Analysis of the MHRA guidance: “Licensing Procedure for Electronic Cigarettes and Other Nicotine Containing Products (NCPs) as Medicines”

By Katherine Devlin and Tom Pruen

 

This is appearing rather belatedly, but is our analysis of the guidance provided for those who wish to seek an MA for electronic cigarette products. It was produced on the 1st of August, immediately following the publication of the guidance by the MHRA.

 

Introduction

The MHRA’s guidance1 is aimed at assisting vendors of NCPs in successfully applying for a Marketing Authorisation for their product(s). Assessing the applicability of this advice to NCPs other than electronic cigarettes is outside our remit, and no comment is made on this.

The MHRA begins its guidance by declaring uncertainty as to the final form the EU regulation will take. Since there is still debate at the European level as to whether electronic cigarettes should be reclassified as medicinal products, there is the possibility that the MHRA’s attempt to pre-empt the regulation may yet have an embarrassing lack of support at EU level. Certainly, France has expressed reservations about this course of action, in part because, in France, this would limit the sale of electronic cigarettes to being through pharmacies only. The same is true of 20 of the 28 EU Member States.

Presumably to avoid this, the MHRA is suggesting that applicants should apply for Marketing Authorisations (MAs) on the basis of presentation (i.e. should make a medicinal claim which will require testing for efficacy). This evades the current debate in Europe, as well as the questionable legality of determining electronic cigarettes as medicines by function. Regulation as a medicine by presentation is universally accepted as a legally viable option; it is the regulation of the products in the absence of medical claims that is legally questionable (according to the Opinion of Sir Francis Jacobs QC2).

The potential future importance of the difference between classification as a medicine by function, or by presentation, is not mentioned in MHRA’s guidance. This is likely to mislead applicants who may not understand that they would be effectively ‘trapped’ by having made medicinal claims for otherwise non-medicinal products.

The vast majority of the advice consists of links to existing documents on the method of applying for an MA, and does not discuss how these relate to electronic cigarettes (or indeed other NCPs). The Q&A section does, however, attempt to clarify the position as regards electronic cigarettes.

Key points

 

  • Emissions testing would require that nicotine liquids are only sold for use on specific devices – this is not the way the market currently operates;
  • Flavours without available literature on inhalation would be impossible to license, even if there is also no evidence of harm;
  • The cost of a single SME electronic cigarette company applying for MAs for its products (£315m, minimum) exceeds the total value of over-the-counter NRT market (£100m);
  • Ability of users to combine different products (an important aspect of the current market) is extremely problematic within the medicines framework in many areas
  • This user combination of products will make pharmacovigilance effectively impossible;
  • Medicines regulation completely ignores electronic cigarettes that do not contain nicotine – even where the devices are the same;
  • The creation of two completely different regulatory frameworks will increase the cost and difficulty of regulation;
  • There is an absence of evidence that such expensive and complicated regulation is actually required.

Detailed analysis

The first question is “What is involved in the marketing authorisation application – what do I need to submit?

This provides guidance on literature searches and pharmacokinetic studies that would be expected. However, it also states:

 “The safety of the product can be supported by literature only, assuming that the vapour produced by the device does not contain any components that may raise concerns and that the literature data supports the safety of all components of the formulation via the inhaled route.”

 This is directly contradicted by comments made in a face to face meeting between ECITA and the MHRA on the same day that the guidance was published. Amongst the MHRA representatives at this meeting was Dr Ryan Tomlinson, Unit Manager of the Product Lifecycle Assessment Team, who, we were told, would be assessing any applications from electronic cigarette companies. Dr Tomlinson said that not only does the MHRA have concerns about the potential for acrolein and formaldehyde in the vapour due to publications in the literature, but it has not had any data submitted to it on this point; in his words: “we don’t know” if the products of vapourisation are acceptably safe. (We would suggest the published literature, particularly a recent meta-study perform by Dr Igor Burstyn3 indicate that there is good evidence to suggest that the products of vapourisation are acceptably safe). When ECITA pointed out that the emissions from an electronic cigarette would depend on both the liquid used and the device used to vapourise it, Dr Tomlinson suggested that data would have to be generated for each liquid and every device it was intended for use in. Given that there are upwards of 20 atomising device designs currently in widespread use, this would require either that the applicant conduct 20 sets of testing for each nicotine solution that they placed on the market, or that the applicant restrict such liquids only for use in a single specified device. This is not the way the market currently functions, and would not fit with the expectations, needs, or use-patterns of consumers.

There is also very limited information in the literature about the safety profile of inhaled flavourings, making such a search much more problematic than the MHRA implies.

