2017 Regulatory, Policy, and Enforcement Developments
FDA Launches Digital Health Innovation Plan and Pre-Cert Program, Announces Major Tobacco Policy Shift, and Cracks Down on Unsubstantiated CBD Treatment Claims
Jonathan A. Havens
Scott Gottlieb, M.D., who was nominated by President Trump to serve as Commissioner of the U.S. Food and Drug Administration (FDA or the agency) on March 10, 2017 and confirmed by the U.S. Senate on May 9, 2017, wasted no time once he arrived at the agency last May. Although he was at FDA for less than eight months last year, Commissioner Gottlieb oversaw significant regulatory, policy, and enforcement developments, including with regard to digital health, tobacco products, and marijuana-derived products.
Digital Health Innovation Plan and Pre-Cert Program
As is often the case, technology in the digital health space has outpaced regulation, commonly forcing developers to seek guidance from FDA on a case-by-case basis. Congress took an important first step to promote more digital health regulatory certainty when it passed the 21st Century Cures Act (21st Century Cures), which President Obama signed into law in late 2016.
On June 15, 2017, Commissioner Gottlieb announced that the agency would be developing a new Digital Health Innovation Plan (the Plan), released later last summer,1 through which FDA hopes to encourage industry growth by providing more regulatory certainty to device developers. Gottlieb also indicated that the agency would soon thereafter pilot a new, risk-based approach toward regulating digital health technologies, which FDA launched on July 27, 2017.2 FDA announced the names of the companies selected to participate in its digital health software precertification pilot program (Pre-Cert program) on September 26, 2017.3 In releasing its Plan, and two final guidances and one draft guidance late last year,4 on when to submit a 510(k) for a change to an existing device, when to submit a 510(k) for a software change to an existing device, and the breakthrough devices program, respectively, FDA continued to implement the digital health provisions of 21st Century Cures. Developers are cautiously optimistic that the Plan, the Pre-Cert program, and agency guidances will help clarify what falls outside the scope of FDA regulation, and will help obviate the need for case-by-case regulatory discussions with FDA.
In describing the digital health pilot, Gottlieb assessed that it represents “an entirely new approach toward regulating this technology” that “will be the cornerstone to a more efficient, risk-based regulatory framework” for such products. One of the things the agency is said to be considering is whether it can, under existing authority, create a third-party certification regime under which lower risk digital health products could be marketed without premarket review and higher risk products could be marketed with a streamlined agency premarket review. Per Gottlieb, certification might be used to assess, say, whether a company consistently and reliably engages in high quality software design and testing (i.e., validation) and ongoing maintenance of its software products. Under such a certification program, development time and market entry cost could be reduced for software as a medical device (SaMD). Gottlieb also indicated that under the pilot program, real-world data collected post market—such as data gathered through the National Evaluation System for health Technology (NEST)—could be leveraged by developers to help expedite market entry and subsequent expansion of indications more efficiently. While FDA does not own or operate NEST, Gottlieb noted that the agency has been establishing strategic alliances among data sources to accelerate NEST’s launch, and that the initial version of a fully operational system is anticipated by the end of 2019.
Tobacco Policy Shift
In arguably one of the biggest FDA policy developments last year, on July 28, 2017, the agency announced a new, comprehensive plan for tobacco and nicotine regulation that places nicotine, and the issue of addiction, at the center of FDA’s tobacco regulatory efforts.5 Since nearly the beginning of his tenure as Director of the Center for Tobacco Products (CTP), Mitch Zeller has discussed that tobacco products represent a “continuum of risk.” However, until FDA’s July 2017 announcement, the meaning of that phrase was never fully understood. We now know that the agency believes that, within that continuum of risk, nicotine is most harmful when delivered through smoke particles in combustible cigarettes. Although FDA did not indicate so directly in its groundbreaking announcement, this approach suggested for the first time the agency’s assessment that e-cigarettes and vapor products are less harmful than combustible cigarettes.
