‘Bad medicines’: The fight to stamp out substandard and falsified medicines in the Indo-Pacific

What are ‘bad medicines’? How do they make it onto our shelves? And what is being done to address substandard and falsified medicines in the Indo-Pacific? 

In this week’s episode, we delve into the ongoing problem of ‘bad medicines’, otherwise known as substandard and falsified medicines. Our guest is Dr. Paul Huleatt, strategic partnerships and programme implementation lead at the international regulatory branch of the Therapeutic Goods Administration.

Based in Singapore, Dr Huleatt works closely with regulators across the Indo-Pacific on a Department of Foreign Affairs and Trade-funded regulatory strengthening programme. Paul also acts as the Australian Chair of the Steering Committee for the World Health Organization's Member State Mechanism on substandard and falsified medicines.

In this episode we discuss: 

• what ‘bad medicines’ are, how they are created, and the history of this issue that dates back 100 years 
• the systems that are in place to detect and prevent bad medicines 
• how the Australian Government’s Pacific Medicines Testing Program is working to detect and prevent bad medicines 
• how the Indo-Pacific Regulatory Strengthening Program is building capacity with regulatory authorities in the Indo Pacific and providing regulatory support to countries that don't have regulatory authorities
• what’s next in the fight against substandard and falsified medicines in the Indo-Pacific

You can find out more about the WHO Member State Mechanism on Substandard and Falsified Medical Products here: https://www.who.int/publications/i/item/WHO-MVP-EMP-SAV-2019.04

A link to a news article on the case study in Indonesia that is discussed in the podcast is here: https://www.reuters.com/world/asia-pacific/indonesia-revokes-firms-fever-syrup-licences-amid-probe-into-150-deaths-2022-10-31/

We encourage you to join the conversation and follow Australia's Ambassador for Regional Health Security Dr Stephanie Williams at @AusAmbRHS.

Transcript

Please note: We provide transcripts for information purposes only. Anyone accessing our transcripts undertake responsibility for assessing the relevance and accuracy of the content. Before using the material contained in a transcript, the permission of the relevant presenter should be obtained.   

The views presented in this podcast are the views of the host and guests. They do not necessarily represent the views or the official position of the Australian Government. 

Andrew Everett 00:35

Hello and welcome to Contain This. I'm Andrew Everett, an adviser at the Indo Pacific Centre for Health Security. I'd like to acknowledge the traditional owners and custodians of country throughout Australia and the region. We recognise their continuing connection to land, waters, and community and would like to pay our respects to Elders past, present and emerging. Today on Contain This our guest is Dr. Paul Huleatt, who was First Secretary and strategic partnerships and programme implementation lead at the international regulatory branch of the Therapeutic Goods Administration within the Australian Government's Department of Health and Aged Care. Paul is based in Singapore and works closely with regulators across the Indo Pacific on a Department of Foreign Affairs and Trade-funded regulatory strengthening programme. Paul has taught me an awful lot about regulation and has been very generous in patiently sharing his knowledge with me. And I hope now he can do the same with you. Paul has built a distinguished career as a regulator and a trusted voice in the region, as well as on the global stage, and I cannot wait to get stuck into this with him. In this episode, we're going to discuss bad medicines, or as you'll hear Paul, call them substandard and falsified medicines. You can count on regulators to be precise with their language. Together, Paul and I are going to try to get to the bottom of how bad medicines are created in the first place. As we explore, it might become clear that this issue is not isolated to any one country. And that regional and global collaboration is essential to working to prevent harmful medicines and ultimately save lives. I hope you enjoy the discussion. So thanks for joining us, Paul.

Dr Paul Huleatt 02:22

Thank you for having me.

Andrew Everett 02:24

So regulation, it sounds like a big scary word sometimes. Do you agree with that?

Dr Paul Huleatt 02:29

Yes, it can. Absolutely.