Since food flavourings (in order to be considered safe for use in food at the levels found) must have a plausible method of metabolism or excretion in order to be safe in food, there is limited prospect of them being dangerous if inhaled. It is also important to note that the quantities of flavoured nicotine solution consumed in a day are quite small, with almost every user consuming between 2 and 5 millilitres per day (approximately 2 to 5 grams) of ‘eliquid’, containing at most 20% flavourings. This would result in users consuming no more than 0.4 to 1 millilitre (approximately 0.4 to 1 gram) of the flavourings over the course of 24 hours. (The amount of flavouring added is usually closer to 10%, so this represents the most extreme example.) The MHRA position, therefore, is a prohibition on flavours that cannot be proven to be safe based on existing data, rather than a more sensible prohibition on flavours that have been proven dangerous, or those that are proven so in the future.

 

This point is also addressed in questions 3 and 12 “What do I need for the non-clinical (safety) part of the marketing authorisation application?” which also discusses the potential problem of leaching from the atomising device into the liquid/vapour, and “Do I need a marketing authorisation if my product is an e-liquid or nicotine liquid only?

 

The MHRA guidance states:

 “A comprehensive evaluation of the potential extractables and leachables originating from all components of the electronic cigarette should also be provided, with associated toxicological review.”

 and

 “It would thus be possible to apply for a MA for the nicotine liquid only. However, it would be necessary to demonstrate that the liquid is safe and effective in specified electronic cigarettes. Furthermore, such electronic cigarettes would need to be licensed.”

 How this might be achieved, when – in the current market – a large proportion of users buy the liquid and hardware separately (and not infrequently from different vendors), is not addressed. We can only assume that this would again require the liquid to be sold for use only in one or more specified licensed devices. As Dr Tomlinson said during the meeting between MHRA and ECITA, “It would become very complicated.”

 

Question 4 addresses efficacy: “What do I need for the clinical (efficacy and safety) part of the marketing authorisation application?Oddly, this does not appear to make any reference back to the claim made when presenting the product (while the MHRA is taking voluntary applications on the basis of presentation), but assumes that nicotine delivery is the key measure, which is to treat the product as a medicine by function. The guidance does, however, then state that the product must “demonstrate safe and efficacious levels of nicotine for each claimed indication”, which seems to contradict this. Furthermore, it does not provide any useful information on the MHRA’s stated intent to regulate the products by function (i.e with no claims made). The bulk of the evidence required for this, according to the guidance, is comparison of bioequivalence of the product with an existing medicinal NRT product, in a small scale clinical trial. The form of these trials was discussed at the meeting between MHRA and ECITA, specifically concerning the effect this might have on the pace of innovation within the market, particularly with regard to the introduction of new electronic cigarettes. During this discussion, Dr Tomlinson informed us that these studies (as well as lab testing) would need to be done to determine if a design change to a product would make it sufficiently different to ‘trigger’ a new Marketing Authorisation. This would have to be done prior to placing a new product on the market, and the clinical trial alone, according to the MHRA estimates, would cost between 50 and 100 thousand pounds.

This would clearly have a negative effect on innovation within the market.

 

Question 5 addresses the regulation of the electronic cigarette hardware as medical devices:

 “The MHRA considers the part of the electronic cigarette containing the battery together with any associated charging accessories to be a Class IIa medical device as an active therapeutic medical device.”

 However, a significant proportion of electronic cigarette products are sold with nicotine supplied separately from hardware (i.e. the liquid is sold separately from the hardware it is to be used with). Where this is the case, the MHRA has stated (in question 10 of their guidance) that if an electronic cigarette contains no nicotine, and makes no medical claims, then they do not intend to regulate it.

This would create a situation where the same hardware would be on the market, but regulated in completely different ways, solely on the basis of the inclusion of nicotine. This places a disproportionate burden on those companies who supply prefilled products, and since in most cases the same hardware would be available with much lighter regulatory costs, prevent such companies remaining competitive.

This combination of heavy-handed and expensive regulation, while simultaneously allowing the current state of regulation to continue will also increase the problems of enforcement, since in order to determine how a product should be regulated, it will first require a determination as to whether or not it contains nicotine. This will make the role of the enforcement agents (Trading Standards Officers) much harder, and increase the costs of enforcement, since samples will have to be analysed for the presence of nicotine prior to even being sure which regulatory framework applies.

Question 6 addresses the costs of an MA, with a link to the MHRA table of periodic fees. This however provides rather less information than the costs estimated in the MHRA’s “Impact assessment to support the UK’s position in EU negotiations on the regulation of Nicotine Containing Products, which are currently being considered along with changes to the Tobacco Products Directive4, which estimates the combined cost of an MA application at between £215,000 and £350,000 per application. Since the MHRA states that “An electronic cigarette would be expected to be a so-called complex application”, it is not unreasonable to assume that the costs would be at the upper end of this estimate.

This led to a situation where an ECITA member company contacted the MHRA directly, and was told that they would require 900 MAs to cover their product range. Based on the MHRA cost estimates, this would cost £315,000,000 purely for MAs. This does not include the associated costs of GMP compliance, nor importing, wholesale, or pharmacovigilance fees, which would also add significant costs. It also takes no account of future costs, such as R&D into new products, which would also require significant expenditure.

This is the cost for a mid-sized company with a turnover of around £5 million. Clearly, it is not possible for this type of company – which is very typical of the SMEs which make up the electronic cigarette industry – to invest such an excessive amount of money.

