Recent regulatory action from the Food and Drug Administration (FDA) was a hot topic at the American Conference Institute’s fourth annual Legal, Regulatory and Compliance forum on Dietary Supplements, held June 27-28 in New York, NY. Industry experts analyzed the FDA’s recent enforcement actions against manufacturers and marketers of dietary supplements, and discussed how leaders in the space can be prepared for meeting the demands from regulators and consumers alike in the post New York Attorney General world.

Steven J. Tave, acting director FDA’s newly formed Office of Dietary Supplement Programs for the Center for Food Safety and Applied Nutrition, outlined the agency’s enforcement actions, which has included the issuing of Warning Letters addressing mislabeled or unapproved ingredients, companies failing to follow current Good Manufacturing Practices (cGMPs), as well as more serious judicial actions such as seizures and injunctions.
 
The majority of FDA’s actions were in the form of Warning Letters, which Mr. Tave said fell into three major categories: misbranding (403(a)(1)) in the form of false or misleading labels, adulteration from companies using ingredients not properly filed for New Dietary Ingredient Notification (NDIN) (402(f)(1)(B), 413), and adulteration from ingredients posing a significant or unreasonable risk of illness or injury (402 (f)(1)(A)).
 
“cGMP enforcement is a big deal for us. The dietary supplement cGMPs have been in effect now for almost 10 years, and the level of compliance we’re seeing overall in our inspections is, frankly, inadequate,” stated Mr. Tave.
 
Good Manufacturing Practices set the groundwork for procedures FDA expects will be in place to ensure quality and safety prior to supplements hitting store shelves. “It’s not feasible to test every single product for quality after it’s produced.” However, Mr. Tave said cGMP adherence puts in place sound manufacturing procedures that will ensure quality output.
 
“There are companies and firms out there who are doing a good job,” he observed. “But there are also those who are not doing a good job, and that’s where we’re going to have increase enforcement.” He added FDA is not “nitpicking … We’re talking about a very basic level of cGMP compliance.”
 
Enforcement of cGMPs has increased in recent years, with roughly 500 inspections taking place annually. Mr. Tave noted that, on average, there are about 70-80 Warning Letters a year just for cGMPs alone. He said be believes the number of Warning Letters for 2016 will be in line with this range as well.
 
Discussing the most frequent violations of cGMPs, Mr. Tave noted the leading issue was companies not establishing finished batch specifications. Finished batch specifications are set in place for each product to document the identity, purity, strength and composition of a finished product, as well as to establish limits on the types of contamination that could adulterate or lead to the adulteration of a dietary supplement.
 
Other common violations include companies not preparing and following a written Master Manufacturing Record (MMR) for each batch size of dietary supplements manufactured (111.205 (a)), or failing to conduct at least one appropriate test or examination to verify the identity of a component that is a dietary ingredient(111.75(a)(1)(i)).
 
Within the past year, injunctions have mostly been the result of unclassified NDIs. Mr. Tave said the sweeping injunction cases last year, which led to civil and criminal charges against manufacturers and marketers of dietary supplements, were, for the majority, a result of supplements containing unapproved new drug(s).
 
Office of Dietary Supplement Programs Goals
While members within the industry can feel targeted by the uptick in regulatory action, Mr. Tave said the new Officeof Dietary Supplement Programs’top priority is protecting consumers from dangerous goods. “Our number one priority, above all else, is consumer safety,” he said.
 
Looking ahead, the Office’s top enforcement goals include:

• Taking action to remove from the market supplement products that are dangerous to consumers;
• Taking action to ensure the integrity of product identity;
• Taking action to enforce dietary supplement cGMPs;
• Taking action against claims in cases involving serious risk of harm to the consumer (such as egregious claims of benefits in treating serious diseases) or widespread economic fraud.

 
Avoiding Warning Letters
According to Ashish Talati, JD, MS, RAC, with Amin Talati & Upadhye, LLC, Chicago, IL, in 2016, 52 out of 247 Warning Letters (21%) related to manufacturing of dietary supplements. “We see a lot of these Warning Letters are related to cGMPs, and you see they’re getting very granular. They do hit on those high level specification issues and MMRs, but they also do dig into cGMPs,” Mr. Talati explained. Furthermore, nearly half of these Warning Letters were in response to cGMP violations.
 
Last year there were around 500 FDA inspections, and Mr. Talati said roughly one in four of these inspections resulted in FDA Form 483s within the dietary supplement space. “So we’re looking at roughly 125 Form 483s,” he said. “So my point is not all Form 483s have to result in a Warning Letter. There is a lot you can do as a company to avoid getting a Warning Letter, and it’s up to you if you want to avoid that.”
 
While there is no legal requirement to respond to a Form 483, Mr. Talati believes it’s in the company’s best interest to address the issue head on and open a dialogue with FDA. He said responding in a timely manner establishes a level of credibility and demonstrates a company’s understanding of regulation and a commitment to compliance.
 
When responding, Mr. Talati advised that companies address each observation from FDA verbatim (for ease of review), and respond to each assessment clearly. In addition, a corrective action plan should be set in place to address the issue, as well as a preventive measure to ensure such issues will not persist in the future.
 
Corrective and preventive actions plans should include documentation of employee training, photos, evidence of updated Standard Operating Procedures (SOPs), and results of retested batches of ingredients. “Documentation is key,” said Mr. Talati. “Don’t just say it. Prove it.”