Graeme Nadasy: 0:15

Welcome to Drug Safety Matters, the podcast from Uppsala Monitoring Centre where we explore the latest issues in pharmacovigilance and patient safety. I'm Graeme Nadasy, and you're listening to a special episode recorded at the 43rd Annual Meeting of the WHO Programme for International Drug Monitoring held in Cairo, Egypt at the end of October. The meeting brought together representatives from more than 80 member states, along with senior experts and regulatory leaders from WHO headquarters and regional offices. Discussions focused on strengthening pharmacovigilance for women of childbearing age and children, in light of WHO's newly finalized Global Smart Pharmacovigilance Strategy. Amid the bustle of staff clearing tables and delegates chatting between sessions, I sat down with WHO Pharmacovigilance team lead Shanthi pal to learn more about the strategy and what it means for countries. The strategy was first presented to regulators at the International Conference of Drug Regulatory Authorities in New Delhi in October 2024 and is based on recommendations from the 2018 meeting in Dublin. It builds on two main ideas: work sharing and regulatory reliance among national authorities. You'll find links to the Global Smart Pharmacovigilance Strategy and the WHO Programme for International Drug Monitoring in the episode show notes. And now over to Shanthi at the Semiramis Intercontinental Hotel in the Garden City area of downtown Cairo. So I'm sitting with Shanthi Pal. We're in Cairo, Egypt, for the 43rd Annual Partners Meeting. And we're here to talk about the Global Smart Surveillance Strategy, which has now been finalised. Shanthi, what's the thinking behind the strategy?

Shanthi Pal: 2:20

So thank you, Graeme, for the question, and thank you also for this opportunity to speak a little bit about the strategy. So we've been working on this for a few years now, but I believe we have brought it to a place where it's comprehensive enough to support a few principles that we are advocating. And that is we don't have enough resources to do everything, and there are competing priorities. So then how do you balance these two paradoxes? So it's about risk-based prioritisation. So the need to use your resources efficiently, effectively, by doing what you have to do so that you can get to where you need to go. And that means that there are a few things that you cannot delegate, so you keep those as your utmost priorities. And then there are some things where you can lean on the work done by other stakeholders, you can adopt those or adapt those. And then there are some where you may come together as a community to take the work forward, and that makes your systems grow in a cost-efficient way and in a sustainable way. So that's the thinking behind it. So when you have competing priorities but resources are finite, how do you work smartly?

Graeme Nadasy: 3:47

There are four main pillars. So could you just in a nutshell explain what those are?

Shanthi Pal: 3:54

Okay, so yes, the strategy definitely builds on four pillars. The first pillar we say is that before you start anything, just look at the landscape. What's already available out there? And that's the existing infrastructure and learning from the past. How did you use those and what have you learned and how can these be put to use? So that's the first pillar, leaning on learnings and existing infrastructure. And the second one is risk-based prioritisation. So you say that where are your highest risks? So you put your precious resources to address those as a priority. So, for instance, if you think you're getting a vaccine for pregnant women, and you know that the volume of use is going to be quite large, and you know that this population in general hasn't received a lot of attention in pharmacovigilance, but you know the scale of use is going to be tremendous and it's a new vaccine, then that becomes a big risk for you. So you would put your efforts into that. So that's risk-based prioritisation. That's the second pillar. And the third pillar is reliance and work sharing. So what you can do use of, either as an individual country or as a group of countries, and that's work sharing, or where one or more countries may rely on the results from another country that's reliance. So that's the third pillar: work sharing and reliance.

Graeme Nadasy: 5:21

Could I be a pain and cut in there and just say it's not lost to me anyway, sitting here in this meeting, that so goes hand in hand with what the programme's about.

