Courtesy Letters: An FDA communication type you may not be aware of

Most regulatory professionals are well aware of a range of FDA communications, including Warning Letters, Untitled Letters, It Has Come To Our Attention Letters and Form 483s. But a lesser-known type of communication, the Courtesy Letter, is often used by the agency to express concerns with newly marketed dietary supplements. Here’s what you need to know.

Regulatory Background

• Companies are supposed to follow the FDA’s regulations but are not always successful in doing do. Either by accident, through negligence, or on purpose, companies sometimes fail to adhere to legal or regulatory standards. When the FDA finds evidence of regulatory lapses, it may – but is not required to – take action to encourage or require the offending party to become compliant.
• FDA has a menu of options available to it to encourage or compel compliance. For example, following an inspection the FDA may send a company a “Voluntary Action Indicated” letter informing a company of voluntary actions that it may wish to take to make optional improvements. If FDA finds that promotional materials violate its fair-balance standards, its Office of Prescription Drug Promotion may issue an “Untitled Letter” to a company requesting that it immediately make changes to that advertisement. Rarely, the FDA may issue letters to industry known as “It Has Come to Our Attention” (IHCTOA) Letters expressing concern about a likely violation, offering the chance for a company to explain its processes and to come into compliance. And more commonly, the FDA will issue Warning Letters to companies if it believes that a company is in clear violation of regulatory practices or standards. These letters often follow the completion of an inspection with the resulting issuance of an Official Action Indicated finding for which the company did not have a satisfactory response.

While many regulatory professionals are well familiar with the aforementioned types of compliance communications, the FDA also has another type of lesser-known communication: Courtesy Letters.

• While the FDA does not maintain a formal definition of Courtesy Letters – also known as Letters of Objection – they are most often sent to sponsors or manufacturers of dietary supplement products. According to a review of these letters by AgencyIQ, many of these letters make reference to claims made under Section 403(r)(6) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. 343(r)(6)). According to the FDA, “Section 343(r)(6) makes clear that a statement included in labeling under the authority of that section may not claim to diagnose, treat, cure, prevent, or mitigate one or more diseases.”
• This is a core tenet of dietary supplement products. In 1994 the Dietary Supplement Health and Education Act (DSHEA) gave the FDA authority to regulate finished dietary supplement products and dietary ingredients. Under DSHEA, manufacturers are responsible for ensuring their products are safe and any claims made are substantiated with evidence. Dietary supplements may only make claims that their products affect the structure or function of the body, and may not make any claim that a drug is effective at treating or preventing a specific disease. These products do not need approval prior to being marketed unless they contain a new dietary ingredient.
• In essence, if a dietary supplement makes a claim related to the treatment, cure, prevention or mitigation of a disease, this would cause the FDA to no longer regulate it as a dietary supplement. Rather, under the terms of 21 U.S.C. 321(g), the article would be considered a drug, and therefore require the product to undergo review through the submission of an NDA.
• In practice, it is not uncommon for dietary supplement companies to violate this regulatory tenet. But rather than send each of these companies a Warning Letter informing them of their likely violations, instead the FDA often issues Courtesy Letters.
• There are other requirements for dietary supplements as well, including that they be “intended to supplement the diet.” Dietary supplements are, by definition, meant to be ingested, but not “represented for use as a conventional food or as a sole item of a meal or the diet,” and must be labeled accordingly.
• According to AgencyIQ’s review, the FDA has sent more than 1,000 Courtesy Letters to companies since June 2003, the oldest year we were able to identify. (We are quite sure there are older letters; however, they are not available on Regulations.gov as the website was only launched in 2003.) Most of these letters were sent by the FDA’s Center for Food Safety and Applied Nutrition (CFSAN), its center in charge of regulating the safety of food products, including dietary supplements. However, in rare circumstances Courtesy Letters have also been issued by the FDA’s Center for Veterinary Medicine (CVM), which oversees veterinary medical products.

