Environmental risk assessment of advanced therapies containing genetically modified organisms in the EU

Abstract

Gene therapy medicinal products have the potential to provide curative treatment for many diseases with current limited therapeutic options. As advanced therapy medicinal products (ATMPs), these therapies undergo a centralised, single European Union authorisation by the European Medicines Agency (EMA), but the risks and potential harm to the environment and population at large are weighted in each application, and different interpretations at national level exist. A streamlined procedure is now in place to facilitate a consistent approach for the assessment of the environmental risks of medicines containing genetically modified organisms for both clinical trial applications and marketing authorisation applications. This article provides an overview of basic requirements across the EU, an overview of the new streamlined process and discusses available guidance for developers with particular emphasis on marketing authorisation applications. All these initiatives are aimed to remove hurdles for ATMP developers and facilitate faster access to patients.

Advanced therapy medicinal products in China: Regulation and development

“…For example, for the clinical use of genetically modified organisms, the environmental risk assessment is crucial in each application to prevent the potential harm to the environment and population. 29 Regarding the genetically engineered cellular products, attentions should be paid to safety risks such as insertional mutations and activation of oncogenes. Tumorigenic/carcinogenic research can be designed based on the risk assessment results, which is typically more important for hPSC‐derived products with higher risky of tumor formation.…”

“…Sound principles are required to regulate such types of complex products in a science‐based and risk‐based manner. For example, for the clinical use of genetically modified organisms, the environmental risk assessment is crucial in each application to prevent the potential harm to the environment and population 29 . Regarding the genetically engineered cellular products, attentions should be paid to safety risks such as insertional mutations and activation of oncogenes.…”

Japanese Pharmaceutical Regulations of Engineered Viral Vectors for Medical Use Compared With Those in the United States and the European Union

“…Now, developers should receive the approval of the T‐1R application before at least the first patient enrollment of the clinical trial in Japan. In the European Union, several countries, such as France, accept the parallel application of CTA and ERA, but some countries, such as Poland, demand the approval of usage of the GMOs in the clinical trials before submitting a CTA 4 …”

ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature

“…Among the data submitted by the developer, an environmental risk assessment (ERA) must be present. The specific guidelines dedicated to genetically modified organism (GMO) (EMEA/CHMP/BWP/473191/2006) for both the clinical trials and marketing authorization have recently been reviewed by Whomsley R. and colleagues ( 24 ). ERA for GMO should include six steps that are: (1) the identification of characteristics which may cause adverse effects, (2) the evaluation of the potential consequences of each adverse effect if it occurs, and of the magnitude of each identified consequence, (3) the evaluation of the likelihood of the occurrence of each identified potential adverse effect, (4) the estimation of the risk posed by each identified characteristic of the GMO, (5) the application of management strategies covering the risks from the marketing of the GMO, and (6) the determination of the overall risk of the GMO.…”