Support for innovative medicines’ development at the EMA level

The services and procedures put in place by EMA are designed to help developers to enter into early contact with the agency and overcome the challenges a developer may encounter when trying to bring an innovative medicine on the European Union market. Therefore, EMA is organising its support in accordance with the needs of the developers. The issues faced may vary with the types of medicines being developed or the methodology used, and this requires a case-by-case approach that is offered by the various schemes proposed for early interaction.

Another challenge to consider is the status of the medicines’ developer targeted as the various schemes are not always available for all types of stakeholders, given that they sometimes depend on different legislative requirements or incentives, and they are not necessarily involved in the same stage of the medicines’ development life cycle. EMA needs to adapt the support to the different actors involved all with the goal of fostering research and the development of new medicines to enable patient’s access to innovative medicines, in accordance with the applicable legislative provisions. In such context, SMEs have less resources to be dedicated to regulatory issues in particular, while academia has often considered to be far from the EMA given its main focus on proof of concept, pre-clinical and clinical studies in the early part of medicines’ life cycle.

Apart from finding new ways to allow dialogue between EMA and developers which is one of the main challenges faced by EMA taking into account its limited human resources, communicating on the existing procedures and services available to support the development of medicine is also fundamental. Despite the organisation of events by EMA, such as stakeholders’ meetings, its very complete website, and its participation in congresses, many stakeholders have no full knowledge of the available tools for early interactions with EMA. Moreover, the complexity of implementing legislative and regulatory requirements to innovative medicines as well as to develop appropriate guidance remain an inherent challenge to the development of these products.

EMA created several early interaction procedures to accompany medicine developers into navigating the legal requirements at any stage of a medicinal product life cycle, especially in order to obtain and maintain marketing authorisation. The available procedures for early interactions between stakeholders and regulators are meant to foster early patient’s access to medicines. For instance, medicines with granted marketing authorisation using the PRIME scheme are consistently experiencing a reduction of the clock-stop duration during the assessment of their applications for marketing authorisation. 

They are mostly regulatory tools that help manufacturer to enter into contact with regulators. For example, EMA designed the procedures described to support the development of new medicines, or new indications, and research and development coming from smaller enterprises. 

The European Medicines Agency tries to foster new ideas coming from SMEs and academia through these procedures for early interaction. The aim is to help developers navigate the complex regulatory landscape to enhance the product’s chances to be manufactured and to access the market later on, especially to have medicines available for unmet medical needs. Some procedures are available at waivered or lowered costs depending on the type of developer asking to enter into early contact with the EMA or the type of medicine developed. 

Some incentives may be designed for a specific type of medicine developer facing more challenges in bringing medicines to the market such as SMEs and Academia. For instance, the services provided by EMA can be divided into two types, the ones providing informal discussion to maybe detect needs for a formal interaction on scientific or regulatory issues faced by the developers, with briefing meetings of the innovation office and the quality innovation group. The second type is a support given to SMEs.

Finally, it should be highlighted that early interaction with EMA do not only help to clarify questions regarding the regulatory pathway to market of innovative medicines, it also contributes to ensure EMA awareness and preparedness for the appropriate evaluation of medicines, including the most recent developments and state of scientific knowledge in innovative medicines.

Services for early interaction with EMA for innovative medicines’ developers

Innovation Task Force briefing meetings

ITF briefing meetings are free of charge. They can be requested at any time. Nevertheless, most of the meetings are organised during early stages (proof of concept) of medicines’ development.

1. How to apply

• For general information on the briefing meetings visit the ITF page on EMA’s website
• Applicant sends ITF briefing meeting request form (available on the ITF page on EMA’s website) , to ITF Secretariat via EudraLink (the EMA’s secure file transfer system) or email to ITF Secretariat: 
  • ITFSecretariat@ema.europa.eu for human medicines
• ITF Secretariat may request the applicant to complete and return a briefing document for additional information
• ITF Secretariat reviews information received and suggested the best suited option for the applicant’s needs: 
  • Referral to other procedure
  • Invitation to ITF Briefing meeting

2. Process of the meeting

• The applicant creates an EMA account
• The applicant registers on the IRIS platform
• Submit the following documents via IRIS once ITF briefing meeting is confirmed
  • Short presentation (3 slides in total) for presentation by the ITF Coordinator to the relevant EMA Scientific Committee containing: 
    • Description of product (e.g., structure/technology/method);
    • Mechanism of action, use in drug development;
    • Key topics for discussion
  • Full presentation and list of participants (for the ITF BM)
    • ITF briefing meeting
• After the ITF briefing meeting 
  • The applicant provides a draft of the meeting report within 10 days of the meeting following the template sent by email with the topics discussed, a participants list and the outcome of the discussion. 
  • Expert review
  • Final report shared by ITF on IRIS upload within 2 to 4 weeks

More information on how to apply for an ITF briefing meeting and on the steps of the ITF briefing meeting are available on the EMA’s website here.

