We prepared this post to provide biotech startups with a quick guide to navigate the complex EU EMA (equivalent to US FDA) approval process. If you are successful with your application, you can receive the coveted EU Market Authorisation (MA) to sell your medical product to over 500,000,000 citizens of the EU.

First, let us list the relevant laws/regulations that concern the MA:

• Directive 2001/83/EC - The core legislation governing the regulation of drugs in the EU

• National Law, implementing the above Directive at national levels

• Regulation (EC) No 726/2004 - Sets out the centralized procedure to be followed.

Now let's get to the fun stuff — the route to market.

In general, there are two ways to get an MA in the EU - 

• the centralized procedure or CP (the new system) and 

• the nationally-based procedure (the old system), which involves applications with individual EU member countries). 

Generally speaking, most biotechs should be looking to apply via the CP to receive a one-stop-shop experience. In fact, the CP route is mandatory for most innovative biotech products. Examples include recombinant DNA technologies, controlled gene expression products, orphan medicines, new active substances for AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases, viral diseases, or advanced therapy products. 

The broad outline of steps-to-market:

1. Biotech submits an electronic CTD (Common Technical Document), a modular application that includes quality clinical and non-clinical data.

2. A committee receives the dossier application. Member scientists from the committee present themselves as candidates to review the application. The committee selects two - a rapporteur and a co-rapporteur. Each of these scientists offers an independent assessment, sometimes with the help of their respective in-country teams. Although the members come from different EU countries, the expectation is that they will perform this role as scientists without any political influence.

3. A third member provides a peer-review based on the earlier two assessments. Together, these three assessments are provided to the whole committee to solicit comments. If necessary, the committee will reach out to Scientific Advisory Groups and Working Groups to get their expertise and input during the evaluation process.

4. Finally, the application is approved or rejected by consensus or majority vote.

5. The last step is to receive approval from the EU Commission in Brussels. The EU Standing Committee on Medicinal Products for Human Use is responsible for this approval.

What happens once you receive the MA

It takes ~277 days to obtain an MA in Europe; the scientific evaluation takes around 210 days, with the remaining days spent on deliberating and voting on the final decision. Orphan drugs can request accelerated assessments (reducing scientific evaluation to 150 days). 

Remember that there is a sunset clause with each MA - if the company does not launch the product in at least one member EU state within the next three years, they will lose the MA.

The type of MA that you receive depends on the level of evidence that you provided in your application. 

1. If you meet the "normal" or "high" level of evidence requirements, you can receive an MA for five years. 

2. You can receive a conditional approval valid one year if you provide insufficient levels of evidence yet serve an unmet medical need. This license will allow you to launch your product in the market; however, you will need to perform studies to complement the evidence over time. With the new evidence, it is possible to receive a five-year approval. 

3. For orphan products with exceptional circumstances, you can receive a one-year approval subject to conditions.

Here are a few unique approaches of the EMA system

1. Due to an increased emphasis on transparency, all assessment reports are published for public knowledge, including agendas and minutes from committee meetings, and even if a company decides to withdraw an application mid-way. This approach is in stark contrast to the old EMA attitude, where a lot of the regulatory paperwork was kept quiet due to NDAs (Non-Disclosure Agreements). This bold move is refreshing as the EMA has taken a stance to respect trade secrets, but not at the cost of secrecy of public safety concerns or evidence of efficacy. If there are divergences in agreements, the minority group can publish its reports on why they disagreed with the committee decision.

2. Unlike the US FDA, the EMA has control over the product's labeling process right from the start of the MA application process. EMA approves the text, which cannot be modified during the lifecycle without approval from the EMA. In the US, the company owns the product label.

We recommend that biotechs reach out to the EMA during the early stages of product development. The Scientific Advice provided by the EMA, although not mandatory, can guide management to know whether the proposed development plan is following the right path for Marketing Authorization approval.