Cutting-Edge Maternal Health Technologies to Address Postpartum Hemorrhage & Preeclampsia/Eclampsia
Good morning good afternoon and good evening to all my name is Patricia Coffey and I work for path path is an international ngo headquartered in Seattle Washington in the united states with a global team of more than 1500 innovators working in more than 70 countries to eliminate health inequities so people communities and economies can thrive next slide I am pleased to be here today to moderate our panel and introduce our product development partnership called the devices diagnostics and drugs to address women's needs pdp or dawn a pdp is a collaborative partnership between public private academic and philanthropic sectors with the goal of developing new products for people suffering from diseases and health threats underserved by traditional markets a report that came out in January of this year entitled keeping the promise product development partnership's role in the new age of health research and product development looked at the role and performance of pdps in the global health sector and they found that pdps are global leaders in developing new health technologies where lack of traditional market incentives have stalled progress pdps achieve impact by developing products appropriate for the people and contexts in which they will be used pdps save money and are a cost effective way to save lives and grow economies they build local capacity to perform research and strengthen health systems and the products that pdps develop are essential to achieve universal health coverage and the un-2030 sustainable development goals next slide the dawn pdp focuses on two of the major direct causes of maternal death postpartum hemorrhage and preeclampsia eclampsia or hypertension as you can see in the pie chart postpartum hemorrhage and preeclampsia eclampsia together make up almost half of all maternal death although the maternal mortality ratio dropped by about 38 worldwide between 2000 and 2017 still every day in 2017 approximately 810 women died from preventable causes related to pregnancy and childbirth and for this reason we are focusing our pdp work on developing innovation to address pph postpartum hemorrhage and preeclampsia eclampsia next slide the dawn pdp supports activities across the spectrum of product and market development shown here on the slide another way of saying this is that we do end-to-end product and market development which enables both a sustainable supply of product and the necessary demand to support product sustainability on the African market we developed these life-saving technologies by using a human-centered design approach and in partnership with ministries of health research institutions manufacturers and companies in Africa we accelerate them through our path product development process and work with public-private partnerships and introduce them into key African markets our products are in various stages of product development ranging from early concept validation on the left hand side of the slide to introduction and scale on the right hand side of the slide next slide the four products that are currently in our dawn portfolio are shown on this slide of note is that the two products on the left hand side of the slide the lrv uterine balloon tamponade and the protein-to-creatinine radiometric diagnostic strip test are downstream in the product development process under the dawn pdp these two products are being introduced and scaled in Ghana and Kenya the two products on the right side of the slide the relied delivery system and heat stable oxytocin in sublingual fast dissolving tablets are more upstream in the concept validation phase of product development next slide the agenda for our presentation is shown on this slide in the interest of time I will introduce all of our presenters now Dr Sylvia Degenes is an accomplished obstetrician gynecologist and public health physician with over 25 years’ experience in safe motherhood and reproductive health Dr Deganus is currently consulting in maternal and newborn health issues in Ghana and elsewhere Ms Charlotte Tavia Ajman is a senior research fellow with post-graduate training in public health nutrition and social sciences she has been working at the contampo health research center in Ghana for the past 20 years especially in the areas of nutrition and maternal newborn and child health Mr. Dan Myers is a product development engineer and has worked for over five years in the path product development and engineering laboratory his work at path is split between drug delivery devices and vaccine cold chain equipment Ms. Jacqueline de la Rosa is a program officer at path she is a public health scientist engineer and acts as a research project manager to facilitate and implement the evaluation development and introduction of product Ms Mitsumi Metzler is a senior commercialization officer at path where she handles the commercialization and introduction of medical devices pharmaceuticals and diagnostics products to improve maternal and newborn health finally please type any questions in the chat and we'll do our best to answer them during the q a at the end of our session thank you very much now I invite Dr Sylvia Degenes to present on the llv ubt next slide thank you Sylvia Sylvia we are not hearing you right now Okay so hello everybody thank you for the invitation to share my presentation with you I’ll be sharing with you the Ghana experience of introducing the larvae and innovative environmental That’s right well in my presentation I will tackle address three main issues I’ll look at the facilitating and individual factors to write producing the larvae uvp I’ll then talk about how we set about training and supporting our providers in using their logic liberty and maybe to end it all I’ll share what the next steps are for this company Sylvia could you speak up just a little bit it's really difficult to hear you um I was saying that in my presentation I’m going to address three main areas I will look at the facilitating and inhibiting factors to introducing larvae into the country our very touch on how we were able to train and support our providers to provide care using their loving ubc and to end my presentation and fashion what the lessons for the country are so when we start up and look at some of the factors that facilitated the introduction of the learning unit into this country the first and most important factor was that we have partners in countries and we're able to mobilize our key stakeholders pub is a well-recognized national partner in fight against pph indeed in the past park have worked with the country nationally on various fronts to address maternal death from pph we have looked at ositosin safety as that surveys in this country they have helped the country develop policies and guidelines and also have gone ahead to how the country's trained in nutrient balance sometimes using condom components which was then the most accessible balance component and these have set the tone for this program indeed this was seen as another step in the fight against gph when our health service was therefore very ready to lend its support too fast to introduce this interventioning country other things that were of benefit to this country was that we have been able to register their product in country and having identified a country distributor who was already engaged to provide in our community next slide there's to introduce this device as well we set about using the implementation research approach we're able to identify in-country champions and recruit