European regulation of ATMPs1

12 October 2018

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European regulations concerning the development of Advanced Therapeutic Medicinal Products (ATMPs) are complex and provide a number of additional challenges to sponsors developing gene therapies, somatic cell therapies and tissue engineered products.

Genetically Modified Organisms (GMOs)

Gene therapies and gene modified somatic cell therapies are subject to additional regulation in relation to the manufacture and use of genetically modified organisms. The regulations to be applied depend on the member state and if use of the GMO is considered “contained use” or “deliberate release”. Table 1 illustrates how this classification can vary between member states.

Additionally, the authority responsible for GMO applications may not be the same health authority that reviews clinical trial applications (CTAs). For example in the UK two agencies, the Heath & Safety Executive (HSE) and the Dept. for Environment & Rural Affairs (DEFRA), are responsible for GMO applications considered contained use and deliberate release respectively.

 

Table 1: Examples of member state classification of GMOs as contained use or deliberate release.

Timelines

The timelines for review of CTAs involving ATMPs may be extended up to 30 days compared to standard timelines, meaning applications can be subject to a 90 day review timeline. This may be extended up a further 90 days in the event that a consultation with a group or committee of experts is required. With all considerations it is possible for a CTA to take up to 9 months to be approved (or rejected). These timelines do not include those required for approval of GMO applications (as above), which may be between 10 and 130 days depending on the product and the member state and not including any periods where the Sponsor is preparing responses to questions.

CMC Considerations

There are a host of regulations that govern the procurement of starting materials, product specifications, traceability and safety, including the Cells & Tissues Directive (2004/23/EC) and the Blood Directive (2002/98/ EC). Such EU Directives may be implemented in different ways in different member states, and sponsors shouldbe aware that not all EU requirements are automatically fulfilled by implementing the requirements of the FDA.

Conclusion

There are a number of additional considerations that must be accounted for in the preparation and execution of clinical and regulatory strategies for ATMPs in the EU. To be successful and avoid delays, the correct advice as well as thorough and extensive planning is required.

Plan ahead and seek input on the relevant regulations and guidelines for your product in order to succeed in Europe.

12 October 2018

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