Shanthi Pal: 5:31

Yes. You know, it's intuitive. I mean, and it is inherent within the entire PIDM, you know, the Programme for International Drug Monitoring. So you're absolutely right. But sometimes you've got to call out, you've got to say, call it. You've got to say, this is what you're doing. So, you know, you give it a name and then it goes further. So that's the thinking behind it. And reliance as a concept has been applied in the regulatory world for some years, where you know you can have a group of countries coming together, assessing a product and registering it. And then a third set of countries would say, we don't need to go through the whole approval process. We'll simply take their decision and introduce a product into our market. The advantage is that you know you save on work, but you also speed up access to products. So reliance as a concept in the regulatory approval was already there. And we have been relying in pharmacovigilance on the global database, you know. All countries are sharing and everybody relies on that shared good, right? But slightly to nuance it a bit further is to say, you know, when you want to do characterise an event, you know, you say this is a say a thrombocytopenia or Guillain-Barré syndrome, and then you want to do a study. It might not be sufficient, you know, to just look at a database even more. Sometimes because of the special demographics of your population or the comorbidities of your population, you may want to study a certain product more deeply for safety in your population. That's when reliance can also be of immense help because then you can come together and do a study together. So you're increasing your the power of your study by pulling the data from between countries. Or the even better option is let's say Ghana or Nigeria is doing it, and maybe Togo can rely on the results of, say, Nigeria rather than starting to do that study. So that's the reliance part of it. So these are those aspects that countries haven't fully grasped. And when we introduced active methodologies, everybody wanted to do active surveillance of malaria, active surveillance of HIV drugs. And we simply don't have that luxury of using resources for asking the same research question, you know. So that's where we wanted to also draw your attention, attention of countries that you have been relying on, the global database, but it's also possible to draw from those principles to your other aspects that you're trying to do independently.

Graeme Nadasy: 8:04

Okay, great. Thank you for explaining that. Sorry, I cut you off. And the fourth pillar.

Shanthi Pal: 8:10

Okay. So the fourth pillar is about being part of a regulatory system strengthening. Because in many countries, pharmacovigilance developed like a research question. It wasn't really part of a regulatory framework, you know, what the regulator needs to do to keep their population safe. So we are saying that by being part of the regulatory framework, you know, there are nine regulatory functions that we assess when we are assessing a regulator's performance, competence, capacity, etc., we do that. And vigilance is one of them. So we are saying that by adding vigilance to the overall regulatory deliverable, you know, you are strengthening the regulator in their deliverable, in their overall function. But at the same time, the regulator becomes responsible for you. Regulator is accountable for you, which means the regulator will fund you, you know, because you make them do well and look good. You know, as a mature system, they can say that we are mature in all nine functions, regulatory functions. So they take you on, you help them, but at the same time, they are responsible for you and they sustain you. So that's a regulatory framework. So let's be part of a bigger picture of the winning team, help them and get helped. So it's a win-win, that's the fourth pillar.

Graeme Nadasy: 9:30

Okay. Obviously, this has been in the works for some time. These things just don't appear overnight. But now that it's here, how do you envisage it being put into practice?

Shanthi Pal: 9:40

So it's it's already being used in different ways between countries, but we'll push it primarily through the global benchmarking tool, and where we go to countries, upon invitation, of course, where we're invited to go assess their regulatory system. And that's where we'll start. So although I talked about the four pillars in a certain order, in reality, it's the bottom-up. You start with the assessment and then you prioritize, then you say, What do I need to do alone? And what can I rely on? But before I do anything, what are the resources available to me already in terms of database, in terms of tools, technology, innovations, etc. So it's a bottom-up. But that's how we plan to do it. We start with an assessment through the global benchmarking tool, and the countries will do that. I mean, countries can do a self-benchmarking, that's the first step, and then when they are ready, they would call WHO to do a formal benchmarking. So, and that's where we are guiding countries, start with this, and while by doing that, you are automatically following the smart strategy because you assess, you identify the gaps, you prioritise which gaps are to be filled ASAP, as soon as possible. And when filling those gaps, how do you do it? Who do you do it with? What are the resources you will use? And we have out of the 50-odd countries, 55, I guess, if you take it as a continent, in Africa, nine already have achieved that optimal maturity level three, you know, of the regulatory function, which includes pharmacovigilance. So it you can really see measurable goals.

Graeme Nadasy: 11:22

Okay.

Shanthi Pal: 11:22

And when you see that, when countries see that it's very satisfying. And it also gives them a clear vision on where they want to go and how they're going there. And when they reach there, they know it and they get acknowledged for it.

Graeme Nadasy: 11:37

Okay.

Shanthi Pal: 11:38

So the strategy is one thing, and then the the success at the national level is another, you know.

Graeme Nadasy: 11:43

As the de facto head of the program, how will you measure the success of the strategy?

