Partnership

UZurich

Common interests

After our post on the Global slack channel about our project topic and asking for potential collaborations, UZurich reached out to us! As they were working on the gut and inflammatory bowel disease, which is known to interplay with pernicious anaemia, we were more than happy to discuss our projects and see where we could go together!

We laid down common goals for the competition: project development, education and regulations. In the lab, the Zürich team was working on a probiotic approach using nanobodies, which is different from our more in vitro approach of mutating a protein to evade autoimmunity. Where we could find common ground was the gut: we both saw that it is a hot area of research at the moment, but also that some diseases lacked effective treatment. Therefore, we set out to increase awareness of the gut’s various actors and the interplay between the gut microbiome and vitamins - our teams’ respective project topics. In addition, our business plans had similar concerns about regulations and clinical trials further down the line, and we had difficulties finding relevant information. Thus, we joined forces to each contact our national drug agencies and figure out how the process works in each country in order to get our medical products approved. We would then compare our results in order to list the differences and hopefully guide future iGEM teams in their choice of market authorisation approach. In addition, we sought to contact the FDA in order to have a more comprehensive comparison.

EMA and Swissmedic - who are they?

We each presented our projects to our respective agencies, EMA and Swissmedic and received clarifications regarding the drug market authorisation processes.

EMA

We got in touch with Lorenzo Montrasio, with whom we discussed the workings of the EMA and he was able to give us clear explanations. Lorenzo has experience working for the Italian medicines agency and has represented it at the EMA.

The European Medicines Agency (EMA) is an agency which coordinates the assessment of new medicinal products in the European Union. The EMA has around 1000 employees, while each national drug agency usually has around 500 - 1000 employees.

For the EMA, the process starts with an application from a company, having gathered all relevant data and completed clinical trials. The data is compiled into a dossier and presented to the EMA, at the headquarters in Amsterdam. The dossier will be picked up and discussed among experts and national authorities. One national agency, with one expert will be assigned to assess the dossier within their national agency. Regularly, experts from all EMA countries meet to discuss ongoing assessments and every national agency can provide feedback and questions about any open dossier. These questions are discussed and pertinent ones are sent to the applicant. These questions can be requests to generate new data, but in most cases they aim to clarify existing data. The company then has to reply to the requests by making the appropriate adjustments. The experts can also decide to send an inspection to the clinical trial site if they suspect fabrication of results. Finally, the EMA gives an opinion about whether the medicinal product should get market authorisation or not, and sends it to the European Commission for legislative approval. Once approved, the product can be sold in any EU nation. If the application is rejected, the company has the possibility to appeal the decision of the European Commission.

Swissmedic

This description was provided by team UZurich:
“Swissmedic is the responsible authority for the authorization and supervision of therapeutic products in Switzerland. Hence, to understand the requirements to submit a clinical trial permit, we got in touch with their contact office. Feedback on the application for a clinical trial permit concerning the use of genetically engineered bacteria revealed that Swissmedics works closely with other federal institutions. When research with genetically modified organisms is conducted, additional data evaluating the risks for the environment and humans is essential to the documents needed for an application. Therefore, we contacted the federal office for the environment (FOEN). We talked to Dr. Andrea Bonini, a scientific collaborator of the federal coordination centre for biotechnology. We could present our project (using synthetic biology to develop a novel treatment option for inflammatory bowel disease (IBD) based on genetically modifying a probiotic bacterium) to him. Mr Bonini took care of involving other critical experts in the answers we were seeking for. Dr Ursula Jenal (FOEN) provided us with informational material to understand how to assess the risks related to the first-time application of genetically modified organisms for clinical purposes. As shown in the scheme above, application for a clinical trial with genetically modified organisms that can be excreted in the environment requires extensive preclinical analysis. Swissmedics demands the submission of data on the handling and production of GMOs, environmental risk mitigation and its preclinical data. To summarise, an application for a clinical trial permit is submitted to Swissmedics, which discusses its approval with other federal institutions. Positive feedback leads to a five-year permit that is additionally monitored by the local cantonal authorities. Up to now, there is no approved GMO-based therapy in Switzerland.”

Conclusion

In both cases, relevant information is scattered on multiple webpages and in numerous documents, which means that getting a clear picture can be challenging, especially for teams or companies starting out with their medical product. In the Swiss case, more focus is put on the clinical trials authorisation since it is an integral part of the drug approval process. For the EU, the clinical trials are performed at the national level, which means that the EMA’s market authorisation process is disconnected from the clinical trials. For either a protein drug like is the case for us, or a probiotic in the case of UZurich, the market authorisation would go through the same steps within both agencies. However, since the EMA Central Procedure allows one to obtain authorisation for the whole EU, an application to the EMA could lead to access to a bigger market than through swissmedic.

The gut microbiome and vitamins - from food to disease to cure

Our projects’ outreach efforts have been complementary to say the least. While we were researching vitamins, we saw that the gut microbiome came up constantly, and we also saw links with pernicious anaemia and gut diseases such as IBD. This is why we found it handy to combine and sum our efforts into one resource with more comprehensive information about the gut than any of us could produce on their own. With an expanded scope, we were able to sum up the relevant background for our work. On our part, we focused on water-soluble vitamins, as B12 is one of them, and their uptake. UZurich provided the information regarding the gut microbiota, with its distribution in the intestines, lifestyle changes that affect it and for which functions it is important.