2014 FDA Warning Letters: Key Takeaways

Warning Letter. Not since Dear John have two little words at the top of a letter evoked more dread-if you’re a food or a supplement company and the letter is from FDA, that is.

The somewhat-good news? After a steady increase in warning letters every year-starting with 104 issued in the first three months of 2009 and culminating in 208 warning letters generated and posted by FDA through March 2013-the number of warning letters dropped by almost 50% in the first quarter of 2014. Through March of this year, FDA sent 110 warning letters to companies in various industries, including food and supplements. This is the lowest number of warning letters FDA has sent through March of any of the past five years.

However, companies would be ill advised to view any decrease as a sign that the FDA has relaxed its regulatory scrutiny.

Warning Letters

FDA warning letters do not represent final agency enforcement action, as affirmed by the D.C. Circuit Court in January 2012 in the case of Holistic Candlers and Consumers Assoc. et al. v. FDA, (D.C. Cir. 2012). FDA warning letters are essentially a notice from the FDA that the agency believes a company has violated the law, demanding that the company indicate to the FDA how it is going to address the situation. However, as shown with increasing frequency over the last several years, if FDA is not satisfied with a company’s response to a warning letter, further action is likely and can take the form of filing a suit in court, seeking injunctive relief, and forcing companies to shut down. The key is to learn by example. Smart firms will heed the warning letters sent to other companies and preemptively adjust their own operations to avoid becoming the target of an FDA warning letter themselves.

FDA posts new warning letters every Tuesday morning at www.fda.gov. Letters can be searched by the sent date, company name, FDA district office, and subject. Of the 110 letters FDA sent during the first three months of 2014, 44 went to food and dietary supplement companies, and the remainder to medical device, drug, and other companies.

Let’s take a brief look at some of the more common themes of the warning letters sent to food, beverage, and dietary supplement companies.

Dietary Supplement Companies

Current Good Manufacturing Practices for Dietary Supplements (DS CGMPs)

FDA continues to place high priority on ensuring compliance with the DS CGMPs. Despite only four letters posted so far in 2014 addressing alleged failures to comply with the DS CGMPs, companies should know that the FDA continues to inspect dietary supplement companies with fervor to ensure compliance with the DS CGMPs.

In the most recent letter to a dietary supplement company-a March 13, 2014, letter to a Florida manufacturer-FDA alleged a number of DS CGMP violations that were observed during a 2013 inspection of the company’s manufacturing facilities. Cited violations include:

• Failure to conduct at least one appropriate test to verify the identity of a dietary ingredient (21 CFR 111.75(a)(1)(i))

• Failure to qualify a supplier of a component by establishing the reliability of the supplier’s Certificate of Analysis (COA) (21 CFR 111.75(a)(2)(ii)(A))

• Failure to prepare and follow a written master manufacturing record (MMR) for each unique formulation of a dietary supplement (21 CFR 111.205(a))

In a letter to a California supplement manufacturer dated January 22, 2014, FDA cited alleged violations, including:

• Failure to ensure that specification tests were appropriate and used scientifically valid methods (21 CFR 111.75(h)(1))

• Failure to establish and follow written procedures for quality-control observations (21 CFR 111.103)

And in a January 31, 2014, letter to a Pennsylvania dietary supplement manufacturer (the second letter sent to the company in the last two years), FDA identified numerous issues, including the failure to investigate complaints and the failure to submit a Serious Adverse Event Report (SAER), as required by the DS CGMPs and the Dietary Supplement and Nonprescription Drug Consumer Protection Act.

It is important to note that, in all three cases, following FDA’s initial inspections and observation of these infractions, the companies had sent written responses to FDA-but the agency found those responses inadequate. A key takeaway? Companies must not simply respond to each observation, but must provide detailed documentation of how any corrections were or will be carried out. Absent a substantial response, a company runs the risk of receiving a warning letter from the FDA.

New Dietary Ingredient Notification

While the dietary supplement industry continues to wait with anticipation for a revised draft guidance from the FDA regarding New Dietary Ingredient (NDI) notifications, FDA representatives have been quick to remind the industry that the obligation to file NDI notifications remains in effect, regardless of the status of any guidance from the agency. With the NDI requirement very much active, recent FDA warning letters have cited companies for failing to meet their NDI obligations.

