The Alliance for Regenerative Medicine (ARM) and other industry groups are urging regulators to consider gene therapy requirements in upcoming reforms, because some advanced therapy medicinal products (ATMPs), such as gene therapies, contain genetically modified organisms (GMOs), and as such, require additional approvals before clinical trials can commence.
The GMO application and clinical trial approval (CTA) process in some European Union (EU) member states places a “significant burden” on gene therapy medicinal product (GTMP) clinical trials, ultimately delaying patient access to “potentially transformative medicines,” according a new position paper from ARM and other industry groups.*
“The key point of the paper was to highlight that these GMO regulations actually hinder the start of clinical trials for gene therapy products in Europe, despite all the advances that have been made for the regulation of advanced therapies,” Anne-Virginie Eggimann, vice president of regulatory affairs at bluebird bio and ARM Regulatory Committee, co-chair told Outsourcing-Pharma.com.
Eggimann explained that many companies, which are primarily based in the US, trying to initiate clinical trials for gene therapy products in the EU run into several issues because the requirements for GMOs are complex.
“These regulations were not set up for medical products – they were set up for GMOs in general – they are very difficult to follow and they are very complex,” said Eggimann.
Additionally, the requirements are purely national, she noted, adding that they follow very general principals from the EU.
“It’s very complex for a company coming in and having to decipher the regulatory path to understand what to do for these GMO applications and understand the process to get approval,” Eggimann explained. The process can also be very lengthy, she said, in some cases taking up to a year.
The key takeaway for developers? Plan early.
“What we always say to developers is to plan very early for this,” said Jacqueline Barry, director of regulatory affairs at Cell and Gene Therapy Catapult, as the process can “significantly” increase the length of time before clinical trials are approved.
In the Netherlands, Barry said it is a 180-day process. “There are very many different systems and [developers] should be planning for it and build it into the timeline,” she told us.
Disparities and the call for harmonization
Looking towards the implementation of new clinical trial regulations in Europe slated for 2019, Annie Hubert, senior director, EU section and public policy at ARM, said the fear is that the changes don’t take the specific requirements of gene therapies into consideration.
“One of the things that we stressed in the paper was that we would like that better consideration is given to GMO requirements in the context of the implementation of the new regulations,” Hubert told us, “So that the objective of this new regulation is not lost for gene therapy.”
Eggimann said one easy to implement strategy would be to list the various member state’s procedures in English on the European Commission website, so sponsors can better understand the requirements and translate forms if needed.
“It would also be helpful to harmonize the process of the application,” she said. “In theory, there is no reason for any member state to have a different process or require different information.”
Some sponsors have proposed using a standardized form.
Hubert also said there needs to be more convergence in the decision-making process, as the different national authorities often make different decisions or conclusions.
“The data are the data, and they are the same, there’s no reason why the authorities should be making different decisions,” she said. “We encourage harmonization and dialogue among the different national authorities so that there is more convergence in the decisions.”
Priorities and implementation
Hubert explained the organization has communicated its position and are in dialogue with the European Commission, though conversations with the national authorities are needed.
Barry said the EMA is reportedly looking into ways to streamline the process, which up to this point has always been a national member state competency with little scope for central coordination.
It could take a year or two before improvements are seen, said Eggimann.
Barry echoed that change won’t happy quickly: “It think it’s important to remember that these offices are set up to do mainly the registration of plant and animal food modifications,” she said. “The gene therapy field is so small for them, so it’s not going to be high on the priority list to make changes.”
A two year time frame is reasonable, but may be ambitious, Barry said.
The EMA did not respond to a request for comment.
*The position paper, "Possible Solutions to Improve European Regulatory Procedures for Clinical Trials with Advanced Therapy Medicinal Products Consisting of or Containing Genetically Modified Organisms," was released by the Alliance for Regenerative Medicine (ARM), the European Biopharmaceutical Enterprises (EBE), the European Federation of Pharmaceutical Industries and Associations (EFPIA), and EuropaBio.