them and these persons who are respected of the facial cardiac ecologist and selected leaders in the facilities that were going to introduce their lobby to also offer to be principal investigators in this elaborate implementation research and also most important was the fact that I experienced the country's experiences from using the condom component have contributed to the development of the navy uvc let's slide first implementation research which we were going to done won the confidence of most providers because we had ethical approval from the Ghana health service and what we were doing was not testing the larvae uvp but to generate evidence for its successful uptake and adoption into the country so it was seen as a long-term process and not just as a research of the product that's life there were a few inhibiting factors as you can see and most important one was the knight country and it also required modification to their study protocols and so we had to introduce combinating guidelines into all our training plans and activities for example the social dispensary limitations meant that only small numbers of participants could be trained at this time and therefore we have to have several of more training sessions to meet this image note that this was a very practical cleaning approach so in the next few slides I’ll share how we were then able to proceed with the lovely training introducing it to care providers and those facilities let's slide to start off what we did was to build on the previous experiences we have gained from in-country condom component training and we adapted the training materials that we have from these previous trainings for using the elaborate training we had locally made for more velvet models which we further adapted for a larva training these models which were made by ourselves were very available and we could even leave some of it for some of the facilities to use we also selected three health facilities with high caseloads and who had familiarity with condom component uses so we could get the numbers and we had the supplies as I said a country in country distributor was available and we had ordered enough supplies for the participating facilities so these preparatory activities were all important and set the tone for the training next slide the training itself was very focused and it focused on three areas we focused on the diagnosis of management of cbs and how elaborate ut could fit into this into case management we also focus on how to prepare and apply their lab and the third component was to prepare them participants for their role in the implementation basis next slide we had three facilities involved in the training and this meant that we're doing an on-site training over 90 percent of care providers on these sites could therefore be trained because we're moving to them within training of in small batches of about 20 persons per day at each facility because of the covid 19 registration and onsite training mentor facility managers and even my district managers could be could participate in the training and see how this was going next slide our training was competency based and we use a variety of interactive learning approaches we use quizzes we use videos and of course we have simulated female models for our practical sessions the first few balls you can see in the picture with the arrow pointing short how we're able to demonstrate severe cpa we had colored water to be able to because we recognized that diagnosing severe cph was a challenge and we use quizzes to elaborate this point next slide learn it was daily by doing in the next few slides you see how participating this learning was that's like So it was demonstrating everybody participated and they could practice the recession and the removal and they had several models we have several stations for the participants this was supported I also used of the labview video which was demonstrated as participants practicing their skills next slide this shows more videos of all the participants in groups of three and four working on their less life more training so it was hands-on training and whereas we believed in the concept of what I do next slide these pictures are all showing everybody was involved in this training we have the doctors we have the nurses we have everybody the managers we're on board next slide and so what were the accounts of these trainings in total 237 persons including two managers from the general health service headquarters were trained in the three facilities the participants included midwives doctors nurses and these were drawn mostly from the labor walls the postnatal the antenatal and maternity unit of those trained about 90 percent were eager to use the device and concentrate to participate in the study we made sure that at the end of the training we had supplied the three facilities with enough ubc's to start up and also had enough for backup and we made sure that these supplies were went through the normal logistics supply channels through the facility stall and normal systems next slide our free and post-course assessment shows that learning indeed has taken place at the beginning the lowest call was 6 over 25 as you can see but at the end the average falls were all about 22 over 25 with a minimum score being 17 over 25 indeed 15 participants for the maximum score of 25 so learning in this took place overall next slide other point of note was that we have directors in charge of family productive health and that's dropped here standing there taking part in the training and learning and seeing these were important we also had the distributor being in alongside with us making up to the managers and the potential users and this was also very important in strengthening his introduction into the facility indeed we also had another case actually while the training was going on we were able to show how effectively love we went because we had kids in case that okay that would be used to demonstrate how effective the program was next slide after training we continue to mentor our clients and our sites we established a 24-hour phone-based contract for support and discussions we set up a WhatsApp system and we have also been able to visit these sites on some occasions to talk to the users and discuss any challenges they have there's been a few very few challenges most of the time this has been that sometimes doctors have used the device but have not reported it to us next slide so what have been the post training outcomes to date the device is being used in all the three facilities and today has been used for about 24 cases we had one unfortunate antenna that it was due to hemorrhagic shock but generally it's been very exciting it's being used by both doctors and midwives directly in case management and the users have often reported that it's very easy to apply we've had very few challenges and we've even recently been approached by the collaboration hospital which is our largest seeking hospital and they are very keen on introducing the device on similar in a similar fashion to their facilities they have initiated steps to purchase the device for use next slide so this shows a breakdown of the use of the device we have 265 persons spraying 210 agreed two other persons have consented to be part of our implementation study after reference and so far we've used it on 24 locations this is after extensive pro next slide so what have the conclusions we have taken the first step as a country and I must say Ghana has successfully introduced the innovative Vietnamese into three facilities in countries we've had effective key