Chair: Okay, so now it’s over to Jeremy Mean who is Group Manager, Access Information for Medicines and Standards at the Medicines Healthcare Regulatory Products Authority. I think is that right? Something like that anyway. So thanks very much, Jeremy, who’s going to talk about the MHRA regulatory process.
Jeremy: Thank you, and thank you to the organisers for this conference. I’ve been here since early this morning and so far it’s been a fantastic day with lots of differing views. I expect the views will be more differing as the day goes on.
I didn’t expect to get up here and quote Clive Bates, Clive Bates from the 12th of November 2013, that he wanted more and better products. That’s exactly what the UK Government wants, and so today what I hope to do is to take you through a journey, the thinking that the Government has been doing about the regulation of nicotine-containing products, how UK Government policy has developed and evolved, and what that means for the UK position on the EU Tobacco Products Directive which is still currently being negotiated, in fact it’s in the second trialogue meeting between the three parties that Linda mentioned is today, so you can think of those in Brussels thinking about where next to go.
So let’s think about regulation of nicotine-containing products in the UK. Maybe I should say a word about this clumsy term, nicotine-containing products. Wouldn’t it be much easier to say e-cigs? Well it would be much easier to say e-cigs if they were the only nicotine-containing products, if they weren’t the latest evolution of a nicotine delivery system that might not be the optimal one. We can look forward to all sorts of other forms of nicotine delivery, whether it’s needleless injections or it’s products that you inhale using dry powder, electronic cigarettes are just one form of drug-delivery device.
They may be around for a long time, they may not. What we need is something that will be a framework for those moving forward. Nicotine replacement therapy has been around since the 1970s and unusually it’s regulated in the same way all over the world. Sometimes in the States or the Far East they do things differently to how we do them in Europe, not with nicotine replacement therapy, it’s always been a medicine, all over the world, and this idea that it’s been completely static is not quite true, we started off with patches and gums, there are now mouth sprays and nasal sprays and tabs you put under your tongue, films you put on your tongue, all sorts of different things.
Now, nothing like the pace of development of e-cigarettes, but it’s not quite true to say that regulation has stifled it, more likely the pharmaceutical industry has not been as bold in thinking there is a market out there for them to develop. And why I wanted to mention this is the regulation of nicotine replacement therapy has of itself gone on a journey, from tightly controlled prescription-only medicines when they were introduced in the 1970s, full of warnings, full of the sorts of labelling that Clive mentioned, but if you look at them now they’ve over-the-counter medicines, you can buy them in the supermarket and the corner shop, they’re brightly coloured, they’re advertised on telly, that’s what medicines regulation can do. Every strength and every form is now available over the counter and they all have the harm reduction indication, and I’ll perhaps come onto that a little more. But medicines regulation is a flexible framework, it allows you to develop products that follow the science. It’s not a fixed set of rules on the face of the legislation, a maximum dose or a minimum dose, it’s an opportunity for the framework to evolve and develop as products do. In the world of medicines regulation everyone says regulation follows science.
All the commentators this morning produced evidence which informed the UK Government’s position, every one of them if you look at the information on the MHRA’s website that was fed into the Commission on Human Medicines Expert Working Group were considered, every paper we could find published across the world, and the objective is to produce safe and effective products that meet public health aims. Now, as those developments were going on in nicotine replacement therapy, the inhalator for example was licensed in the late 1980s, by the late 2000s ecigarettes were appearing on the market in number. Now all these products contain nicotine, probably about a similar amount actually, but only some of them are regulated by the MHRA, others are regulated by the General Product Safety Directive, which looks at things like labelling, whether they’ve got a skull and crossbones depending on how much nicotine is in them. They look at electrical safety, plugs and chargers and batteries and so on, but not really fit for purpose for these kinds of products. They have allowed the market to develop and it’s developed very quickly. There are very many products, whether very many products necessarily meets public health objectives is perhaps another question, but this growth in the market did lead UK Government, actually governments across the world, to think about regulation. And that’s a difficult and complex issue. That’s why these debates are going on across Europe, but also in the States the FDA is going to come to its position on regulating these products, and in other countries, other countries where these products have been banned, for all sorts of reasons. So some of the safety concerns that we’ve heard about here earlier, but also because they look like cigarettes and many countries have legislation which legislate against products that look like they’re being smoked. So there’s a variety of solutions, the UK has not jumped to banning or indeed imposing medicines regulation as some other member states have done immediately. We wanted to think about, what were the challenges of regulation? What did we really want to achieve? What we really want to achieve is safe and effective products that help to reduce the harms of smoking to smokers and those around them. We don’t want regulation for its own sake. We don’t want to impose something for no reason.
