Although the regulatory landscape for advanced therapy medicinal products (ATMPs) is rapidly evolving, varying regulatory requirements across different regions are hindering cell and gene therapy (CGT) adoption.
The US Food and Drug Administration (FDA)’s donor eligibility guidelines from 2007 state that donors from European countries should be deferred as a source for products in the US, said Anna Koptina, Head of Regulatory Affairs at the Swedish biotech Mendus, at a panel discussion on 19 March at the Advanced Therapies 2025 Conference in London. Thus, if a biotech manufactures a product in Europe and wants to supply it in the US, it cannot use European donor material to supply a CGT to the US.
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In a freewheeling discussion at the meeting, Koptina and other CGT experts described how distinct regulatory processes in different regions are influencing biotech research.
Margareth Jorvid, Head of Regulatory Affairs and consultant at the Swedish consultancy Methra Uppsala, highlighted that the genetically modified organism (GMO) requirements in Europe pose a significant challenge, noting there have been some improvements, but called for further changes. The limited time for discussions with agencies is a barrier, especially during early development, said Shirley Bartido, director of Global Regulatory Affairs Oncology Cell Therapy at Takeda Pharmaceutical: “Early discussion is key to success,” she said. Bartido also questioned if the new US administration would mean a return to more stringent times with less communication between companies and regulatory bodies.
Variations in regulatory requirements across regions
Given the different regulatory approaches across regions, experts say there is a need for a single, aligned development route for ATMPs.
There should be a universal and optimised method with no differentiations between regions and regulatory strategies need to be streamlined, said Sean Russell, head of Regulatory Affairs at the Italian nonprofit Telethon Foundation. “Different agencies ask for different things with nuances for specific attributes, such as the finer details of potency assays or clinical trial designs,” he added. Russell echoed Bartido’s statements that there need to be opportunities to converse with agencies early in development to avoid delayed timelines.
These factors influence a biotech’s overall strategy too. Trying to expand into Europe is complex, so companies turn to the US, which has a clearer and more predictable regulatory pathway, said Jorvid. Koptina agreed that approval in the US is faster and easier, possessing more liberal requirements for unmet medical needs in certain indications, while the EMA has been much stricter with that. She referenced examples of approvals that were successful in the US and not in Europe, like Adaptimmune Therapeutics’ Tecelra (afamitresgene autoleucel), which received an FDA accelerated approval last year, but has not been approved yet in Europe.
According to Koptina, clinical trial authorisation approval timelines in Europe may be 50–156 days, versus 30–60 days in the US, which is a significant difference. The US offers a more pragmatic and risk-benefit-based approach to CGT development, at least in the early stages, making more biotechs turn to the US to conduct CGT trials instead of Asia and Europe, explained Bartido. Russell claimed that faster timelines for clinical trials in the US are appealing, although conducting trials there might be more expensive.
The impact of regulatory designations
Regulatory designations can be valuable in this backdrop. The FDA’s Regenerative Medicine Advanced Therapy Designation (RMAT), EMA’s PRIME designation, and others are essential in accelerating late-stage conversations. Obtaining a PRIME designation is an essential asset in interacting with senior members of regulatory agencies at the EMA filing stage, said Russell. According to Russell, one can receive an Innovative Licensing and Access Pathway (ILAP) designation from the UK Medicines and Healthcare products Research Authority (MHRA) based on preclinical and clinical data. The ILAP—which will be relaunched this month, potentially with stricter entry criteria—will become a valuable designation to obtain in the future, Russell added.
On the topic of designations, the FDA’s fast track designation can be obtained quite early, sometimes even based on preclinical and Phase I data, added Koptina. As per published research based on applications recorded in the 2012–18 period, 70% of 737 fast track applications were successful. Alternately, RMAT applications require more solid data but can have an immediate benefit, says Koptina. In her experience, Koptina said an RMAT designation resulted in the first official RMAT meeting with more than 21 FDA experts, and every meeting after that was a type B meeting with shorter timelines.
Bartido highlighted some key differences across different designations; the FDA’s breakthrough designation programme has evolved and requires data collected over a long duration of at least twelve months and a larger patient population, while a smaller trial with four to six months data is still sufficient for an RMAT designation. While pursuing such designations can be resource-intensive for small biotechs, experts advised companies to pursue them since they are crucial to getting early engagement from senior FDA staff and alignment on certain topics so a programme will not be held back. Additionally, Jorvid emphasised that these designations are “investor magnets”.
Europe is making efforts to facilitate clinical trials
Despite the more stringent regulatory pathway for CGT development in Europe compared to the US, panelists believe that Europe is making strides to facilitate clinical trials, referencing the Clinical Trial Regulation (CTR). Regarding its implementation, Koptina, Russell, and Jorvid mentioned that the transition to the clinical trial transformation system (CTIS) was smooth in their personal experience, once the transparency rules were modified. However, this transition was a learning curve for regulatory authorities as they still need to define if countries will maintain any nuance in national decisions.
Overall, there is a need to harmonise the development processes and requirements across regions and foster dialogue and early interaction between companies and regulators. The CoGenT Global pilot scheme, which aims to reduce the duplication of efforts across countries and create a collaborative review of MAA and BLA submissions, is one such programme that has suffused experts with some optimism.
