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. 2017 Dec 19;90(4):683-693.
eCollection 2017 Dec.

Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan

Celine-Lea Halioua-Haubold  1   2 , James G Peyer  3 , James A Smith  4   5 , Zeeshaan Arshad  6   5 , Matthew Scholz  7 , David A Brindley  1   5 , Robert E MacLaren  8   2   9
Affiliations

Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan

Celine-Lea Halioua-Haubold et al. Yale J Biol Med. .

Abstract

Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

Keywords: ATMP; EMA; FDA; Japan; MHLW; advanced therapeutic medicinal product; gene therapy; regulation.

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Figures

Figure 1
Figure 1
The regulatory structure of the US, EU, and Japanese regulatory bodies as relevant to gene therapies. Unlike the FDA and MHLW, the EMA is not a completely centralized approval body – developers may pursue market approval also via the “national procedure” (single EU state application), “decentralized procedure” (concurrent application to multiple EU states) or “mutual recognition” (first via a single EU state, then centralized via the EMA). However, ATMPs including GTs are mandated to seek approval under the centralized EMA pathway, along with specific therapeutics of certain modalities and indications.
Figure 2
Figure 2
Case Study on Gene Therapy Product Glybera.
See this image and copyright information in PMC

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