#14 Advancing pharmacovigilance in Africa – Eleni Aklillu & Abbie Barry

Access to medical products has increased considerably in Africa in recent years, but safety monitoring systems haven’t exactly kept pace and many African countries still struggle to address safety issues. We sat down with Eleni Aklillu and Abbie Barry of the PROFORMA project to learn about their efforts to strengthen pharmacovigilance capacity in East Africa – especially within public health programmes.

Tune in to find out:

• How comorbidities and genetic variation affect drug safety monitoring
• Why pharmacovigilance centres should strengthen their ties with academia
• How to apply the PROFORMA model elsewhere 

Want to know more?

• Low- and middle-income countries like the PROFORMA target nations face unique challenges in establishing robust pharmacovigilance systems, as described in this comprehensive review.
• PROFORMA’s baseline assessment of national pharmacovigilance systems in Ethiopia, Kenya, Rwanda, and Tanzania identified gaps and laid the groundwork for targeted interventions.
• Their subsequent assessment of pharmacovigilance capacity within the neglected tropical diseases programmes highlighted the urgent need for collaboration between those programmes and the national pharmacovigilance centres.
• You can read about PROFORMA’s accomplishments in more detail on Uppsala Reports and on the PROFORMA website, which also lists the consortium’s publications and upcoming events.

For more on the influence of genetic factors on drug response, revisit this interview with UMC’s pharmacogenetics specialist Qun-Ying Yue or this Uppsala Reports Long Read on pharmacogenomics research in Africa.

Transcript

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Federica Santoro 0:15

Africa, the world's second largest continent, suffers more than its fair share of disease. And new medicines and vaccines are rolled out all the time to fight public health emergencies. But even though access to medical products has increased in recent years, safety monitoring systems haven't exactly kept pace. And many African countries still struggle to address safety issues. Thankfully, efforts to change that are now underway. Joining me today are Elenia Klilu, Professor of Tropical Pharmacology at Karolinska Institut in Sweden, and Abi Berry, one of our doctoral students. For the last four years, Eleni and Abby have been leading Proforma, a five-year international project funded by the European and Developing Countries Clinical Trials Partnership, or EDCTP, to strengthen pharmacovigilance capacity in East Africa. We spoke about mass drug administrations, genetic diversity, and how creative solutions can save the day. Hi Eleni and hi Abby. Welcome to Drug Safety Matters. It's a special honor to have you on the podcast today because you're actually the first external guests to step foot in this studio after two years of pandemic isolation, and I have to say it's lovely to see people in person again. So an extra warm welcome to both of you. So I'd like to start with you, Eleni. You coordinate the Proforma project. That's an initiative to boost pharmacovigilance in four East African countries: Ethiopia, Kenya, Rwanda, and Tanzania. So, first of all, why East Africa? I know you come from Ethiopia, so I can see a link there. But were there other reasons for focusing your efforts on these countries?

SPEAKER_01 2:32

Yes, all of the Proforma participating countries are from East Africa. And I happen to be from Ethiopia, and my research group has established a lot of collaboration long-lasting with various African universities in East Africa. So it was natural for me to build up on the already existing collaboration. Of course, through the Proforma project, we do have national medicine regulatory authorities, which we have never been working together, but through the local investigators from the academia, it was very much easy for us to engage with regulatory authorities. So the existing platform was really easy for us to embark on. That makes a lot of sense.

Federica Santoro 3:11

You take advantage of existing collaborations. Abby, over to you. One of the first things you needed to do when Proforma launched back in 2018 was to assess the status quo. So you could identify gaps and obviously plan accordingly. What was pharmacovigilance like in those four countries back then?

SPEAKER_00 3:32

Very interesting question. When we did the baseline assessment, we did identify the gaps. And one thing that stood out was that the countries were at different levels of maturity. Rwanda, for example, had not established the Rwanda FDA. Then the National Pharmacovigilance Center was hosted at the Ministry of Health. And there were also limitations in some of the regulations which have now been addressed. And there were other components such as electronic reporting systems that were not in place, that are now in place. So that assessment really provided sort of a foundation to identify the gaps, what we needed to strengthen, and then interventions were made and tailored for each of the countries, addressing the specific needs of the countries.

