Scientific advice and protocol assistance

The European Medicines Agency (EMA) can advise medicine developers on the most appropriate way to generate robust evidence on a medicine's benefits and risks. EMA provides scientific advice to support the timely and sound development of high-quality, effective and safe medicines. This benefits patients.

Updated on 17 November 2025:
Page introduction - to include information on scientific advice for developers of medicines targeting declared or potential public health emergencies and threats

Added on 17 November 2025:
'Scientific advice for public health emergencies and threats' section - linking to a new page on this topic

At any medicine development stage, a developer can ask guidance and direction from EMA on the best methods and study designs to generate robust information on how well a medicine works and how safe it is. This is regardless of whether the medicine is eligible for the centralised authorisation procedure or not.

Scientific advice helps to ensure that developers perform the appropriate tests and studies. This prevents major objections regarding the design of the tests from being be raised during the evaluation of the marketing authorisation application. This also helps avoid patients taking part in studies that will not produce useful evidence.

For human medicines, the EMA's Committee for Medicinal Products for Human Use (CHMP) provides scientific advice and protocol assistance on the recommendation of its Scientific Advice Working Party (SAWP).

For human medicines intended to treat, prevent or diagnose a disease causing a declared or potential public health emergency (like COVID-19 or avian influenza), CHMP bases its scientific advice on recommendations from the EMA's Emergency Task Force (ETF). 

The ETF also makes recommendations to CHMP for scientific advice on medicines targeting selected pathogens and other threats that have the potential to cause public health emergencies (like Zika or radio-nuclear threats). For a list of pathogens and threats under the ETF remit, see the ETF's workplan.

ETF's scientific advice also covers aspects of clinical trial applications for related medicines.

The information on this page applies to both SAWP and ETF advice procedures during crisis preparedness.

For more information on EMA's guidance and support for medicine developers, see: 

• Research and development

Also on this topic

• Requesting scientific advice or protocol assistance from EMA
• Qualification of novel methodologies for medicine development
• Parallel scientific advice and special development aspects or product types

From lab to patient: journey of a medicine

Prospective applicants who are completely new to scientific advice or have little prior interaction with medicines regulators may benefit from reviewing the journey of a medicine for human use assessed by EMA in this interactive timeline, as a first step.

The interactive timeline linked below explains all stages, from initial research to patient access. This includes how EMA supports medicine development, assesses the benefits and risks and monitors the safety of medicines.

The timeline is available at: From lab to patient: The journey of a medicine assessed by EMA. 

For information on how to request scientific advice from EMA, see:

• Requesting scientific advice or protocol assistance from EMA

How scientific advice works

EMA gives scientific advice by responding to specific questions from the medicine developer on the development of a particular medicine. 

The developer of a medicine presents the way it plans to develop its medicine and identifies questions and possible solutions. EMA then gives advice on the developer’s proposals.

Scientific advice is prospective in nature. EMA does not pre-evaluate the results of the studies and in no way concludes on whether the benefits of the medicine outweigh the risks.

Scientific advice from EMA is not legally binding on EMA or on the medicine developer with regard to any future marketing authorisation applications for the medicine concerned.

When is scientific advice most useful

Scientific advice and protocol assistance are particularly useful to medicine developers when:

• they are developing an innovative medicine and there appears to be no or insufficient relevant detail in EU guidelines or guidance documents, or in Pharmacopoeia monographs, including draft documents or monographs released for consultation;
• they are developing new or repurposed medicines targeting (re)emerging pathogens for which there is an unmet medical need but insufficient or no guidance is available;
• the developer chooses to deviate from scientific guidelines in its development plan;
• the medicine developer has limited knowledge about medicine regulation, such as some academic groups or micro, small and medium sized enterprises (SMEs).

Medicine developers can request scientific advice or protocol assistance either during the initial development of a medicine before submission of a marketing authorisation application or later on, during the post-authorisation phase.

For more information, see:

• Academia
• Support to SMEs

Types of questions addressed

Questions during scientific advice can relate to:

• quality aspects (e.g. manufacturing, chemical, pharmaceutical and biological testing of the medicine);
• non-clinical aspects (e.g. toxicological and pharmacological tests designed to show the activity of the medicine in the laboratory);
• clinical aspects (e.g. appropriateness of studies in patients or healthy volunteers, selection of endpoints, i.e. how best to measure effects in a study, post-authorisation activities including risk management plans);
• methodological issues (e.g. statistical tests to use, data analysis, modelling and simulation);
• overall development strategy (e.g., conditional marketing authorisation, bridging strategy for generics, safety database), significant benefit for maintaining orphan designation, and paediatric developments.

Examples of questions

• Are the patients to be included in a study sufficiently representative of the population for whom the medicine is intended?
• Are the planned measures to assess the benefits of a medicine valid and relevant?
• Is the proposed plan to analyse results appropriate?
• Does the study last long enough and include enough patients to provide the necessary data for the benefit-risk assessment?
• Is the medicine being compared with an appropriate control?
• Are the plans to follow the long-term safety of the product appropriately designed?

