EU Marketing Authorisation Application
What is a marketing authorisation application in the EU?
A marketing authorisation application (MAA) is the dossier a company submits to get permission to place a medicine on the EU/EEA market. Under the European Commission's Notice to Applicants, a medicine "may only be placed on the market" in the EEA once it has either a national marketing authorisation from a Member State's competent authority or a Union authorisation granted under Regulation (EC) No 726/2004. The marketing authorisation holder "must be established within the EEA" (Notice to Applicants, Vol. 2A, Ch. 1, p. 4).
What the authorisation consists of A granted marketing authorisation has two parts (Ch. 1, p. 4):
- the decision granting it;
- the technical dossier the applicant submitted under Articles 8(3) to 11 of Directive 2001/83/EC and its Annex I, Articles 6(2) and 31(2) of Regulation 726/2004, or Article 7 of Regulation (EC) No 1394/2007.
It must include the SmPC (Summary of Product Characteristics), labelling and package leaflet (pp. 6-7). A stand-alone application under Article 8(3) must include pharmaceutical, preclinical and clinical trial data, plus the relevant published literature (p. 29). The dossier format is set out separately in the Common Technical Document (CTD, Volume 2B) (p. 28).
Where you submit it (the four routes)
- Centralised procedure: you send one application to EMA. EMA's committee for human medicines (CHMP) assesses it and gives a scientific opinion. The European Commission then consults Member States and grants an authorisation valid throughout the Union (p. 7). EMA says the Commission is "the authorising body" and decides within 67 days of EMA's recommendation (EMA, Authorisation of medicines).
- It is mandatory for products in the Annex to Regulation 726/2004. EMA lists these as new active substances for HIV/AIDS, cancer, diabetes, neurodegenerative, immune and viral diseases, plus biotech medicines, advanced-therapy medicines and orphan medicines.
- It is optional under Article 3(2) for new active substances or significant innovations. You have to ask EMA to confirm that the product is eligible (pp. 6-7).
- National procedure: you apply to one Member State's competent authority (p. 6).
- Mutual recognition procedure: use this if the product is already authorised in one Member State. The other Member States should recognise that authorisation (p. 6).
- Decentralised procedure: use this if the product has no EU authorisation yet. You apply in several Member States at once and choose one as reference Member State. The dossier has to be identical in all of them, and the result is a set of national authorisations (pp. 6, 17).
Legal bases (application types) Chapter 1 sets out these application types under Directive 2001/83/EC (p. 27):
- Article 8(3): full or "mixed" application.
- Article 10: generic, hybrid and biosimilar applications.
- Article 10a: well-established use, supported by published literature.
- Article 10b: new fixed combination of active substances.
- Article 10c: informed consent from the holder of an authorised product.
After authorisation An authorisation is first valid for five years. You apply to renew it at least nine months before it expires, and once renewed it is normally valid for an unlimited period. It "will cease to be valid" if the product is not placed on the market within three years, or is off the market for three consecutive years (pp. 10-11).
The Notice to Applicants (Rev. 11, July 2019) states it "is not legally binding". If in doubt, the Directive and Regulation themselves govern (p. 3).
Approach: I couldn't check the texts of Directive 2001/83/EC and Regulation 726/2004 in our datasets this time. This answer rests on the Commission's Notice to Applicants Volume 2A, Chapter 1, and EMA's official page on authorising medicines.
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How long does the centralised procedure take?
EMA's assessment of a centralised application takes up to 210 "active" days. The clock-stops while the applicant answers questions don't count towards that, and EMA says the assessment of a new medicine "usually lasts around a year". The European Commission then has 67 days from EMA's recommendation to issue the authorisation decision.
Standard timetable (EMA, step-by-step evaluation page)
- Day 0 to 120: the first evaluation "lasts up to 120 days" and ends with a list of questions. The clock then stops. The first clock-stop "usually lasts three months", and the developer "generally has up to three months" to reply.
- Day 121 to 180: an updated assessment report is "discussed and adopted at a plenary meeting of the CHMP by day 180". Any remaining issues go to the applicant, and the second clock-stop usually lasts "one month".