Andrew Everett 02:33

But it boils down to, and I'll try to do a summary you can let me know if it's still accurate and factual, Paul, but medicine regulation is essentially enabling people and communities to go to pharmacies or wherever they get their medicines to buy them and expect the medicine to help them do what it says it says it's going to do, there's a degree of trust within this transaction that the medicine is safe, and that it is going to do what they want them to do. This sounds simple, but there are huge efforts behind the scenes, often where regulators work tirelessly to make sure people have timely access to safe and effective medicines they need. Medicines need to be approved for certain uses, where they're manufactured needs to be inspected, and there's an ongoing monitoring of medicines safety that's required. So why do bad medicines even exist? What even is a bad medicine to start us off Paul? 

Dr Paul Huleatt 03:29

So, before, before we go to that, do you mind if I say just make a couple of points about what regulators do?  

Andrew Everett 03:37

Go for it. 

Dr Paul Huleatt 03:39

Yes, so essentially, we regulate products that have therapeutic claims. So if you think about devices, that's everything from band aids to pacemakers, or vaccines, you know, think, think about our mRNA vaccines that we've had for COVID recently, and in medicines, that's everything from the ibuprofen pills that you might buy at a supermarket through to cutting edge Scylla gene therapies. So for health product regulators, our job is to maintain a balance and manage risk in that space. So you'll often hear about risk-based regulation. And on the one hand, we don't want to be a bottleneck to access. We don't want to stifle innovation disincentivise sponsors bringing products to the market. We don't want to overregulate, we want to reduce regulatory burden. But at the same time, we need to safeguard public health through ensuring only products that are high quality, safe, and efficacious, come onto the market in the first place, and that their quality, safety, and efficacy is ensured whilst they remain on the market. 

Andrew Everett 03:48

I guess we're going to focus today on what happens when that system that you've just described breaks down, when a bad medicine makes it onto a pharmacy shelf somewhere in the world. What is a bad medicine and how does it actually get on that shelf? 

Dr Paul Huleatt 05:02

So bad medicines we typically define as either being substandard or falsified. You'll often hear people talking about SF medical products. So substandard are also called out of specification. These are authorised medical products that fail to meet either their quality standards or specifications, or both. And when we talk about falsified medicines, these are what you and I and the general public would think of as fakes or counterfeit medicines. So the definition from the WHO is that falsified medical products deliberately or fraudulently misrepresent their identity, composition, or source. Now, these products affect every region of the world. Unfortunately, they tend to disproportionately affect poorer nations. They cause harm to patients, and they fail to treat the diseases for which they're intended. And this can lead to a loss of confidence in medicines, in healthcare providers, and also the health system. These substandard and falsified medical products have been reported to the WHO across all therapeutic categories, so medicines, vaccines, and in vitro diagnostics. And unfortunately, most prominently we see we see them penetrate in products such as antimalarials and antibiotics. And that can lead to or can contribute to antimicrobial resistant and drug resistant infections. They affect both generic products and innovative medicines. They can be found in illegal street markets and via unregulated websites. But unfortunately, also in pharmacies, clinics, and hospitals as well. The question of why they occur, I think this all comes down to the almighty dollar. So in the case of falsified medications, where there's an opportunity to make money, nefarious actors will produce them and try to sell them. In the case of substandard products, there are a whole range of possibilities, including manufacturers who make out of specification batches who don't want to dump the product and want to unseal and then, at the other extreme, you might have pharmacies or merchants in informal markets, where people sell expired medicines because they want to make money rather than throw them out.

Andrew Everett 07:25

Thanks, Paul, and I welcome your comment on the connection between substandard falsified medicines and antimicrobial resistance. Listeners may have heard about the poisoning events in Indonesia in 2022 or in Gambia in 2022. But this problem isn't a new problem. Is that right, Paul?

Dr Paul Huleatt 07:45

Yes, Andrew. That's correct. So unfortunately, this problem goes back almost 100 years. And to define it, in very simple terms, we have legitimate diluents that are used in syrup medications, like propylene glycol, and glycerin, that can be readily replaced with toxins like ethylene glycol, and diethylene glycol, which are typically readily available and a lot cheaper than the legitimate, legitimate excipients. So in 1937, in the United States, unfortunately, there were about 100 deaths due to the consumption of antibiotics that had been formulated with diethylene glycol, and that event led to the establishment of the US FDA. And from about 1986 onwards, we've had a steady stream of poisoning events happen around the globe. So India in 1986, Nigeria in 1990, Bangladesh from 1990 to 1992, Haiti in 95, Panama in 2006, China also in 2006, Bangladesh in 2009, Nigeria in 2009, India in 2020. And then last year, Gambia, Indonesia, Uzbekistan, and this year, Cameroon. And these are only events that have had deaths associated with them. There have been many more occasions where tainted syrups have been identified most recently as Monday this week, when a tainted product was identified in Zimbabwe. So this is an old problem, but it continues to recur.