Federica Santoro 4:31

People are often affected by more than one disease at the same time, be it HIV, tuberculosis, malaria, or perhaps one of the so-called neglected tropical diseases. And that means people are often taking more than one medicine at the same time. How do you tease out the side effects of specific medications in such complex scenarios?

SPEAKER_01 4:56

Yes, this is a very good question. The situation and the scenario in Africa is quite different from what we see in Europe and US or the Western world. There is a lot of co-infection, co-medication, traditional medicine. All this affects a treatment outcome and the safety and efficacy of drugs. And this situation has to be considered always when we are testing the safety of a drug. A drug can be safe when it's given to a healthy individual, probably. If it is given to another patient who has concomitant medication or comorbidity, the safety can be questioned. So that is why we need to do post-marketing surveillance in sub-Saharan African population, where these confounders are existing. Based on the outcome, we identify the type, the incidence, and risk factors for safety of medicines. Based on this, we can predict what kind of outcome we are expecting. For example, if an HIV patient who is taking anterior drugs is taking a drug which is meant for prevention of neglected tropical diseases. So not purely studying drug safety in a controlled situation, but in the real society, post-marketing surveillance is all about what happens after the drug is marketed so that we know the risk factors and what is expected to predict the outcome so that we can have a warning measure and precocious measure, even regulatory interventions should be done. Of course, we cannot control this situation in real life, but we can predict and prevent harm.

Federica Santoro 6:34

And there's another reason for wanting to look at the safety profile of drugs in African populations directly, and that's that African people display enormous genetic variation, which affects obviously how they react to medicines. But the problem is that most medicines and vaccines, even those that are designed for use primarily in Africa, are tested outside Africa on white people. So it's not surprising that certain drugs, while they may look pretty safe in clinical trials, they can end up harming African patients. Do you take pharmacogenetic differences into account in the Proforma project? And if so, how?

SPEAKER_01 7:18

Yes, that's very interesting. Apart from this co-infection, concomitant medication, and so on, genetic variation influences treatment outcome. And interestingly, the black African population is genetically so diverse than any other population. So these factors are contributing for treatment response, and some are affecting the safety and also efficacy of drugs. So having this pharmacogenetic component in safety surveillance study is very, very important, which has not been done before. There are some clinical trials and some specific studies that are studying one drug in patient, but when drug is given for mass in public, where the genetic diversity is also so huge, so there might be some individuals who are susceptible because of their genetic makeup to adverse events. So putting genetic studies, pharmacogenetic studies in safety surveillance, in pharmacovigilance is very important. And Proforma is unique in this way, I would say. That all the PhD students that are working under the Proforma project on the pharmacovigilance of neglected tropical disease drug that are used for immunization vaccines, they are taking into consideration also the genetic makeup of the East African population. So based on this genetic makeup, we can identify who are susceptible for toxicity. My research group has been doing a lot of research on pharmacogenetics in African population. And we have identified, for instance, a genetic mutation, which is highly prevalent in general in black African population, which predisposes a patient who is taking antritroviral drug, efavorens. Efaverance is known to induce CNN toxicity and liver toxicity. Not all patients are developing this, but there are a few individuals that are developing this. And we have identified later that CP2P6, an enzyme which metabolizes efavorens expressed in the liver, have a genetic mutation, deleterious mutation, which reduces or prevents metabolism of efavorens. So now we have identified this polymorphism as a biomarker, a safety biomarker for efavorens. So although at this moment, Africa is not a situation to use genotype-based dose adjustment, at least generating the information for future application will be very helpful.

Federica Santoro 9:40

I agree, and that's really good to hear. We actually covered the pharmacogenomics in a couple of episodes on drug safety matters. So I invite all our listeners who want to know more about that topic to dig in the archive and go listen to those episodes. Eleni, you mentioned the surveillance of medicines and vaccines in mass administration. So that leads nicely into my next question. But over to you, Abby, for this one. One of the main areas of work of the Proforma project is active surveillance of drugs administered to large parts of the population as part of public health programs. How well, first of all, how do you make authorities see how important it is to have effective monitoring systems in place when you're giving drugs to thousands of people?