stakeholder engagement we have committed champions and these have facilitated our competency-based trading today 23 lives have been saved and I think this is a good beginning thank you all and I wish to end my presentation thank you for your attention yes I just missed the next slide let me go on yes what are the next steps the next steps are that we will continue to find ways to scale up 11 in country we hope to be able to disseminate the information about Belarus to our national and regional key stakeholders and work through the associations like the society of sufficient gynecologists and regional associations that midwives association we hope to cross the use of larvae and make sure it's integrated into pph management costs under the national health insurance system and we want to plan for progressively expanding training nationally to all emergency of capital units in countries thank you all very much thank you so much Dr Degenes we really appreciate that next slide please and now we'll move to charlotte ajimon we'll talk a little bit about our proteinuria creatinine test charlotte thank you very much Patricia for giving me the opportunity so I would like to talk about understanding uses their needs and wants and as a critical approach to increase adoption of protein creatinine tests by anc healthcare providers next slide please so as part of them as a background pre-eclampsia it's among the leading causes of maternal death in worldwide and as Sylvia mentioned it is a a challenge also for us in Ghana so and preeclampsia is responsible for about 10 to 15 percent of maternal deaths worldwide and in Ghana I’m a maternal mortality ratio it's about m3 per 100 000 live bits of which about 10 percent is attributed to pph or eclampsia and preeclampsia so as part of this study that we conducted in kintampu north and south in the central and belt of Ghana we understudied some midwives and community health nurses who are mainly responsible for attending to pregnant women at the community level when they attend and antenatal pay so our location we are based in now no east it used to be the bronze half region now the region has been divided into three so we we are now based in the puno east region and preeclampsia and eclampsia and other hypertensive disorders in pregnancy account for about 20 percent of maternal mortality in this region where I currently work and midwives like I mentioned earlier are the primary care providers who provide anc services to pregnant women as at the time that we are conducting the study we had about five community health nurses to one midwife so it was really a challenge we had most community health nurses providing anc services with few midwives and also providing the services at the community level next slide please so who recommends that at every anc contact every woman is craned for preeclampsia and what they are to look out for is elevated blood pressure and proteinuria in the urine and protein in the urine so these are the key indicators that we were looking out for so for the life assay diagnostics that we were testing in our study area we set out there to test the protein creatinine dipsticks which is a simple tool to use it has two parameters first to read within one minute your result is ready sorry and then it also helped increase accuracy over protein only dipsticks as an account of the level of urine dilution and then in terms of course it was comparable to protein only dipsticks and what we see on the screen is a graphical presentation of what's the protein creatinine lipstick that we used let's like please so sample health research center where I work and pass we collaborated to do a usability usability tests on the protein creatinine test using the life acid diagnostics this was in 2016 and our aim was to evaluate the usability and acceptability of the test with focus on test interpretation and then getting feedback from the end users because at the end of the day is the anc workers who are going to use the device so we wanted to find out from them get their feedback in product development and for our results for the usability tests we the anc providers agreed that it's acceptable and easy to use and they also identified some common challenges which was to do with timing and then interpretation of the results in 2019 2020 we went ahead to test the results in a real sample of 1482 pregnant women in six facilities health and facilities across our study area so our aim was also to assess the accuracy of the prcr tests for detection of proteinuria in the study area and our results showed that there has been a 10 to 15 percent improvement over what's the protein dipstick that is already in the system this was our expectation was lower than normal because we're expecting between 75 percent sensitivity but at the end of it we had between 50 and 65 sensitivity which also was not bad it had an improvement over what was already in the system let's like please so as part of that we also wanted to find out to understand and how the users would also come up with a digital tool or we coming up with a digital to how are these also going to help with the screening processes of pre-eclampsia in our anc settings so as part of that user research we set out three objectives one to understand the process of preeclampsia screening and care in asc settings in our study area and also to identify challenges and opportunities for improvement our second objective was to understand the typical day in the life of an anc provider that is once they are working from morning to evening what are the challenges how are they able to screen women for pre-eclampsia we wanted to find out that and then also to evaluate the usability of a digital application if it's in use for automatic interpretation of the urine dipsticks among our staff that we or the healthcare providers that we did the study with let's slide please so for our first objectives um sorry yes for our first objective the method that we used was a focus group day discussion with the midwives and then the community health nurses that we used we used 20 of in all for them to come out with their challenges that they face in their work and also probably to also introduce a screening process where midwives are supposed to go through this that's from first to last or from a to z I mean there's a strict projection that they need to go through so for this one we gave it to our community health nurses and our midwives to go through it and then they revised this screening process based on the work that they do in their facilities and for the findings urine screening in decay tests of plus two shows that you really end coupled with elevated blood pressure you need to refer to the district hospitals I mentioned that these health workers are coming from a lower level facilities so it's not the district hospital but it's from the community level facilities and for the chips compounders the community health plan based planning services that's the lowest of the health services they have different referral practices due to availability of the dipsticks or sometimes they don't even have the logistics to test for preeclampsia or to screen for pre-eclampsia so the urine intestine was also conducted at first anc and when the bp is elevated area in the district hospitals they always do these testing anytime the pregnant woman comes in contact with the health care provider next slide please so for our second objective and we also wanted to define the key challenges of anc providers to better inform the product development so we gave them the opportunity and they came up with some