Andrew Everett 09:19

That is a concerning list of events that affect people that are just trying to consume medicine to make them feel better. And as a result they they've got some unfortunate consequences and some as bad as death. I just wanted to I've seen a plot where the there's poisoning events that you've just listed out on a graph, I think presented by the World Health Organization that shows that these events that are notified are on the rise. Is that a fair characterisation that it's an old problem that seems to be escalating?

Dr Paul Huleatt 09:51

Yes, I think we've seen a very dramatic spike in the last six months of these poisoning events, and it's drawn our attention to it once more. The reasons for this remain unclear. But it's certainly an ongoing risk that these toxins can penetrate the supply chain of raw materials and find their ways and find their way into syrup medications. So if you'd like me to run through one of the more recent case studies, in Indonesia, in 2022, there were more than 200 deaths of children. In at the end of last year, on the 15th of October, there were media reports that began to emerge declaring of the Indonesian FDA declaring that diethylene glycol and ethylene glycol were not allowed in syrups and that they were looking into 20 cases of acute kidney injury resulting in death in Jakarta. By the 20th of October 2022, 99 deaths had been established, recorded and 200 cases of acute kidney injury were being investigated. There was a comprehensive testing campaign of syrup medications. By the end of October, the regulatory authority had discovered drums of propylene glycol from Dow Chemical Thailand had been used to hold the raw materials that had been used in the manufacture of these tainted medications. Then by the second of November, the WHO had published a medical product alert for eight products, some of these were subsequently found in Timor Leste and products manufactured in Indonesia were also found in the Philippines, although no deaths in those countries were confirmed from consumption of those products. Then on the 7th of November, the death toll was already 195. And it turned out that there was a chemical supply company in Indonesia who had been recycling drums from a legitimate supplier, Dow Chemical Thailand and filling them with tainted excipient. The fallout from that, obviously has been extreme, there's a class action lawsuit. The finger is pointed at the companies, the companies have pointed their finger at suppliers. The investigation goes beyond those commercial entities through to staff in the regulatory authority as well. So you can see that the focus after a tragedy occurs is very broad. And identifying the root cause is very difficult.

Andrew Everett 12:17

The numbers are staggering, and, and heartbreaking frankly. But help me out here, Paul. So we know that essentially liquid cough syrups in this instance, or some medicines in general, are not going to be what they say they are and potentially added intentionally by bad actors, which have been doing this for many years making their way into pharmacy shelves across the world. If we know all of this, why can't we stop it happening? Is it hard to detect these poisoning, you know these poisoning additives being added to it what are otherwise functional medicines? Is it there's so many medicines that need to be tested? Is it hard to attribute responsibility like you just mentioned? Where is it breaking down?

Dr Paul Huleatt 13:00

I think it's all of the above Andrew. So I think in terms of, if we focus on testing, at least the propylene glycol and glycerin do not have dissimilar properties from the toxins, ethylene glycol and diethylene glycol, so, your nose and your eyes and your mouth, aren’t going to detect them, your kidneys certainly will. But that means that too, for a manufacturer, visual inspection is not going to help. So, analysis of the raw materials is crucial. And this means that manufacturers have to use analytical techniques, very simple screening techniques from TLC, through to some more sophisticated screening methodologies, like something known as GC or GCMS. 

Andrew Everett 13:45

Right. And that's a more advanced technique that would be available to some but not all countries in our region? 

Dr Paul Huleatt 13:41

So yes, so for regulators, yes, for manufacturers it could be argued, and it certainly would be argued in high income countries that anyone who wants to make medicines should have the capacity to do this type of testing. For countries in our region, these are relatively in relative terms, expensive analytical techniques that they don't always have access to domestically. And that's why regional laboratory networks and things like programmes like the Pacific Medicines Testing Program that Australia runs is so crucial.

