Team:UPMC PARIS/Entrepreneurship manufacturing

Impact UPMC

Entrepreneurship

Days after days, the recombinant proteins production is growing as a vital industrial science, in major fields of work such as healthcare or agronomy. Optimization of this production, that to says reducing the cost and time of production of these molecules, is the main priorty of companies of this sector. Another major challenge remain to further automatize these processes.

When we started the project our main goal was to find a solution that could help to resolve the issues of the lack of access to proper healthcare in developing contries. To do so, we investigated the causes of the healthcare failures in different regions of the world that leads to a lower life span compared to developed countries. Beyond a lack of basal hygienic prevention in an environment often favourable to the growth of various pathogenic agents, the lack of access to healthcare appeared as an obvious source of this lower quality of health.

Through our box, we focused more specifically on the lack of access to preventive and curative protein drugs. We want to innovate in the way we produce already existing therapeutic molecules.

We then focused on 3 main causes of the lack of access to drugs in the world :

1) The lack of financial means for the purchase and setting up of drug production
2) Geographical isolation of the countries concerned
3) Storage and transport of drugs issues

Strategic Business Unit (SBU)

In order to have a more general view of the drug market, we have set up a SBU table around the question of the lack of access to healthcare.

Large companies do not provide sufficient answers to the 3 main reasons of the lack of access to care in developing countries. This explains the specific lack of drugs in these countries even though The BioMaker Factory Lack of access to healthcare Alternative Solutions Companies from developed or in developing countries Client expectations profile Companies TBMF Geographical accessibility + /- ++ Affordability + /- ++ Significant amount /storage + /- - Emergency / Quick obtaining + - Multiple drugs through a same tool + ++ Safe ++ ++ Userfriendly + ++ (automation ) Efficiency Risk-Benefit balance ++ ++ Users Geographically isolated countries and / or having financial problems Hospitals / clinics Local dispensaries NGO Any access to care system there are existing treatments. In addition, this table allows us to highlight the customers expectations and place the contribution of our box according to them.

Our major difference from large companies lies in the ability to get instantaneously :
- A significant amount of therapeutic molecules
- Wich palliate the medical emergency.
Moreover, for a simplified heterologous synthesis we limited our box to the production of protein drugs for now, which is already a sufficient challenge. Although they are criteria of the client expectations profile there is a notable market around drugs needed in a quantity and in a short time lapse which correspond to one cycle production of our box. This specifity of our project will be a key asset for our future business development. Moreover, the local production through our box bypasses the storage and transport of drugs issues that can often occur, and allow a controlled and reliable production of the drugs which is a main issue, in sub-Saharan Africa for example. We can therefore place our box on the market of protein drugs with a punctual need that can wait for a 8-10 hours production and that are needed in micrograms to milligrams per dose. This drugs dosage would enable the treatment of multiple people with one production cycle of our box. In this market, we can answer the 3 main causes of the lack of access to healthcare mentioned before. We are therefore innovating on the production process of already existing protein drugs. Thus, our strategic segment is the developing countries.

Drug candidates

We then researched therapeutic proteins which are nowadays needed, and matching with the specific reasons regarding the lack of access to healthcare we explained before and that our box can constitue a solution for. The pathology treated by these drug candidates has to:
- Allow a minimum action time of about 8h to 10 hours
- Be curable by a quantity of active substances from micrograms to milligrams

We then selected the 3 types of diseases, we presented in the state of art of the current medical needs worldwide.

We have presented here the pathologies illustrating the most the mortality due to the lack of access to healthcare. However, we can imagine that our box can also respond to certain chronic conditions. Besides, we should not forget that our box is not a frozen project. Around its role of automated production and purification, it leaves a large room for its optimization and allows us to work on a decreased production time and an increased quantity of proteins production. The possible optimization of the box could also revolve in the creation of a more or less storage, an ephemeral method to compensate for the time variable of production. It should be noted that this box is also a solution to the ethical problems related to obtaining of some serum proteins from animal immunization or for the production of hormones. In this way, it would be a solution to the problem of immunogenicity of these serotherapies in humans. In fact, this could be an alternative to the animal use for the production of drugs in general.

