The legal framework for market approval in Europe is provided by EU directives and regulations. There are two fundamental pieces of regulation for ATMPs: The European Tissue and Cells Directive (EUTCD) [Directive 2004/23/EC and implementing directives] and the Advance Therapy Medicinal Product (ATMP) Regulations (1394/2007 and 668/2009). European Medicines Agency and its Committee for Advanced Therapies (CAT) are the two most relevant regulatory bodies. A product may be an ATMP scientifically, but legally it may not be so. ATMP classification can be sought from CAT. Market authorisation can be sought nationally, through mutual recognition in a number of states, or centralised in the EU through the European Medicines Agency.
Dr Nihal Engin Vrana, PROTiP Medical, and Dr Mercedes Dragovits, Immodgel, discussed building an evidence base for advanced therapeutics in this webinar.
To provide a strong evidence base for an advanced therapeutic a following must be performed:
- The proof of concept must be demonstrated both in vitro and in vivo.
- The safety of each component in the therapeutic must be tested (risk assessment, possible side effects, stability).
Efficacy and ideal parameters of each component must be tested.
- Fundamental research must be performed to understand the underlying science of the proposed mechanism of the therapeutic.
- A systematic review of scientific literature should be performed.
- Meta-analyses must be carried out: What kind of proof does your experimental work provide in light of the analysis of the aggregate results in the relevant field? Randomised control trials have to be performed: What is the clinical and pre-clinical scenario for your product/idea? What are the measures to prevent bias?
Lot of innovation. There has been plenty of innovation in the past 5-10 years in regenerative medicine. A traditionally overlooked, but essential, area of innovation is manufacturing: Without the ability to scale up for mass production, a new technology is highly likely to fail. Accordingly, a lot of innovation was put into this side of regenerative medicine recently by a diverse range of companies.
Financing is “white hot”, but cooling off. Most of the funds now come from public investment. The preferred way of raising funds is venture capital. Initial Public Offerings do not meet their targets.
Clinical trial success is mixed. 728 clinical trials are under way as per the second quarter of 2016 (Phase I: 223; Phase II: 439; Phase III: 66). Regenerative medicine therapies will have to demonstrate a much higher standard of care compared to alternatives to justify the high price point and to ensure the long-term success of the field.
Commercial success has not been achieved yet. More than 700 regenerative medicine companies have been set up worldwide. The majority of these are in North America (371), followed by Europe and Israel at 195, and Asia with 112. Cost has to be pushed down, the supply chain improved. Health-economic research is essential. A start-up should invest into demonstrating the health-economic benefit of its product, and also into better understanding the mechanism of action of its therapy as this has significant implications on how clinical trials will need to be designed and what patient groups must be targeted.
Some of the most common reasons for failure are: The discovery/invention does not fit well with industrial needs; the discovery/invention cannot be scaled up, the benefits that the discovery/invention provides is not worth the expenses of commercialisation. Not all interesting scientific solutions are fiscally worthwhile to pursue; target market, market analysis or business plan are not right due to lack of experience; and the “fish out of the water” effect: It is hard for a scientist to suddenly become a businessman.