Specific procedures for early interaction for SMEs

SME support 

1. SME office

• The EMA has put in place an office with “dedicated administrative structures and specific procedures” for Small and Medium Enterprises (SMEs).
• The SME Office has a number of designated tasks:
• “to give advice to applicants on the administrative and procedural steps necessary to comply with the requirements laid down in Regulation (EC) No 726/2004”
• “to ensure the appropriate monitoring of all requests and applications submitted by the same applicant and related to a particular medicinal product;”
• “to organise workshops and training sessions for applicants on the administrative and procedural steps necessary to comply with the requirements laid down in Regulation (EC) No 726/2004.”

(Article 11 current version Commission Regulation (EC) No 2049/2005 of 15 December 2005 laying down, pursuant to Regulation (EC) No 726/2004 of the European Parliament and of the Council)

More information here on the SME Office on the EMA’s website.

2. SME Status

The SME status is required for a company to be able to benefit from the incentives of the SME office. The companies must apply for SME status with the SME office. 

To acquire the SME status, conditions must be fulfilled: 

• The company must be a registered company in a Member State of the EU or the European Economic Area.
• And the company must meet the definition of an SME: 
  • Less than 250 employees AND annual turnover not more than 50 million euros 
  • or Balance Sheet total not more than 43 M euros.

(Article 1  and Article 2 of the Commission Recommendation 2003/361/EC of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises)

If the company meets the criteria, it will be added on the EMA public register of SMEs. 

More information on how to apply for a SME status on the EMA’s website here.

Regulatory procedures for early interaction with EMA for innovative medicines’ developers

Scientific advice and Protocol assistance

Medicines’ developers may ask the EMA for scientific advice/ protocol assistance regarding the development of a specific medicine. One of the EMA’s roles is "advising undertakings on the conduct of the various tests and trials necessary to demonstrate the quality, safety and efficacy of medicinal products" (Article 57-1 (n) of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004)

The advice/assistance is given by the CHMP following the recommendation of the scientific advice working party, and the CAT for ATMPs. Although scientific advice or protocol assistance is not legally binding, how it was followed by the developer is considered when assessing a marketing authorisation application. The developer will have to explain the reasons why they did not follow the advice given to them through the early interaction procedure. 

EMA charges a fee for scientific advice/protocol assistance. Its amount varies according to the scope of the advice. Reductions or full waivers are possible for certain types of medicines (e.g., orphan medicines, PRIME products) and applicants (e.g., SMEs, academia). More information on fees payable to the EMA here.

1. Eligibility for scientific advice 

Scientific advice is available to multiple types of medicines and specific methodologies. The procedure can be used by sponsors developing medicines based on Novel methodologies for medicine development or for Medicine repurposing. The advice can be given for different types of medicines, such as for orphan medicines with Protocol assistance (art.6 of the Regulation on Orphan Medicinal Products (EC) 141/2000.), Paediatrics, Biosimilars, medicines intended for a disease causing public health emergency, notably vaccines tackling COVID-19. 

All types of stakeholders can benefit from scientific advice for all the different types of medicines and methodologies listed above except for Medicine repurposing which is reserved for sponsors from Academia and non-profit organisations. Therefore, for medicine repurposing the eligibility for scientific advice depends not only on the type of medicine but also on the status of the developer asking to enter into contact with the EMA. 

2. Registering on EMA’s secure online platform IRIS

Use EMA’s secure online platform IRIS to request scientific advice or protocol assistance. The process is common to all of the types of scientific advice and to protocol assistance.

• Register before applying for scientific advice using the interactive guide 
• Upload a draft briefing document, using the template provided by EMA, introducing the medicine being developed and the questions
• EMA published a guidance for applicants who wish to apply for scientific advice and protocol assistance. 

3. Requesting “preparatory meetings”: Preparatory meetings from EMA for scientific advice 

The aim: Formerly known as “Pre-submission meetings”, preparatory meetings may be used for different reasons, to get feedback on the development plan, feedback on the questions, identifying other issues, get detailed information on the scientific advice procedure, regulatory questions outside the scope of scientific advice, establish contact with Agency staff.

Target: First time users of the mechanism, SME’s, general advice on specific types of products such as complex medicines.