- Day 181 to 210: "By day 210 of the active evaluation time at the latest, the CHMP will adopt an opinion."
- Commission decision: "This decision is issued within 67 days of receipt of EMA's recommendation" (EMA, Authorisation of medicines page).
Adding these up: 210 active days, plus about three months and one month of clock-stops, plus up to 67 days for the Commission decision. That is how EMA gets to its "around a year" figure. The actual length depends mostly on how long you take to answer the questions. The CHMP has to agree the length of each clock-stop.
Accelerated assessment
- The CHMP "can reduce the timeframe to 150 days" if the product is "of major interest for public health and therapeutic innovation" and you justify that well enough.
- You should ask for it "at least two to three months before submitting" the application. EMA recommends a pre-submission meeting "six to seven months before submission".
Re-examination
- If you ask for the opinion to be re-examined, the re-examination "lasts up to 60 active days" and ends with a final CHMP opinion.
Approach: I tried the Commission's Notice to Applicants (EudraLex Volume 2) in our datasets first, but couldn't search it this time. The timings above come from EMA's official pages on the evaluation steps, accelerated assessment and authorisation of medicines.
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How do accelerated assessment and conditional authorisation differ?
Accelerated assessment shortens EMA's review timetable. Conditional marketing authorisation is a type of authorisation that lets a medicine reach the market on less complete data. They do different jobs and can be used together: EMA "encourages applicants to also consider requesting accelerated assessment" when applying for a conditional authorisation.
| Accelerated assessment | Conditional marketing authorisation | |
|---|---|---|
| What it changes | How fast the CHMP assesses the application: from up to 210 days (clock-stops excluded) down "to 150 days" | What the authorisation is: granted before comprehensive data are available |
| Legal basis | Recital 33 and Article 14(9) of Regulation (EC) No 726/2004 | Article 14-a of Regulation (EC) No 726/2004, with detailed rules in Regulation (EC) No 507/2006 |
| Who qualifies | Products "of major interest for public health and therapeutic innovation", which the applicant must justify | Medicines for "treating, preventing or diagnosing seriously debilitating or life-threatening diseases", including orphan medicines and medicines for a "public health emergency" (e.g. a pandemic) |
| Test applied | Whether the product is of major public-health interest, particularly for therapeutic innovation | All four must be met: (1) the benefit-risk balance is positive; (2) the applicant is likely to be able to provide comprehensive data after authorisation; (3) the medicine fulfils an unmet medical need; (4) the benefit of immediate availability outweighs the risk that more data are still needed |
| Data standard | The normal full dossier. Only the review is faster | Less complete data are accepted, and comprehensive data follow after authorisation |
| What you get | A standard authorisation, if the opinion is positive | An authorisation "valid for one year" that "can be renewed annually" |
| Obligations afterwards | None that come from the accelerated status itself | The holder must fulfil "specific obligations within defined timelines", such as completing ongoing or new studies or collecting more data |
| End state | Not applicable | Converts to a standard authorisation once the obligations are met and the complete data confirm the benefits still outweigh the risks |
| When to engage EMA | Send the request "at least two to three months before" submitting the application. A pre-submission meeting 6 to 7 months before is "strongly recommended" | Notify EMA "6 to 7 month[s] before submitting the application" |
How the two connect
- Accelerated assessment is about speed of review, and conditional authorisation is about how much evidence is needed at approval. A product can use either one alone or both at once.
- Under PRIME, developers "can receive confirmation during the clinical development phase" that their medicine might be eligible for accelerated assessment. EMA's accelerated assessment page does not describe any direct link between PRIME and conditional authorisation.
- EMA's accelerated assessment page does not say what happens if accelerated status is not confirmed or is withdrawn during the review.
Approach: I tried the Commission's Notice to Applicants (EudraLex Volume 2) and EMA's register of centralised medicines first, but couldn't search them this time. This answer comes from EMA's official pages on conditional marketing authorisation and accelerated assessment.
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