document (CTD) dossier over 18–24 months.

In addition to drafting the dossier itself, planning your MAA in its entirety should start 2–3 years before you submit it. This is to ensure that you have sufficient time to assemble all the dossier components and gather the required resources for the project. 

But where to begin?

We are assuming your small molecule, biologic or advanced therapy medicinal product (ATMP; cell or gene therapy) has reached the registrational stage of clinical development, and you’ve completed all of your regulatory deliverables thus far. 

You now find yourself 18-24 months before the date you hope to submit your MAA, which is when certain pre-authorisation requirements come into play.

Important regulatory milestones you should have completed at this stage include:

Each milestone is important for different reasons – perhaps the most critical are the paediatric requirements – without which your MAA will not pass validation and will be rejected by the EMA. 

What must you do in the lead up to to filing your MAA?

There are several pre-submission milestones you must reach to get to the MAA submission, and these preparatory steps should create a smooth evaluation process with the European Medicines Agency (EMA).

Two initial questions you should know the answers to are:

  1. What is the legal basis for our MAA?
  2. Is our product eligible for evaluation under the centralised procedure?

You must choose which legal basis your MAA falls under based on Directive 2001/83/EC.1

  • Article 8(3) – Full application
  • Article 10 – Generic, hybrid or similar biological application
  • Article 10a – Well-established use application
  • Article 10b – Fixed combination application
  • Article 10c – Informed consent application

Each legal basis has different requirements for the scope of data you should have collected throughout your product’s development and included in your MAA dossier.

Is your medicinal product eligible for the centralised procedure?

If your medicinal product is eligible for the centralised procedure, this means that you submit one MAA to the EMA. If you are granted Marketing Authorisation (MA) under the centralised procedure, your product can then be marketed throughout all the European Union member states.

Some medicinal products can only be submitted for MA under the centralised procedure (the so-called mandatory scope), and Regulation (EC) No 726/20042 lays out in detail which types of products this applies to. Worth noting are products developed using biotechnological processes. These include:

  • Recombinant DNA technology,
  • controlled expression of genes coding for biologically active proteins, and
  • monoclonal antibody methods/hybridoma.

Biosimilars using the above-mentioned biotechnological processes will be required to go through the centralised procedure, as will ATMPs (cell and gene therapies), and tissue engineered products.

Specific therapy areas that are required to be evaluated under the centralised procedure include:

  • human immunodeficiency virus (HIV),
  • acquired immune deficiency syndrome (AIDS),
  • cancer,
  • diabetes,
  • neurodegenerative diseases,
  • viral diseases, and
  • auto-immune and other immune dysfunctions.

Now that you know what legal basis your MAA falls under and if your product should be evaluated under the centralised procedure, you must inform the EMA that you will be submitting an MAA and submit the eligibility request and letter of intent.

Eligibility request and letter of intent to submit an MAA

Submitting an eligibility request is required to obtain access to the centralised procedure, whereas submitting the letter of intent is required to assign the rapporteurs to the procedure. You must use the EMA Pre-submission request form, which also provides an overview of the type of MAA the EMA should expect to receive from you.

Timeline

You can submit your eligibility request up to 18 months and at least 7 months before you plan to submit your MAA.3

The pre-submission application form requests the following information:3

  • legal basis your MAA falls under,
  • basis for eligibility under the centralised procedure,
  • intended date for ATMP certification request (advanced therapies),
  • company contact information,
  • information on your medicinal product and active substance,
  • anatomical therapeutic chemical code (ATC) classification,
  • therapeutic indication,
  • PIP information, and
  • orphan designation status (for drugs developed for rare diseases).

For the eligibility request, you must also submit a draft version of your Summary of Product Characteristics (SmPC) and a justification of eligibility for evaluation through the centralised procedure.3

Being assigned rapporteurs and co-rapporteurs

The rapporteur and co-rapporteur are members of the Committee for Medicinal Products for Human Use (CHMP) that sits within the EMA and will be responsible for leading your MAA evaluation.

In the case of an MAA of a small molecule or biologic, rapporteurs will be assigned directly from the CHMP. Throughout the MAA evaluation members from other committees will also be involved in different aspects of your MAA, including the Pharmacovigilance Risk Assessment Committee (PRAC).