How: The meetings are held via teleconference since September 2018.

Find out more on preparatory meeting on the dedicated webpage on the EMA’s website and within the European Medicine Agency Guidance for Applicants seeking scientific advice and protocol assistance.

4. Types of question on scientific issues for scientific advice and protocol assistance and procedure 

 To understand the types of questions a developer can ask through scientific advice refer to EMA’s guidance on scientific advice and protocol assistance. 

Source: EMA, From Laboratory to patient: the journey of a medicine assessed by EMA, 2019, p. 9.

More information on scientific advice and protocol assistance are available here.

PRIME: PRIority Medicines scheme

1. Who

All types of seekers of interaction but special incentive for SMEs and Academia to support interaction demands from developers. 

For SMEs, they should acquire the SME status through the dedicated office following criteria and steps listed above. 

For Academia, they should meet the academia definition. To be considered as Academia the seeker of interaction wishing to have early interaction with EMA through the PRIME scheme needs to be: 

• A public or private higher education establishments awarding academic degrees
• A public or private non-profit research organisations whose primary mission is to pursue research
• Or an international European interest organisations as set out in Commission Regulation (EU) No 1290/2013 of 11 December 2013. 
• Applicants should not be financed or managed by private profit organisations in the pharmaceutical sector (“PPO”), nor should they have concluded any operating agreements with any PPO concerning their sponsorship or participation to the specific research project for which a fee exemption is sought for scientific advice under the PRIME scheme 

(European Medicines Agency Guidance for applicants seeking access to PRIME scheme EMA/191104/2015, page 5/18)

2. When

PRIME is available to sponsors engaged in the exploratory clinical trial phase of development, as the applicants need to give preliminary clinical evidence. 

Nevertheless, earlier support is provided for SMEs and Academia, who generally have less resource and experience on regulatory aspects. They can request an Early Entry PRIME Status “if:

• compelling non-clinical data in a relevant model provide early evidence of promising activity, or proof of principle;
• first-in-human studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability”. (See the EMA’s website here)

Further data will be expected later on for granting full PRIME designation for SMEs and Academia.

More generally, PRIME support is tailored to the stage of development of the medicine.

3. How

• Register on IRIS platform before submitting a request following the steps detailed in the Quick interactive guide to IRIS registration process
• Possibility of a pre-submission meeting for developers planning to apply for PRIME, you should send a pre-submission meeting request.
• Request a research product identifier (RPI) for the medicine you are developing
• Submit a request for eligibility to the PRIME scheme on the IRIS platform following the steps listed above, there is no fee applicable to submit a request
• Follow this link to find guidance on the registration process on IRIS, IRIS guide to registration and RPIs Preliminary requirements for all IRIS submissions
• For PRIME eligibility request, send the following documents through the platform:
  • The Applicant’s justification based on the template (this should be submitted in MS Word format): Follow the template by giving a concise but comprehensive account of the research developed of not more than 30 pages. The document should explain why the medicine developed is a priority one by meeting an unmet need and therefore how the product is of Major Public Health interest.
  • Literature references cited in the justification (this should be appended in a zip file)

4. Review of the application to enter the PRIME scheme  

• The EMA has to confirm the request fits into the scope of the scheme.
• A member of the SAWP and an EMA scientific officer (for ATMPs, CAT Rapporteur and CHMP co-ordinator) are appointed as reviewers of the request, and they will give reports on the request.
• By day 30, the reports will be sent to the SAWP and the CHMP for comments. If the medicine developed falls into the category of an ATMP, the CAT will also review the request and give a recommendation to the CHMP. 
• The CHMP is the organ responsible for giving the outcome of the requests. 
• By day 40, The CHMP final recommendation will be adopted.
• If an applicant receives a positive outcome, it means the product is eligible to benefit and enter the PRIME scheme.
• All of the submission deadlines and timetables for the PRIME scheme are published on the EMA website here. 

For a more detailed overview of the process to apply to PRIME and what it entails, the EMA has published a Guidance for applicants seeking access to PRIME scheme. 

Published: 31/07/2023

Last updated: 18/05/2024

Author:

Auxane Delage, EuroGCT information officer on Ethical, Legal and Societal Issues

Aurélie Mahalatchimy, EuroGCT WP4 Convenor, UMR 7318 DICE CERIC, Aix-Marseille University, CNRS, Aix-en-Provence- France

The authors deeply thank Valentin Brunel for his support in the design of figure 1.

Reviewed by:

Under internal review by EuroGCT Research and Innovation Working Group.