In its letter to the Pennsylvania company mentioned earlier, FDA indicated that the ingredient 4-etioallocholen-3,6,17-trione is a NDI (assuming it meets one of the criteria for a dietary ingredient). FDA said that a NDI notification is required, unless the company can show proof that 4-etioallocholen-3,6,17-trione has been present in the food supply as an article used for food (which would negate the need for a NDI notification). FDA said that because the company did not submit a NDI notification, the product containing the NDI is considered adulterated.

FDA sent a similar letter to the company in 2012, which also cited the firm’s failure to file a NDI notification for DMAA, an ingredient that underwent much regulatory scrutiny in 2012. While the number of warning letters addressing failures to submit NDI notifications has been sparse, these letters should serve as notice that companies are still at risk of receiving a warning letter from the FDA if a required NDI notification is not submitted.

Disease Claims

FDA sent letters to several companies marketing products that were labeled as dietary supplements but whose claims FDA said cause the products to be deemed drugs.

A January 31, 2014, letter to a dietary supplement company located in Utah highlighted numerous allegations of disease claims made on the company’s website. Examples included “May help fight off viruses, bacteria, toxins, and parasites,” “May provide pain relief for some individuals who have minor arthritis pain,” and claims mentioning the words skin sores, antiseptic, and inflammation.

In a letter to an Oregon dietary supplement marketer dated January 23, 2014, the FDA catalogued claims that included “Fucoidan…[a substance in the product] causes certain types of rapidly growing cancer cells to self-destruct” and “Laminarin [a substance in the product] is a polysaccharide helpful in the prevention and treatment of cardiovascular diseases.”

In the letter to the Utah company, the FDA also cited the use of online metatags like “cancer,” “diabetes,” and “autistic” as indicating the company’s intent to sell a product as a drug.

These letters all serve to reinforce one of the fundamental principles of dietary supplements, as restated in the disclaimer for dietary supplements set forth in 21 CFR 101.93: namely, that dietary supplement products may not be intended to “diagnose, treat, cure or prevent any disease.”

Labeling Violations

Finally, FDA warning letters to food and supplement companies often cite labeling violations. In several letters-including a February 11, 2014, letter to a California company that packages and distributes dietary supplements-alleged labeling violations included:

• Failure to list vitamins and minerals in the proper order

• Failure to list “Other Ingredients” outside of the Supplement Facts Panel

• Failure to list parts of the plant for botanical ingredients

• Failure to include place of business of the manufacturer, packer, or distributor

• The inconsistency of serving size (1 capsule) versus recommended use (2-3 capsules, three times daily)

Expiration dating is another labeling area that FDA warning letters have frequently cited over the last several years. Companies have no regulatory obligation to include an expiration date, shelf life date, or “best if used by” date. However, as confirmed by letters addressing expiration dates, if a company does include such information on a label, it “should be supported by stability data [See 72 Fed. Reg. 34752, 34856 (June 25, 2007)],” FDA says.

While, at the outset, some labeling violations may seem very technical and minor in nature, there are much bigger implications, as far as warning letters go. Observing labeling violations will often lead FDA to pay closer attention to other aspects of a company’s business. Ensuring that all labeling is compliant is the best way for companies to avoid this added scrutiny.

Food Companies

Food CGMP/Unsanitary Conditions

The food business can be a dirty business-or, at least, the FDA believes so. The majority of FDA warning letters to food companies highlighted food safety. The bulk of warning letters to food companies addressed perceived deficiencies in food safety plans, or observations made during facility inspections of some egregiously unsanitary conditions. Of note, due to the potential health risk created by unsanitary conditions, the time frame in which these warning letters were sent was often shorter than the normal turnaround.

Examples include letters to several bakeries that were sent just over a month after the closeout of inspections of the companies’ manufacturing facilities. In a letter to a Washington bakery on March 6, 2014, FDA detailed the rampant presence of rodent pellets in the bakery’s production facilities, which violates food CGMPs requiring sanitary conditions.

Other letters to food companies identified potential contamination situations. A February 12, 2014, letter to a Connecticut whey powder manufacturer disclosed the finding of Salmonella during an inspection of the manufacturing facility. A January 23, 2014, letter to a New York cheese processor documented the discovery of Listeria monocytogenes during an inspection. And a January 21, 2014, letter to a California pistachio processor described finding Salmonella during an inspection.