SPEAKER_00 10:32

Right. I think it starts from the beginning by expressing that the information that is captured during clinical trials are not sufficient because it's just for short duration, but also very carefully selected individuals are enrolled in these clinical trials, which is not reflective of the people that you'll be giving these mass immunization or drugs to. And more and more we have new vaccines and other medicinal products like drugs and treatment regimens that are being introduced for targeting different infectious diseases, poverty-related diseases. And if this is new, then that is definitely a reason to monitor the safety, I think. But also that through this initiative, we're generating information that will highlight that yes, these medicinal products may be safe, but they are not completely safe. And there is a certain profile of subpopulation that are at a more increased risk of adverse events. So that will be another reason why safety monitoring is essential. And they now see this because it's based on the evidence that we have. So it's not just what someone thinks. I think that makes a difference as well. But another thing is that you want to sustain the confidence of the public for the programs, right? So if the public don't have confidence in the public health programs or they're questioning the safety, then there is hesitancy, especially for vaccines. That's a problem today. But if you have comprehensive safety monitoring systems in place, I think that will give the public confidence in the programs, that they prioritize the safety of the public. And this confidence does have a direct association with coverage, eliminating the diseases as public health problems does really depend on the coverage of the mass immunizations and mass drug administration. So I think that is also another important reason for why the authorities should really integrate safety monitoring systems in the programs in the countries.

Federica Santoro 12:46

Absolutely. And convincing the authorities is part of the challenge. But there's often another problem, and that's the lack of communication between public health program officials and pharmacovigilance center staff. It happens often that they simply don't share data with each other.

SPEAKER_01 13:04

How do you bridge that gap? We have conducted a baseline assessment of the National Tropical Disease Public Health Program for Pharmacovigilance activity during mass drug administration. And we have found in 2017 and 2018, despite millions of children and adults receiving drug as a preventive chemotherapy for various infectious diseases, there was no reporting of adverse events from the public health program to the national medicine regulatory. It shows that there is almost no collaboration between the public health program and the National Medicine Regulatory Authority. So we wanted to take this gap and work on it and establish a collaboration. Share data, monitor safety of drugs, and also work together during this mass drug administration. In addition to that, we also assessed the academia. There was no collaboration between the regulatory authorities and academia and between public health programs and academia. So these three institutions who are stakeholders for safety monitoring in the public, we wanted to have this triangle model, which is called Proforma Model, where we are bridging the gaps. Proforma triangle model is tested in the field. In each of the countries, we have conducted active safety monitoring of one drug that is used for mass drug administration and also vaccine. So by doing so, we have trained and engaged investigators from the three institutions, and we're together in the field doing active safety monitoring, which we are really proud of. So we have been very successful in that, I would say.

Federica Santoro 14:51

And you should be proud. So you're acting a bit like the glue between these different stakeholders.

SPEAKER_01 14:56

Yes, we are.

Federica Santoro 14:57

Where do patients fit in the picture? Are you planning to engage them too?

SPEAKER_01 15:02

This is a good question. Engaging pharmacovigilance training of patients, it increases immediate response reporting of adverse events. But there are some limitations in this approach. One is that sustainability, you have to teach each and every patient every time. That is a lot of resource. And the other one is that the number of patients is so big. So you need a lot of trainers to reach all the patients. But PROFOMA has adopted another strategy that is training of the trainers. So we train the pharmacovigilance experts in the regulatory authorities, academia, and the public health programs who are involved in master administration and vaccination. And along the casket, the trained trainers also train another trainer. And at the end, the patients are at the down the casket, we reach them. So I think we maintain sustainability. When the project is finished, the training continues. And at the same time, the number of patients who will be trained in pharmacovigilance will be so big that even if we are not teaching directly the patient, through this approach, we are reaching the patients.

Federica Santoro 16:17

That sounds like a sensible approach and a smart use of resources. Abby, I have a question for you. How has this affected Proforma's efforts to raise awareness of the pharmacovigilance process?

SPEAKER_00 16:42

I think this actually complements the efforts of the Proforma project because one of the objectives is transparent communication to the consumers and the general public about the potential side effects of drugs. So we want the consumers and the patients to be aware that no drug is 100% safe and there are potential side effects that can and do occur. So we encourage people to report these events. And in doing so, we also understand that communication should be done. It's delicate, right? Because you don't want to discourage people to not use the medication in the manner in which it is to be used. But also you want them to be aware that there are potential side effects that may occur as a result of using this. So this is why performa is also training on risk communication and management, because there needs to be a balance where the information that needs to go out goes out to the people, but also in a manner that they understand that there's always a risk-benefit assessment going on. So it does actually complement the efforts of the performer project. And this is the reason why we're doing that risk management and communication training.