What a Courtesy Letters conveys

• In general, Courtesy Letters have a common format, with a focus on brevity, clarity, and the basics of dietary supplement regulation. Take, for example, a June 2018 letter to Pricklee, a company marketing a cactus-based beverage. The FDA’s Courtesy Letter contains just two paragraphs of substantive content notifying the company that its beverage was represented as “a conventional food or as a sole item of a meal or the diet,” and is therefore “not a dietary supplement.”
• In another example of a letter sent to Nzuri Gold, the FDA cited the company’s “Awali Ital Body Cleanser” for its claims to “revitalize, rejuvenate and heal the user’s skin.” FDA took issue with claims made by the company, including that its product cleanses the skin. Dietary supplements are intended to be ingested, rather than used upon the body, and therefore the product was determined by FDA to not be a supplement.
• Missing information may be cited as well in the letters, such as this letter to a New York-based manufacturer cited for an application that failed to include essential information about who was expected to make and distribute the product, as well as a required statement that the product has not been evaluated by the FDA and “is not intended to diagnose, treat, cure, or prevent any disease.”
• In many other examples, the FDA cites companies for making prohibited claims. Take, for example, this May 2018 letter to Pronaphyt. FDA notes that the company claimed its product could be used “as an anti-inflammatory to help relieve joint pain.” As the FDA explained in its Courtesy Letter, this claim would cause the product to be a drug, requiring review by FDA’s Center for Drug Evaluation and Research under an NDA.
• It’s worth noting that these letters almost always refer to a specific notification sent to the FDA, known as a Structure/Function Claims Notification. Under the FD&C Act (Section 403(r)(6)), companies wishing to make, pack or distribute a dietary supplement are required to notify the FDA “regarding the statement on the label or in the labeling of its product.” This process is different than pre-market approval, since companies must send the Notification within 30 days of first marketing the product.
• In rare cases, Courtesy Letters have also been used to notify sponsors of voluntarily withdrawn products. In February 2012, CVM issued such a letter to six sponsors of 20 New Animal Drug Applications that had been withdrawn.
• While many regulatory professionals might not have heard about Courtesy Letters, they are remarkably common. So far in 2022, between January 1 and August 23, FDA has sent 143 Courtesy Letters. In 2021, FDA sent 236 Courtesy Letters, and 163 in 2020. According to Regulations.gov, the agency did not send any Courtesy Letters in 2019, 2017 or 2016, although it sent 126 in 2018 and 37 in 2015. However, it appears that this may be the result of gaps between when letters were sent and when they were posted to Regulations.gov. For example, this letter indicates that it was sent in 2017, but it was only posted to the federal docket in 2018.
• Courtesy letters are comparable in some ways to what FDA calls an “Untitled Letter.” Per the FDA, “Untitled letters are used for violations that may not meet the threshold of regulatory significance for a warning letter and request correction of the violations.” Courtesy letters share a wide variety of similarities in that they can be viewed as an initial form of notification that the FDA is aware of the violation and serve to document the deficiency. Another similarity is that both do not explicitly warn the applicant of an impending enforcement action if the violation is not addressed and per the FDA, allow “the firm to come into compliance without further FDA action.”

Other thoughts

• While Courtesy Letters may be better known to some companies than others (and in particular sponsors of dietary supplement applications), little else is publicly known about them. Based on our research, there don’t seem to be any internal or external facing policies, such as a manual of policies and procedures, compliance guide or Regulatory Procedures Manual explaining how the FDA formulates or issues a Courtesy Letter.
• As with Untitled Letters, while Courtesy Letters don’t directly threaten action, it would be unwise of a company to ignore its suggestions. Failure to make corrections can result in a company receiving a Warning Letter or other regulatory enforcement from CFSAN or FDA’s Office of Regulatory Affairs. This is especially true for Structure/Function Claims since companies typically begin marketing the product prior to FDA’s review.
• Based on the data we reviewed, FDA appears to be sending more Courtesy Letters in recent years. While we aren’t entirely sure if the Regulations.gov database contains all Courtesy Letters from the agency (and we do know that some letters aren’t posted in the same year in which they were issued), if the numbers are accurate it would indicate that FDA sent more Courtesy Letters in 2021 than in any year since at least 2003, and perhaps ever. We aren’t aware of any statements by the FDA indicating why that might be the case, or why the use of Courtesy Letters appears to have increased substantially since 2018 (with the exception of 2019, when it did not appear to release any).

To contact the authors of this item, please email Bennie Johnson and Alexander Gaffney.
To contact the editors of this item, please email Alexander Gaffney and Kari Oakes ( [email protected]).

Key Documents and Dates

• Courtesy letters listed on regulations.gov
• Final guidance: “Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act”