challenges which we ranked they came up with several of them and each health care worker was given three votes to come up with the challenges so after ranking them these five came up as stops communicating with patients because in our study area it is a multilingual area and we there are about 21 languages so the midwives have challenges speaking with directly with their healthcare and their pregnant women and sometimes finding an interpreter at the point of care was very difficult and which also makes in healthcare a bit challenging to provide quality of care shortage of staff was one thing that was mentioned fortunately Ghana health service is providing more midwives into our facilities now availability of essential supplies does the drugs the diagnostics to even test for or screen for pre-eclampsia late a nck seeking which is also a very big challenge it cuts across all not only for pre-eclampsia but women attending anc fights leads and then shortages of the anc booklets for record-skipping in terms of their death takes they also came up with some challenges which they mentioned about the color not matching what is on the bottle that is if you are able to do the the testing matching it on there but colors on the bottle really doesn't match so most of the time they lose confidence in the interpretation and then reading the results at the correct time this was also another thing when clinics are busy was another challenge that they talked about and then availability of the urine strips sometimes they are not there and trying to attend to most of the women the some of the healthcare providers were cutting their strips into two just to make sure that the women that they are saving at that particular time would also be getting to get to be tested next slide please so out of the challenges that they came up with we developed a persona for the local providers to inform the design of the new interventions and our main aim was to communicate user needs and then inform products development and also build understanding within the multi-disciplinary teams and keep the users at the forefront of the design efforts because at the end of the day they will be the end users so we thought that we should engage them at every stage on the way so we developed two personas one for the community health nurses and one for the midwives and the results and also we validated and refined through secondary research we did another follow on interviews with another 15 and 20 healthcare providers coming from 19 facilities all within our study area and this was by focus group discussions and interviews with the healthcare providers next slide please so in terms of understanding the considerations for new digestive supports for pre-eclampsia screening based on the challenges that they've mentioned if we introduce something that will help interpret the results how do you take it so we use an existing digital solution this can well dipstick test which this one was for uti but we thought that if something like this is developed for pre-eclampsia screening how are you going to do that so for this one we gave this this scan well test for them to try their hands on and also to feedback to us so we did observational interviews as well as individual interviews and after trying their hands on we also interviewed them on ease of use priority features for digital applications in terms of key findings and there were priority features that the end users also informed as timeless they needed clinical decision making support paper and digital instructions and optional training videos these are some of the things that the way requiring to be features of the digital application another key considerations were reduction in time to run the test compatibility with android phones which of course most of them have and connectivity both internet and electricity was something that they also mentioned will be of key interest and compatibility with different multi-parameter lipsticks so in case you are doing the protein-only lipstick of protein and creatinine will it be possible for us to also add glucose and hemoglobin to it as well so that at the end of the day they can also interpret all these things using the digital tools application next slide please so in summary shortages of their supply kits was limited they were abandoned staff and communication barrier was also another challenge that was informed that was communicated to us precise windows and color metric interpretation poses a challenge for the healthcare workers with analyzing their urinative states and the guitar tools they really supported it and the health workers supported the digital use in interpreting these information but they required the adaptations environmental content contextualization to solve the challenge in our anc setting and also in pre-eclampsia screening next slide please so in terms of next steps there is future considerations to optimize anc for preeclampsia and eclampsia screening so what we intend to do is that the potential value of bundling innovations to provide more comprehensive solutions to end user users including new diagnostics like that protein creatinine with emerging m health tools will be of immense help to our health care providers and under the dawn pdp that's Patricia mentioned two implementation research in the planning phase to evaluate introduction track strategies to the protein peritoneum test within anc settings in Ghana and also potentially self monitoring in Ghana and then in Kenya next life please thank you very much charlotte we really appreciate thank you very much for the opportunity and I will be on standby for any questions that might come up thank you excellent thank you so much and now we'll move to Dan Myers who will talk about the rely delivery system Dan thank you Trish good morning everyone yes I’ll be talking about the windy light delivery system a hybrid pneumatic electric syringe driver for magnesium sulfate infusions next slide please so to get everyone thinking about infusion pumps this morning I wanted to start off with a survey question and I understand from our technical support that the audience will need to refresh their browsers in order for the poll question to show up so I’ll give everyone a few seconds to do that okay so hopefully everyone's refreshed now so there was a survey that was completed in December 2016 where surgeons were asked about the availability of essential medical equipment at an annual meeting of the college of surgeons of east central and south Africa and 42 Africa-based surgeons participated in the survey and of these 10 of the surgeons identified as working in public district hospitals so my question is of these 10 surgeons how many had access to an infusion pump at their hospital so I’ll give everyone a half a minute or so to respond to the poll question there Okay let's see I’m not seeing any of the results just yet doesn't seem like we had any responses so in the interest of time I’ll go ahead and move on next slide please so of those 10 respondents at public district hospitals it actually turns out that only two of them had access to an infusion pump there were a couple other categories of hospitals that were included in the in the study as well at the public referral hospitals 7 out of 16 respondents had access to an infusion pump and then at the other category which were the private ngo and mission hospitals 13 out of 16 respondents had access to an infusion club so even at the best equipped hospitals there still not all of them have access to this very important life-saving piece of equipment next slide please