Federica Santoro 18:02

You're operating in four countries, as we said, but despite the similarities, there must be unique challenges. Let's think just about the number of inhabitants. Rwanda, for example, has a population of about 13 million, while Kenya and Tanzania are both above 50 million inhabitants. Can you give me some examples of how you had to adapt solutions to local circumstances?

SPEAKER_01 18:30

Yes, we do have similarities and differences between the four East African countries that are participating in the PROMA project. And we experienced a different challenge also during our project implementation, and the way administrative work, the channel of communication is different. So we had to adapt to these country-specific routines, particularly when we are doing the safety surveillance in the field. For instance, when we started this project in Ethiopia, when we were about to embark the safety surveillance of drugs used for prevention of schistosomiasis and soil-transmitted elements, at our study site there was a social unrest. So that was a big challenging. So we had to make some interventions to continue our study in that area. For example, in Rwanda, there were some studies sites where there was no road access to do the safety surveillance. So we had to use wooden boats. It was really exciting because most of these studies were done in a rural community, and we in the field have experienced and really enjoyed advocating for pharmacovigilance for the villagers, community leaders, and the local authorities preaching about pharmacovigilance and telling the benefit of the safety surveillance and also what is the objective of our study and what is the benefit of that study. It was really an eye-opening and very passionate. Although we had some challenges, we enjoyed really the outcome of our study. For example, in Kenya and Tanzania, we conducted active safety surveillance of drugs used for lymphatic faleriasis for prevention of lymphatic faleriasis. And in Tanzania, we followed 10,000 individuals in 24 villages in the Tanga region where lymphatic faleriasis is very prevalent. There, we were doing house-to-house visits to monitor drugs that were given as mass drug administration. And we had done community sensitization through horno speakers on a motorbike. So engaging the community was very critical and very important. So we followed the advice of our local investigators, knowing the routines in that area so that we approach keeping the hierarchy. Even religious leaders will have met them and explained what our study was. And the response was really very positive.

Federica Santoro 21:07

Proforma's fourth annual meeting was held in February this year. Are there other important milestones the project achieved that we haven't mentioned yet and that you'd like to bring up?

SPEAKER_00 21:19

Now I'll give Elaine a pat on the back because I can't give myself a pat on the back, you know. But I'm very proud of the project and how far we as a consortium have come, we've come a long way. And we together have shown that if many people come together and put efforts, what you can achieve is limitless, so to speak. So each individual country, based on the findings of the baseline assessment, developed a national pharmacovigilance plan addressing the gaps that were identified on the assessment. And from there, we have implemented some. The interventions in the National Pharmacovigilance Plan. And that included updating the acts, the pharmacovigilance acts, the regulations, and the guidelines. And one example of such is that when we started, it was not a requirement for the marketing authorization holders to have uh qualified persons for pharmacovigilance, a QPPV person. But now we've seen that that is one of the interventions that have been applied in Kenya. And since then also, Tanzania has reached maturity level three. And I think in sub-Saharan Africa, besides Tanzania, Ghana is the only other country that has attained this level. And the establishment of Rwanda FDA, of course, is something that we are very, very proud of. And now they're even aiming to reach maturity level three. So there's been a lot of development and success that have happened since that establishment as well. And in Ethiopia, when we also started, there was no electronic adverse event reporting mechanism. But now people can report electronically. So you don't need to use the paper base or go to the office. You can just report electronically, which is very convenient and will result in the increase of adverse event reports. Now, with regards to training, I think it's just right that I give that over to Elaine because she is the main supervisor of all the students under the Performer Project.