If your MAA is related to an ATMP (cell or gene therapy), the Committee for Advanced Therapies (CAT) will be involved in your MAA evaluation.

Timeline

The EMA advises that you submit your rapporteur appointment request 7 months before you intend to submit your MAA dossier so that they can begin their internal planning process, as it takes one month for rapporteurs to be assigned.3

You can submit your eligibility request and appointment of rapporteurs request in parallel.

Product name suitability

Under the centralised procedure, your medicinal product must use a single name that is assessed by a committee of representatives of EU member states, known as the Naming Review Group (NRG). Chaired by an EMA representative, the NRG meets 5-6 times per year.3

Therefore, you must factor in enough time to have your proposed product name reviewed by the NRG, to mitigate any unforeseen problems as early as possible.

Timeline

Preferably you should submit your proposed product name 4-6 months before you submit your MAA, but your proposed name can be submitted up to 18 months before you plan to submit your MAA.3

Under Article 1(20) of Directive 2001/83/EC you can choose either the product’s invented name, so long as it doesn’t cause confusion with the common name or  “…a common name or scientific name accompanied by a trademark or the name of the Marketing Authorisation Holder”.1

You must submit a ‘Proposed invented name request form’ along with a draft SmPC or Target Product Profile, and you can submit up to two proposed names for review.3  

Our regulatory experts have filed numerous MAA and NDA/BLA submissions across different therapeutic areas and can guide you through the best practices for submission planning.

EMA pre-submission meeting request

You can—and the EMA recommends—that you open MAA pre-submission interactions with the committees within the EMA before you submit your MAA. This is to ensure you meet the relevant legal and regulatory requirements in advance of your MAA submission and to promote a smooth evaluation of your MAA once it has been submitted. 

The pre-submission interactions are also an opportunity to meet the EMA project lead and other EMA team members involved in evaluating your MAA. Depending on the topics you wish to discuss, members of different committees within the EMA (orphan medicines, SME, paediatric medicines, CMC, and specialised disciplines) may be called upon to assist you.

You must submit the MAA pre-submission interactions form and include specific draft annexes relating to Module 1 of the MAA dossier.

The EMA will discuss your questions internally and respond in writing within 3 weeks of your request. 3  To highlight the usefulness of the EMA pre-submission interactions, their written responses may also include additional guidance such as:

  • A proposed revision to the legal basis for your MAA,
  • views on the possibility of requesting approval under exceptional circumstances or conditional approval, and
  • proposed revisions to MAA dossier modules based on the data you provided.

You may also request a teleconference meeting with the EMA to discuss any further clarifications based on the written responses you received from them. All of this information offers valuable insight aimed to help you mitigate unforeseen road bumps in your MAA submission and potentially open regulatory approval avenues you weren’t aware of. 

Timeline

The EMA recommends you request pre-submission interactions 6 months before you plan to submit your MAA.3

Special considerations for Small and Medium-sized Enterprises

The EMA offers several incentives for small and medium-sized enterprises (SMEs) submitting an MAA, including:

  • help with translations of product information leaflets and related documents,
  • MAA fee exemptions for SMEs who received and applied EMA SME advice (even if the MAA was unsuccessful),
  • fee deferral for MAA or inspection,
  • fee reduction for inspections, and
  • procedural and administrative assistance from the SME Office.

Read more about the challenges pharmaceutical SMEs face and how the EMA supports SMEs.

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EMA MAA pre-submission requirements

Summary

Submitting your marketing authorization application is a mammoth task. Careful planning and forethought are necessary to mitigate the risk of your MAA dossier being rejected, and preparing way in advance can streamline the entire MAA evaluation process. 

How Somerville Development Partners can help

We can support every aspect of the 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: Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Official Journal of the European Union. L 311, 28/11/2001 P. 0067 – 0128. Available at: https://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A32001L0083

2: Commission Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Official Journal of the European Union. L 136, 30/04/2004 P. 0001 – 0033. Available at:https://eur-lex.europa.eu/eli/reg/2004/726/oj

3: European Medicines Agency (2024). Human regulatory-Marketing Authorisation-Pre-authorisation Guidance. Available at: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/pre-authorisation-guidance