so as was discussed earlier in the presentations today preeclampsia and eclampsia are the second leading cause of maternal mortality and morbidity and there is an effective treatment magnesium sulfate it's safe it's low cost but unfortunately it's underutilized and there are a couple of reasons for this one relates around the complex intravenous and intramuscular dosing regimens but then there's also concern around risks related to over infusion if magnesium sulfate is over infused it can lead to depression respiratory depression and even respiratory arrest however if so clearly there's a need for very controlled infusion of magnesium sulfate when it's used and fusion pumps provide a safe controlled method for iv infusion of magnesium sulfate but unfortunately they see limited use in low and middle income countries next slide please so the slow you spin from several issues so the existing electronic infusion pumps and syringe drivers that are on the market have a few shortcomings first of all they're fairly expensive most of them range in the 500 to several thousand dollars in in price the interfaces on these infusion pumps can be rather complicated they may require programming and extensive training to learn to use they require electricity and of course electricity isn't always available in health facilities in low and middle income countries and if it is available it may not always be reliable many of the electronic infusion pumps come with a battery backup for when the power goes out however the battery life typically ranges from 5 to 12 hours and that may not be long enough during a prolonged outage similarly generators may not be reliable enough to ensure that there is power to run infusion pumps during an outage next slide please there are existing non-electric options one option are our spring driven syringe drivers you can see an example of that on the on the right in the picture and they work however one issue with them is that to control the flow rate you they rely on a small diameter flow control tubing which you can see in this image it's the it's the tubing coming off of the syringe going towards the towards the needle and this flow control tubing is proprietary and it's disposable which means it has to be replaced after every infusion and of course over time that that cost adds up the other big disadvantages are if you need to change the flow rate during an infusion it's very difficult because that requires you to actually change the flow rate swap out the flow rate tubing during the infusion and furthermore the syringe these spring driven syringe pumps are less accurate than electronic pumps typically their accuracies are in the range of 15 whereas electronic pumps are have accuracies flow rate accuracies of 5 or better next slide please so clearly there's a need for a low low-cost robust simple to use infusion pump that has a has a long battery life next slide so the rely delivery system is a pneumatic hybrid pneumatic electric syringe driver that's meant to address a lot of these issues so this is a system that is in development right now so the we've done a lot of work on the pneumatic side of it and are only just getting to the to the electronics at this point but the target specifications are that will have a very low power consumption which means it will use have a very long battery life it will be inexpensive relative to existing electronic confusion pumps people have a simple user interface so that not it will not require extensive training to learn to use the rely there will not be any proprietary consumables the flow rate will be adjustable during infusion and it will be compatible with a range of 5 milliliter to 60 milliliter syringes it will be robust easy to maintain and serviceable in the field and we have a target flow rate range of 0.1 to 200 milliliters per hour with a target flow rate accuracy of 3 and over here on the right you can see a picture of the pneumatic subsystems this this is the these are the subsystems that are actually responsible for driving the syringe and go to the next slide please explain a little bit about how this pneumatic subsystem works so the rely has an air pressure air reservoir that's pressurized using a hand pump then a pressure regulator adjusts how much of that pressure is applied to a drive piston and that drive piston is what pushes the syringe plunger and of course infuses the medication into the patient on the part of the drive piston opposite of the air side there is oil and that oil is forced through a narrow tubing a flow restricting tubing and this is what helps control the flow rate so then when you go to reset the device you switch to a larger diameter reset tubing that has low flow resistance and it makes it easy to reset the piston for the next infusion next slide please so just to show a little bit of data on how the rely is has both steady flow rates and is adjustable during infusion we have a graph here of the two minute average flow rate in milliliters per hour over time and we did a test that ran over three hours and you can see how we start off it takes a little a few minutes for the for the rely to get up to the target infusion rate and that infusion rate and on this left side of the graph is about 0.7 milliliters per hour and then it proceeds at a very steady rate until we adjust it up at around the hour one hour mark there's a brief spike at the beginning of that but then it settles down very quickly to a steady rate of 8.8 milliliters per hour and then around the two hour mark we adjust it back down to a steady flow rate of 0.5 milliliters per hour next slide please
so how might this be used in treatment of preeclampsia with magnesium sulfate so over on the right is one of the existing protocols for using magnesium sulfate to treat preeclampsia and eclampsia this is from the managing complications in pregnancy and childbirth published by the world health organization and we can take these dosages and using some recommended dilutions and infusion rates from a publication by hull and rucklage we can determine that a loading dose of eight milliliters of 15 magnesium sulfate which corresponds to four grams of magnesium sulfate diluted in 22 milliliters of five percent glucose for total volume of 30 milliliters could be infused at 60 milliliters per hour and then to achieve a maintenance dose you could use four milliliters of 50 magnesium sulfate which corresponds to two grams of magnesium sulfate diluted in 56 milliliters of 5 glucose and infused at 30 milliliters per hour to achieve a 1 gram per hour infusion rate of magnesium sulfate so you can see that these infusion rates of 60 milliliters per hour and 30 milliliters per hour fall within the range of what rely is capable of again its range is 0.1 milliliters per hour to 200 milliliters per hour and the volumes of 30 milliliters and 60 milliliters of diluted magnesium sulfate can be handled by syringes in the 5 milliliter to 16 milliliter range next slide please so what are the next steps in the real eye development well since we have the pneumatic side the system worked out pretty well at this point we are moving on to the electronic interface and the electronic interface that we're developing will have a number of benefits to it and it'll give real-time flow rate information back to the user we'll have a full suite of alarms and safety features including alarms for occlusion and over infusion or under infusion the electronic interface is going to increase syringe compatibility so that we can use syringes from a range of different manufacturers and it will greatly simplify the process of