Questions outside the scope of scientific advice

Questions about the topics below are outside the scope of scientific advice:

• Compassionate use, advanced therapy medicinal product (ATMP) classification, PRIME eligibility, and accelerated assessment
• Changes to the key elements of paediatric investigation plan (PIP) measures and paediatric waivers or deferrals, which EMA addresses via a paediatric procedure
• Matters of a purely regulatory nature (please use the ‘Submission Details’ field in your submission via the IRIS portal)
• Adequacy of existing data for assessment of a regulatory application (e.g. a clinical trial application or marketing authorisation application). However, please include existing data expected to inform the discussion of questions on further development steps in the scientific advice briefing documentation

Examples of questions

• Could the proposed modelling and simulation approach replace study X in the agreed PIP? (only the PDCO can endorse such matters)
• Are the proposed active substance/finished product specifications acceptable? (as opposed to: Is the plan to derive the specifications acceptable?)
• Are the non-clinical data adequate to support a first-in-human study? (this would require a full review of the non-clinical data before EMA can respond and the question would belong to a clinical trial application under national competent authority remit)
• Are the phase 3 study results adequate to support marketing authorisation? (this is a question for the marketing authorisation application)

For more information, see:

• Compassionate use
• Advanced therapy classification
• PRIME: priority medicines
• Accelerated assessment
• Paediatric investigation plans
• Paediatric medicines: Overview
• Clinical trials in human medicines

Protocol assistance

Protocol assistance is the special form of scientific advice available for developers of designated orphan medicines for rare diseases.

In addition to scientific advice, developers of orphan medicines can receive answers to questions relating to the criteria for authorisation of an orphan medicine. These include:

• the demonstration of significant benefit within the scope of the designated orphan indication;
• similarity or clinical superiority over other medicines. This is relevant if other orphan medicinal products exist that might be similar to the product concerned and which have market exclusivity in the same indication.

For more information, see:

• Orphan designation: Overview

Steps of the process

1. Registration with EMA
Unless already registered with EMA, a medicine developer who wishes to request scientific advice first needs to register themselves, their organisation and product in development with EMA. A preparatory meeting can be organised, in particular for first users of scientific advice or for complex medicines.

2. Formal request and validation
The developer then submits their scientific advice request via the IRIS platform which contains a Briefing Document including a list of specific scientific questions and proposed responses. EMA determines whether the questions are valid or not for scientific advice.

3. Appointment of coordinators
For each scientific advice procedure (or ‘protocol assistance’ procedure for orphan medicines) validated, two members of the Scientific Advice Working Party (SAWP) who have sound expertise to address the scientific questions are appointed as coordinators.

4. coordinators form assessment teams and prepare report
Each coordinator forms an assessment team calling on assessors from their national agency or other EU agencies. Each team prepares a report addressing the scientific questions; they draft a list of issues for discussion with all the other members of the SAWP and may ask the applicant for any additional documents or clarifications.

5. Meeting with developer (if requested by SAWP)
If the SAWP wishes to discuss specific issues with the medicine developer it will organise a meeting, particularly where it disagrees with the proposed plan and proposes alternative development plans.

6. Consulting experts
The SAWP consults relevant EMA committees (for example EMA’s Committee for Advanced Therapies (CAT) or EMA’s Committee for Orphan Medicinal Products (COMP) and scientific working parties. Additional external experts may also be consulted, further widening the pool of expertise the SAWP can call on.

7. Consulting patients
Patients are also often consulted. If EMA decides to respond to the medicine developer in writing, patients are asked to provide comments; if EMA decides to meet with the medicine developer, patients are invited to attend.

 

7. EMA final response
The SAWP consolidates a response to the scientific questions. Final advice is discussed and adopted by the CHMP and then sent to the medicine developer.

Standard operating procedure for scientific advice and protocol assistance procedure

Adopted Reference Number: SOP/H/3037 Legal effective date: 15/02/2023

Why following scientific advice does not guarantee marketing authorisation

Scientific advice and the assessment of the benefits and risks of a medicine are different by nature.

Scientific advice looks at how a medicine should be tested in studies to generate robust evidence, while the assessment at the time of marketing authorisation looks at the evidence generated to determine whether the medicine’s benefits outweigh its risks, regardless of any advice previously given.

Scientific advice can make the evaluation of a medicine easier and quicker because the evidence is likely to be more robust, appropriate and complete, but it does not affect the stringent assessment of safety and efficacy.

Complying with scientific advice therefore increases the chances of receiving marketing authorisation but it does not guarantee it.

What EMA publishes on outcomes of scientific advice

During the development and assessment phases, the detailed advice given to a medicine developer is not made public. This is because disclosing information at this stage may undermine research and development efforts and discourage research in new medicines.

However, information is made available after a medicine obtains marketing authorisation. All medicines whose assessment report was finalised after 1 January 2019 include a summary of the developer’s questions and key elements of EMA's advice and whether or not the developer complied with this advice within the assessment report.

During a declared public health emergency, EMA publishes a list of medicines that have received informal or formal advice from the CHMP and the ETF.

In addition, the full advice can be made available upon request. For more information, see Access to documents.

Scientific advice is also one of the main sources for updating EMA scientific guidelines on medicine development, including, in particular, disease-specific guidelines.

Parallel scientific advice and special development aspects or product types

EMA carries out scientific advice in cooperation with other decision-making bodies in the European Union (EU) and beyond. It also offers scientific advice on special development aspects and / or product types, as follows:

• Parallel scientific advice processes - with the United States Food and Drug Administration (FDA), and with the EU Member State Coordination Group on HTA (HTACG)
• Scientific advice for special purposes - on clinical trials and post-authorisation safety studies (PASS)
• Scientific advice for special product types - on medicine repurposing and for biosimilar medicines

For more information, see:

• Parallel scientific advice and special development aspects or product types

Scientific advice for public health emergencies and threats

EMA's ETF provides medicine developers scientific advice for medicines used in declared or potential public health emergencies and threats. 

Related medicines include those:

• targeting public health emergencies (like COVID-19 and Mpox);
• addressing antimicrobial resistance (AMR);
• tackling outbreaks (like Zika and Dengue).

For more information on the ETF's remint, see Annex 1 of ETF's work plan:

• ETF work plan

For more information on ETF's scientific advice, including advice on aspects related to clinical trials applications, see:

• Scientific advice for public health emergencies and threats
• Clinical trials in human medicines: Scientific advice for public health emergencies and threats