In its document “Proportionate regulation5 the MHRA states that the value of the over-the-counter market in licensed NRT products is £100 million – less than the cost of a single electronic cigarette company applying for MAs for its product range, and with no guarantee that it will receive them.

It is also not clear why electronic cigarette companies should engage in pharmacovigilance for their products, when tobacco cigarettes – the most direct competition as a nicotine delivery method – do not, despite the very clearly demonstrated harms caused by smoking. It is also not clear how the MHRA intends to apply pharmacovigilance in an industry where a consumer can buy the three components of an electronic cigarette (battery, atomiser and nicotine solution) from three completely unrelated suppliers (except that, as noted, the current market would be destroyed by the MHRA’s regulatory proposal). It is difficult to reconcile this with the MHRA statement that “The cost of regulation need not affect price or competition…”.

This is precisely why the vast majority in the industry, and also the consumers of these products, view medicines regulation of these products as a de facto ban.

This does not appear to be proportionate regulation by any measure, particularly since the MHRA has not made a compelling argument that electronic cigarettes need to be shoe-horned into medicines regulation – despite the demonstrable lack of ‘fit’. The fact that the electronic cigarette industry covers such a vast range of products, supplied with and without nicotine, makes it particularly inappropriate to apply the medicinal regulatory framework, since this would leave all non-nicotine containing electronic cigarettes under an entirely different regulatory regime. If the MHRA considers the current regulations so unfit for purpose as to require the sledgehammer of medical regulations, why are they so willing to leave products on the market under the current regulatory framework?

Perhaps this is because, despite the concern they express over the current regulations, they have stated in their published documents:

 

However, as yet there is an absence of scientific evidence that shows long term harm to health is occurring in reality because of product safety6

While contaminants in ENDS have been identified, and the long term health effects of inhaling ENDS vapour are unknown, so far there is an absence of evidence that shows that these problems create significant harm to health.7

Safety concerns have been reported. Given the extent of use, however, and despite the lack of a formal reporting mechanism (such as the yellow card scheme), these do not of themselves suggest a major public health concern.8

Given the low toxicity of nicotine at the doses observed and the fact that long before any dangerous levels of nicotine concentration could be reached, an over-enthusiastic user would be warned by nausea, there is little concern that e-cigarettes can harm their users by delivering toxic nicotine levels.9

 

 

 

 

 

 

 

 

5 http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con286850.pdf (Note also, on this document, that ‘Light Touch Regulation’ has been recast as ‘Right Touch Regulation’.)

Posted in Uncategorized | 3 Comments

The Daily Fail strikes again

By Tom Pruen

The Daily Mail has a considerable history of reporting on e-cigs that is not so much poor as pathetic (for the past history of the Mail’s ineptitude on this subject, Try our blog here, and here, and Clive Bates complaint to the Press Complaints Commission (PCC) here, which was resolved in his favour).

It seems that the Mail are not only so lacking in journalists that can do research that they are happy to publish other peoples press releases as verbatim truth, but also that these journalists feel the need to add in their own interpretation of the press release. Sadly, it is immediately evident that these reporters lack the basic knowledge which would make these interpretations anything other than scaremongering nonsense.

The Mail’s headline is “E-cigarettes are as harmful as cigarettes and could cause cancer, claims study”. Unfortunately, however, this is not what the study claims, nor is it what they found. Of the varied models and brands that were studied, some had levels of a single potential carcinogen that rivalled those in traditional tobacco cigarettes. They did not find many of the thousands of other carcinogens in tobacco smoke. It is therefore incorrect to claim the E-cigarettes are as harmful as tobacco ones, based on the evidence in this study. It does not take an expert in toxicology or risk assessment to discern this; it is well within the grasp of any educated individual.

It is true to say that e-cigs do appear to have some slight risk associated with them, something which we would agree with. The study also calls for further research, which we would also agree with, since if the risks can be reduced even further, it can only be a good thing. There is nothing in this study to suggest that our long held position is incorrect, however. E-cigs offer massively reduced harm compared with tobacco cigarettes, and offer a huge potential for smokers to be able to choose, for themselves, a safer alternative.

Given that this headline is similar to the last one, “E-cigarette ‘can cause more harm than smoking’, experts say” and the evidence to support it is just as lacking now as it was then, we expect the verdict of the PCC to be very similar. What this means that in contrast to the big headlines the Mail are currently misleading people with, in a couple of months, they will publish a small paragraph (probably virtually identical to this one) retracting it. But by then, of course, the damage is already done, and people will have been dissuaded from switching to e-cigs, or even worse scared into swapping back from e-cigarettes to the deadly tobacco ones.

This is journalism that is shoddy to the point of potentially causing actual harm to consumers.

So there we have it, the Daily Fail – where having a scary headline about electronic cigarettes is more important than anything resembling the truth – seem to be a clear example of why there must be controls on a free press.

We can only hope the PCC insists on a more robust retraction this time.