setting the flow rate once we've got the electronic interface developed we'll be integrating the electronic and mechanical systems and followed by benchtop verification testing and some usability studies and that concludes my presentation thank you for your attention thank you very much Dan next slide please we really appreciate your presentation and now we're going to be moving to Jacqueline de la Rosa we'll be talking a bit about our heat stable oxytocin and sublingual fast dissolving tablets Jacqueline thank you very much today I’ll be presenting on an innovative technology that's currently under development underneath the don product development partnership and that's the heat stable fast dissolving tablet formulation of oxytocin that is delivered underneath the tongue for the use and the prevention and management of postpartum hemorrhage you may refer you may hear me refer to these as oxytocin fdts for fast dissolving tablet throughout the presentation next slide please so excessive bleeding or postpartum hemorrhage after birth is the single most common cause of maternal mortality and oxytocin is a drug used to stimulate uterine contractions and is the first line treatment but there are three main challenges to ensuring its utilization for women giving birth in low and middle income countries the first major obstacle is that oxytocin is a protein that is very susceptible to high temperatures and current products for oxytocin degrade more rapidly and lose its potency when exposed to heat therefore it must be stored at either controlled temperatures to ensure its quality however refrigerated storage is not always available or reliable in some settings the second challenge is the affordability of a heat stable product although there may be other heat stable products for postpartum hemorrhage management it is very expensive lastly oxytocin in its current violent needle parental format for intravenous or intramuscular administration requires training in skilled health workers however an easy to use sublingual tablet format could potentially make it possible to administer oxytocin in more remote settings these challenges together are resulting in a gap in ensuring global coverage of oxytocin for all women giving birth next slide please so path's solution was to develop a very simple fast dissolving tablet fdt dosage format of oxytocin that is heat stable easy to administer under the tongue and affordable for women everywhere there are many advantages of our fdt technology because it addresses several of the challenges I just mentioned with the current products for postpartum hemorrhage management I’ll mention just a few of these reasons that are listed here in no particular order most obviously it removes the complications of needle injections making it more convenient to administer in wider settings in reducing the training burden on health workers our oxytocin in an fdt format is not only heat stable and does not require refrigeration as I’ve mentioned already but it is robust and has compact packaging making it easier to distribute and store compared to other products the oxytocin and the sublingual fdt completely disintegrates very quickly in less than 30 seconds under the tongue to achieve an immediate response the product is made with ingredients that are generally regarded as safe and are low cost making the fdt's affordable it also uses a well-established process to make it easy to transfer to manufacturers in low and middle income countries in the future next slide please another unique feature to highlight about our oxytocin in a heat stable fdt is that it can be made into any size or shape making it available in multiple different packaging options for improved distribution and storage shown on this slide are just a few examples of a couple of different options on the top row of images you can see the fdt's are in bulk packaging in bottles and if you look closely inside these bottles you can see that the fdt's are shown in different geometries as one alternative option on the bottom row of images you can see the fdt's individually packaged in blister packaging next please next I want to show you a couple of different video demonstrations of the fdt's so it'll give you a better sense of what they look like how they're made and how they dissolve so the first video shows how flexible the fdt's are and how they can be produced in our path lab using an off-the-shelf reusable silicon tray the fdt's can be made into any type of tray and into any different size their shape depending on the trade that you use in addition this reusable tray could potentially further reduce the manufacturing costs lastly the fdt's you can see are being placed into a bottle just to show how robust they are the second video is just a five second clip of the fdt on a spoon just to show how quickly it disintegrates even with very little fluid they're using a micropipette to deliver just a tenth of a millimeter of fluid and the third and last video will show the complete transformation oh sorry next slide please so this last video shows the complete transformation of the fdt from a tablet to a viscous muco adhesive gel in less than 20 seconds we show decreasing amounts of fluid being added to the fdt starting with half a milliliter down to a tenth of a milliliter and the fdt disintegrating rapidly within each one and you can see the fdt's is completely dissolved into this gel to make it easy for it to be delivered and absorbed underneath the tongue some paths formulation contains low-cost very safe non-toxic ingredients the full ingredient list is shown here and it is with this combination of both the unique formulation composition and the manufacturing process together that achieves a very heat stable product at relevant elevated temperature and humidity conditions at path we have three formulation candidates for oxytocin in an fdt format that after a two year stability study that we conducted in our lab it shows really promising results with no loss in oxytocin potency at 30 degrees Celsius and 65 degrees relative humidity after two years next slide please we have also completed a pk and toxicology study in rabbits and have demonstrated we were able to achieve uptake and absorption by sublingual delivery of the fdts the results confirmed the formulation is safe there was no inflammation toxicity or adverse events and the sublingual groups showed rapid uptake within five minutes of administration similar to the intramuscular control next slide please so path is continuing to develop our heat stable oxytocin in a sublingual fdt and to summarize a few of our key next steps are to establish the plasma bio equivalence using sublingual route of delivery in healthy volunteers investigate leveraging the abbreviated usfda505b2 regulatory pathway which has the potential to accelerate approval in lower middle income countries and we are also working on obtaining clinical guidance on the relevance of low bio availability of sublingual oxytocin in the management of postpartum hemorrhage and that concludes my presentation thank you all for listening thanks so much Jacqueline we appreciate your presentation very much next slide and now we will move to Mitsumi Metzler who will be talking a bit about commercialization strategies for introduction and scale of this new innovation Mitsumi thank you Chris so I will be talking about how dawn pdp project working with the various partners to accelerate the technology uptake for pph and also pre-eclampsia glands their package of care so in my presentation I will focus mostly on ubt and also prcl tests because those