Within the announcement of its multi-year tobacco and nicotine regulatory plan, the agency stated its intentions to:
- Extend timelines to submit tobacco product review applications for newly-regulated tobacco products that were on the market as of August 8, 2016 to afford FDA more time to explore clear and meaningful measures to make tobacco products less toxic, appealing, and addictive. Applications for newly-regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco were extended until August 8, 2021, and applications for non-combustible products such as electronic nicotine delivery systems (ENDS) or e-cigarettes were delayed until August 8, 2022. Manufacturers are able to continue to market such products until product applications for the same are required to be submitted and while FDA reviews such product applications.
- Issue advance notices of proposed rulemaking (ANPRMs) to: (1) seek input on the potential public health benefits and any possible adverse effects of lowering nicotine in cigarettes; (2) seek public comment on the role that flavors (including menthol) in tobacco products play in attracting youth and may play in helping some smokers switch to potentially less harmful forms of nicotine delivery; and (3) solicit additional comments and scientific data related to the patterns of use and resulting public health impacts from premium cigars, which were included in FDA’s 2016 Deeming Rule.6
- Issue foundational rules to make the tobacco product review process more efficient, predictable, and transparent for manufacturers, while upholding the agency’s public health mission. Among other things, FDA intends to issue regulations outlining what information FDA expects to be included in Premarket Tobacco Applications (PMTAs), Modified Risk Tobacco Product (MRTP) applications, and reports to demonstrate Substantial Equivalence (SE). The agency also plans to finalize guidance on how it intends to review PMTAs for ENDS products.
While the stated purpose of FDA’s multi-year plan is to better protect kids and significantly reduce tobacco-related disease and death, the product review application delay portions of the same were a major win for ENDS, cigar, pipe tobacco, and hookah tobacco manufacturers. When President Trump nominated now FDA Commissioner Scott Gottlieb, industry was hopeful that under his watch, the agency would roll back or delay certain portions of the Deeming Rule. Industry had been lobbying hard against the Rule’s premarket requirements since they were first proposed, as they will result in major industry consolidation because of the $1 million-plus cost involved in preparing certain marketing applications (a trend that has already started). Before the announced delays, manufacturers would have had to comply with the onerous premarket review requirements starting in November 2017.
Also notable in the agency’s July 2017 tobacco and nicotine regulatory announcement is its inclusion of menthol, which Congress specifically carved out of the flavored cigarette ban enacted as part of the Family Smoking Prevention and Tobacco Control Act, the legislation that gave FDA its authority to regulate tobacco products. In July 2013, the agency issued an ANPRM to obtain public input on menthol in cigarettes but the agency never moved forward with regulatory action on the same, due in large part to a successful industry challenge to the menthol report issued by FDA’s Tobacco Products Scientific Advisory Committee (TPSAC). While the U.S. Court of Appeals for the D.C. Circuit eventually upheld the agency’s right to rely on TPSAC’s menthol report, FDA did not pursue further regulatory action. It remains to be seen, how, if at all, the agency will now decide to regulate menthol in cigarettes and/or other tobacco products.
Unsubstantiated CBD Treatment Claims
On October 31, 2017, FDA issued Warning Letters to four companies—Greenroads Health,7 Natural Alchemist,8 That’s Natural! Marketing and Consulting,9 and Stanley Brothers Social Enterprises LLC10—citing unsubstantiated claims related to more than 25 different products sold online that allegedly contain cannabidiol (CBD), a component of the marijuana plant that is not currently FDA-approved in any drug product for any indication.
