The Importance of Shelf-Life Studies

Electronic cigarettes, more commonly known as vape products and e-cigarettes, operate by heating a nicotine-containing liquid formulation (commonly referred to as an e-liquid) to generate an inhaleable aerosol that is delivered to the user’s lungs. Shelf-life studies are critical for assessing how electronic cigarettes respond to intrinsic and extrinsic factors and are crucial in ensuring product quality. Here, Paul Barr, Principal Scientist at Broughton, explains the value of shelf-life studies in the production of e-cigarettes.

The e-liquid in electronic cigarettes predominantly comprises propylene glycol and glycerol, which are used as the aerosol formers, nicotine as the active ingredient, and flavour mixtures and organic acids. The e-liquid is contained within the cartridge or device for closed systems and disposables. However, due to the airflow passage required to activate these devices and generate an aerosol, these e-liquids are typically exposed to the environment outside the cartridge.

The propylene glycol and glycerol component in the e-liquid itself is hygroscopic and, therefore, may readily take on the water from the environmental moisture. Additionally, nicotine readily degrades via oxidation. The mode of operation, design, and contents of electronic cigarettes would strongly imply that shelf-life assessments that evaluate and substantiate the long-term stability of these products should be critical studies at the cornerstone of their quality framework.

Meeting Regulatory Demands

Regulatory requirements often drive the scientific assessment of electronic cigarettes. However, the regulatory demand for shelf-life studies on these consumer products can vary significantly between global markets depending on the local legislation.

In the US, these products are regulated through the Premarket Tobacco Product Application (PMTA) process, where stability information is a mandatory requirement to demonstrate that the product does not generate different considerations for public health over its proposed shelf-life. Failure to provide such stability data may result in deficiency responses and, ultimately, marketing denial orders (MDO). 

All vape products, pods, and e-liquids sold in the UK or EU must be notified under the UK’s Tobacco and Related Products Regulations (TRPR) and the EU’s Tobacco Product Directive (TPD). Currently, these regulations have no specific requirement for stability data. However, MHRA Chapter 9, which covers general advice on due diligence for electronic cigarette devices and refill containers, states that to demonstrate that your product is of acceptable quality and safety throughout the shelf-life of the product, you should have data on the stability of representative batches. Although this is not mandated, it highlights the level of testing that would be expected for these products.

Nevertheless, an update to these regulations is currently planned and under consultation. However, it is difficult to predict if the stability study required to substantiate shelf-life will be included in the newest iteration of these regulations. In the absence of stability study requirements, several recent European Committee for Standardisation (CEN) publications address the need for shelf-life evaluation for these products. The CEN standards for General Principles for manufacturing, filling, and holding e-liquids for pre-filled containers or products (EN 17647:2022) and e-liquid ingredients (EN17648:2022) propose that shelf-life should be established for the product with supporting documentation.

For electronic cigarettes, regardless of the regulatory requirements of each market, stability studies and shelf-life assessments are essential studies. Therefore, manufacturers should ensure a comprehensive understanding of the stability and potential breakdown or formation of degradation products, as this is pivotal in the characterisation of the product and in substantiating the shelf-life.

The Risks

Poor product stability or inadequate protection from the environment due to an unsatisfactory quality of packaging can result in moisture ingress. Water ingress may dilute the nicotine concentration in the e-liquid, resulting in an inconsistent delivery of nicotine over the shelf-life and potential changes in the physical characteristics of the e-liquid, such as density and viscosity.

Changes in viscosity can contribute to product leakage but may also result in non-functioning products as some commonly used wicking materials, i.e., ceramic, will only function properly with liquids within a specific viscosity range. Furthermore, increased levels of water content may influence other chemical reactions and impact the levels of unwanted products such as carbonyls and diacetyl.

Additionally, exposure to the environment can result in the oxidation of nicotine, leading to changes in the product appearance and formation of degradation products. This may result in an increased toxicological risk to the consumer. These risks represent just some of the concerns that should be considered over the shelf-life of electronic cigarettes.

Ensuring Efficacy

E-cigarettes provide a nicotine alternative for millions of smokers. Therefore, maintenance of nicotine delivery as advertised on the label throughout the shelf-life is vital to prevent users from transitioning back to combustible alternatives due to unsatisfactory product performance. Additionally, all products must not impact the consumer above the toxicological limits of concern across their shelf-life, so any contribution of breakdown products to toxicological effects must be negligible. As a consumer product, these extensive characterisation studies help build consumer and regulatory trust and demonstrate that manufacturers understand how their product performs throughout the shelf-life.

As well as maintaining efficacy and ensuring consumer safety, stability evaluation can have other significant benefits for manufacturers’ understanding of their products. For example, stability data can inform packaging selection and is valuable in new product development. Additionally, stability data allows manufacturers to control their supply chain more efficiently and may help plan manufacturing schedules to meet market needs and minimise the risk of financial losses due to overproduction.

Generating this data now with a robustly designed stability program bespoke for individual products will help prepare for potential future regulation. In addition, it may be used as supporting data or to check the feasibility of a different regulatory route, such as pivoting from a consumer-based product to a licensed medicinal product via the Marketing Authorisation Application (MAA) pathway.

In conclusion, from a regulatory perspective, the requirement for stability studies on consumer vape products primarily depends on the regulations within the local market. However, it is a manufacturer’s responsibility to fully characterise their product and understand how it performs over its shelf-life. Shelf-life claims on consumer products must be substantiated with analytical data. Even in the absence of specific regulation around stability, manufacturers have a duty of care towards consumers and must create their own product safety and stewardship frameworks. Stability studies should be a pillar of these frameworks to ensure the quality, efficacy, and safety of these products.

With the recent scrutiny in the vaping industry, reports of non-compliant products, and increased quantities of illicit vaping products, it is more critical than ever that rigorous scientific studies are performed. This will allow manufacturers to build trust with consumers, regulators, and policymakers and maintain a good reputation.