Table 1.

Summary of the major regulations and guidelines for the environmental risk assessment or vector-shedding studies required by the FDA, EU, MHLW regulatory authorities, and the ICH

Region	ICH region	EU		JP		US
Issuer	ICH	EMA	The European Parliament and the Council of the European Union	MHLW (and five other ministries)	MHLW	FDA
Relevant document	ICH considerations: General principles to address virus and vector shedding44	Guideline on scientific requirements for the ERA of gene therapy medicinal products45	EU directive on the deliberate release9 and EU directive on the contained use of GMOs10	Cartagena Act (Type 1 use and Type 2 use for medicinal products containing GMOs)12	Points to consider in ERA for approval of the Type 1 use for medicinal products containing GMOs13	Design and analysis of shedding studies for gene therapy and oncolytic products43	Determining the need for and content of ERA for gene therapies, etc.17
Year of issue	2009	2008	2001/2009	2003	2007	2015	2015
Positioning of each document	ICH considerations	EMA guideline based on EU Directive 2001/18/EC	EU directive	Japan local act	MHLW notification based on the Cartagena Act	FDA Guidance for Industry	FDA Guidance for Industry
Description of ERA for GMOs	NO	YES	YES	YES	YES	NO	YES
Description of requirements for vector shedding	YES	NO	NO	NO	YES	YES	NO
Description of timing of vector shedding studies	NO	YES	NO	NO	NO	YES	NO
Description of timing of submission of shedding data or ERA data	NO	YES	YES	NO	YES (for ERA)/NO (for shedding data)	YES	YES

ICH, International Council for Harmonization of the Technical Requirements for Pharmaceuticals for Human Use; EU, European Union; JP, Japan; US, United States; EMA, European Medicines Agency; MHLW, Ministry of Health, Labour and Welfare; FDA, US Food and Drug Administration; ERA, environmental risk assessment; GMO, genetically modified organism.