Report

May 19

What is Toxicology for ENDS

This article provides an overview of the different types of toxicological studies typically undertaken, and how they support regulatory submissions for ENDS products.

What is Toxicology for ENDS?

Toxicology studies for Electronic Nicotine Delivery Systems (ENDS) products involves establishing which chemical compounds are present within a product (typically an e-liquid or a e-cigarette device) or are emitted by a product, and the level of safety concern posed by the level of any such compounds.

This article provides an overview of the different types of toxicological studies typically undertaken, and how they support regulatory submissions for ENDS products.

What is toxicological analysis?

Toxicological analysis is a scientific process designed to identify and measure chemical compounds present within a product’s ingredients, impurities or emissions. An important element of this is to confirm the level of such compounds, as exposure levels define whether there is a risk to user safety.

A wide variety of desk based, experimental and computational techniques are applied as detailed below.

Desk-based risk assessment

As its name suggests, this initial stage involves carrying out a systematic review of the latest, peer-reviewed literature available to assess any known risks posed by the chemical compounds within a product.

An important aspect of this is a stage called risk characterization, which involves:

  • identifying hazards

  • reviewing toxicity thresholds (i.e. the level at which a compound would start to have an adverse effect)

  • confirming exposure levels (i.e. measuring typical exposure levels delivered during usage)

In-vitro testing

In-vitro translates in Latin to “in glass”, and as such the name refers to tests carried out in a laboratory test tube scenario. Hazard assessment data is gathered through specifically designed experimental studies to rigorous standards which determine the effect of chemical substances within an e-liquid or from a device in the case of ENDS. Typical in-vitro tests include screening for mutagenicity, carcinogenicity and cell toxicity.

In-vivo testing

In-vivo testing refers to experimentation using a whole living organism. Animal studies are typically not carried out within the ENDS sector. However human subject studies (clinical studies) are required as part of many regulatory requirements to determine typical usage, behavioural effects, abuse liability and to perform a population risk-benefit assessment by comparing outcomes from ENDS products with those for combustible tobacco products.

Clinical Studies

Data obtained from human pharmacokinetic studies, behavioural assessments and topography studies are evaluated to determine levels of concern (if any) posed by exposure levels.

In-silico testing

This computational method involves utilizing specialist tools and software to predict and assess the risk associated with a chemical compound.

Information and data applied through such tools includes statistical modelling and expert review data.

Every regulation is different

Not all toxicological safety evaluation programs will include all the different types of studies. A tailored approach is most effective, based on the nature of the product and regulatory requirements. However, it’s worth pointing out that there is a high level of integration between the different studies undertaken, as data obtained from one study will inform and support further investigation within an alternative study.

Toxicology plays an important role in both new product development, and regulatory submissions to demonstrate the acceptability, safety and compliance of a particular product and ongoing product stewardship of commercial products.

Both clinical and non-clinical assessments are performed to GCP or GLP standard respectively and are scrutinized and assessed by a team of accredited clinical scientists or toxicologists  - sufficient to meet the most exacting of global regulatory standards.

Toxicology experts delivering an integrated study

Broughton Nicotine Services operate exclusively in the ENDS sector and provide a range of toxicological strategies and studies to support ENDS manufacturers.

To discuss your toxicological requirements, contact our team to book a meeting so we can help you advance a smoke free future.

 

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About the Author

Yvonne Wilding is the Director of Product Safety and Compliance. She has over 10 years of broad regulatory toxicology experience and 20 years of pharmaceutical drug development Research & Development leadership. She has been responsible for numerous MAA and NDA submissions, for both small molecules and biologics and has experience stretching from early candidate selection through life cycle management of new medicines. Her toxicology experience was gained with GlaxoSmithKline's (GSK) large portfolio of respiratory products in a specialized inhalation toxicology department. Yvonne began her career as a regulatory toxicologist for GSK responsible for designing the strategic drug safety evaluation programs to satisfy all global markets using both in-vivo and in-vitro approaches; for operational delivery both with an in-house team and with Contract Research Organisations (CRO). This involved working closely with clinical teams and key opinion leaders to ensure patient safety at each stage of development. She has extensive experience of interacting with regulatory agencies. Following on from Toxicology, Yvonne was responsible for managing and leading drug development programs encompassing all functional disciplines to ensure delivery of successful marketing applications and to maximise the commercial opportunity for each product. Yvonne’s clinical experience encompasses clinical program strategy, study management, clinical portfolio management and pharmacovigilance. Most recently, Yvonne worked with AstraZeneca in the Precision Medicine department to develop new diagnostic tests and submit PMA applications for companion diagnostics devices evaluating genetic biomarkers of disease susceptibility in collaboration with major diagnostic companies.