The FDA Tobacco Products Scientific Advisory Committee
(TPSAC) on January 25 unanimously endorsed a claim by Philip Morris
International that switching completely from cigarettes to its heat-not-burn
IQOS system significantly reduces smokers’ exposure to harmful and potentially
harmful chemicals (here). The committee, however, denied two other
claims, that switchers “can reduce the risks of tobacco-related diseases” (8
against, 1 abstention) and that switching “presents less risk of harm” than
continued smoking (5-4 against).
PMI published numerous short-term studies documenting that
toxicant levels from IQOS aerosols were substantially lower than those in
smoke, and demonstrating the biologic and medical impact of these differences
in cells, animals and humans. The
committee’s denial of the diseases claim was understandable: risks manifest after
three or four decades of steady smoke exposure, so risk reduction from
switching to IQOS “can” occur over longer time periods. However, TPSAC’s close vote rejecting the reduced harm claim is problematic.
In 2012, the FDA published a list of 93 Harmful and Potentially Harmful Constituents (HPHC) in Tobacco Products and Tobacco Smoke (here and here). The agency declared that the HPHCs variously posed health hazards as carcinogens, respiratory toxicants, cardiovascular toxicants, reproductive or developmental toxicants, and/or addictive agents. The agency provided no guidance for the levels of exposure that constitute harm. This is important, as seen in the case of formaldehyde, a weak carcinogen to which nearly everyone is exposed, but smokers significantly more so (discussed here).
TPSAC rejected impressive evidence of HPHCs reduction in IQOS vapor. I collected the following information from Appendix C of the FDA Briefing Materials (available here), which standardized toxins in IQOS aerosol and smoke according to nicotine intake.
On average, the reduction in the level of all potential and proven carcinogens (n=29) in IQOS aerosol was 90%. For the most important carcinogens (n=9), the reduction was 96%. Average reductions in respiratory (n=18) and cardiovascular (n=8) toxicants were 91% and 93% respectively. The reductions for all of these individual agents are illustrated in the charts that follow.
The substantial reductions in all tested HPHCs support the claim that switching completely to IQOS “presents less risk of harm” than continuing to smoke. There is adequate justification for the FDA to set aside TPSAC’s narrow 5-4 rejection of this claim.
The two-day hearing raised no significant roadblocks to FDA market authorization for IQOS, which would allow U.S. sales. Given the significant relative health benefits of this smoke-free product, market authorization is the appropriate action.
1 comment:
From a colleague who wishes to remain anonymous:
Nice job summarizing the iQOS/TPSAC deliberations.
One thing bothers me about the TPSAC failing to endorse the risk-reduction claim. The CTP, possibly in a well-intentioned attempt to offer TPSAC a less nuanced risk question, posed it this way as Question 2b:
“…has the applicant demonstrated that the reductions in exposure are reasonably likely to translate to a measurable and substantial reduction in morbidity and/or mortality?”
Whereas the FSPTCA stated it this way: [emphasis added]
‘‘(iv) the scientific evidence that is available without
conducting long-term epidemiological studies demonstrates
that a measurable and substantial reduction
in morbidity or mortality among individual tobacco
users is reasonably likely in subsequent studies.”
To me, the explicit wording of the Act more clearly shows that Congress fully appreciated and properly anticipated that full “proof” of reduced risk-especially for a new-to-market product- would not be available.
I think the requirement that the evidence show a reasonable likelihood of reducing risk in future postmarket studies was very proper, but unfortunately that was lost in CTP’s re-phrasing of the intent of the regulation.
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