 Welcome back. So I'm very pleased and privileged to introduce to you Professor Fouad who is a Syrian doctor and General surgeon by training and he's currently undertaking research in particular in On on displacement around Syria and the impact on the well-being Of that displacement and the crisis in Syria. So welcome and thank you very much for presenting dr. As you've heard that my name is full out so it's an easy name So the main problem is which is first name, which is last name, but it's okay So as you know mentioned that I'm Syrian physician general surgeon and public health I moved because of war to Lebanon, you know from Syria from Aleppo my city and I'm working now as a Research professor at the Faculty of Health Sciences American University of Beirut Good morning. Good day Happy to To be in the MSF scientific day The second session will be about the long view innovation in meeting chronic health Needs, but why actually? Chronic diseases and what about innovative waves as you as you all know now We are witnessing different contexts of conflict and crisis, you know Syria crisis and before that Iraq war and Kosovo Ukraine Libya Yemen so all that new crisis are Characterized with main issues, you know first it's sort of unsolved war second it's sort of protracted crisis third actually happened mainly in urban settlements and All that, you know countries, you know have the same also Health indicators mainly they are middle-income countries with high incidence of Chronic diseases to tell one example in Syria for example before crisis 2010 16 percent of adults suffered from diabetes type 2 48 percent have hypertension Now during the the last four years And in addition to two thousand two hundred fifteen thousand death because of direct violence There's an estimate that two hundred thousand also died because of chronic disease So we are witnessing now a new model actually of Crises that needs some sort of different approach So our our session now is about, you know this innovative approach when we're looking in long-term crisis I'm happy to Present the first session Dr. Beatrice Kuffman senior scientific collaborator in the school of Pharmaceutical Sciences at the University of Geneva and her presentation about a potential revolution and type 1 diabetes care Thank you So good morning everyone I Will now present you some promising results we obtained during a collaborative studies between school of pharmaceutical sciences at the University of Geneva and MSF Switzerland and This study was related to the heat stability of insulin in tropical temperature conditions The goal for MSF is to ensure a proper treatment for diabetic patients in this particular case But a scientific question raised concerning the stability of insulin under field tropical temperature conditions because mainly Insulin storage is recommended To be in a fridge, which is not everywhere possible and a certain Time is possible a certain period of storage is possible at room temperature But recommendation is below 30 degrees during the usage period of the vials once they are open and the field ambient temperature in this particular case of the Daga Halle camp in North Kenya was found to vary continuously between 25 and 37 degrees We know that active forms of insulin are either soluble or homogeneously suspended into aqueous media We also know that inactivation of insulin results in the formation of insoluble particles Insulin is particularly sensitive to freezing and we measured Decrease in insulin concentration in the formulation after a short contact of 15 minutes with a cold pack as could occur during transportation for instance Insulin also needs to be protected from direct sunlight From the literature we found that the correlation between the liquid chromatographic quantification in the lab and the biological activity of insulin is well Assessed so that is why we will use this kind of methods to conduct our study known of the previously conducted stability studies about insulin Applied the same temperature scheme as in is interesting as today either there was no temperature monitoring at all either they put the samples Under isothermal high temperatures either they vary the temperature but more like big steps and not in continuous loops Furthermore, there is a clear lack of data about the recent formulations of insulin especially the pen cartridges First of all, we needed to develop all the analytical tools Necessary to conduct the whole stability that we desired to conduct because of the lack of Consequent data from the literature First of all concerning the sample preparation It consisted in a simple delusion of the formulations Followed by acidification prior to chroma liquid chromatographic analysis This sample preparation procedure was extensively tested investigated and we were not able to detect any artifact formation Concerning the liquid chromatographic analytical conditions, I will not go deep into details But as you can see on the diagram the selectivity of separation is excellent and no preservative present in the formulation interferes with the analysis and Total time of analysis per one sample is less than four minutes This analytical method was validated in terms of both linearity and reproducibility and the excellent performances We obtained will allow us to interpret small variations in insulin concentration In a first setup of experiment, we tested five Formulations of insulin you have in green on this table three Formulations of insulin that are already used by MSF on the field the two analog pens and the human intermediate acting Insulin which you may know as humulin and pH We also included two other analogs of insulin a Ultra-short acting one the novel rapid and especially the long-acting lentus Which may represent a potential good option for MSF to use in the future mainly for two reasons because it's a solution So the homogeneity