Shanthi Pal: 11:48

Right. So for us, the strategy, success of the strategy would be in its uptake. How many countries are using this approach? So what we plan to do is maybe a year from now, we will do a survey and ask how many countries have applied this, the benchmarking system, has it an IDP, which is, sorry for the acronym, the Institutional Development Plan, and what maturity level have they reached, and where were they a year ago, etc. For us, having a plan is even more important than getting there, because I keep telling the countries that maturity level three is the, you know, the gold standard, you want to go there, but the journey is just as important because it's filled with you know many challenges and many breaks and stations that they have to get on and off. So every bit of that journey is important. So if they have a plan, for me, that would be a huge success metric.

Graeme Nadasy: 12:49

And to be super clear about this, are we talking about low and middle-income countries only here?

Shanthi Pal: 12:56

Our focus has been in the vigilance has been on low and middle-income countries, but the benchmarking tool is for all member states. I mean, EMA has gone through it. So, you know, it's it's intended for all of them. And especially because if you're going to promote reliance, they still have to play by the same rules and standards, right?

Graeme Nadasy: 13:17

Okay. So last but not least, what will you look to UMC for, in terms of support?

Shanthi Pal: 13:24

So they (UMC) could already support in the assessments, you know, on the technical: are they up to scratch? Do they have the relevant standards, know-how, expertise, etc.? They can help that. So they can work with WHO as assessors and they are considering that. But I think their major support is going to be in the development plan. Once a development plan has been crafted by the country, then you need technical groups to help implement that development plan. Because a development plan can be something as simple as having a report management system. It can be as simple as that, or it can be as complex as pharmacogenomics. You know, I keep telling the countries, low and middle-income countries that pace yourselves, have your development plan. It should be a, you know, a four or five-year plan, and you will have short-term, medium-term, and long-term goals. And short-term, you will do the minimum, and medium term you will build more competence and expand the scope of work, and long term you will aim to become maturity level three or best of class, you know. So UMC can help with the actual technical tools and skills and competency building in the country.

Graeme Nadasy: 14:42

Okay. Does that also include scientific expertise and know-how?

Shanthi Pal: 14:46

Absolutely. Absolutely. Because, so you have, let's take signal detection, for instance, right? So you have, UMC has clearly the lead. They have global data, and they have a certain advantage in having that global data, and they can through their own development and research are improving their signal detection every day. And you know, the data sources they consider is also growing, not just the database, but they're also looking at other data sources. So they clearly are, in my view, and can become even stronger as a lead group for signal detection. So they will be the lead science group for signal detection and innovations around that. And then breaking it down to countries so that you can help them do case analysis, understanding how these signals look in their country, the characterisation of those signals for their population, those kinds of capacity building in science can also be from UMC. So, you know, at the global level, the scientific leader, and at the at the national level, you know, the mentor. You know, we have also, as a part of all of this, we have something called Coalition of Interested Parties. And Coalition of Interested Parties was created primarily to support countries towards a mature regulatory system. And UMC has been recently recognized as that coalition partner. And so that's another way because not only as their role as a collaborating centre, but they also wear this hat now. So we bring them to the table, we say ten countries have a development plan. Who can do what amongst the CIP partners? And UMC has a certain historical engagement in this, but then also under this hat, we can give them more visibility but also engage more for the smart strategy.

Graeme Nadasy: 16:38

Okay. Well, that's all we have time for, Shanthi. Thank you. It was a pleasure talking to you. That's all for now. But if you'd like to learn more about the Global Smart Pharmacovigilance strategy and the WHO Programme for International Drug Monitoring, we put together some links for you in the episode show notes. Apart from the Drug Safety Matters podcast, we have our pharmacovigilance magazine, Uppsala Reports. Visit UppsalaReports.org to stay up to date with news, research and trends in the field. And don't forget to subscribe to the newsletter for the latest articles. If you have any comments or suggestions for the podcast or the magazine, please feel free to reach out on Facebook, LinkedIn, Blue sky or X. You can also visit our website to learn more about what we do to promote safe use of medicines and vaccines for everyone everywhere. If you like the podcast, please subscribe to make sure you won't miss an episode. And spread the word so other listeners can find us too. For Drug Safety Matters, I'm Graeme Nadasy. Thanks for listening.