DR. GALLI GAINED A UNIVERSITY DEGREE IN BIOLOGICAL SCIENCES IN 1976 AND A PH.D. IN MOLECULAR MEDICINE IN 1988. CURRENTLY, SHE IS THE IN-STAFF SENIOR RESEARCHER, CELL BIOLOGY AND NEUROSCIENCES DEPARTMENT, ISTITUTO SUPERIORE DI SANITÀ, ROMA, ITALY.
Phacilitate: The regulatory and ethical review processes and requirements that accompany clinical trial applications for GMO-classified therapeutics in Europe clearly cause strategic challenges for academics and biotechs alike, not least due to the potential for extended timelines and differences in requirements from one country to another. Based on your experience, what are the most common pitfalls or errors that could be avoided to mitigate these issues? What learnings could help those seeking to conduct first-in-man clinical trials in Europe to navigate the process more efficiently?
Dr Galli: Many errors stem from an unclear definition of what the product is that the patients will be treated with. The first suggestion is to have clear in mind what is the final product, as it will guide the whole process.
The second point is to interact with the regulatory bodies as early and continuously as possible, to avoid the risk of overlooking requirements.
It is important to remember that in Europe there are two different sets of regulations to be followed for GMO-classified therapeutics. In the clinical trial approval process, Directive 2001/20 is presently followed. It will be replaced in one year’s time by Regulation 536. So far, the clinical trial would be approved at national level.
The other regulatory requirement concerns GMO handling. This is managed through directive 1998/81 on the contained use of Genetically Modified Micro-Organisms (GMMO) or through directive 2001/18 on deliberate release of Genetically Modified Organisms (GMO), both implemented at Member State level. Here, the landscape is complicated not only because each Member State decides which directive to apply to gene therapy products during clinical trials, but also because frequently the regulatory body involved with the GMO/GMMO procedures is different from the clinical trial competent authority. Separate approval according to both sets of requirements (for the clinical trial itself as well as for GMMO/GMO) is needed in each Member State involved in the clinical trial. Those wishing to conduct a first-in-human clinical trial in EU with a GMO-classified product should know which regulatory body to apply to for each procedure in each Member State where the clinical trial is to be conducted.
Phacilitate: With more and more CAR T-cell immunotherapy product candidates set to enter the clinic over the next few years, what pointers could you give ATMP developers newly active in this particular technology area to help them navigate the regulations?
Dr Galli: In order to determine if there is sufficient preclinical rationale and data for such a gene therapy approach to be translated into a clinical trial, most EU national regulatory agencies offer to developers an ad hoc procedure for early interaction. Further in development, EMA scientific advice procedure can be used to gain a European consensus view on the development plan. I recommend that ATMP developers take advantage of such opportunities because they are very helpful in designing a development path acceptable to regulators, thus contributing to a reduction in the waste of time and resources. Developers should always keep in mind the regulators’ golden rule “on a case-by-case basis". What can be acceptable for one gene therapy product may not be such for another one, even of the same type.
Phacilitate: Finally, what do you hope to get out of your involvement and participation in Phacilitate events?
Dr Galli: Gene therapy is such a fast-moving field and there are so many interesting projects, both at level of basic science and those being translated into clinical trials. As a regulator, I welcome the opportunity to meet researchers and developers and learn from them what will be the future areas in which my expertise and work will be required and tested.
I have participated in Phacilitate meetings in the past and I really enjoyed them because they provide a great forum for discussion of cutting-edge new technologies and updates on clinical progress.
I also enjoy very much meeting with people from all over the world, who bring in different experience and various points of view that can help me in reconsidering problems related to my work as a regulator in the gene therapy field. On the same ground, I also enjoy visiting the vendor booths to learn about the latest innovative instruments and new technology.