ACI-CRN Legal, Regulatory and Compliance Forum: ‘The whiplash with everything going on this year can be a little disorienting'

Co-hosted by the American Conference Institute (ACI) and the Council for Responsible Nutrition (CRN) ​– the conference highlighted the latest policy, regulatory, and business developments affecting the state-of-play of an industry marked by unprecedented regulatory activity and open-ended questions. 

“The whiplash with everything going on this year can be a little disorienting; it’s a lot to keep up with,” Taneesha Routier, director of regulatory affairs at Xymogen, said in her opening remarks as conference co-chair.

Some of the issues top of mind: the implications of the draft guidance on new dietary ingredient (NDI) notification​ and the proposed investigational new drug (IND) amendments​, the potential crossover of FDA’s updated definition of “healthy” to dietary supplements, the rigor of good manufacturing practice (GMP) inspections, the unexpected Federal Trade Commission (FTC) claim substantiation guidance, the fate of mandatory product listing, packaging challenges across a patchwork of states​, combatting counterfeit and ensuring product quality, and avoiding class action lawsuits and inadvertent missteps in advertising.

Fellow conference chair Megan Olsen, senior vice president & general counsel ​at CRN, ​called for unity, noting that “the industry regulations and policies are bigger than any one company” in the face of current challenges that are “unique in both their number and type”.

“I like to think of this meeting as the neighborhood watch of the industry,” Routier added. “We want to make sure that we are able to shine while the light is on the industry.”

FDA paying attention, focused on safety​

Gerie Voss, director of the Division of Policy and Regulations Implementation at the Office of Dietary Supplement Programs (ODSP) ​at the Food and Drug Administration (FDA), spoke about the efficiencies and prioritization expected to come out of the recent reorganization of the Human Foods Program and the new leadership hires at ODSP. 

“We really hope and believe that this will be more effective and allow for quicker decision on evolving issues,” she said. “The Agency needs to modernize itself to quickly respond to these types of issues.”

Interviewed by Steve Mister, president & CEO at CRN, Voss highlighted that FDA continues to focus on safety, whether for overages (which it requires but for which it does not have preset allowances), CBD (which it does not believe meets the expectation of safety), N-acetyle cysteine (which remains on FDA’s to do list), or product packaging (which should be fit for purpose regardless of sustainability practices).

In terms of guidance and regulation, she said that the pathway for CBD now lies with Congress​, there is no intention to remove N-acetyle cysteine (NAC) guidance​ pending rulemaking or a major safety risk, mandatory product listing​ would provide needed visibility and an enforcement hook in the marketplace, and the release of an initial section of the NDI guidance​ is a near-term project.

She also noted that industry is responsible for product integrity and addressing any questions that may arise from consumers about dietary supplements in the media​. 

FTC synthesizing experience, looking upstream​

Top of mind was the recent issuance of the Federal Trade Commission (FTC) Health Products Compliance Guidance​ and the nearly 700 notice letters​ that followed shortly thereafter. These caught industry off guard and prompted most to question why they had not been given any advanced notice. 

Christine DeLorme, attorney in the division of advertising practices at FTC, explained that the non-legally binding business guidance, unlike items voted on by the Commission, are not put out for comment and are intended to provide guardrails for industry.

“If you follow FTC law, I don’t think there is anything in here that is really surprising,” she said. “All are derived from cases and investigations that we have been involved in over the last 25 years. What this is really is just synthesizing our experience about what has happened.” 

She added that the new guidance is intended to preserve the high standards for health claims and that she expects the Commission will be more focused on the source of deceptive claims than on the smaller businesses downstream.

Tanaz Dietz, chief legal officer at Vytalogy, advised that companies “close any substantiation gaps” and make “longer term investments to make sure documentation is aligned with guidance.”

Things to look out for: implied disease or deceptive claims (graphics in ads matter), that the science matches the claim, the totality of the evidence counts (including no-effect findings), and that disclaimers are clear and conspicuous.