*Update*

The Mail have since modified the news story to make it a little more accurate, but it still does a very poor job of providing accurate information.

Posted in Uncategorized | 1 Comment

The full text of Sir Francis Jacobs QC’s Opinion on the legality of medicines regulation of electronic cigarettes in the revisions to the TPD (and elsewhere)

Please be patient while the embedded document loads.

Posted in EU, MHRA | 7 Comments

Sorry… WHO??

By Vicky Grant

Yet another ‘damning’ article, written by the World Harm Organisation, was published today and yet again they have singularly failed to demonstrate any understanding – or even ability to read! Why is it that, with all the research out there in the ether, the WHO is incapable of finding it, even when sent this information directly? So I shall endeavour, World ‘Health’ Organisation, to fill in some blanks for you. (Don’t worry – I’ll use small words, and try to communicate plainly.)

Vapers, correct me if I am wrong, but I have never heard of, nor experienced a cartridge filled with 100mg/ml strength of nicotine!? In fact this would be not only stupid, but very cost ineffective, from the point of the manufacturer and/or supplier. Maybe, rather than making this stuff up, the WHO could spend a little time purchasing a few of these items so that they could see for themselves, or better still actually DO some unbiased research on the products they ‘believe’ to be, and publicly decry as, so terrible. But maybe I am missing the point, and I digress.

Now this makes my blood boil…. ‘The safety of ENDS has not been scientifically demonstrated’ Have these people been living under rocks all this time?? Are you seriously telling me that NO scientific research has been done on the safety of these products? Was I imagining listening to Professor  Jean-François Etter, make an unbiased presentation of his research on electronic cigarettes at the ENVI workshop? (Link to Professor Etter’s thoughts.) Clearly I must have, since his research does not actually exist! The fact that Dr Roberto Bertollini, Chief Scientist and World Harm Organisation representative, was sitting on the same panel, indicates he had either fallen asleep, had his fingers in his ears, or just simply didn’t understand that he should have been paying attention. If you wish to know more please cast your eyes over this.  The fact that this research would have probably landed on all their desks, prior to the event for them to have a read through, means that the research probably contained information that the World Harm Organisation doesn’t want to hear.  Now, you see, if this was the only research done, I could probably find it in my heart to forgive them for missing it…. But it’s not! There are many other pieces of research and reports out there for all to see:

Dr Tobias Schripp performed a study, ‘Does e-cigarette consumption cause passive vaping?’ which researched the effect of vapour on indoor-air and second-hand vapour.

Dr Maciej L. Goniewicz has done another research paper: Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Again, this examines the safety of e-cigarettes.

Oh look!  There are 2 research papers I have managed to find and there are more out there, so why is it, I ask myself, apparently completely impossible for the World ‘Health’ Organisation to find this information for themselves?? In my honest opinion, it isn’t that they haven’t read this – and more.  It is that, for some reason, it does not say what they want to hear.

So why is the WHO still bleating on about not knowing anything about e-cigs and vapour? Is it because of the money that stands to be lost by the big ‘I am’s’; the health of the world’s citizens; or (more likely) due the fact that they have considerable quantities of ‘egg on their faces’, since it is the smokers themselves – yes, those very pariahs so resoundingly reviled and viewed as a scourge by the WHO – who have sounded the death knell for deadly tobacco smoking? All by themselves? Without any help from the Public Health Industry, the Tobacco Control Industry, or the WHO?

Well good on you, WHO. You should feel embarrassed; you have done nothing; you continue to do nothing to help. The best thing to do would be to slither off, back to your rock, and let the people decide if electronic cigarettes are right for them to use, because – let’s face it – we have found something miraculous all by ourselves. And all you can do is scaremonger and watch your coffers empty away. You have seriously lost sight of your role in public health. According to your website, you are “responsible for providing leadership on global health matters, shaping the health research agenda…”.

Isn’t it closer to the truth that you are responsible for making bucket-loads of cash for your pharma buddies from the suffering of others??

I will leave that to you to answer, but know this: others will make up their own minds and judge you on your actions.

Posted in EU, FDA, MHRA, Uncategorized, WHO | 8 Comments

Counsel Opinion Confirms No Justification for Changes to E-Cig Regulation

Sir Francis Jacobs QC, President of the European Law Institute and former Advocate-General to the European Court of Justice describes the proposed ban on e-cigs as “an unreasonable measure which is liable to be annulled as being contrary to the principle of proportionality and/or the principle of non-discrimination.

At the request of ECITA (EU) Ltd, Sir Francis Jacobs has provided his expert Opinion on the Commission’s proposals for a revised Tobacco Products Directive, as they pertain to electronic cigarettes. There are one or two surprises, but it comes as no surprise whatsoever to the growing community of vapers, who have already made the switch to electronic cigarettes, often entirely replacing their smoking habit, that Sir Francis is of the opinion that the proposed change to the regulation of these revolutionary products:

represents a very extreme and intrusive form of regulation.

