Section 904(a)(3) of the Food, Drug and Cosmetic Act, as amended by the Tobacco Control Act, (FDCA) requires manufacturers and importers to report the quantities of Harmful and Potentially Harmful Constituents (HPHCs) found in their tobacco products, or in the smoke produced by their products, by brand and sub-brand. 21 U.S.C. § 387d(a)(3). This requirement was extended to all deemed products such as e-cigarettes, e-liquid, cigars, hookah and pipe tobacco when the Deeming Rule went into effect on August 8, 2016.
Pursuant to the initial compliance policy set forth in the Deeming Rule, HPHC reports for all deemed finished tobacco products on the market at that time were due by August 8, 2019. Not long after soon-to-be-departing FDA Commissioner Dr. Scott Gottlieb began his term in 2017, FDA announced that it would be delaying several compliance dates, including the HPHC reporting deadline, by three months to November 8, 2019 for all deemed products. Since then, FDA has failed to provide any actual guidance on which HPHCs should be assessed and how. Now, FDA has published a Revised Guidance for Industry: Extension of Certain Tobacco Product Compliance Deadlines Related to the Final Deeming Rule that further extends the reporting deadline for deemed finished tobacco products to a date to be determined in the future depending on when FDA publishes its final guidance on the HPHC reporting requirement (the “Final HPHC Guidance”). Specifically, HPHC reports for deemed products are now due either nine (9) months after the Final HPHC Guidance is published for small tobacco product manufacturers, or six (6) months after the Final HPHC Guidance is published for large tobacco product manufacturers. Importantly, FDA has indicated that here a small tobacco product manufacturer is any company (including any entity that it controls, is controlled by, or is under common control with) that has fewer than 350 employees pursuant to Section 900(16) of the FDCA, 21 U.S.C. § 387(16).
In 2012, FDA finalized a list of 93 HPHCs, focusing on five disease outcomes: cancer, cardiovascular disease, respiratory effects, developmental or reproductive effects, and addiction. See 77 Fed. Reg. 20034 (Apr. 3, 2012). When this list was published, only cigarettes, smokeless tobacco and roll-your-own tobacco products were regulated by FDA. In recognition of testing limitations, laboratory capacity concerns, and the short time between the establishment of the HPHC list and the reporting deadline, rather than require manufacturers to test for and report on all 93 HPHCs, FDA published a guidance document identifying abbreviated lists of representative HPHCs for which testing methods were well established for each of the product categories (cigarettes, roll-your-own, and smokeless tobacco). FDA also extended the compliance date by 6 months for small tobacco product manufacturers and by 3 months for large tobacco product manufacturers.
|Abbreviated List of HPHCs for Traditional Tobacco Products|
|HPHCs in Cigarette Smoke||HPHCs in Smokeless Tobacco||HPHCs in Roll-your-own Tobacco and Cigarette Filler|
|Ammonia||Nicotine (total and free)||–|
With respect to deemed products, other than broadening the definition of an HPHC to include chemicals in the “aerosol (vapor) or any other emission” that may be potentially inhaled, ingested, or absorbed into the body, FDA has not yet provided any meaningful guidance (or initiated rulemaking) to help companies meet the reporting requirement.
For vapor products, potential HPHCs of interest to FDA may be found in the draft guidance document on Premarket Tobacco Product Applications (PMTA) for Electronic Nicotine Delivery Systems (ENDS) that was published in May 2016 along with the final Deeming Rule. In that guidance, and in the context of developing PMTAs, FDA identified 29 constituents, along with “other chemicals and toxic chemicals as appropriate,” that it recommends ENDS manufacturers analyze in the aerosol produced by their products (see pages 26-27). Other than a handful of substances, e.g., acetyl propionyl, diacetyl, diethylene glycol, ethylene glycol, glycerol, menthol, propylene glycol, all of the below substances are also on FDA’s official 93 HPHC list:
|FDA PMTA Draft Guidance Analyte List for ENDS|
|Acetaldehyde (CASRN 75-07-0)||2-Aminonaphthalene (CASRN 91-59-8)||Cadmium (CASRN 7440-43-9)||Formaldehyde (CASRN 50-00-0)||Nicotine, including total nicotine and unprotonated nicotine (CASRN 54-11-5)|
|Acetyl Propionyl (CASRN 600-14-6)||Ammonia (CASRN 7664-41-7)||Chromium (CASRN 7440-47-3)||Glycerol (CASRN 56-81-5)||4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (CAS Reg. No. 64091-91-4)|
|Acrolein (CASRN 107-02-8)||Anabasine (CASRN 494-52-0)||Crotonaldehyde (CASRN 4170-30-3)||Isoprene (CASRN 78-79-5)||N-nitrosonornicotine (CASRN 16543-55-8)|
|Acrylonitrile (CASRN 107-13-1)||Benzene (CASRN 71-43-2)||Diacetyl (CASRN 431-03-8)||Lead (CASRN 7439-92-1)||Propylene glycol (CASRN 57-55-6)|
|4-Aminobiphenyl (CASRN 92-67-1)||Benzo[a]pyrene (CASRN 50-32-8)||Diethylene glycol (CASRN 111-46-6);||Menthol (CASRN 1490-04-6)||
|1-Aminonaphthalene (CASRN 134-32-7)||1,3-Butadiene (CASRN 106-99-0)||Ethylene glycol (CASRN 107-21-1)||Nickel (CASRN 7440-02-0)||Other chemicals and toxic chemicals as appropriate (e.g., potentially toxic pyrolytic products of the chemicals listed above)|
Of relevance, in Footnote 28 of the draft PMTA guidance FDA states (emphasis added):
These constituents are constituents that, to FDA’s current thinking, potentially could cause health hazards depending on the level, absorption, or interaction with other constituents. FDA intends to establish a revised list of harmful and potentially harmful constituents (HPHCs) that include HPHCs in ENDS products in the Federal Register, issue guidance regarding constituent reporting (i.e., harmful or potentially harmful constituent (HPHC) reporting) under section 904(a)(3) of the FD&C Act, and later issue a testing and reporting regulation as required by section 915. While applicants should submit certain information about HPHCs as part of their applications, the requirement to submit HPHC listings under section 904 of the FD&C Act (21 U.S.C. 387d) is separate and distinct from the premarket review requirements under section 910. HPHC information submitted under section 904 will assist FDA in assessing potential health risks and determining if future regulations to address a product’s health risks are warranted. For PMTAs, FDA expects that applicants will report the levels of HPHCs as appropriate for each product, so the reported HPHCs will differ among different product categories. The Agency recommends that manufacturers consult with CTP’s Office of Science about what is appropriate in the context of a specific application.
For manufacturers of deemed products seeking to comply with the HPHC requirement, critical areas remain unclear, including (1) which HPHCs must be assessed, (2) whether such HPHCs will need to be identified in the e-liquid or tobacco itself or in the vapor/aerosol/smoke produced (particularly for open-system products), (3) what analytical methodologies and testing equipment should be used, and (4) the number of appropriate test samples and replicates, among other things. These are all issues that should be addressed in FDA’s Final HPHC Guidance, which could take several more months or longer to be finalized (especially considering that FDA will be transitioning to a new Commissioner). At that point, pursuant to FDA’s announced extension, large and small tobacco product manufacturers must submit HPHC reports for their products by six and nine months, respectively, thereafter.
If you have any questions regarding HPHC reporting requirements contact Azim Chowdhury (firstname.lastname@example.org). For more information about our Tobacco and E-vapor Practice, visit https://www.khlaw.com/evapor.