We don’t want to ban potentially useful products. We’ve listened to stakeholders; I’ve been meeting with e-cigarette manufacturers and importers since before ECITA was born when we started to engage and to really listen to stakeholders. We held a public consultation in 2010, partly because of the growing concerns around safety of products but also about the growing wisdom of harm reduction and the opportunities that Clive so eloquently pointed out, but also because of that harm-reduction indication. To cut down, to quit, but also to assist smokers who are unwilling and unable to smoke, and as a safer alternative to smoking to smokers and those around them. Very unusual for medicines regulation. No other medicine I know has an indication which talks about people around them or the benefits to other people. But then you see medicines regulation is very flexible. So the outcome of that consultation was that the public health community exclusively supported medicines regulation as a way of providing some safeguards around these products, to ensure that they work and that they’re safe. I won’t use the safety and efficacy words, people just want to have reassurance that they work and they are effective.
Now, we had also about 900 odd responses from users, from vapers, telling us some of the stories that we saw on the screen in the last presentation about how they’d revolutionised their lives, how they had found these products to work when no other would. And we listened, and we listened very carefully to that, because we do not want to remove products from the market which people potentially find useful when the safety evidence doesn’t support that sort of action.
So the MHRA, the Government once again didn’t move immediately to ban the products, didn’t move immediately to bring them into regulation; said clearly that they thought medicines regulation was the best way but decided to work with stakeholders, with a range of people, with some of the public health organisations who are here, the academics who presented this morning, right across Government with the Department for Health, Number 10, the Cabinet Office, Behavioural Insights Team, right across the spectrum of Government of what the right form of regulation for these sorts of products might be. We agreed to undertake additional research steered by an expert working group, thinking about the levels of nicotine and whether it really made sense to regulate by a level, to look at the nature and quality of products on the market. We brought together all the data from right across the globe that’s published on the safety and efficacy of these products.
The actual use of the products, how people were actually using them. Their efficacy, and we heard a little bit this morning about the extent to which there is not as much evidence as we’d like on any of these things but particularly on efficacy, and the potential impact of bringing them into regulation. Now, I’ll give you a very quick summary of the findings because I want to move on to think about regulation a bit more, but the consistent evidence from a variety of sources was that products out there today have variable nicotine levels within them that don’t match the labels, some may or may not have batch numbers but if they do they rarely match, the delivery of the nicotine is highly variable from batch to batch from product to product, that the unlicensed products generally speaking are not well made, the ones we’ve looked at do have leaking nicotine liquids in them, they are poorly manufactured, they are easy to break, they are easy to make them overheat.
There’s very limited evidence of their effectiveness, their most recent Lancet study was that they are about as effective as nicotine replacement therapy, so they’re not a magic bullet. They have the potential to be, and we want them to be, but certainly the products that are out there now are not. And we also listened to those who are involved in the general product safety directive in terms of imposing those standards, local trading standards, the Fire Service, concerns about exploding batteries and chargers, who all told us that they thought the product safety directive provisions were not fit for the purpose of regulating these sorts of products.
So a bit more about medicines regulation and the position that the UK Government announced on the 12th of June this year. Medicines regulation can be proportionate. Medicines regulation is a spectrum, from something that regulates cutting-edge biological vaccines that are created cell from nothing, to over-the-counter medicines at the other end of the spectrum, and it’s a framework that can accommodate all those different things because the maximum and minimum levels and all those sorts of things aren’t specified in law, they evolve and follow science. Labelling and product information doesn’t need to be boring, it doesn’t need not to have trade names. Sale and supply in the UK, all our over-the-counter medicines can be available in the supermarket and the corner store. In fact everywhere you can buy cigarettes you can buy OTC medicines, and they can be displayed by the way. There are advertising controls in medicines regulation which again are not fixed. They don’t say you will do this, you will do that, the law says you must promote the rational use of the product, and within that there’s a huge amount of flexibility into how that’s done, and when you look at advertising on the telly for OTC medicines you will see that it is innovative, exciting, fun, all the things that medicines regulation is in fact. (Laughter) Safety monitoring, we just don’t know enough about the safety of these products. What medicines regulation gives us is a framework so that over time we can learn about these things. When we’re licensing medicines often we don’t know about the safety in the exposure to a wide population, but we learn about it because there’s a framework there that requires if any issues occur the MHRA is told. There’s an obligation on the marketing authorisation holders. We can and have been monitoring every published study since we did our own work, but actually reports we get from users are really helpful in monitoring long-term safety. Many times you will find that we learn more about the safety of drugs over a period of time and that we can do something about it, we can exclude certain patient populations or certain ages of people or certain groups of people that will make it much safer for the products to be used. But if we haven't got a framework in place for us to learn about that then there’s no opportunity to use those risk management tools.