SPEAKER_01 23:37

Thank you, Abby. Yes, we are providing training of pharmacovigilance at different levels. The short-term training is led by the Netherland Pharmacovigilance Center, LAREP, by Professor Eugene and Dr. Lien. We have given so far four pharmacovigilance short workshops conducted in different performer participating countries, and also some of them were given online during the pandemic. We have given introduction to pharmacovigilance and also signal detection and management, also QQPV trained personnel. And we are planning to give risk management and communication in the next short-term training. And the midterm training involves training of the regulatory staff at the master's level in pharmacovigilance. And five MSc students are being trained through the Performa project. And this is done also led by the Pharmacy and Poison Board and the University of Nairobi in Kenya and also at Addisaba University at the CDT Africa. The other one, long-term training, is done at the PhD level. Seven PhD students are being trained. Five of them are registered at Karolinska Institute. One is registered at the University of Rwanda, and the other one is registered at Addisaba University. These PhD projects are being done as part of the work package for where we are doing safety surveillance of master drug administration and vaccination. In addition to the safety monitoring, we have a little bit of scientific component. We have integrated pharmacogenetics, pharmacokinetics, and pharmacodynamic component for the safety to identify risk factors. And above that, we have established a regional networking between these four East African countries because the PhD students are working together on a similar project. And there is a friendship and connection and really motivation. When the Proforma project is finished, they will continue to fulfill the vision and mission of the Proforma project. We have developed also undergraduate pharmacovigilance curriculum. When we started the Proforma project, we have also done assessment of the current teaching practice of pharmacovigilance in these academic centers and universities. And we have found that pharmacovigilance was given like two hours just lecture, which was not really good enough. And we have developed a one-week examinable undergraduate PV curriculum that is developed through the performer project and approved, and now being implemented at the medical universities. It's given to medical students, nurses, and dentist students. We have developed also a postgraduate curriculum in pharmacovigilance and pharmacoepidemiology, which is now adopted and being implemented, for example, at Muhimbeli University. The other one is that we have developed an e-learning module for healthcare professionals, now present on the several of the medical universities in this participating East African countries. And this is being used as a pre-service and in-service training for pharmacovigilance. And we are very much proud of that. So we have really invested in the academia because focusing on the academia is very important for sustainability. This is what makes performa unique.

SPEAKER_00 27:09

And I think academia is often forgotten as an important collaborator for pharmacovigilance. But they are the ones to train these future healthcare professionals, integrating PV there and then will make sure that these healthcare professionals will understand the need and importance of it, and then will also actively report any suspected adverse events to the authorities.

Federica Santoro 27:36

And I wish people could see the twinkle in your eyes when you talk about this. It's clear that you're both very passionate about it, and congratulations on all these achievements. When we advertised your interview on our social media channels, one of our followers asked a question on Twitter. He says, Is there a similar initiative in West Africa? I will take this.

SPEAKER_00 28:00

I am from West Africa. I'm from the Gambia. So there's definitely a need to also strengthen the national pharmacovigilance systems in the countries in West Africa as well. And we would love to do that. We would love to expand the performer project beyond these four participating countries. But we need funding for that. So I'm calling on the funders. You know, we want a performer too.

SPEAKER_01 28:26

Yes, I think we have established, tested a model which happened to be very successful in strengthening the pharmacovigilance capacity in African setting. We don't want to stop here. Of course, the project has limitations at the time, when it's finished, the project is finished. But we have built really a good trained cohort that can continue the vision and mission of Proforma in East Africa. We have established a regional networking and collaboration through our PhD students who are trained together and they are the key person in the national level for pharmacovigilance. And we would like to establish and also do the same work in other parts of Africa. So we have ambition to do this in the future. So hope there will be Proforma too.

Federica Santoro 29:17

The call is out there, right? So whoever's interested can reach out to you and maybe set up a new project. Who knows? There's another pharmacovigilance project that operates in Ethiopia and Tanzania. It's called Pavia. And you even held a joint kickoff meeting in 2018.

SPEAKER_01 29:36

How do you make sure your efforts are not redundant? Indeed, Pavia is a complementary consortium investing on strengthening pharmacovigilance in Africa countries. And we do have two overlapping countries, Ethiopia and Tanzania. In those countries, we did a baseline assessment together. We wrote jointly the report and submitted. And the national PV road map was also developed by the countries. But the intervention and the gaps is so huge that should engage so many different stakeholders. And this is one thing that we are not really replicating one another, but also complementing each other. But there are also differences in our focus area. Pavia, they are focusing on TV, where patients are getting medications through healthcare system. For Proforma, we are focusing on mass drug administration and immunization, where people are receiving drugs and vaccines without prior diagnosis, not through the healthcare system, but as a mass. So our target area is really very different. And the other difference between the two projects is that we are also focusing on academia, making better the teaching practice of pharmacovigilance. But as I said, we are communicating together. For example, we co-sponsored pharmacovigilance session symposium during the EDCTP forum in last October in 2021. And we both are communicating and collaborating together. Thanks for clarifying that.

