Understanding EMA scientific advice
The European Medicines Agency (EMA) scientific advice procedure was introduced with the aim to improve communication between companies developing medicinal products (sponsors) and regulators to enable streamlining of the development of high-quality, effective and safe medicinal products toward marketing authorisation. Scientific advice may be requested for all medicinal products for use in humans; it has proven particularly valuable for innovative products for rare indications, for products for which insufficient relevant guidance documents exist, as well as for sponsors with limited knowledge about medicine regulations such as some academic groups and small-medium companies.1 The scientific advice procedure allows sponsors to ask the EMA specific questions and gain regulators’ insights into any aspects of the development program of a medicinal products, from quality of the manufacturing process to non-clinical and clinical aspects as well as methodological issues, at any stage in development.2 It promotes efficient use of resources during product development by providing feedback on the most appropriate tests and studies to ensure the generation of appropriate data for a solid benefit-risk evaluation upon marketing authorisation application.1
To apply for scientific advice, the sponsor must prepare a briefing document in which 1) an introduction of the applicable disease indication and medicinal product is given, 2) the development program for the applicable medicinal product is described, 3) the development program questions requiring scientific advice are presented, and 4) the sponsor’s proposed solutions to the questions are described in applicant position statements. The briefing document is submitted to and reviewed by the EMA, specifically the Committee for Medicinal Products for Human Use (CHMP), who provide recommendations to the posed questions.3 While the EMA scientific advice recommendations are not legally binding, they will be taken into consideration upon review of the medicinal product marketing authorisation application; any deviations from the recommendations must be well justified. Studies have demonstrated that compliance with the scientific advice recommendations is correlated with successful marketing authorisation applications: analysis of the marketing authorisation applications between 2008 and 2012 that received scientific advice, found programs that complied with the scientific advice trial design recommendations had a marketing authorisation application success rate of 84% versus 43% for non‑compliant programs.4
Best practices for briefing document preparation
The preparation of a clear, complete, well-targeted and unambiguous briefing document is an important step to obtain meaningful advice from the EMA. At Orfenix we regularly support academic groups as well as small companies looking to obtain medicinal product development program advice from the EMA with the preparation of scientific advice briefing documents. From our experience, we present several useful tips & tricks to consider when writing a briefing document for the EMA CHMP.
Tips & tricks to writing briefing document development program questions
- Each question should be worded unambiguously, precisely and with a defined scope to ask a specific question. Do not combine multiple questions in one and justify the proposed sponsor’s approach with a single applicant position statement; rather, split the questions into separate items with separate applicant position statements.
- Do not word the questions in such a manner that they ask for a pre-evaluation of data or approvability of the product. Typically, briefing document questions use the wording ‘Considering … does the CHMP agree that/with…’.
Tips & tricks to writing briefing document applicant position statements
- The applicant position statement should describe the sponsor’s proposed solution to the question. It should be written in such a manner that the EMA CHMP can follow the sponsor’s rationale for the chosen approach. Additionally, it should include alternative options that were considered and critical reasoning why these options are not preferred by the sponsor.
- Consider any concerns the EMA CHMP may raise and try to address these proactively.
- Support the sponsor’s proposal with evidence and data; comprehensive scientific data should be included in the statement.
- Each applicant position statement should be able to stand alone, however, reference to other parts of the briefing document may be made.
General briefing document tips & tricks
- Use the EMA CHMP scientific advice briefing document template. Follow the clear structure and format of the template to ensure inclusion of all required information and facilitate EMA CHMP review.
- Include subject-matter experts in the briefing document review, prior to EMA submission.
- Where applicable, present relevant data concisely using tables and figures.
- Add relevant annexes to the document such as the investigator’s brochure, clinical study protocol, literature references, etc.
- Save all references separately to be able to upload them to the EMA portal upon submission of the briefing document.
- Be aware that the briefing document uploaded to the EMA portal should be the final version from the sponsor’s side; it is labelled as ‘draft’ in the guidelines because the EMA CHMP may still request some changes.
For further questions or insights into scientific advice briefing document writing, feel free to contact Orfenix.
References:
1. Broz DK, Galliverti G, Bührer A. Scientific advice procedures in the EU – an overview of the regulatory background. Medical Writing. 2020;29(3):36-45. (https://journal.emwa.org/eu-regulations/scientific-advice-procedures-in-the-eu-an-overview-ofthe-regulatory-background/article/6002/scientific-advice-procedures-in-the-eu.pdf)
2. Murphy A, Bere N, Vamvakas S, Mavris M. The added value of patient engagement in early dialogue at EMA: Scientific advice as a case study. Front Med. 2022;8:811855. (https://pubmed.ncbi.nlm.nih.gov/35127766/)
3. European Medicines Agency. Scientific advice and protocol assistence. Hofer MP, Jakobsson C, Zafiropoulos N, et al. Impact of scientific advice from the European Medicines Agency. Nat Rev Drug Discov. 2015;14(5):302-303. (https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-advice-protocol-assistance)