These actions were not surprising given Commissioner Scott Gottlieb’s testimony before Congress last year, during which he addressed the agency’s role in cracking down on such claims and said that FDA would “have some answers . . . soon because I think we do bear some responsibility to start to address these questions.”11
The companies receiving the Warning Letters made claims regarding their products preventing, reversing, or curing cancer, killing/inhibiting cancer cells or tumors, or other similar anti-cancer claims. More specifically, the companies said about their products:
- “Combats tumor and cancer cells;”
- “CBD makes cancer cells commit ‘suicide’ without killing other cells;”
- “CBD . . . [has] anti-proliferative properties that inhibit cell division and growth in certain types of cancer, not allowing the tumor to grow;” and
- “Non-psychoactive cannabinoids like CBD (cannabidiol) may be effective in treating tumors from cancer – including breast cancer.”
Some of the products were also marketed as an alternative or additional treatment for Alzheimer’s and other serious diseases.
This is not the first time the agency has taken enforcement action against firms selling CBD products with unsubstantiated claims.12 However, FDA’s October 2017 actions will no doubt have a chilling effect on marketing efforts in the rapidly-expanding medical marijuana industry. Leaving no doubt about what industry can expect, Commissioner Gottlieb said that “[w]e don’t let companies market products that deliberately prey on sick people with baseless claims that their substance can shrink or cure cancer and we’re not going to look the other way on enforcing these principles when it comes to marijuana-containing products.”13 The agency is not alone in addressing cannabis product marketing practices. For example, in September 2017, the Office of the Attorney General (OAG) of Washington State sent a letter to marijuana retailers in which OAG reminded industry of the State’s ban on making curative or therapeutic claims in marijuana advertisements, including on websites. In the letter, Shannon Smith, Senior Assistant Attorney General and Chief of the Consumer Protection Division, said that despite the State’s prohibition, her office has investigated several marijuana retailers for making medical claims on their websites.
As noted above, FDA has not approved marijuana, a Schedule I controlled substance, for any indication. However, the agency has approved Marinol® and Syndros™ for therapeutic uses, including for the treatment of anorexia associated with weight loss in AIDS patients.14 Marinol® and Syndros™ include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive component of marijuana. Another FDA-approved drug, Cesamet™, contains the active ingredient nabilone, which has a chemical structure similar to THC and is synthetically derived.
FDA has indicated that it supports access to investigational drugs derived from marijuana. For example, the agency granted an investigational new drug application (IND) for a Phase II/III clinical trial of Epidiolex® (cannabidiol) in the treatment of Dravet Syndrome. In October 2017, GW Pharmaceuticals announced that it completed its rolling new drug application (NDA) submission to FDA for Epidiolex® (cannabidiol) as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, two highly treatment-resistant forms of childhood-onset epilepsy.15 GW Pharmaceuticals announced on December 28, 2017 that FDA had accepted the company’s Epidiolex® NDA filing for priority review, and that the Prescription Drug User Fee Act (PDUFA) goal date for completion of agency review of the same is June 27, 2018.16 If FDA approves the NDA, the drug would be subject to U.S. Drug Enforcement Administration (DEA) scheduling, a decision which industry will follow closely. While marijuana is a Schedule I drug, meaning DEA believe it has “no currently accepted medical use and a high potential for abuse,” it will be interesting to see how DEA schedules Epidiolex®, particularly in light of GW Pharmaceuticals’ completion of a clinical trial assessing the abuse potential of CBD in October 2017. If DEA believes Epidiolex® has a low potential for abuse and low risk of dependence, it could schedule the drug as Schedule IV.
As Commissioner Gottlieb completes his first year at FDA, the agency he leads shows no signs of slowing down. It will be interesting to see if/how Gottlieb, his deputies, and FDA staff:
- Build on the lessons learned from Pre-Cert program participation, and use those lessons to inform digital health policy development, broadly;
- Reshape the agency’s approach to tobacco products regulation, and finally put in place tenable regulations that acknowledge that certain tobacco products present more risk than others;
- Continue to respond to claims made about CBD products that have not been approved by the agency; and
- Decide on CBD drug product applications before the agency.
