EU Orphan Drug Designation (ODD): overcoming key challenges during preparation, submission and beyond

Orphan drugs are medicines involved in the diagnosis, prevention and treatment of rare diseases which affect a relatively small number of people within the broader population. In the EU, over 6,000 rare diseases have been identified, affecting about 36 million people. Within EU member states, the development of orphan drugs is governed by regulations that differ from those for other medicines.

This article seeks to explain the benefits of seeking ODD, offers an overview of the orphan drug designation application process, and explains what drug sponsors can do to improve their chances of a successful outcome.

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Orphan drug designation requirements

To be classed as an orphan drug, medicines must meet all orphan drug designation criteria:

• The drug must address a life-threatening or chronically debilitating condition
• The condition must have a prevalence of no greater than 5 in 10,000 people
• There must not be a satisfactory method of treatment in existence

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Why apply for orphan drug designation in Europe?

Despite the large number of people affected by rare diseases, each disease only affects a relatively small number of people. This means, historically, drug development for rare diseases hasn’t been profitable, so drug sponsors haven’t prioritised it. To counter this public health challenge, the EU offers incentives to research and develop medicines that wouldn’t otherwise exist.

Incentives available:

• Fee reductions during the marketing authorisation process
• Protocol assistance – a type of scientific advice specific to orphan medicines
• EU market exclusivity for ten years once the drug is on the market, meaning no other sponsor can launch a similar product after marketing authorisation has been granted
• Access to grants available from the European Commission

With advantageous incentives available, understanding and successfully navigating the complex paperwork and processes involved with ODD is essential. As there is much to consider and master before submission, during the application process and after the submission is complete, many sponsors use regulatory consultants who specialise in orphan drug designation guidance to help them navigate this complicated process. These services can be particularly valuable for smaller companies without internal regulatory expertise, first-time orphan drug developers, those with complex or time-sensitive submissions, and companies managing multiple applications in the EU or parallel applications in different regions (the UK, US etc) simultaneously.

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The EU Orphan Drug Designation application process

Pre-submission

Even before beginning the application process, it pays to get on the front foot. Drug sponsors should thoroughly research the process and requirements and consult the relevant guidelines before they begin the process. Learning more about similar orphan drug designations via the European Medicines Agency (EMA) orphan drug register is also advisable. Drug sponsors who qualify can also benefit from obtaining Small/Medium Enterprise (SME) status before they apply for ODD. This allows them to access specific regulatory or administrative advice and additional fee reductions.

The EMA encourages sponsors to request a meeting before completing an ODD application via the IRIS online platform. This must be done at least two months before their planned submission date to allow enough time to complete the necessary paperwork and any amendments needed. At least one week before the meeting, they must also submit a draft application, complete with the required data and documents.

During this pre-submission stage, many sponsors choose to work with regulatory consultants. The ODD evaluation process is fixed at 90 days and cannot be lengthened if vital data or documents are missing. Many sponsors work with regulatory consultants at this pre-submission stage to give themselves the best chance of success. Consultancies, like MWB Consulting, are available to help sponsors apply for SME status, complete the required paperwork correctly, prepare for meetings and check they have included all the necessary documentation.

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Submission

1. Sponsors submit the ODD application through EMA‘s online IRIS platform

Applications must include information about the sponsor, the active ingredient name and a description of the condition being addressed. Additional scientific documentation should include medical plausibility data, a prevalence calculation with supporting documentation, a review of available treatments and more. The EMA recommends that sponsors ensure they clearly identify studies of the active ingredient in relevant models of the condition and (if possible) include preliminary clinical data in patients with the condition.

2. Pay applicable fees

3. Initial validation of the ODD application by the EMA within 10 days

4. Scientific evaluation by the Committee for Orphan Medicinal Products (COMP)

The committee may raise a list of questions and invite the sponsor to give an oral explanation at their next meeting. Here, the team at MWB Consulting can play a key role in ensuring data and documentation is correctly prepared and teams have an in-depth understanding of what to expect from the meeting and know how to best present their proposed orphan drug.

5. COMP opinion issued within 90 days

If the opinion is negative, the sponsor can appeal. Regulatory consultants can also play a role here, as they have in-depth experience helping sponsors achieve a successful outcome.

6. The European Commission orphan drug designation decision (based on the COMP’s opinion) is made within 30 days.

Information about the designation is officially registered and made available publicly via the IRIS platform.

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After designation

The ODD process doesn’t end with a successful decision. Drug sponsors will need to think about:

• Writing annual reports on development progress
• These must be submitted to the EMA every year, outlining a summary of the ongoing development status of the drug
• Maintaining documentation on orphan drug designation
• Planning for market exclusivity application

When applying for marketing authorisation from the EMA, sponsors must also apply to maintain the orphan designation to be eligible for ten-year market exclusivity.

It’s also important to remember that ODD isn’t the same as marketing authorisation and not all orphan drugs reach the marketing authorisation stage. The drugs that do are evaluated via the same strict safety and efficacy standards as all other drugs evaluated by the EMA. This part of the overall development process also needs to be planned for as far ahead as possible.

• How best to make use of protocol assistance for development

Post-application paperwork and processes are ongoing and time-consuming and can tie up smaller drug sponsors without dedicated teams. Here, we can also play a role, allowing sponsors to outsource these resource-heavy administrative tasks to free up their teams to concentrate on core functions like drug development and innovation.