Pete Lomas, managing consultant at Broughton, a scientific consultancy and contract research organisation, discusses how manufacturers can design vapes to improve their chances of MAA approval, giving a particular focus to delivered dose uniformity (DDU) which is a critical parameter for any authorised medical inhalation device.
To further support the transition from smoking to reduced-risk nicotine products, the Medicine and Healthcare Products Regulatory Agency (MHRA) is encouraging next generation nicotine product manufacturers to consider the Marketing Authorisation Application (MAA) route to market. Nicotine products, such as vape devices, authorised via this regulatory pathway, can be marketed as smoking cessation tools, and prescribed by healthcare professionals.
Medicinal vapes will be classified in a similar way as conventional pressurised metered dose inhalers (pMDIs), meaning they must meet similar criteria for approval. One key criterion is DDU, a measure used to ensure patients are getting the same amount of drug delivery both within and between devices.
Achieving DDU is challenging in vapes for several reasons. Most consumer vapes rely on traditional coil and wick technology — the wick is saturated with e-liquid and when the coil heats up, the wick releases vapor for the user to inhale. Coil and wick-based vapes are prone to inconsistency caused by a variety of issues, such as variation in battery life, power delivery, and temperature, to highlight a few.
The MHRA recognises that vapes are fundamentally different from pMDIs and has made some concessions related to DDU. However, manufacturers must achieve nine out of ten doses within 25% of the mean, and all doses within 35% of the mean. In addition, the mean of ten puffs must fall within 15% of the label claim. To have the best chance of MAA approval, manufacturers should design vapes well within these limits. Manufacturers can achieve this by adapting existing vape designs, or by turning to novel technology.
Adapting existing technology
Several areas of product development influence DDU including airflow, e-liquid properties, test methods, e-liquid delivery, packaging, production, and power delivery. Ceramic heating elements are one example of a way manufacturers are changing their designs to improve DDU. Ceramic elements improve the consistency of power delivery, while more accurately controlling the wicking rate via engineering of the wick’s pore size.
Another way a design can be adapted is with the introduction of thermocontrols that regulate power delivery and therefore the temperature of the coil. Thermocontrols help ensure the same amount of vapor is being released with each inhale, by setting a temperature limit that applies to the wick no matter the battery level of the device. Vape manufacturers can also consider the influence of the airflow path on DDU, such as tightening manufacturing tolerances.
Emerging technologies
Alternatively, vape manufacturers can make use of emerging electronic nicotine delivery system (ENDS) technologies to improve dosage consistency. Better control of droplet size can be achieved with devices based on piezo ceramic meshes, a similar technology to that used in medical nebulizers. E-cigarette devices based on piezo technology use mechanical forces, in the form of ultrasonic waves, to convert the e-liquid into vapor in a process known as atomisation. The droplet size and dosage can be predefined through the mesh dimensions allowing for uniformity in the vapor.
Another emerging technology is microfluidic liquid delivery. This technology uses the surface tension of the liquid to transport it along micro channels for “wicking” and is a more engineered solution than conventional wicks.
Regulatory insight
Businesses with products undergoing a PMTA process can reuse this data to reduce the number of new studies required for an MAA. However, MAA applicants should expect the process to be extended. Working with a scientific and regulatory compliance partner that can support you through the process, from product design to regulatory approval, can increase your chances of success.