Preparedness key for GMP investigations​

Manufacturing facility inspection and readiness was also on the agenda as both an issue keeping the panel of industry leaders up at night and as subject of a session that paired Routier with Greer Lautrup, partner at Sidley Austin LLP.​

In view of the explosive growth of the industry, they noted that the Food and Drug Administration (FDA) has only been able to inspect 500 to 600 of the approximately 10,000 registered manufacturing facilities a year. 

“FDA is aware that they aren’t where they want to be,” Greer said. “Not only is FDA trying to get out and do inspections, but they are also trying to cover the backlog from the last few years. It’s really a matter of resources.”

She added that ultimately it is the bad actors garnering Agency attention but that all companies should brush up on their inspection preparedness and practice like “a well-orchestrated ballet” because the FDA is taking things seriously.

Practical tips for handling inspections: locate documents quickly, meet all inspector requirements and requests, have duplicate copies of anything provided to the FDA, compile evidence binders for prior FDA commitments, make sure everyone from the guard station to the subject matter experts know what to do, and be aware that whiteboard notes and dumpster diving are fair game.

Combatting counterfeits and ensuring product integrity​

The panel on dietary supplement integrity brought together the Amazon Counterfeit Crimes Unit (CCU), the Department of Justice (DOJ) and third-part lab Alkemists Labs to discuss how to protect product purity and identify risks along the supply chain. 

Elan Sudberg, CEO at Alkemist Labs, underscored that “not all labs are created equal” and the importance of hiring one with transparent processes and fit-for-purpose testing methods that can provide meticulous certificates of analysis (CoA). He also noted that the “gates for counterfeit products need to be higher”, pointing to the recent case of the fake Fungi Perfecti products sold on Amazon​, not long after NOW Foods detected a range of fraudulent supplement products on the ecommerce platform​.

Joseph Wheatley, senior corporate counsel at Amazon’s CCU, said that the company is closing gaps with its internal proactive controls and “aggressively working to identify bad actors and work upstream”. He screened a company video​ that featured footage of facility searches and affirmed the reach of the task force up the counterfeit chain.

“Our view is that if a brand is impacted by counterfeiting, we want to do everything we can to work with that brand to bring bad actors to justice,” he said.

Patrick Runkle, trial attorney with the Consumer Protection Branch at DOJ, referenced a list of egregious cases​ as examples of when the department has stepped in on behalf of FDA. He also confirmed continued efforts to chase down false CoAs and identify how adulterated ingredients are entering the country.

“Internal documentation is the friend of the industry because of the perception that the industry isn’t regulated,” he added, echoing common conference advice that companies maintain robust documentation for nearly everything.

The search for certainty, cost of uncertainty​

Another critical concern is the confusion surrounding NDIs and INDs and what any new rulemaking might mean for innovation and clinical research in the supplement marketplace. 

At issue are the implications of recent draft guidance on NDI requirements for pre-market notification​, informing manufacturers and distributors of the Agency’s “intent to exercise enforcement discretion, for a limited time and in limited circumstances, to encourage firms to correct past failures to submit an NDI notification”.  

Meanwhile, industry continues to object to FDA’s interpretation of the drug preclusion clause, which does not allow a new dietary ingredient to live alongside an investigational new drug, regardless of dose or route of administration (currently subject of a CRN Citizen Petition​). A panel also looped in the Agency’s proposal to exempt certain clinical investigations of dietary supplements from IND requirements – presenting the conundrum as to whether that would clear a major roadblock for the supplement industry or risk triggering drug preclusion.

“For investigators to get published, they need to look at something that publishers will find interesting and that is usually disease states,” Yasmeen Nkrumah-Elie, Ph.D., global director for external research at ChromaDex, noted.

In this muddle, there was a repeated call for clarity and consistency by panelists so as to avoid the costs associated with uncertainty i.e., investing millions of dollars in research, safety and marketing only to be told that a supplement ingredient is precluded.

“Yes, we want flexibility, even more so, it’s a level of certainty that we want so that we understand how to plan and move forward,” said Todd Halpern, assistant general counsel at ​Haleon.

Despite the whiplash brought on by the rash of activity, several speakers noted that counsel can cull insight from intent to bolster conversations with clients about the potential risks.