Jonathan A. Havens is an attorney at Saul Ewing Arnstein & Lehr LLP, where he is co-chair of the firm’s Cannabis Law Practice, vice chair of the firm’s Food and Beverage Practice, and a member of the firm’s Life Sciences Practice. He counsels clients on regulatory, compliance, enforcement, and transactional matters related to products regulated by, among others, the U.S. Food and Drug Administration (FDA), the Federal Trade Commission (FTC), the U.S. Department of Agriculture (USDA), the U.S. Drug Enforcement Administration (DEA), the U.S. Consumer Product Safety Commission (CPSC), and myriad state agencies.
- See FDA, Digital Health Innovation Action Plan, https://www.fda.gov/downloads/MedicalDevices/DigitalHealth/UCM568735.pdf (last visited Mar. 11, 2018).
- FDA, “FDA Announces New Steps to Empower Consumers and Advance Digital Healthcare,” July 27, 2017, https://blogs.fda.gov/fdavoice/index.php/2017/07/fda-announces-new-steps-to-empower-consumers-and-advance-digital-healthcare/.
- FDA, “FDA selects participants for new digital health software precertification pilot program,” Sept. 26, 2017, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm577480.htm.
- See FDA, Guidance- “Deciding When to Submit a 510(k) for a Change to an Existing Device,” Oct. 25, 2017, https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm514771.pdf; FDA, Guidance- “Deciding When to Submit a 510(k) for a Software Change to an Existing Device,” Oct. 25, 2017, https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm514737.pdf; and FDA, Draft Guidance- “Breakthrough Devices Program,” Oct. 25, 2017, https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM581664.pdf.
- FDA, “FDA announces comprehensive regulatory plan to shift trajectory of tobacco-related disease, death,” July 28, 2017, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm568923.html
- FDA, Deeming Tobacco Products to Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products; Final Rule, 81 Fed. Reg. 28,974 (May 10, 2016) (codified at 21 C.F.R. Parts 1100, 1140, and 1143).
- FDA, Warning Letter issued to Green Roads of Florida LLC, Oct. 31, 2017, https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm583188.htm.
- FDA, Warning Letter issued to Natural Alchemist, Oct. 31, 2017, https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm583205.htm.
- FDA, Warning Letter issued to That’s Natural, Oct. 31, 2017, https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm583197.htm.
- FDA, Warning Letter issued to Stanley Brothers Social Enterprises, LLC, Oct. 31, 2017, https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm583192.htm.
- Michelle Cortez, “FDA Hints It May Look Into Marijuana Health Claims,” Bloomberg, Oct. 3, 2017, https://www.bloomberg.com/news/articles/2017-10-03/fda-hints-it-may-look-into-medical-marijuana-health-claims.
- See, e.g., FDA, Warning Letters and Test Results for Cannabidiol-Related Products, https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm (last visited Mar. 11, 2018).
- FDA, “FDA warns companies marketing unproven products, derived from marijuana, that claim to treat or cure cancer,” Nov. 1, 2017, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm583295.htm.
- FDA, “FDA and Marijuana: Questions and Answers,” https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm421168.htm (last visited Apr. 9, 2018).
- GW Pharmaceuticals, “GW Pharmaceuticals and Its U.S. Subsidiary Greenwich Biosciences Completes Rolling New Drug Application Submission to U.S. Food and Drug Administration for Epidiolex® (cannabidiol) in the treatment of Lennox-Gastaut syndrome and Dravet syndrome,” Oct. 30, 2017, https://www.gwpharm.com/about-us/news/gw-pharmaceuticals-and-its-us-subsidiary-greenwich-biosciences-completes-rolling-new.
- GW Pharmaceuticals, “GW Pharmaceuticals Announces Acceptance of NDA Filing for Epidiolex® (cannabidiol) in the treatment of Lennox-Gastaut syndrome and Dravet syndrome,” Dec. 28, 2017, https://www.gwpharm.com/about-us/news/gw-pharmaceuticals-announces-acceptance-nda-filing-epidiolex%C2%AE-cannabidiol-treatment.