Long-term safety surveillance with Tobacco Heating System
How do we collect safety surveillance information on THS?
PMI’s safety surveillance follows all of the relevant regulations, standards, and guidelines mandated in the countries where our products are commercialized. We follow the highest standards for safety surveillance, inspired by the EU Good Vigilance Practice (GVP) for medicinal products and we also comply with the U.S. Tobacco Control Act and U.S. Food and Drug Administration’s (FDA’s) guidelines.
Health-related events are collected worldwide from a number of different channels, including:
- Call centers with agents trained in collection of adverse event (AE) information
- Social media
- National poison centers
- Scientific literature
- Local market campaigns and surveys
- Corporate website
- Market research studies
All of these events are then logged into a validated safety database—LifeSphere MultiVigilance. The data is processed in five steps:
- Intake: The collection of data
- Translation: When applicable, all event-related information is translated into English
- Review: This includes coding, and validity and duplication checks
- Medical review: To determine the extent of the event, such as its seriousness, causality, and expectedness
- Potential submission to regulatory authorities
Throughout, our gold standard safety reference is nicotine replacement therapy (NRT).
What is an adverse event?
The FDA has defined an adverse event (AE) in its draft guidance for modified risk tobacco product (MRTP) applications as “any health-related event associated with the use of a [product] in humans that is adverse or unfavorable, whether it is considered product-related or not.”
Examples of AEs may include:
- Nausea after product use
- Burning sensation from device overheating
- Increased incidence of coughing following product use
Solely product-related incidents, such as the blade in the device breaking, are not considered AEs, as they are not health-related.
The seriousness of an AE is assessed during the medical review step of the logging process. During this step, the different elements of an AE case are verified. These elements include:
- Identification of the AE
- Medical Dictionary for Regulatory Activities (MedDRA) coding: This assigns a standardized code to the event to facilitate the exchange of clinical information through a single internationally recognized medical terminology
- Seriousness assessment: This is based on International Council for Harmonization (ICH) criteria. A serious event could result in one or more of: Inpatient hospitalization or prolongation of existing hospitalization; a medically important event; persistent or significant disability/incapacity; congenital anomaly/birth defects; death
- Expectedness
- Causality
- Case Narrative
Adverse events medical review process
Have significant adverse events been recorded for THS?
THS use has increased greatly since the commercial introduction of IQOS in 2014, and today we estimate that in 2024 more than 30 million adults were using our heated tobacco products (HTPs). However, with the exception of “thermal burn” and “accidental exposure to product by child,” the safety profile of IQOS remains close to that of NRTs.
In fact, although the number of THS users continues to increase, the overall profile of both serious and nonserious AEs has remained steady. In the period from November 2014 to December 2024, the most frequently reported events were cough, headache, throat irritation, thermal burn, and oropharyngeal pain. During that same period, only 2.28% of reported events met the criteria for seriousness.
How does PMI identify and respond to safety issues?
PMI conducts signal detection activities to identify potential or emerging safety issues. Signals are information which suggests a new, potentially causal association, or a new aspect of a known association, between an intervention and an event or set of related events. Signal information may come from one or multiple sources, such as reported events, observations, and/or experiments. Signal events are those judged to be of sufficient likelihood to justify verificatory action.
A signal may represent either a potential or an identified risk. A potential risk is an unexpected event that might be linked to the product but where the link has not been proven yet. In contrast, an identified risk is an unexpected event where there is enough evidence to show that it is linked to the product.
PMI’s signal detection process has five steps, including detection, validation, assessment, safety actions, and risk communication.
For example, signal detection may begin when consumers contact a call center to report an AE. The signals then undergo the validation process during which more information is gathered to confirm the signal.
Signal assessment can then take place. This may include literature and laboratory research to determine the cause of the signal. Once a cause is scientifically determined, safety actions and mitigation measures can be undertaken. These can include changes to the product, additional safety warnings or changes to existing warnings, and/or regulatory notifications.
The last step in the signal detection and response process is risk communication. This may include providing information to consumers, reporting to the relevant regulatory authorities, and any other measures deemed necessary, based on the specific signal. Further monitoring is also conducted to ensure the risk is sufficiently mitigated.
Conclusion
With the commercial launch of THS in 2014, PMI was the first tobacco company to establish a safety surveillance system in concomitance with the launch of the new product. By 2024, this safety surveillance system was available in more than 80 countries and included more than 4,000 call center agents trained to collect information on AEs. The system covers the collection of cases from multiple sources, case processing within the safety database, and individual submissions to the authorities.
Our aggregate data analysis and signal detection activities enable rapid identification of potential risks. This analysis has shown a steady safety profile for THS products from November 2014 up to the end of 2024—the most recent period for which data is available—and PMI will continue to collect and evaluate safety information so that it can conduct monitoring of the safety profile of THS products.