the reproducibility of injection volume is better and the second Reason is that you only need to inject it once per day in this first setup we decided to reproduce in the lab exactly the Temperature conditions that were measured on the field during the hottest period of the year on the left you have the diagram of the data provided directly from Daga Halle and We were able to reproduce those conditions in terms of frequency and amplitude and also the minimal and maximal temperatures Let's come to the results Three independent series of each formulations were submitted to this temperature cycling and Were found found to be perfectly stable over four weeks of this treatment All the insulin concentration in all the investigated formulations remained in the hundred percent range An acceptable range from the pharmacopeia indicates 100 more or less 10 percent of target Which is acceptable in terms of both activity and toxicity We were curious and went up to 12 weeks of temperature cycling phenomenon and all the formulations remained perfectly stable You know that in another setup of experiment we put our five formulations at a temperature of 31 degrees but in continuous This is exactly the median temperature between our two extreme temperatures and What we found is that all insulin formulations started to degrade after four weeks of Isothermal exposure to a 31 degrees and all of them were out of range after eight weeks of this treatment So it seems that a continuous exposure to a temperature above 31 degrees is bad for Insulin stability whereas temperature cycling seems not so we decided to increase the temperature range And that we applied to our samples and to work from 17 to 45 degrees Which are time extreme temperatures compatible with tropical settings in a more desertic region for instance In this second step besides our five formulations We were able also to add the two other human insulin that are already used by MSF on the field The regular and the b-phasic so the humulin or and the humulin profile 30 and We found that after four weeks of this thermocycling treatment All of the tested formulations remains stable If we have a quick look at the samples After four weeks of this treatment in comparison to the references that were stored at in the fridge We could not see any visible alterations Whereas if we submit the same samples to very harsh conditions then We may be able to see some differences with a milky appearance for solutions or even crystals formations But this does not mean that if you see any if you see nothing hundred percent of activity is guaranteed So as a conclusion we were able to determine that Insulin formulations analogues and human ones are stable for four week period At temperatures up to 45 degrees as long as the exposure to a temperature above 31 remains limited And it means that as long as we keep insulin in the shade and let it Chains to cool down at nine at night Below 30 degrees then it can be stored at ambient temperature In settings with maximal temperature not exceeding 45 degrees As a general rule a visual inspection of the formulations remains crucial And when you see any degradation then you must throw the formulations away and of course Analyzing real samples coming back directly from the field would allow us to validate all the study. I Would like to thank the whole team of MSF in Geneva and my colleagues from the University of Geneva David Baron from the Division of Tropical and Humanitarian Medicine and my supervisor the professor Leonardo Scapuzza and you all for your kind attention This is a great example about how you know technology can serve the idea of you know different approach different policy in terms of you know, NCDs in Crucial and difficult settings. I will open the floor for One or two technical questions. So please raise your hand introduce yourself and your organization Good morning tanker at MSF Germany, I mean listen to what you said. Thank you so much Basically, we have to say the the sort of strict cooling Paradigm for for insulin we can at least question now. Is that correct? I Mean if it comes if we have to save lives and in diabetes case your study just shows that Yes, of course ideally we can we have to cool them But it's also possible for at least a month to use the insulin. Yes It is it would be possible for the patients to use the insulin at ambient temperature during one month, which is already possible in Everywhere on the in the world, I mean in Switzerland and in France or in England It is tolerated that the patient keeps The opened vial for four weeks at room temperature during its usage period And he has to discard the rest of the insulin Still present in the vial after this period, but the maximal temperature recommended by the manufacturers in those conditions Was 30 degrees. So we were wondering if our tropical temperature conditions In this particular case would also allow a good stability of insulin So we can affirm we can say yes during four weeks at ambient temperature varying Continuously, but staying half of the time below 30 degrees. Then yes, it is stable Yes, good morning Kieran, Joe run putcher from MSF UK. Thank you very much. It is just a quick clarification I noticed in the title you the original question was about type 1 diabetes But obviously I think this applies equally to to type 2 diabetes the majority of the patients in for example the Syrian Setting are going to be typed to insulate Patients who are using insulin. So of course this has very important implications for them So I just unless I misunderstand maybe you could just clarify that I Just wanted to speak about the patient the diabetic patients who need insulin injections I thought they are type 1 or type 2, but as I know type 2 diabetic patients Often take anti-diabetic Peels more than insulin but sometimes that they also need insulina another question Okay, thank you very much