two technologies are more downstream in terms of product development and introduction process next study please so I want to start my presentation with this quote that I found in the in idea to impact published by USAID the center for accelerating innovation and impact and this code is really relevant to our work establishing a partnership and collaborating with the local players is important but also that's important with collaborating with our global and regional stakeholders are also critical and at the same time we needed to collaborate not only public sector but also private sector partners in order to achieve access to innovations next slide please so as pdp we collaborate with the various partners so we work with some partners from the beginning to the end and we work with some partners more closely at the beginning or early stage of product development introduction process or more closely work with them at the later stage so for example we work with global regional and national policy makers and users and influencers from the beginning understanding their voice is really critical to understand the needs and also identify gaps and create target product profiles that will meet the need of low and indoor income countries and they will continue to be important the partnership for us until very end to implement innovations in the package of care or in existing programs on the other hand at the research in the design phase we start working with the product developers but when we move it to a validated developed phase we start working with a commercialization partner that has the capacity to actually produce products get regulatory airflow about and also distribute the product to low in the middle incoming countries so in case of lwg we are partnering with synaptic biomedical located in south Africa and as for our prco test we are working with like acid diagnostics which is also located in south Africa and we also collaborate with research organizations regulatory agencies and also procurement agencies and then however type of types of organizations we work with really changes depending on the stage we are at and also activities we conduct at that time next slide please so how we are part learning with various organizations before introducing the racl test and then scaling up the dust so as a charlotte I explained in her presentation earlier we are working with the king temple health research center to conduct the various research and also currently we are working with university of Utrecht to conduct implementation research later this year to assess clinical utility and also operational effect of the prcr test in Ghana in Kenya we engaged with county with management teams and worked with various levels of health facilities to understand what's the current practice around the protein unit testing and access opportunities for a new prcr test and we are currently planning to do implementation research both in Kenya and Ghana and in Kenya as a preparation we will convene workshop with various stakeholders including ministerial health county health management teams and professional associations and the medical practitioners to really identify research questions for implementation research and by doing so we are hoping that the result we will generate through implementation research will be relevant and then also useful for those partners when they are thinking about nationally rolling out cl test in the future let's just start with you please so here is the partnership for lwbt introduction and scale up so we have been engaging with the ministry of health professional organizations and other key opinion leaders to incorporate the ubts into a pbh package of care and we started to work with those partners to really incorporate the uvg training into emomp training program together with other interventions necessary for pbh management and also we are currently collaborating with the ministry of health and research organizations and also public and private sector facilities to conduct implementation research and then in Kenya in particular we have opportunity to receive additional funding from another donor and using that opportunity we will soon conduct pirate introductions in two counties in Kenya so when health systems are devolved it's really important to ensure coordination between national level and also of national level governments and therefore we are making sure that all the information or data we are generating through throughout the project are available for those partners so that they can have the same information at the same time and have a collaboration in a timely manner and as for users as disability explained we provided a very interactive and hands-on training to users and the training is a really great opportunity to make sure that users have adequate skill set and knowledge not only for product to use but also a pbh artist management and also training is a great opportunity to raise awareness and a generic demand for our product and finally I want to make a point about commercialization partners in this case synaptic biomedical and then also are there distributors we are in a very close collaboration with them and close communication with them constantly to ensure that their introduction strategy and our mission and their strategies are in well aligned and including a pricing Australia so that products will continue to be available at affordable pricing in the lower and the middle income countries and also for the training for example we involved snappy biomedical and also their distributors when provided training to users so by doing this so we can ensure that commercialization partners will listen about the product issues and the questions directly from users and if necessary they can address those in by modifying information on rejection for use or training materials in the future next slide please so as we continue to work with the various partners on how we are doing in terms of calendar status while the prcl product is a little bit more in introduction here is the mark showing you that the current status of our introduction effort for energy so lmubg received cd marking in re 2020 and as of march 2021 snappy already received the market authorization for the product in 13 countries and then still a number of countries are is accounting next slide please so what are key lessons we learned through this dawn project as the court I introduced in the beginning of my presentation establishing a partnership with various national and global organizations in public and the private sector is really important to accelerate introduction and scale up of innovations and secondly product introduction is really a program implementation so therefore it's critically important to incorporate products as a participle care and leveraging existing systems and also pdp can categorize collaborative effort of all partners to scale innovations but pdp involvement cannot be infinite and the partners must play leading roles to scale innovations eventually therefore we believe pdp must share evidence information with all relevant partners to enable transparent and timely communications and also effective collaboration among those parties and also developing maintaining healthy partnership with commercialization partners is critical because they are the ones who will continue to produce any distributed products and ensure sustainable availability of products in low and middle income countries and finally fostering direct interactions between commercialization partners and also user policy makers is really important to do at right