So let’s think about medicines regulation, this terribly burdensome thing that means you’ll never ever get a product to market. Frankly it’s just not true. If you think of something as exciting as athlete’s foot treatments it’s probably about half the size of the current market for e-cigarettes, it’s maybe £60/70 million annually. But you can get a gel, a cream, a spray, a tablet, a powder, you can get them in five different active substances. You can get branded ones, you can get generic ones, you can get them at the supermarket. They’re brightly coloured, they’re nice labelling.
If you think about something as exciting as antiseptic cream which I often do, you can get them in every shape and form. This market is worth maybe £10 million, maybe 10%, maybe a bit less, than the e-cig market, but there are supermarket varieties, there are household names, these products change their livery on a regular basis. If you think of OTC medicines like hay fever products or cough and cold products they change their liveries every year, they’ve got new delivery devices, they’re constantly innovating.
The OTC market is fare more like a fast-moving consumer goods market than a high-end medicines market. And medicines regulation can deliver that. If you go into your supermarket and walk down the OTC medicines isle you will see a variety of brightly coloured products that are advertised on the television, on the radio, attractive, some niche products, some wider products, but a thriving market that’s worth £2.5 billion in the UK each and every year.
Now, we heard a little bit about safety issues earlier on from our esteemed academic panel. The MHRA has never been shroud-waving about the safety of these products. That’s not to say there aren’t safety concerns. We have had yellow cards, this is the MHRA’s reporting scheme for where healthcare professionals have concerns about whether there is a link between something they’ve seen, a side effect or an effect and a product that somebody has used. We’ve had about a dozen reports, and some of these have been really quite serious, things like lipoid pneumonia, interstitial lung disease, palpitations, and the obvious vomiting, nausea, and those sorts of things from overdose, probably from defective products. But we’ve never drawn attention to those, we’ve never said we must regulate for safety purposes. The focus actually has been on effective products that work and help to reduce the harms of smoking. We heard a little bit this morning about the risks of using these products for those who smoke, and the MHRA shares that view. These products should be for people who smoke, and the relative risk to smoking is infinitesimally smaller, there’s no question about that, but it’s not for non-smokers, for never smokers, and we have started to see some evidence of an increase. I’ll give you most of it is a theoretical risk, but we have seen some studies in the States showing a doubling of the number of young people who have tried electronic cigarettes, and yes they might have tried cigarettes if they hadn’t tried those. But the story is starting to change from one where these products first emerged and their typical audience was in their 40s, well off, well healed, the sort of data that Lynne presented earlier, and we are starting to see more and more younger people using them, so we need to think about that, we need to monitor whether there is a gateway effect, and we need to be able to do something about it if there is. Without a regulatory framework we wouldn't be able to do that. And the same is true of smoking maintenance. This is the theory around the extent to which at the moment these products, we want them to be targeted at smokers but we heard this morning about the risks associated with introducing new users of nicotine or reintroducing people to the use of nicotine or acting as a gateway into smoking.
Now, I agree, these are theoretical risks and there isn’t a lot of evidence for them, but we want to be able to have a framework that allows us to learn the lessons from the past, we would have never allowed cigarettes onto the market, we can’t make the same mistake again. So that brings us on to the Tobacco Products Directive, as I said, currently in negotiation in its trialog as we sit here this afternoon. Part of a wider set of measures much broader than e-cigarettes, there’s one provision, nicotine containing products. Interestingly this was published in December 2012, a full six months before the MHRA came out with the Government’s position on medicines regulation. It had broad support from all the member states in the Council working group, wasn’t controversial at all, easy decision to make for the member states.
