EDGE's Response to US Vape Related Concerns

Executive Summary

➢ There has been widespread speculation that has connected a rapid onset of severe lung symptoms, with the vaping of THC and substances that have subsequently been added to it. Alongside this, Vitamin E acetate has emerged as another prime candidate, with many in the public-health community observing that this would explain the mystery outbreak.

➢ Toxic amounts of THC can cause irritated lungs, central nervous system effects and asthma attacks with many scientists linking it to ‘lipoid pneumonia’ which is caused through vaping oils that aren’t designed for this purpose.

➢ Prior to the PMTA – Premarket Tobacco Application (regulatory submission process for e Liquid products within America) – e Liquid manufacturers did not have to provide any information regarding toxicological/ scientific product analysis. The timescale for these applications to be complete is May 12th, 2020. This still leaves the USA market open for inexperienced manufacturers/ retailers to sell products that pose a threat to consumers.

➢ The EU regulatory landscape is far more advanced and follows the strict regime of the Tobacco Products Directive 2014/14/EU (TPD). The products must be registered via the EU Portal, where an indepth Technical Dossier must be submitted, including full Toxicological data obtained from emissions testing and signed declarations of conformity.

➢ Despite TPD regulations being put in place, there are still issues within EU regulations that need addressing, Short Fill products being the main area for concern. These products do not require emissions testing or toxicological assessment of ingredients as they do not fall into the scope of the TPD as they contain 0mg of Nicotine.

➢ NextGEN360 recognised this early on and ensured that all products launched that were 0mg or Short Fill went through the same rigorous testing regime that nicotine-containing products follow.

➢ NextGEN360 have invested heavily in analytical equipment that will allow us to carry out in-house testing to ensure our products not only meet the requirements of the TPD but also develop methods to further investigate an array of products and formulations.

➢ As a company we are ISO 9001:2015 accredited and work to GMP standards, with accreditation planned for the end of 2019. Furthermore, within the laboratory, ISO 17025 and UKAS accreditation is being implemented, with certification planned for Q2, 2020.

➢ NextGEN360 had an independent report commissioned by BIBRA (toxicology advice and consulting) for potentially harmful carbonyls found in the vapour of e liquids. The report defined the tolerable maximum levels that e liquids should not exceed, something other companies have not determined and that the TPD does not take into consideration within the regulations.

➢ Through expertise and meticulous compliance with the regulations, NextGEN360 are confident our products are of the highest quality and meet all safety parameters that will consequently avoid any issues arising, like those that are currently occurring in America.

➢ NextGEN360 recommend that you do not purchase products that are for Shake & Vape purposes, such as Short Fill or 0mg products whilst the market is in disrepute, unless the manufacturer can prove TPD registrations for the nicotine version of the product or can provide technical specifications including toxicological data and ingredient hazard classifications.

➢ Further media coverage has been released today (17/09/2019) regarding the pulegone additive (a constituent of oil extracts from mint plants) being present within menthol and peppermint vapes that could potentially cause liver cancer if absorbed in high enough quantities (The Telegraph, 2019). NextGEN360 do not use any flavourings that contain this additive. All our flavourings are sourced from the UK and full ingredient breakdowns are sent prior to launching the flavour for chemical hazards analysis.

Recently, the media have published numerous reports regarding the apparent ‘mysterious and deadly lung disease’ that are being closely linked to vaping nicotine or cannabis-related products. NextGEN360, EDGE's parent company, have compiled a response in relation to these reports and clarified how, as a company, we are fully compliant and pride ourselves on ensuring that our products are of the highest quality and meet the legislative requirements set out in all legally binding regulations and beyond.

The outbreak of lung illness apparently relating to vaping has now claimed five lives and affected 45 people across the US, according to the Centers for Disease Control and Prevention (CDC). Reports published have stated “Five deaths have been confirmed in California, Illinois, Indiana, Minnesota & Oregon”, the CD said some apparently preceding the case in Illinois in late August was the first to be linked to the vaping-related outbreak. In a media briefing on Friday 6^th September 2019, the federal agency said the preliminary results of its investigation suggest that of at least 60 hospitalised patients in North Carolina and Wisconsin reporting vaping, most of them had used THC-containing e-liquids and only a small proportion just nicotine products. There has been widespread speculation that has connected the rapid onset of severe lung symptoms, seemingly mostly in young males, with the vaping of THC and substances that have subsequently been added to it. Alongside this, Vitamin E acetate has emerged as another prime candidate, with many in the public-health community observing that this would explain the mystery of the outbreak (ECigIntelligence, 2019).

