It’s never too early to start crafting a global regulatory submissions strategy. Both the European Medicines Agency (EMA) and EU Member State National Competent Authorities (NCAs) offer scientific advice (SA) to drug sponsors from the early stages of the development process. The EMA’s SA often comes in written form, although the Scientific Advice Working Party (SAWP) may invite the sponsor to meet, if warranted. In contrast, many NCAs offer face to face meetings. Likewise, the FDA grants meetings in advance of an investigational new drug (IND) application filing, as well as End of Phase I or End of Phase II (EOPI or EOPII) meetings to those who request one.
But while early engagement with regulatory authorities sounds like an obviously good thing to do, there are some potential pitfalls.
EMA data suggest advice can boost success: between 2008 and 2012, 85% of marketing authorization applications (MAAs) that received and followed early SA were approved, as opposed to only 41% that did not (Hofer et al., 2015).
Early meetings can also shorten clinical development timelines. One recent study looked at 132 new product applications submitted to the FDA’s Center for Drug Evaluation and Research (CDER) between 2008 and 2012. It found that the 49 marketing applications which followed a pre-IND (PIND) meeting had a median clinical development time (CDT) of 6.4 years; whereas the 83 applications submitted without a PIND meeting had a median CDT of 8.3 years (Vu and Pariser, 2014).
The EMA recommended 93 medicines for marketing authorization in 2015, including 39 novel drugs. According to the agency’s annual report, about half of all applicants who won a positive recommendation had requested and received SA at some point during development; that figure rose to 85% for medicines containing a new active substance (European Medicines Agency, 2016).
Advice provided by the SAWP or by an NCA is not binding, but it can certainly be useful. However, minutes from scientific advice sessions must be included in any future MAA, whether a sponsor is pursuing a centralized or decentralized approach. Sponsors who choose not to follow advice must explain and justify that decision.
Companies must, therefore, carefully consider the issues on which they would like advice, and reflect on the possible consequences beforehand. In PAREXEL’s experience, there are several benefits of obtaining SA, and some hazards to avoid.
PIND meetings, by definition, can be conducted at any time before an IND submission, and may include discussions of clinical data developed outside the US. Early meetings can be especially helpful for new chemical entities, novel indications, orphan drug products, and biologics – in other words, for situations where there is no established regulatory roadmap regarding clinical efficacy endpoints or pharmacologic or toxicological signals of concern.
To reap the full benefits of meetings with the FDA, sponsors should:
In PAREXEL’s experience, the positives of early regulatory engagement outweigh the negatives. However, only for sponsors that are well-prepared.
European Medicines Agency, (2016). Annual activity report 2015. London: European Medicines Agency. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2016/07/WC500210118.pdf [Accessed 20 Sep. 2016.]
Hofer, M., Jakobsson, C., Zafiropoulos, N., Vamvakas, S., Vetter, T., Regnstrom, J. and Hemmings, R. (2015). Regulatory watch: Impact of scientific advice from the European Medicines Agency. Nature Reviews Drug Discovery, 14(5), pp.302-303.
Vu, H. and Pariser, A. (2014). Pre-Investigational New Drug Meetings with the FDA: Evaluation of Meeting Content and Characteristics of Applications for New Drug and Biologic Products. Therapeutic Innovation & Regulatory Science, 49(3), pp.434-442.
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