It was only when it came to the Parliament that the issues came up in relation to nicotine containing products and as Clive Bates has said, what they’ve produced is something of a dog’s dinner. It allows for medicines regulation for products that make claims, but for others it has an odd set of controls, some of them a bit like tobacco ones, some of them a bit like medicines ones, reporting. The provisions are conflicting, they would apply to licensed medicines as well as to other products. They attempt to produce some sort of regime but the problem is, when you think about regulation as I do all the time, what you need is a system, you need a framework in place. It’s no point having reporting if there’s no-one to report to and then if you report it something can’t be done in it. You can have reporting saying it’s got all sorts of toxicants in it but if you can’t suspend a licence, if you can’t close a factory, if you can’t do something about it there’s no point in knowing. You need regulatory levers and controls to make a system work. That’s what medicines regulation gives you and it also gives you a future proofing for products that people in this room might not have even imagined but will doubtless come.
So the UK’s position continues to be that we see medicines regulation as the right framework to get more and better products, to get products that will support smokers to reduce the harm of smoking to smokers and those around them. We stand ready to licence products now, there’s a couple going through the system. I’ve met with between 20 and 30 companies interested in pursuing a licensing route. To support true innovation. True innovation is not the next flavour, the sweet shop bubblegum flavour, it’s about engineering the size of droplets so that the flavour stays in the mouth and the nicotine goes to the lung where it can relieve the craving, that’s true innovation, and that’s what a medicines framework can deliver. We support getting a Europe-wide solution to the regulation of these Page 47 of 102 products, it is unfortunate for the smoking community of Europe that we don’t have a single answer on this, so the UK will continue to press in the trialog today and as the negations go forward, hopefully concluded by March with the Tobacco Products Directive going through with a single level playing field for these sorts of products. So I’ll stop there and thank you for listening. (Applause)
Chair: Thank you very much indeed, Jeremy, for a very informative overview of the MHRA’s position. We have got time for one or two questions, so I saw a hand up there first and then over here. Quite a few questions. Now this is going to be an issue we will return to at the end of the morning so if we don’t get time for a question, don’t worry.
Katherine: Thank you. It’s Katherine Devlin from ECITA. We sent you recently some costs analysis which we also published about the actual cost based on four case studies of actual businesses operating in this sector at the moment with electronic cigarettes, looking at the cost for achieving a medicinal licence for the products, and in each case it was going to cost more than the entire market value. How is that proportionate?
Jeremy: Okay, thank you for that question, because it does give me an opportunity to say that I am disappointed that I can’t give you as much information as I would like to give you about the costs associated with regulation, and part of that is because it is evolving as medicines regulation gives us the opportunity to do. And I’ll give you an example of this. One of the issues that was raised earlier in the discussion today was flavour and how flavour is important and how for this particular market it’s important to keep that moving and keep a number of flavours and keep innovating in that area. Now, we recognise that. In medicines regulation as it currently stands it hasn’t really been an issue, there hasn’t been products where people have been clamouring for lots of different flavours, so we’ve been thinking hard about how we can make the medicines regulation framework deliver that. So we’ve been thinking about, once you’ve got a product licence, adding flavours by means of variation to that licence, not creating a new one but with a small addition to each licence so that we can make the framework work. Now, we haven’t been able to publish that as readily as I would like to because what we’re trying to do is to show some leadership in Europe, to design a framework that other member states will be able to sign up to that won’t be burdensome in different parts of Europe and to say that’s the way to do it. So we’re trying, we’re looking at how to keep the costs and burdens of regulation down, but it is an evolving piece and will be going forwards.
Chair: Last question.
Steve: Hi. Steve Stotesbury, Imperial Tobacco. Jeremy, I have some sympathy for you as you look at the European process, your frustrations are shared, I think, by many in this room. But looking back to your announcement in July you cited the European Product Directive as one of the things that you would pin medicines regulation on. If that changes in the trialog process will the position of the UK Government change and how will that develop as a result?
Jeremy: It’s a dynamic process, negotiation. Whatever legislation is produced, the UK will have to abide by. The current position and the one the UK Government is hanging out for is medicines regulation for all nicotine-containing products, as in the general agreement that all member states signed up to, and we’re not thinking about any other options.
Chair: Thank you very much, Jeremy. We’ll stop now and move on to the final speaker this morning, and then we’ll have more questions. So I know a few of you did have your hands up, we’ll have more questions at the end in the Q & A session.
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