Federica Santoro 31:15

And how do all these projects fit in with efforts to harmonize medicines regulation across the African continent? I'm thinking specifically of efforts to establish an African medicines agency.

SPEAKER_01 31:28

One thing which Proforma has contributed is that generating a trained, PV-trained cohort, which can be really a good source for African medicine agency to utilize them. And they can be engaged in African Medicine Agency and also implement the objective of the regulating harmonization at the African level. And there is, as I said, established a strong collaboration between the strong PV centers and at the regional level. And we have established a good collaboration between the public health program and the regulatory authorities, which will be also a good source for African Medicine Agency to continue what we have already established. And apart from strengthening the regional pharmacovilence collaboration in East Africa, we have shown the feasibility of safety, active safety surveillance in the community when new drugs are given as a mass or new vaccines. Our experience in Ethiopia for HPV vaccine surveillance has been utilized and very been useful to engage into COVID vaccine surveillance. So what we have established is really a good resource for future African medicine harmonization program to be used as a resource. An excellent platform to build on, basically. Yes, exactly, to build on, exactly.

Federica Santoro 32:56

I'm gonna let you off the hook really soon, but before we wrap up, one final question. What's next for Proforma? What challenges remain to be tackled?

SPEAKER_01 33:05

Yes, I mean there is a huge need to strengthen pharmacovigilance in Sub-Saharan Africa. New medicines and new vaccines, new interventions, new diagnostics are being introduced through the country. And as we discussed earlier, Sub-Saharan Africa is very different compared to other populations where drugs and vaccines are mostly produced and developed and being implemented as one dose-fit-all purpose. But in real scenario, it's very different. Sub-Saharan Africa situation, the environment, the nutrition, coexistence of co-infections, co-medications, this makes African population unique. So we have to really invest. There is a huge gap still to be filled. And there is a need for post-marketing surveillance and reporting of adverse events. How can we improve the gaps between the different stakeholder institutions that are existing to promote public medicine safety? And not only that, but how to use the data. After collecting the regulatory authorities, after they collect adverse event reporting, how to use, analyze that data, and also communicate risk management and communication is very important. So there is a lot of gaps to be filled. We really need to work on more, and also community outreach is very important. And there is also limited finance for pharmacovigilance activity. Most of this work are project-based, and projects have limited duration and capacity. So engagement from the national government to promote pharmacovigilance activity and also fund them is very important. So there is really a lot to be done in Africa to promote pharmacovigilance.

Federica Santoro 34:57

It certainly sounds like that, but it also sounds like you've built a strong foundation. Thank you both for taking the time to talk to me, and I wish you all the best with your work. And I'm really looking forward to hearing more news about Proforma.

SPEAKER_01 35:12

Thank you very much for giving up the opportunity and share our experience through the Proforma project. And on the behalf of the Proforma Consortium and the 10 institution partners from Ethiopia, Kenya, Rwanda, Tanzania, and the Netherlands, and of course from Sweden, Karuniskan Institute. On behalf of our consortium, I'd say big thank you for giving up the opportunity to tell our story.

SPEAKER_00 35:35

Thank you very much, Frederica, for this opportunity. I don't have anything else to add. Prof. Elaine has said what I wanted to say, and a very big thanks to you for having us here today.

Federica Santoro 35:52

That's all for now, but we'll be back soon with more conversations on medicine safety. If you'd like to know more about the Proforma project, check out the episode show notes for useful links. While if you're interested in pharmacogenomics, go dig through the Drug Safety Matters archive where you'll find two episodes on the topic. If you like our podcast, subscribe to it in your favorite player so you won't miss an episode. And spread the word on social media so other listeners can find us. Apart from these in-depth conversations with experts, we host a series called Uppsala Reports Long Reads, a selection of audio stories from UMC's pharmacovigilance magazine. So do check that out too. Uppsala Monitoring Center is on Facebook, LinkedIn and Twitter, and we'd love to hear from you. Send us comments or suggestions for the show, or send in questions for our guests next time we open up for that. For Drug Safety Matters, I'm Federica Santoro. I'd like to thank Elenia Klilu and Abby Berry for their time. Matthew Barwick for production support. Till next time!