In summary, Sir Francis concludes:

As far as we are aware, those (few) national courts that have addressed this issue to date have held that, on the facts of the cases before them, electronic cigarettes are not medicinal devices.”

Elsewhere in his Opinion, Sir Francis specifically mentions the MHRA in the UK:

In the UK, the MHRA has recently announced that it intends to subject electronic cigarettes to this [medicinal] kind of regulation by 2016. [...] we would expect future [court] decisions to follow the clear trend of the existing case law, which excludes them from the definition of medicinal products by function on the basis that they are effectively a substitute, not a cure, for conventional smoking.” [Our emphasis.]

Sir Francis finishes by stating:

…we are of the opinion that by effectively excluding a significant proportion of electronic cigarettes from the EU market Article 18(1) is manifestly inappropriate to the objective of removing barriers to intra-state trade and thus contrary to the principle of proportionality, and is also unjustifiably discriminatory towards manufacturers of electronic cigarettes by comparison with manufacturers of tobacco cigarettes. This provision of the revised TPD would therefore be likely to be invalidated by the Court of Justice on a reference under Article 267 TFEU.” [Our emphasis.]

Time for an honourable climb-down from the proponents of this proposal, methinks.

Posted in EU, MHRA, WHO | 15 Comments

Propaganda by press release

By Tom Pruen

A press release has been issued by Corporate Europe Observatory (CEO). CEO describe themselves as “a research and campaign group working to expose and challenge the privileged access and influence enjoyed by corporations and their lobby groups in EU policy making”

To the outrage of everyone here at ECITA, they appear to have assumed (on the basis of no evidence) that the electronic cigarette industry and the tobacco lobby are at least allied, and possibly one and the same.

The truth is that there are very few tobacco companies currently investing in the EU electronic cigarette market – and none of the ones who are is a member of ECITA. In point of fact, the only major e-cig company owned by a tobacco company is also the only one currently seeking approval for its products as a medicine. The tobacco lobby and the e-cig industry are not fighting the same corner here.

To put it simply, the current EU proposal to regulate e-cigs as medicines is APPROVED BY BIG TOBACCO – and OPPOSED BY THE E-CIG INDUSTRY.

Millions of Euros are quoted for the funding of big tobacco lobbying, but other than by implication, no mention is made of how much the e-cig industry is spending. Now, I cannot speak for those companies outside of ECITA, but for those within it:  Our spend on ‘lobbying’ (much of which is spent on travel to and from Brussels for meetings) is in the low tens of thousands. We are not some sort of troll-like corporate giant, bludgeoning people with sacks of money – we are the little guy in this fight.

As for the talk of ‘Astroturfing’ – all of us here at ECITA find this extremely offensive! The community of e-cig users (vapers) PREDATES the forming of our association. All of us were members of that community before forming the trade association to help OUR suppliers. All of us still emotionally belong to that community – not the other way round!

And on that note, I dread to think how completely outraged the community is going to be by this.

This is the thing that the pencil pushers of all ilks seem unaware of – the community of vapers is active, and extremely passionate. I cannot think of any other product that has such huge support from its users, not because the industry has brain-washed them, but because these are people who feel that these products have really changed their lives – and maybe even saved them. These are people who have read the scientific research, done the homework – and REALLY, REALLY care about this issue.

This press release is an insult to not only the electronic cigarette industry (we can take it) but it is a deathly insult to the millions of everyday vapers who have attempted to engage with the political process – exactly as they are supposed to!

CEO has clearly failed to do any research at all – and their prejudice is insulting to me, my colleagues, and ESPECIALLY to the ordinary vapers.

This press release is a travesty.

Posted in EU | 2 Comments

The World Health Organisation: To idiocy and beyond.

By Tom Pruen

On Philippine television (video available on YouTube) the following statement was made:

“The most dangerous thing about this product is that the nicotine goes directly to the lungs while regular cigarettes have a filter. With this delivery device the nicotine goes directly to the lungs.”

Now if this was the statement of some well-intentioned but clueless member of the public, it would be wrong, but understandable. However, this was the pronouncement of a doctor (of what, I am not entirely sure, given the complete lack of knowledge expressed in this brief statement, possibly a PhD in media studies?); even worse, a doctor who works for the World Health Organisation as a ‘technical officer’ advising, it would seem, on tobacco products.

On the face of it, this is a person who could (and should) be expected to be able to tell the difference between nicotine and smoke. But in a statement of complete ignorance and stupidity, he apparently does not know the difference – or indeed know what the filter on a cigarette is for.

The filter on a cigarette is intended to reduce the amount of tar (essentially combustion by-products including a wide range of polyaromatic hydrocarbons, and other products of pyrolysis, several of which are known to be strongly carcinogenic) delivered to the users’ lungs.

It is worth noting that despite the filter, a significant amount of tar is still delivered to the user, which is why smoking is one of the leading causes of preventable death.

Electronic cigarettes do not have (and do not need) a filter for one, very simple, reason:

They do not generate any smoke, and hence contain no tar. None at all. There is nothing to filter out.