Andrew Everett 14:25

Yeah, let's talk about the Pacific Medicines Testing Program for a moment. We've spoken a bit about the worst-case scenarios with some horrifying numbers. But let's talk about a good news story, because we do have safeguards in place to detect and prevent some bad medicines making to market. So recently, the Australian Government's Pacific Medicines Testing Program, and colleagues in the Marshall Islands, they were part of a success story. 

Dr Paul Huleatt 14:54

Yeah, that's correct. So through the Pacific Medicines Testing Program, we work with countries to identify products, either through through pre planned testing campaigns or through complaints samples to be screened or analysed by our TGA laboratories. So we have state of the art sophisticated laboratories, and world class experts who work within those and we can provide analytical services to countries and on the back of the emerging crisis, global crisis at the end of 2022, the Pacific Medicine Testing Program was proactive and solicited samples from around the countries that they work with, and they discovered one tainted medicine, as you pointed out, worked with the country and with the WHO to communicate that information more broadly, not least of which is through a WHO medical product alert. The product was removed from the market in the countries where it was found. And the company responsible was subsequently shut down by the authorities in India. So this is certainly an example of a success story. But it also raises the issue of prevalence. So the more you look, often, the more you find. And unfortunately, in relative terms, we looked at a small number of products, and we found something so this is also cause for concern.

Andrew Everett 16:14

And we'll never know the potential impact of that medicine if it were to make it on market. So it's also hard to measure how much of a success story this actually is, but still definitely worth talking about. But there are other safeguards that regulators or Ministries of Health can and are using to protect a community. It's not just testing once, products on the market.

Dr Paul Huleatt 16:39

Yes, you're absolutely right. There are a range of organisations involved and measures that can be taken. So everything from customs law enforcement through to health products, regulators, like the TGA. Where through our suite of regulatory functions, we look at medicines before they receive market authorisation, and monitor medicines that are on the market, which return post market surveillance, which can incorporate elements of pharmacovigilance. 

Andrew Everett 17:08

And let's just talk briefly about what Australia is doing to support and work with and partner with regulators from the region to build these systems and to strengthen regulatory capacity. 

Dr Paul Huleatt 17:24

So with the support of DFAT, the TGA is delivering the Indo Pacific Regulatory Strengthening Program, where we work with counterpart regulatory authorities, other technical assistance providers and organisations like the WHO, to build capacity with regulatory authorities in a number of countries in the Indo Pacific and provide regulatory support to those countries that don't have regulatory authorities. As part of that, we work with our counterpart regulators on various regulatory functions that are defined by WHO’s global benchmarking tool. So from premarket, we look at market authorization, we look at regulatory systems, we look at legislation, we look at regulations, we look at the tools and the processes that they use to carry out those regulatory functions. We strengthen the technical capability of the people who are involved in in carrying out those functions. And in the back end, we look at things like pharmacovigilance and market surveillance recalls, inspections. So think about things like GMP inspection, as well.

Andrew Everett 18:40

So Paul, you're also currently acting as Australia's representative as Chair of the World Health Organization's Member State Mechanism for Substandard and Falsified Medicines, a role that later in 2023 you're going to finish up. So what actually is this Member State Mechanism and what gets done in that meeting? 

Dr Paul Huleatt 19:02

So the Member State Mechanism is our only global forum where countries can come together to address the issue of substandard and falsified medical products in terms of prevention, detection, and response. It was established in 2012, as per the World Health Assembly resolution 6519. And its goal is to address the problem from a public health perspective. So to promote access to affordable, safe, efficacious, and quality medical products, and to promote collaboration among the member states and also the WHO to deal with the problem. That's the goal. And as you pointed out, Australia is currently the chair of the steering committee. There is a plenary meeting, which is the meeting of the mechanism once a year, but the steering committee also meets three times a year to review and guide the activities of the mechanism. There are nine working groups and they look at every From building the capacity of regulatory authorities to developing global focal point networks. In terms of products, they look at traceability. There is another working group on detection technologies. We look at things like risk communication, and impact and awareness from SF medical products and emerging issues or growing issues like the proliferation of internet sales and informal markets. So you can see the fight against SF Medical Products has many fronts, and the member state mechanism is active on all of them.