Potential partners

As described in the state of art we talked to MSF and the start up MedTrucks to know more about the qualitative and quantitative data from the field. Then, our discussions went forward to thinking on a possible partnership with each of them in the futur. More precisely, our discussion with MedTrucks first focused on the abilities of their trucks to insert our box. The size of some of their trucks allows our partnership. In fact, we all think that working in partnership could change the face of the actual access to healthcare through the assembly of our box and their travels in places and knowledge of the work in the ground. We are also currently working on a potential partnership with a woman working on the creation of a clinic in a isolated region of Cameroon.

In conclusion, Our Biomaker Factory aims to completely disrupt today's global healthcare system. Indeed, thanks to our machine and with the cooperation of other structures such as MedTrucks, the production will be relocated to the place where medicines are needed with lower cost and no problem due to conservation. Moreover, the production will directly meet the demand; thus, there will be no intermediaries and no overproduction: this will allow to make medicine with a low price, as close to the cost of production as possible.

Limit on a short term: Legal Issues

As a part of our Human Practices collaboration, we asked the Jurist of the Evry/Paris-Saclay team, Maxime de la Fouchardière, to help us about the legal issues that could come with the production if recombinant proteins in France and in general in the EU.
Our first question was about the production of recombinant proteins for the research purposes, would it create any issues. Maxime told us that research in France and moreover in Europe knows actually very few regulations regarding the act in itself or its subject. This freedom is guaranteed by the French Code of Research. Besides this legal freedom, there are strong regulations regarding biomedical studies if they are conduct on animals or on human beings. Nevertheless, if GMO in research are authorized, their use and their deliberate release is strictly set by the French Environment Code. It means for us, that we can use and produce recombinant proteins as long as the GMO we use to produce them are safely kept.
But let’s not forget that our project is to produce recombinant proteins for a human therapeutic use. Maxime then explained us that in France the drug market is tightly controlled by the French Agency for Drugs Safety, the ANSM. According to the French Public Health Code, is considered as a drug any substance that is said to have any curative or preventive properties. To be authorized, a drug candidate must go through the Drug Marketing Authorization process or AMM in France. This a difficult procedure in which the drug needs to fulfil precise criteria: it must have a favorable risk-benefits balance, have a therapeutic effect and have the same composition as the one registered in the application form. It must go to through several test phases on animals and humans where lot of data will be gathered to provide the right information on the well-use of the drug.

This whole process can take up to 10 years and costs billions of euros. However, it exists few cases in which a drug can be sold with no AMM:
The Temporary Authorization of Use (ATU):
If a drug doesn’t have any AMM and has significant positive result in the clinical trials, doctors can be authorized to prescribe the drug. But this is only possible if the disease concerned is sufficiently rare or severe.
The Temporary Recommendation of Use (RTU):
Grant the possibility for a doctor to prescribe a drug if there is no other possibility of treatments, with conditions ruled by the ANSM
Doing further analysis on how our box and the proteins it produces could be used in the market we thought that the we could produce proteins or hormones used in the livestock industry.
Maxime has then given us insight on how such molecules could be authorized: In France, and on the European scale, the companies that want to sell a new molecule on the European market, must get their products assess buy the European Food Safety Agency (ENSA). They will go through a process where they must produce a study of the risk of their molecule. the result will be analyzed by the ENSA, which will allow the molecule if it doesn’t present any harmful effect for the human and animal health and also if it doesn’t show any unacceptable risk for the environment. If allowed the molecule will be registered in the list of authorized molecules. To be then authorized in France the molecule will be analyzed by the French regulating agency for food and sanitary security (ANSES). The ANSES will verify if the molecule registered has the right composition and basically do a similar work as the ENSA.
This whole process is much shorter than the AMM and can take up to 3 to 5 years.

Going forward with this new mode of production

We can easily imagine many other uses for our box. The necessary production of these proteins must therefore be consistent with the capacity of the box in terms of time and quantity of production. Thus, we can offer a specific production between manual work at the benchtop and companies large-scale bioproduction. This would be a major gain of time and money relative to the optimization of a specific strain research and to the production of the protein by a research laboratory engineer. In addition, this box is an invitation to the development of synthetic biology in the countries it will be used in. We can hope for an independent development of these countries through diverse and varied opportunities would be the source of potential local partners and therefore enable the specific development of our own strain library according to the local needs and regulations for instance.