Why is a technical officer, who is also allegedly a doctor advising on tobacco on behalf of the WHO, so utterly clueless that he is unable to differentiate between smoke, with all the dangerous combustion by-products it contains, and nicotine?

Clearly this is a man who has spent too long reading his own (and his organisation’s) propaganda.

To add even more insanity to this pronouncement, I suspect that Dr Trinidad’s recommended treatment for tobacco addiction is NRT, despite the fact it contains the same nicotine he assumes to be so dangerous.

He even goes so far as to imply that tobacco cigarettes are safer than electronic ones – completely ignoring all the evidence to the contrary.

The World Harm Organisation strikes again.

Posted in Uncategorized | 2 Comments

Good News from the MHRA (yes, really!)

While the MHRA decision to reclassify and regulate (via the EU, provided, of course, that the EU is willing to go along with the idea) electronic cigarettes as medicines is far from good news, the documents they provided as part of their study provide a wealth of good news. Good news from a fairly unimpeachable source, the UK’s medicines regulator.

For example, remember the DKFZ allegation that glycerol causes Lipoid Pneumonia? I rubbished it, Prof. Seigel rubbished it. The MHRA rubbish it too:

“As the major constituents of electronic cigarette vapour, propylene glycol and glycerine, are water soluble the potential for these compounds to be involved [in] lipoid pneumonia is not clear at present. The MHRA is not aware of any other cases of lipoid pneumonia associated with propylene glycol or glycerine products.”

 

Similarly, the WHO suggested a terrible risk of poor, uninformed users accidently killing themselves by overusing their e-cig.

Nic content and toxicity slide 4

Anyone with even the vaguest hint of knowledge about e-cigs recognised that as rubbish, but so did the MHRA:

“Given the low toxicity of nicotine at the doses observed and the fact that long before any dangerous nicotine concentrations could be reached, an over-enthusiastic user would be warned by nausea, there is little concern that e-cigarettes can harm their users by delivering toxic nicotine levels.”

 

They also have a rather less strident and panicky view than many about the potential of electronic cigarettes to be a gateway into smoking:

“There is little evidence of non-smokers taking up electronic cigarettes.”

“The available evidence from the UK, Europe and the USA suggest that only very low proportions of adults who have never reported smoking have tried electronic cigarettes.”

and

“What little use that was reported was confined almost entirely to children who currently smoke or used to smoke.”

 

The MHRA is clearly not overwhelmed by the argument that electronic cigarettes renormalize smoking, either:

“The denormalisation of smoking behaviour, if electronic cigarettes become commonly used indoors, is as likely to occur whether electronic cigarettes remain regulated under the current legislation or under medicines regulation.”

 

What the MHRA documents DON’T do is make a case for interfering in the electronic cigarette market at all.

As I quoted in a previous blog:

“However, as yet there is an absence of scientific evidence that shows long term harm to health is occurring in reality because of product safety.”

“While contaminants in ENDS have been identified, and the long term health effects of inhaling ENDS vapour are unknown, so far there is an absence of evidence that shows that these problems create significant harm to health.”

“Safety concerns have been reported. Given the extent of use, however, and despite the lack of a formal reporting mechanism (such as the yellow card scheme), these do not of themselves suggest a major public health concern.”

So the final bit of good news is that the MHRA has demonstrated that there is no need for further regulation, identifying as they have that there is a total “absence of scientific evidence that shows long-term harm to health”. Clearly, it would be completely disproportionate, therefore, to increase the regulatory burden on our thriving young industry. Evidence, it would seem, that even a regulator with an extreme preconceived bias, cannot justify reclassification as a medicine.

 

It appears that the MHRA can’t ‘level the playing field’ for the tobacco industry after all….

Posted in Uncategorized | 4 Comments

MHRA Cost Analysis of Creating a Medicinal E-Cig – A Tour de Force of Ignorance

By Tom Pruen, Chief Scientific Officer of ECITA

The lowest estimate they have generated for an imported product is a one-off cost of £252,000 and an annual cost of £65,000.

The highest estimate is a one off of £390,000 and annual costs of £249,000.

This, according to their figures gives annual costs of £87,000 (low) and £266,000 (high).

The problem is that this averages the cost over 10 years. However, based on my knowledge of the e-cig market, I would arrive at rather different figures. The pace of innovation in the electronic cigarette market is remarkably rapid, and my estimate is that at a minimum, a  new product hits the market about every three months. Even for companies that use a small range of products, I would anticipate a minimum of one new product every year.

What does this do to the MHRA estimates?

The annual cost of a company that tries to keep up with innovation, and stocks the latest developments would have 4 new products a year, so would be expected to pay:

(4 x £252,000) + (4 x £65,000) = £1,268,000 (low estimate)

(4 x £390,000) + (4 x £249,000) = £2,556,000 (high estimate)

So, that’s a cost of between £1.2 and £2.5 MILLION extra per year added to the cost of doing business, just for new hardware.