appropriate times so that they can collaborate and communicate in a timely manner to ensure introduction and scalable innovations in in a timely manner so this is the end of my presentation thank you so much for listening and I would like to turn over to Trish thank you so much Mitsumi for that interesting presentation next slide please so at this point we've come to the end of our presentations and we are happy to engage in a dialogue with the audience answer any questions I think we have a specific question around rely Dan and the approximate cost person was wondering about that so perhaps we could start off there if you don't mind sure yeah so since the rely is still in development we don't have an exact cost figure for it yet but what we're targeting is a a cost of 500 or preferably less than that great thank you so I encourage everybody to put any questions or comments that you might have into the chat and while we're waiting for you to do that I thought I would just reach out to all the panelists today and ask you a very broad question which is around introduction and scale of maternal health innovation so what do you all see as the biggest challenge for introducing and scale lean maternal health innovations like this so perhaps you could turn on your videos except charlotte and Sylvia I know you have bandwidth issues so maybe you can just respond without your video on if possible so anybody have any thoughts around that so maybe I can start while other people are thinking about challenges so in the beginning I think that Theresa said that pvp works to idealize the need of low-income countries or markets which are not usually advised by a you know traditional market so that's actually a challenge so the growing government are low in the middle income countries market may not be really a so-called lucrative market for commercialization partners so that means that you know volume of sales they are expecting maybe very small or could be total profit margin they can't expect could it be a sling compared to other traditional markets so for challenge for me as a commercialization officer how to find the right partner which can share a mission with us and also continue to address the need of low-income incoming countries perhaps martini you also might speak a little bit to the different ways that path addresses that issue yeah so yeah yeah thank you for that and I think there are a couple of ways to address that and then from that get go I think we will do a very ambiguous due diligence to really understand the corporate culture and also technical capability and commercialization capability like a distribution network so that's the way to find the right partner so very big residual divisions and then another way to do is that I think that pdp is a perfect to do this but you know working with the partners we can reduce entry barriers to markets for example like we can do much research and also articulate healthy systems and also like the demand regenerations or understanding regulatory systems and those are usually needed to be carried out by commercialization partners using their investment so we can work with the partners to carry out those activities by doing this so that the market entry values can be reduced so even though that may be the income or revenues commercialization partners can generate from a low in the middle income markets still it might make sense for them to enter the market because of course to do so can be lower thank you charlotte or Sylvia I was wondering if you have faced any barriers in your work in Ghana that you might be able to share this is so weird what I want to think is that the first and most important thing is dressing stitch holder by ink people must recognize the need for the device and be willing to use it and another thing especially for pth is to have the device as a point of check because when you have a device for some time you don't have much time so it's a logistic management system in addition to the cost of the device because that tends to be a big disincentive when it's expensive people are reluctant to use it and the third thing is to find a sustainable system of building it into pre-qualification training and also on the job training there must be a system criteria to ensure that as new persons enter the profession there is a system for continuing training so that it can become integrated thank you Sylvia it was a little difficult to hear you but I think your main points were definitely well taken that you needed to make sure that you had innovation that was able to be delivered at the point of care and that it needed to be integrated into the existing system including the package of care I think was your last point and do you want to just reiterate your first point because I didn't catch that very well the first point was to get stakeholder buy right okay so that's great thank you charlotte I don't know did you have anything you wanted to add in terms of your experiences in Ghana yeah add to the points that Sylvia just mentioned about the policy makers you know buying into whatever yeah we want to introduce into the country and I would also talk about another thing that we also need to talk about is the food and drugs authority in whether the product is registered because that's also another big step that's all header that we need to jump over otherwise you know it might really cause a whole lot of issues for us so I mean for us policy or advocacy in the first place sorry is very important and also getting the product registered in country that's what I’ll add thank you thank you charlotte anybody else on the panel want to respond at all sure I can say just a little bit and this really comes back to the question we got earlier they so it's interesting that the study that that I cited for the you know where the surgeons were entered were surveyed for availability of various medical devices they were also asked about what some of the reasons were why their facilities lack these devices and by far the most common response was cost so that's clearly a big driver and I mean as far as rely goes we're in a good situation right now because we're you know since we're in the development phase we can do a lot to try to control cost just by right-sizing the features to what's really essential for the device and not including a lot of extraneous bells and whistles and we can make sure that we're using affordable but quality components in the device and then also partnering early with manufacturers to work on the design in such a way that it's really designed for manufacturer there's a lot you know there's obviously those cost of components but then there's the cost of doing all the assembly and packaging so on so anything we can do ahead of time in the design to make it easy to manufacture the device is going to help bring down bring down costs thank you Dan um well we have just five minutes left in our presentation today so I’m wondering if maybe do any of the panelists have any final thing you'd like to share or any thoughts around your specific product that you're working on or what you see as the future for this particular innovation in your country I think you did touch on that already a bit in the next steps but any final words from the from the panelists I guess everybody has said everything they need to say for the moment so with that I think what we'll do is we just have a couple of minutes left in our session so I think what we'll do is we can just close now and give everybody a couple of extra minutes to get to your next session so thank you so much for being
2021-09-04 23:31