No single vaping device or e-liquid product was found to unify all of the cases studied. However, 84 percent of patients reported using THC product, and the symptomatic progression of the disease was relatively similar across all cases. Despite the illness showing symptoms of an infectious pneumonia-like condition, no infectious agent has been found (New Atlas, 2019). Vaping THC does not protect consumers from negative health effects. There are residual irritants, solvents and pesticides being taken into the body through vapours that can have serious health consequences. Toxic amounts of ammonia residue from THC can cause irritated lungs, central nervous system effects and asthma attacks with many scientists linking it to ‘lipoid pneumonia’ which is caused through vaping products that contain a high percentage of oils that aren’t safe for vaping e.g. Butane Hash Oil.  Many consumers in America are reported to adding additional material to their e-liquids such as synthetic cannabis, contaminated THC or nicotine from an unreputable supplier (USA Today, 2019).

This all comes down to the regulatory landscape that is present within America. Prior to the PMTA (Premarket Tobacco Application), e-liquid manufacturers within the US did not have to provide any information regarding toxicological or scientific product analysis - The projected timescale for compilation of a validated submission is up to 10 months, and the deadline for submission is May 12, 2020. This is still leaving the market open for inexperienced manufacturers/retailers to sell products that pose a threat to consumers. In comparison, within the EU, the regulatory landscape is far more advanced and follows the strict regime of the Tobacco Products Directive 2014/14/EU (TPD). The TPD has been transposed in most EU countries and in the UK has been implemented as the Tobacco and Related Products 2016, which came into force May 2016. The TPD enforces strict rules on all aspects of vaping products and regulations surrounding the marketing and advertising of vaping products. Through the EU portal, all manufacturers/retailers must submit an in-depth dossier of each individual product that they wish to sell on the EU market to the MHRA. Manufacturer details, submitter details, full ingredient declaration including CLP (Classification, Labelling and Packaging (CLP) Regulation ((EC) No 1272/2008) classifications, Nicotine content (maximum amount 20mg/ml), full toxicological data obtained from emissions testing and signed declarations of conformity are all included within the submission. In comparison to America, the UK is far more progressive in terms of regulations and the implementation of a controlled regime has led to a more respected industry. Currently, manufacturers within America are permitted to market products with an unrestricted amount of nicotine, a plethora of ingredients that would be banned in the UK and other EU countries and products manufactured in an uncontrolled environment, with no quality or safety systems implemented.

Despite the TPD being fully enforced within the EU, there are still issues that need addressing in relation to the regulations. One of the main issues being the lack of regulations surrounding Short Fill products. Short Fill or Shake & Vape products are 0mg e-Liquid products designed to have an additional ‘shot’ of nicotine added. They are attractive to the consumer as they can buy a Short Fill product in a larger size bottle that is half-filled to allow room for the nicotine to be added. This gives the consumer more product as the 10ml bottle size restriction does not apply to 0mg products, it also allows consumers to make the product up to a nicotine level above the restricted 20mg/ml. Due to the product not containing nicotine, it does not fall within the scope of the Tobacco Products Directive, therefore the aforementioned restrictions do not apply to these types of products. This opens a floodgate for a variety of issues, one of the most concerning being the addition of ingredients that under normal TPD circumstances would not be permitted. The uncontrolled addition of certain flavourings could lead to the unknown addition of certain by-products such as Acetyl Propionyl, 2-3, Pentanedione and Diacetyl. These ingredients have been proven to cause a variety of health issues including the development of respiratory dysfunction, damage to the airways and abnormal lung function (Hubbs et al, 2002).  NextGEN360 recognised this issue early on and ensured that all products launched that were 0mg and for Short Fill purposes, went through the same rigorous testing regime that nicotine-containing products do, including a toxicological assessment of the ingredients and the emissions from the flavourings. We feel that this is the only way to ensure that all products available in the market, regardless of their nicotine content, meet the same high level of safety and quality objectives as communicated in the regulations. As a company, we are pushing for this to become part of the regulations to ensure optimum consumer safety across all product sets. Through our pharmaceutical backing and extensive expertise within the area, we are communicating this prospect with other manufacturers and retailers to ensure we are all on the same page and can take an industry-lead with shaping the regulatory future.