For a company that conservatively has one new product a year:

£252,000 + £65,000 = £317,000 (low estimate)

£390,000 + £249,000 = £639,000 (high estimate)

An extra cost of between £300 and £600 thousand per year, just for new hardware.

Does the MHRA really think that this will not have a significant effect on the development of the market, made up as it is of mostly small to medium enterprises? Is anyone going to invest an EXTRA £2 million a year, just to introduce new products?

I very much doubt it.

This doesn’t even account for all the costs – the MHRA haven’t even decided if there ARE other costs involved.

Our MA cost estimates assume that applicants would not have to conduct expensive animal and post-market-authorisation human clinical trials to satisfy MHRA that the risks to health from long term inhalation of ENDS vapour are acceptable. However this may not be the case and MHRA assessors might ask for these additional trials.

If the MHRA doesn’t even know how much the cost of regulation is, what use is its impact assessment?

Then of course, there are the liquids to use in the hardware; most vendors have more than one flavour (even if it is only tobacco and menthol), and some have literally hundreds. Not only will a cost of between £87,000 and £266,000 per flavour, per strength, per year be a major disincentive to having flavours (and indeed having different nicotine levels), the MHRA has made clear that it views flavours as a potential problem, due to an evidence-free assertion that these only appeal to children. (After all, adults don’t have any interest in things that taste nice; everyone apparently eats bland food and drinks only water).

And all of this completely ignores the fact that e-cigs are currently not designed to operate as medical devices – they are designed to closely mimic the physical and psychological actions of smoking.

Despite this the MHRA concluded that:

The cost of regulation need not affect price or competition…”

and

Regulation as medicines can make such products more widely available.”

So, what justifies these huge costs?

According to the MHRA itself – NOT VERY MUCH AT ALL!

However, as yet there is an absence of scientific evidence that shows long term harm to health is occurring in reality because of product safety”

 “While contaminants in ENDS have been identified, and the long term health effects of inhaling ENDS vapour are unknown, so far there is an absence of evidence that shows that these problems create significant harm to health.

Apparently important enough to be mentioned twice:

“Safety concerns have been reported. Given the extent of use, however, and despite the lack of a formal reporting mechanism (such as the yellow card scheme), these do not of themselves suggest a major public health concern.”

And as for the terrible danger of users poisoning themselves raised by the WHO (as well as several others)? The MHRA disagrees

“There is little risk that EC deliver toxic levels of nicotine.”

 “Given the low toxicity of nicotine at the doses observed and the fact that long before any dangerous levels of nicotine concentration could be reached, an over-enthusiastic user would be warned by nausea, there is little concern that e-cigarettes can harm their users by delivering toxic nicotine levels.”

So, given that the costs are massively higher than the MHRA estimates, and they themselves suggest there is little evidence of risk, where exactly is the justification for such heavy-handed and expensive regulation?

Posted in EU, FDA, MHRA, WHO | 12 Comments

Regulation by Press Release: Is this what Nanny is now reduced to?

Thank goodness, electronic cigarettes will never be regulated as medicines, despite what the recent headlines might say.

The MHRA’s announcement on Wednesday was the latest in an alarmingly long line of government proposals that have no hope of ever reaching the statute books. Remember HS2, the high speed rail proposal? It was much touted in the press, with the government describing it as practically having already happened (sound familiar?), but the business case for HS2 was described by Margaret Hodge, Chairwoman of the Public Accounts Committee, as “clearly not up to scratch”. She said there was “virtually no evidence” to support the claims that HS2 would deliver regional economic growth, going on to describe some of the Department of Transport’s assumptions as “just ludicrous”. The National Audit Office also pointed out fatal flaws. As a result, HS2 is now unlikely to make it onto the statutes.

And what of the press attention, also on Wednesday this week, concerning the Health Secretary, Jeremy Hunt’s proposals to close several children’s hospitals? Umm… now that’s not happening either, following scrutiny from the much-needed Oversight Committees.

It is sadly and shockingly easy for the government to propose legislation by press release, and the detail of any robust research or evidence to support such proposals be damned. The absence of any such evidence usually comes to light later on, often after several months, since the legally-required scrutiny of the various Oversight Committees is a long-winded and intricate process; by which time, the public has already adopted the idea that whatever the proposal is (however ludicrous), is happening – and must already be legally binding.

This is what we have once again seen happening since Wednesday’s MHRA media circus: the pharmaceutical peripherals industry has been circling like vultures around the supposed corpse of the electronic cigarette industry, offering various products and services to assist us with getting in line with incoming medicines regulation, as if it has already happened, while the tobacco industry rubs its hands with glee, believing they have successfully seen off the biggest threat yet to its cancer-causing sticks. Well, we’re sorry to disappoint them all, but this corpse is far from dead yet. In fact, it’s vibrant, successful and will continue to actually address the huge public health problems caused by the combined efforts of the tobacco and pharmaceutical industry to ensure that 25% of UK citizens remain trapped on the ‘quit or die’ tobacco/pharma cycle.

