Scientific advice and protocol assistance

The European Medicines Agency (EMA) can provide medicine developers advice on the most approproate 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, efefctive and safe medicines, for the benefit of patients.

At any stage of a medicine's development, 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, 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, so that no major objections regarding the design of the tests are likely to 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, scientific advice and protocol assistance are given by the Committee for Medicinal Products for Human Use (CHMP) on the recommendation of the Scientific Advice Working Party (SAWP).

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 posed by 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 scientific advice is most useful

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

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.

Types of questions addressed

Questions during scientific advice can relate to:

  • quality aspects (manufacturing, chemical, pharmaceutical and biological testing of the medicine);
  • non-clinical aspects (toxicological and pharmacological tests designed to show the activity of the medicine in the laboratory);
  • clinical aspects (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 riskmanagement plans);
  • methodological issues (statistical tests to use, data analysis, modelling and simulation).

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 alternative?
  • Are the plans to follow the long-term safety of the product appropriately designed?

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.

Scientific advice on post-authorisation safety studies (PASS)

EMA encourages medicine developers to seek scientific advice for PASS protocols. This voluntary, optional procedure will help to improve the design of studies meant to collect further information on a medicine's safety once it is on the market.

EMA ran a 12-month pilot for this procedure between July 2015-2016.

For more information, see:

Parallel consultations from regulators and HTA bodies

EMA offers consultations in parallel with European Network for Health Technology Assessment (EUnetHTA) as of July 2017. This aims to allow medicine developers to obtain feedback from regulators and HTA bodies on their evidence-generation plans to support decision-making on marketing authorisation and reimbursement of new medicines at the same time.

The procedure is a single gateway for parallel consultations with EMA, EUnetHTA and HTA bodies on their evidence-generation plans.

Consultations can take place before or after the product is made available on the market. The objective is to help generate optimal and robust evidence that satisfies the needs of both regulators and HTA bodies.

This initiative replaces the parallel scientific advice procedure by EMA and HTA bodies which required medicine developers to contact Member States' HTA bodies individually.

For more information, see Parallel consultation with regulators and health technology assessment bodies.

Tailored scientific advice on biosimilars

EMA is running a tailored scientific advice pilot project to support the development of new biosimilars.

The tailored procedure advises developers on the studies they should conduct, based on a review of the quality, analytical and functional data they already have available.

The pilot is open to all types of biosimilars and companies are encouraged to request a pre-submission meeting to review the suitability of the data package. Applicants should note that the SAWP will need an extra month in addition to normal scientific advice timelines to review applications.

EMA plans to run the pilot until it has completed six scientific advice requests. The Agency will analyse the outcome after completing the pilot.

For more information:

Fees and fee reductions

EMA charges a fee for scientific advice, which varies depending on the scope of the advice.

Reductions apply for certain types of medicines and applicants, including a 75% fee reduction for medicines for orphan medicines and a 90% fee reduction for SMEs.

For more information, see fees payable to EMA.

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 report was finalsied 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.

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.

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