Andrew Everett 20:38

It sounds like quite a busy place, and not just a forum for people to come together and talk. But did you have any, anything you're proud of in your time, as Chair or any interesting stories?  

Dr Paul Huleatt 20:51

In terms of the role of being Chair, we have to recognise that it rotates through the six regions of the WHO and the Western Pacific region therefore only gets to chair the mechanism, once every 12 years. So it's an incredible honour, and a responsibility that I'm particularly cognisant of, to have the opportunity to chair on behalf of Australia. And given that responsibility, I think it was very important that we took the opportunity on behalf of Australia to drive the work of the mechanism forward in that two-year period as far as possible. So there are a number of things that I think are a real credit to the steering committee, and the member states who work in the working groups and participate in plenary meetings that we've been able to achieve. Now the mechanism has been running for 10 years. And I think there's a lot to learn from that 10 years of experience. And it's not always easy to go back and do that. So one of the one of the things we've been able to do is get or advocate for, and get the buy in from the, from the mechanism for an independent review of the last 10 years, that was subsequently stewarded through the Executive Board meeting of the WHO, in January or February this year, and then through the World Health Assembly, also in the first quarter of this year, so that was particularly important. And I think the outcomes of that review will feed into another piece of work, important piece of work that we've done, and that is to transition some of the thinking and planning of the mechanism away from the two-year funding cycle of the of the mechanism to a broader long term strategic way of thinking about the work. And to go along with that strategic thinking we've tried to make the work of the mechanism, more outcome oriented, particularly in the working groups with the introduction of metrics and tangible outcomes, not just a iteration of the same thing, in each two year cycle. 

Andrew Everett 22:52

So, Paul, where do we go from here? Do you want to give us a glass half full or a glass half empty, closing remark? 

Dr Paul Huleatt 23:02

Well, I think I think it's glass half full. Andrew, to be honest, I think last year, given you well, you'd be forgiven at this point, considering everything that's happened over the last almost 12 months now that it's a very dark time. But as the saying goes, the darkest hour is just before the dawn, and I think this has given us all pause for thought and renewed impetus for addressing the problem of SF medical products. So that's positive. So I'm glass half full because I think there's a lot of opportunity. But that comes with responsibility to recognise those opportunities and be proactive in taking them.

Andrew Everett 23:33

Paul, you've convinced me, I'll leave despite the heaviness of this conversation with an optimistic frame in the in the hope and the knowledge that there's a lot of dedicated people like yourself and regulators from across our region working tirelessly to try and turn a corner and get on top of what is a truly devastating problem. So thank you, Paul.

Dr Paul Huleatt 23:58

And thank you, Andrew.

Andrew Everett 24:00

You've been listening to Dr Paul Hewlett speak about substandard and falsified medicines, or as I like to call them bad medicines. Paul explained how tragic poisoning events are a global problem, and that the tragedy experienced in Indonesia recently has affected far too many other countries for many years. Bad medicines seem to be on the rise, or potentially we might just be detecting and reporting more of them. We discussed how an Australian Government initiative the Pacific Medicines Testing Program has recently identified a bad medicine which potentially saved countless lives in the region. And despite the growing concern Paul closed with an optimistic note, we have new technology to detect and test poisonous additives. We have new tools to process this information. And we are sharing this these results at a global level through the Member State Mechanism and through the World Health Organization's global surveillance and monitoring system. Regionally, regulators are connecting and sharing information and arising to meet the challenge that substandard and falsified medicines pose. You can find the link a report that the World Health Organization's member state mechanism on substandard falsified medicines produced, and news articles on the events that occurred in Indonesia in 2022 in the show notes for this episode. Thank you for listening. I'm Andrew Everett from the Indo Pacific Centre for Health Security. We look forward to your company on the next episode of Contain This. Have a great day.

Contain This is produced by the Indo-Pacific Centre for Health Security. You can follow Australia's Ambassador for Regional Health Security, Dr Stephanie Williams, on Twitter at @AusAmbRHS. You can also find that link in the show notes.