To further optimise our in-house capabilities and continue to assist in shaping the industry legislation and regulatory expectations, NextGEN360 have invested heavily in analytical equipment that will allow us to not only carry out in-house testing for TPD purposes, but develop methods to further investigate and analyse an array of products and their formulations to ensure paramount safety. We have a state-of-the-art laboratory that contains brand new analytical equipment (HPLC, GC-FID, GCMS and smoking machine) and have worked alongside well-known industry experts/scientists to develop methods for a range of nicotine, CBD and emissions testing. All methods have been independently verified by third-party consultants to ensure accuracy and validity across the board. NextGEN360 is ISO 9001:2015 accredited and works to GMP standards, with accreditation planned for the end of 2019. Furthermore, within the laboratory, ISO 17025 and UKAS accreditation is being implemented, with certification planned for Q2, 2020. Using all these in-house tools we can ensure as a company, that every product that leaves the building not only meets the requirements of the TPD but goes above and beyond expectations.

Alongside our in-house testing capabilities, we also commissioned an independent report in relation to health-precautionary tolerable levels for six key carbonyl e-liquid analytes. BIBRA (Toxicology advice & consulting) was asked to propose health-based tolerable inhalation levels (health criteria values (HCV)) for six specific carbonyl compounds that are routinely detected in vape emissions from e-liquids. Within the industry, the tolerable levels are not determined therefore the results that are obtained for submission purposes are obsolete due to no industry thresholds being determined. The maximum exposure limits that are determined allow us to review results and decipher those that do not meet criteria, and therefore fail this stage of the process. This is not a requirement of the TPD and the MHRA do not state maximum exposure limits, therefore leaving the industry open for manufacturers to market products that contain higher levels of potentially dangerous carbonyls – a foreseen issue within America as well as no set limits for carbonyls, the need to report these is only just being introduced as part of the PMTA.

In summary, based on the information and processes NextGEN360 have implemented, we are confident that our products are of the highest quality and meet all safety parameters that will consequently avoid any issue arising, like those that are currently occurring in America. Alongside the fundamental rules and regulations set out in the TPD, NextGEN360 have also implemented further protocols to ensure full transparency and safety for consumers. Our True Zero THC initiative communicates to the customer that none of our CBD products contain any THC, this is reflected in our analytical certificates that are provided to customers with every batch of CBD product that is sold. Alongside this, all our raw materials including Nicotine and CBD come in with a certificate of analysis and third-part analytical certificates.

We are constantly reviewing our processes to ensure we are up to date and consistent in our approach. To further validate our toxicological analysis methods and the maximum tolerable levels we will be re-commissioning BIBRA to re-validate the original study that was conducted to review the stated tolerable levels and to verify that the results take into account the array of products recently launched into the vaping market such as CBD vapes, Nicotine Salts and complex flavoured e-liquids. NextGEN360 have also been asked to be board members for the CMC (Centre for Medicinal Cannabis) to assist in the implementation of regulations from assisting in writing up regulatory standards to visiting third-party sites for audit purposes and becoming a kitemark company for the industry. 

Lizi Jenkins
Head of Technical & Development   

References:

1. Five deaths in US lung outbreak; 450 cases now identified. (September 9^th, 2010). Rubio, David Palacios. ECigIntelligence. https://ecigintelligence.com/third-death-in-us-lung-outbreak-450-cases-now-identified-says-cdc/
2. Mystery vaping illness clarified vitamin E acetate under the spotlight. (September 8^th, 2019). Haridy, Rich. News Atlas. https://newatlas.com/health-wellbeing/mystery-vaping-illness-clarified-vitamin-e-acetate/
3. People are vaping THC. Lung injuries being reported nationwide. Why is the CDC staying quiet?. (August, 28^th, 2019). O’Donnell, Jayne & Alltucker, Ken. USA Today. https://eu.usatoday.com/story/news/health/2019/08/28/critics-cdc-silent-vaping-thc-injuries-mount/2121523001/
4. Accumulation of Ubiquitin and Sequestomose-1 Implicate Protein Damage in Diacetyl-Induced Cytotoxicity. (November 18^th, 2016). Hubbs, AF. PubMed.Gov. https://www.ncbi.nlm.nih.gov/pubmed/27643531