Balancing Innovation and Safety

The latest cell and gene therapies have the potential to save sight and dramatically improve the lives of patients.

Proposed changes to the regulatory framework for advanced therapy medicinal products (ATMPs) in Europe, however, could potentially hinder innovation and limit access to new treatments for patients, according to Mor Dickman MD, PhD.

ATMPs are medicines for human use based on genes, tissues, or cells. Under the current ATMP Regulation (EC) No 1394/2007, the principle of hospital exemption (HE) allows for the use of an ATMP without a marketing authorization under certain circumstances. This only applies in a hospital setting on a non-routine basis for an individual patient and when no centrally authorized treatment or clinical trial is available.

Revision of the EU general pharmaceutical legislation is currently under discussion, and the fear is the hospital exemption will be abolished or severely restricted.

Proponents of the reform argue academic centres might abuse the hospital exemption to bypass the traditional route for marketing authorization. They further claim the exemption impacts negatively on the attractiveness of the European Union for research and innovation, as commercial partners may be reluctant to commit to Europe if hospitals are able to administer these therapies to patients anyway. They have also highlighted concerns about the availability of data to support the safety and efficacy of treatments approved under the HE, especially in the long term.

Dr Dickman believes, however, that a compromise in the form of a more clearly defined HE might satisfy all parties in the negotiations.

“Opponents of the HE raise concerns about the quality, safety, and efficacy of these treatments, and I totally agree that the HE should stay exceptional,” he said. “I also think the HE should be subjected to the same high levels of quality and safety as other ATMPs approved in the standard way. Ideally, there also should be a clearly defined pathway to regulate ATMPs under the HE through the European Medicines Agency.”

Although well intentioned, suppressing the HE would have a negative impact on researchers, doctors, and patients.

“It would restrict patient access to treatments, especially in rare disease conditions, which are of limited interest to commercial entities,” Dr Dickman said. “And it will limit research and development activities within academia if there is ultimately no possibility of bringing these treatments to patients outside the expensive commercial domain.” Balancing the interests of different parties will be challenging but not impossible, he observed.

“I think we can all agree how important it is to ensure that the therapies given to patients are subjected to the most stringent quality and safety standards available. However, we have seen examples of companies starting clinical trials for a promising new therapy, which is then abandoned, often for financial reasons rather than any deficiency of the product itself. And in the end, the patients are left without a treatment,” he said. “So, while we all want Europe to remain a competitive arena for companies to act and to bring new therapies to market, it should not be at the cost of blocking research and development in academia.”

Dr Dickman also highlighted the important role national and international registries could play in collecting reliable data relating to ATMPs. “There is a need to impose data collection in a way that collects long-term data and captures patient-reported outcome measures (PROMs) in an independent platform in collaboration with the industry,” he concluded.

Mor Dickman MD, PhD is Professor of Ophthalmology at Maastricht University, Netherlands. m.dickman@maastrichtuniversity.nl