Seafood processors and importers amassed more warning letters than any other group of food companies: a total of 22 warning letters in January–March 2014. The primary focal point seems to be non-compliance with the seafood Hazard Analysis and Critical Control Point (HACCP) regulations of 21 CFR Part 123.6(g) and the CGMPs for foods. Warning letters to seafood processors-like one sent to a Connecticut processor on March 24, 2014-often allege failure to implement HACCP plans, as well as failure to meet food CGMPs, creating potentially dangerous and unsanitary conditions. Seafood importers, such as the recipient of a letter dated March 6, 2014, are usually alleged to be in violation of 21 CFR 123.12, which requires importers to take affirmative steps to ensure that imported seafood complies with HACCP regulations.

Especially following media coverage surrounding several Iowa egg farms that produced a nationwide Salmonella scare, egg farms have received their share of FDA attention and warning letters. Five egg farms received warning letters during January–March 2014 for alleged violations, ranging from the failure to implement proper pest-control procedures for rodents and insects to the failure to keep wildlife out of the facilities, in violation of the shell egg regulations and the Public Safety Act.

Warning letters aren’t just limited to companies on the ground. An airline services company received a 2014 warning letter for alleged food issues that could contribute to safety concerns. In a letter dated March 24, 2014, the FDA asserted that a 2013 inspection of the company observed numerous violations of the Public Safety Act.

Labeling Violations

Labeling issues frequently prompt warning letters to food companies as well. In the first quarter of 2014, only one warning letter addressed labeling issues related to a food company. The January 21, 2014, letter to a Wisconsin snack food company cited a number of alleged labeling violations, in addition to alleged CGMP violations and other issues. Alleged labeling violations included:

• Failure to properly identify a color additive

• Failure to identify a food allergen (milk)

• Failure to list nutrition information properly, pursuant to 21 CFR 101.9

• Improper use of nutrient content claims like “high in fiber.” (A “high in fiber” claim should only be used when a food contains at least 20% or more of the recommended daily intake (RDI), or daily reference value (DRV), but the company’s product only contained 2% fiber.)

Beverage or Supplement?

A March 27, 2014, letter to a Las Vegas marketer of liquid products is the first warning letter FDA has issued since the agency released its Guidance for Industry: Distinguishing Liquid Dietary Supplements from Beverages in January 2014. In the letter, the agency determined that the products were “represented for use as a conventional food,” despite use of the term “dietary supplement” below the nutrition information.

FDA cited a litany of factors that caused it to deem the products beverages, and not supplements:

• The use of a Nutrition Facts Panel

1. References on the company’s website to the products as “#1 relaxation beverage” and “the most potent relaxation drink”
2. Descriptions of the products as beverages on the product labels
3. Ingredients, appearance, and packaging similar to that of typical beverage products

Because FDA considers the products to be beverages, the agency said that one of the products’ ingredients, melatonin, is present in the products as an unapproved food additive, without evidence of being Generally Recognized as Safe (GRAS). FDA also asserted that the safety of melatonin and its use in conventional food products is still in question. The FDA took a similar stance on melatonin in warning letters sent to companies in 2011 for liquid products and brownies containing melatonin.

This recent letter reinforces the notion that marketers must be consistent in the marketing and advertising of products as supplements or beverages. 

The Rest of the Year

While the FDA was less active with warning letters during the first quarter of 2014 compared to previous years, companies should not expect the same for the remainder of 2014. As always, CGMP compliance and food safety will continue to be high priorities of the FDA, and inspections will continue with frequency.

Companies should be especially vigilant if they operate in areas covered by recently revised or final FDA guidances. Companies should expect FDA to continue issuing warning letters related to the recently released, final guidance on beverages versus supplements, just as the medical foods industry last year saw increased FDA attention after the agency revised its medical foods guidance.

In addition to beverages and supplements, be aware that these upcoming regulatory developments could influence the FDA warning letters we’ll see later this year: 1) FDA’s “gluten free” regulation, set to go into effect in September, 2) pending revisions to NDI notification guidance, and 3) pending revisions to the guidance for the labeling of ingredients as “evaporated cane juice.”

Most importantly, if that letter with the dreaded words Warning Letter should come, companies should take it very seriously and address it comprehensively to avoid subsequent action from the FDA.

* This article is issued for informational purposes only and is not intended to be construed or used as general legal advice. The opinions expressed are those of the author exclusively.