The Importance of Scientific Advice from the Regulatory Authorities in Clinical Research

April 21, 2021

The process of marketing authorization is a crucial step in the entire drug development process. Deciphering the most effective way to generate robust evidence on the safety and efficacy of the medicine is essential to bring in new therapies for patients.

To conduct successful clinical trials and ensure that the drug development process runs seamlessly, companies can engage in early regulatory dialogues with the regulatory authorities and seek expert advice.

What is Scientific Advice, and who can give it?

Scientific advice (SA) is a fee-based voluntary service conferred by regulatory agencies to companies seeking expert opinion while developing new medicinal products. During SA, regulatory experts respond to specific questions related to the development of a particular medicine.\(^1\)

SA allows early communication between the companies and the regulators. With SA, companies can seek the regulator's opinion on quality, nonclinical, and various clinical aspects (e.g., study design, choice of endpoint, indication) of drug development.\(^{2,3}\)

SA can be requested from national agencies, EMA, or FDA, as applicable. Companies can also request joint (parallel) advice from the regulatory agencies.\(^4\)

What questions can be raised in a Scientific Advice request?

Companies can request SA throughout the drug development phases - Early phase before the conduction of clinical trials, clinical development phase (planning for pivotal trial), and late-stage before regulatory submission.

Companies can seek SA on the below topics or scenarios:\(^{5-8}\)

- Choice of trial design

Meticulously designed trials can yield better outcomes. Companies can seek guidance on the study population, comparator choice, endpoints, and statistical methods to be used.

- Advice on orphan designated products and pediatric trials

SA may present significant benefits for orphan medicines, including protocol assistance and a reduced fee. Companies can also request advice to support the authorization of medicinal products intended for the pediatric population.

- Advice on SmPC

Companies can present the draft summary of product characteristics (SmPC) with the proposed indication. Companies can also seek advice on the quality, safety, and efficacy data in product dossiers.

- Economic assessments

In parallel with regulatory advice, SA requests may also include early health-technology assessment (HTA) advice when the product is planned for future state reimbursement programs.

- Exceptional cases

SA can be sought for novel therapeutic areas/products for which scientific guidance is not established, is unclear, or is limited. SA is also recommended when there is a need to deviate from the existing guidelines.

What are the advantages of getting Scientific Advice?

Seeking SA on time can support the development of safe and efficacious medicines and ensure that the patients get access to effective treatments in time.\(^3\)

SA promotes the efficient use of resources as companies receive feedback on viable strategies and methodologies for product development. Companies can plan and design better trials and choose the best endpoints.\(^7\)

By refining the trial design and other aspects as per the SA, companies can save valuable time on prospective queries which may arise during the Clinical Trial Application (CTA) or Marketing Authorization Application (MAA).\(^2\)

By fostering scientific collaboration, SA facilitates a working relationship between the company and the regulatory authority. When incorporated into the drug development program, SA can add significant value to the marketing authorization application. This can significantly enhance the chances of bringing a medicinal product to market.\(^5\)

Are there any risks to consider?

To achieve fruitful outcomes, companies must prepare well for the SA meetings. Preparing the briefing documents and SA questions is a crucial undertaking, and any inaccuracy may lead to misunderstandings between the regulators and the company.

SA presentations can create an informational background for future applications. Hence, briefing documents and questions should be prepared judiciously, taking into consideration the consequences of the regulator's responses. In cases where the companies deviate from the past SA, companies may need to justify the reasons for not following the recommendations. \(^7\)

Timing is an essential factor when considering SA. If SA is sought too early, the process may fail to address the issues arising after the onset of the clinical trials. If sought too late, companies may be unable to complete the clinical trial and launch the product in the market by the target date.\(^4\)

Why is it beneficial to have support in the Scientific Advice process?

To achieve the best outcome, companies planning to seek SA need to be well prepared with the questions and the related documents. While companies may have valuable knowledge in drug development, collaborating with a clinical research organization (CRO) can keep the SA process on track and help companies navigate this crucial phase effortlessly.

By teaming with experts, companies can benefit from the strategic advice supporting their ideas and interests. It can facilitate pre-discussion of all possible challenges and strategies confidentially. The collaboration presents an opportunity to have a "third eye" for information and ideas that the company plans to be present to the regulatory authorities.

The CRO can assist companies in developing concise and well-phrased documents that focus on the relevant questions and ideas. This will allow companies to focus on technical and organizational issues related to the SA request. The timely assistance from a CRO can increase the chances to get timely scientific advice which can be advantageous for further product development and regulatory activities.

Dokumeds is a trusted long-term partner with unique experience in all stages of clinical drug development. Dokumeds has extensive and successful experience in communication with major regulatory authorities across the EU. Our strong team of professionals can help companies present their ideas in the SA process and ensure that meaningful outcomes are achieved.


  1. Putzeist, Michelle, Aukje K. Mantel-Teeuwisse, Christine C. Gispen-De Wied, Arno W. Hoes, and Hubert G. Leufkens. "Regulatory scientific advice in drug development: does company size make a difference?." European journal of clinical pharmacology 67, no. 2 (2011): 157-164.
  2. Broz, D.K., Galliverti, G. and Bührer, A., 2020. Scientific advice procedures in the EU–an overview of the regulatory background. Medical Writing, 29, pp.36-45.
  3. European Medicine Agency. How scientific Advice works. https://www.ema.europa.eu/en/hument/scientific-advice-protocol-assistance/how-scientific-advice-worksman-regulatory/research-develop
  4. Bramley, T., Hebborn, A., and Parcher, 2017. To Seek or Not to Seek Parallel European Medicine Agency and Health Technology Assessment Scientific Advice? Health policy, pp. 11-15
  5. Guidelines for parallel EMA-HTA joint scientific advice: https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-advice-protocol-assistance/parallel-consultation-regulators-health-technology-assessment-bodies
  6. EMA 2017. General principles for EMA-FDA parallel scientific advice: https://www.ema.europa.eu/en/parallel-advice
  7. Dallmann, G., 2017. Scientific Advice in the EU and US: Practical Experience and Rules of the Game on Both Sides of the Atlantic. Pharmazeutische Medizin, 2, pp. 92-99
  8. EMA. 2012. Orphan designation: research and development. Orphan designation:research and development | European Medicines Agency (europa.eu)

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