Keeping track of the Food and Drug Administration’s enforcement of advertising and promotion of drugs, devices, and biologics is a challenging task that requires constant monitoring. At this year’s 2015 DIA Annual Meeting in Washington, DC, FDA representatives from the Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER) provided a good summary of enforcement activity and priority areas that manufacturers should take note of.
CDRH Update: Promotion and Advertising of Devices
Deboarah Wolf spoke from her perspective as Regulatory Counsel within the Division of Premarketing and Labeling Compliance (DPLC) of CDRH’s Office of Compliance. The DPLC enforces premarket clearance and approval requirements, as well as labeling and promotion and advertising requirements for medical devices. Wolf focused on a number of particular products and promotional activities that have drawn DPLC’s ire.
Devices promoted without approval or without a prescription
Decorative Contact Lenses, which Wolf noted are Class II or Class III prescription medical devices, have been sold at dollar stores or street kiosks either without a prescription or that are unapproved. There was also an increase in websites offering these decorative lenses for sale without a prescription—including lenses offered on Ebay and Amazon. Wolf noted that FDA, along with the FTC, sent a warning to these websites in 2013, resulting in 64 percent compliance—either the site shut down or began requiring prescriptions—within just a few weeks.
Devices approved as low risk promoted for uses associated with high risk devices
Class I Nasal Splints Marketed Off-Label as Class III Dermal Fillers: Wolf highlighted an off-label promotion case whereby a product registered as an “intranasal splint,” (a low risk Class 1 lubricating gel, intended to minimize bleeding and prevent adhesion between the septum and nasal cavity after surgery) was being marketed to dermatologists to fill in facial wrinkles. Other devices approved as “dermal fillers” are class III devices, and indeed off-label uses of the splint allegedly resulted in numerous adverse events to patients.
Wolf also noted that problematic promotion includes when manufacturers promote devices cleared under a 510(k) as being substantially equivalent to one device, and then promoting it for a separate use that would constitute a “major change.” She also spoke to certain off-label promotions that expanded the use of a device and resulted in serious patient harm. One example was a bone growth protein approved by CDRH that was promoted off-label for use in an unapproved portion of the spine that resulted in patients suffocating.
Misleading claims
Wolf was critical of device companies who, in the review process make commitments about what they will not say in labeling, but as soon as the product gets on the market, will include these claims in brochures and on websites. For example, she included a snippet from a Warning Letter targeting contact lenses again, which stated in part: “[Y]our firm ‘s promotional materials show the “HD High Definition” representation on the carton labeling of the PureVision 2 contact lenses even though FDA specifically objected to the inclusion of this representation in the labeling due to insufficient performance data during the course of review of the PMA supplement for these lenses.”
Independent off-label promotion of devices by healthcare practitioners
While there is a fair amount of overlap between the types of drug and device promotion that results in enforcement, there are some notable differences. One difference in particular is where practitioners, who buy the products and then need to recoup the costs, will themselves promote the device. Wolf stated that some practitioners “promote unapproved uses and provide no risk information,” and that companies may not always dissuade such promotion. An example of this includes eye care professionals’ promotion of Lasik, Wolf noted. Healthcare practitioners don’t often independently promote drugs, she noted.
Comparative claims to other FDA-regulated products
Wolf also ran through a number considerations for companies looking to make comparative claims. First, a product is misbranded if the labeling makes misleading comparisons to other FDA-regulated products. FDA requires head-to-head trials for such comparative claims. Wolf also noted that “‘substantially equivalent’ does not mean ‘much better’ than a predicate device;” nor does “safe and effective” mean “safer and more effective.”
CDER Update: Promotion and Advertising of Drugs
Thomas Abrams of CDER’s Office of Prescription Drug Promotion split his presentation into two sections—first providing a high level overview of the seven guidance documents OPDP has released since 2014, and second, highlighting one case that implicated a number of priority areas for the agency.
Indeed, OPDP has been busy issuing a number of guidances related to social media, how manufacturers may distribute scientific and medical publications on unapproved new uses, new recommendations for disclosing risk information in consumer advertisements, and most recently, OPDP’s document outlining firms’ responsibilities to submit promotional materials in electronic formats. Abrams made clear that the agency was working to align its guidance with First Amendment considerations, but did not specify a date for a promised guidance on manufacturer communications regarding unapproved uses.
On the enforcement side, Abrams noted that the most common violations cited in OPDP regulatory letters since January 2014 were: omission and minimization of risk information; unsubstantiated superiority claims; and overstatement of efficacy claims.
He specifically brought up an untitled letter to Mission Pharmacal Company’s Tindamex product. The promotional materials for the drug–approved for bacterial vaginosis–touched on numerous priority areas for OPDP. These included unsubstantiated superiority claims as well as omission of risk information–the materials promoted efficacy claims but failed to present any contraindications or common adverse reactions.
CBER Update: Promotion and Advertising of Biologics
Lisa Stockbridge, Ph.D, the Branch Chief at CBER’s Advertising and Promotional Labeling branch began by noting that CDER and CBER share guidance documents, and thus promotional guidances for drugs are applicable to biologics as well. CBER products include blood and blood components; vaccines; allergenic extracts; human tissue and cellular products; gene therapy products; and biological devices and test kits.
Stockbridge noted that common issues within CBER were similar to the drug side, including where companies expand the indication of their products, comparison/superiority claims without adequate support; and absence of risk information.
She also highlighted an enforcement action from March 2015—an Untitled Letter directed at Protein Sciences Corporation for a video interview posted on their website. The interview addressed the product FLUBLOK, and in it, the CEO of the company states that FLUBOK has “three times more protein in there, so it is also a high dose vaccine. More protein means your body will form more antibodies that will help you fight the flu.”
CBER found these claims suggested that higher “antigen content” translated into greater protection for the patient. Specifically, it suggested that more protein is equivalent to a higher dose flue vaccine. However, CBER found no data to substantiate such a claim, and further that the video omitted risk information about FLUBOK.