The reality, as confirmed in the MHRA’s own documentation ‘supporting’ this flawed proposal, is that: “Current evidence on the size of the [Nicotine Containing Products] NCP market in the UK suggests more than 7% of all UK smokers (around 700,000 people) are now regularly using electronic cigarettes in some form.”

Actually, this is dramatically underestimated. Even the anti-public-health organisation ASH, in a briefing also (and coincidentally?) released on Wednesday “estimates that there are 1.3 million current users of e-cigarettes in the UK”, and goes on to confirm that “this number is almost entirely made of current and ex-smokers; with perhaps as many as 400,000 people having replaced smoking with e-cigarette use. There is little evidence to suggest that anything more than a negligible number of non-smokers regularly use the product.”

Again, this dramatically underestimates the number of smokers who have completely switched.

ASH also points out that: “growing evidence suggests that e-cigarettes are becoming more reliable in their nicotine delivery and that they have a beneficial impact in reducing subjective cravings and, in turn, number of cigarettes smoked.”

So where exactly is the problem then? The MHRA’s quoted 7% smoking prevalence reduction is actually more like 10%, bringing the UK’s smoking prevalence rate down from 25% to 15% – one of the lowest in Europe, and comparable to Sweden’s – with their so-called ‘Swedish Miracle’ of Snus.

And yet, the MHRA and the UK Government, in its ‘wisdom’, seeks to remove from the market every single product currently in the hands of those “current and ex-smokers”, because, as Jeremy Mean announced in his press release on Wednesday:

“Our research has shown that existing electronic cigarettes and other nicotine containing products on the market are not good enough to meet this public health priority.”

 So the products that have already successfully reduced smoking prevalence more dramatically than seen anywhere else in the world (outside Sweden) are apparently not good enough, and should be taken away completely, redesigned as ‘medicines’, and offered alongside the existing Nicotine Replacement Therapy (NRT) products, (with their dismal failure rate of over 90%) which the Tobacco Control Industry (and the MHRA) continues to peddle:

“People should used licensed NCPs – gums, patches, mouth sprays etc – to reduce the harms of smoking.”

To put that in context: either we can continue to enjoy the significant decrease in our smoking prevalence which is currently happening thanks to the wide range of electronic cigarette products, which clearly appeal to smokers and make them very willing to make the switch, or we can effectively give them up and sentence about half of that 25% of the population who continue to smoke to a slow and painful death from a smoking-related disease, since smoking is known to kill about half of smokers.

The MHRA even admits, in its Impact Assessment:

59. The calculation reveals that very few additional successful quit attempts would be needed in order to justify the costs borne by a single UK Medical Authorisation holder. Given the uncertainty of our estimates, we think that the precise result (between 1 and 3 additional successful quit attempts a year) is much less important than the orders of magnitude of our estimates. These suggest that the policy would only need to be marginally successful (generate very few additional successful quit attempts) for it to be justified.

 60. However the reverse might also be true. The policy might only need to be marginally unsuccessful for it to be considered a costly failure. If the design and implementation of the policy has the effect of reducing access to NCPs (particularly ENDS) then it is possible that the number of successful quit attempts could decline. If there were no substantial countervailing health gains from improvements in safety, the policy’s overall impact could be highly negative.” (our emphasis.)

How true – and how very likely!

Fortunately, as confirmed by the MHRA (albeit much more quietly, while they tried to dictate public policy by press release) this decision is actually being made at the EU level; the MHRA is nothing more than a watchdog in this, with no teeth whatsoever.

Clive Bates, a staunch public health advocate and former director of ASH (UK) has raised his own concerns about the global Tobacco Control Industry’s behaviour, as it feeds into the EU processes:

1. That the depth of denial about harm reduction (in this case snus, but also e-cigarettes) is deep and shocking, as it amounts to a casual disregard for health and a nasty authoritarian instinct that in Europe denies people access to products that can save their life and improve their health, and are proven beyond doubt to do so in Sweden (and Norway).

 2. That ‘experts’ have been brought in to advise members of the European Parliament on what works in tobacco control at a critical time in the development of legislation, but they did nothing to show scientifically what does work – the presentation was full of assertions and cherry-picked data, followed by flawed advice on which countries are the best models to follow.

 3. That agencies like WHO are losing scientific credibility as sources of public health advice, and have come to resemble activists and ideologues. That is no good for public health, but it also erodes trust in WHO and international institutions more generally.  Member states will increasingly ask what they are paying them for.

 

So for now, let us leave you with a few facts:

Electronic cigarettes will never be regulated as medicines;

  • A licensed electronic cigarette would no longer be an electronic cigarette as we know it;
  • Only the tobacco industry has applied for medical marketing authorisations for ecigs;
  • No medical marketing authorisation has ever been granted for an electronic cigarette to date;
  • 4 courts in the EU have already ruled that reclassification of electronic cigarettes as medicinal products is illegal.

We look forward to the Regulatory Policy Committee’s report on this proposal, which we are confident will be as damning as their last one was.

Posted in Uncategorized | 10 Comments