2014 FDA Warning Letters Summary

2014 FDA Warning Letters Infographic

By Curtis Walcker, M.S.
January 20, 2015

In 2014, 31 of 71 (44%) of FDA Warning Letters sent to dietary supplement companies cited label violations. Compared to 2013, the number of label Warning Letters, as well as the percent were virtually the same (30 letters and 45%, respectively). The Supplement Facts panel, ingredient statement, and statement of identity were the label components holding the most violations. Specifically, the most cited violations (by number of Warning Letters) were improper statements of identity, failing to include the plant parts from which botanical ingredients were derived, and failing to declare ingredients in the ingredient statements, such as the ingredients of capsules.

2014 FDA Warning Letters Summary

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Does The Practice of Having a Weight Range of 95% – 105% Produce a Misbranded Product for Class I Nutrients?

Andy Swenson
November 17, 2014

weight-varianceA common practice within the Dietary Supplement industry is to manufacture a solid dose batch using a weight range of ± X%, where X equals the percentage over/under a Target weight (100%) and Target equals the minimum weight at which all of the label claim is delivered plus any amount added for shelf life overages. Some companies claim this practice yields misbranded product per the labeling regulations found in 21 CFR Part 101.9 because, statistically speaking, approximately half of the batch will be under 100% and all product which contain Class I nutrients must be at 100% of label claim. While this statement is true (half the batch would fall under 100%) it does not necessarily make the batch misbranded. This review will (i) provide a clear understanding of the sampling and testing methods used to verify label claims, (ii) provide a clear under-standing of what constitutes a misbranded product, and (iii) determine if using a weight range of 95% – 105% yields product that is suitable for distribution (not misbranded).

GENERAL PRACTICE

Dietary supplement solid dosage forms, such as capsules, tablets & softgels, but hereafter referred to only as capsules, are formulated to meet specific nutrient claims stated on the product label. This is done by calculating the quantity of a material required to meet the label claim based on its purity. Then, depending on the number of capsules per serving, i.e. 3 capsules per serving, the amount is converted into the weight of the material required for a single capsule. The resulting capsule weight is referred to as “Target” and represents the exact weight a single capsule must attain to deliver 100% of the nutrients claimed on the label when taken as directed (capsules/serving size).

Because of equipment limitations it is impossible to produce a batch in which each capsule weight is at exactly Target. To compensate for this inherent variation and still ensure the nutrient label claims are delivered, individual capsule weights are allowed to fluctuate within a specified range with the intent of the average capsule weight of the batch to be at or above Target. While this weight range varies between companies it is typically 95%―105% relative to Target (100%).

The conundrum lies in statistical population distribution. Theoretically, if a batch were produced in this manner, half of the capsules would be over Target and half of the capsules would be under Target, i.e. servings would not deliver 100% of the nutrient label claims. Because the labeling regulations require Class I nutrients to be at 100% of the stated label value this approach would produce a batch which is misbranded.

SAMPLING & TESTING

In order to determine if a product is misbranded the compliance requirements must first be understood. Because dietary supplements are categorized as Food, the applicable labeling regulations are found in Part 101―Food Labeling, April 1, 2012 Revision, Section (g).

21CFR PART 101.9 – Food Labeling, (g)(1) & (2)

Paragraphs (g)(1) through (2) describe the sampling plan and composite sample preparation used to verify the nutrient content of a product when compared to its label claim.

The sampling plan consists of obtaining 12 primary containers/units (bottles) at random throughout a batch. Then, a subsample (consumer unit) is taken from each container and combined to form a composite sample. Per the law of averages this represents the entire batch.

21CFR PART 101.9 – Food Labeling, (g)(7)

Once the sampling and testing of a batch is determined acceptance criteria is defined as…

“Compliance of the composite is based on the metric measure specified in the label statement of serving size.”

Based on this and relative to a capsule, the term “Consumer Units” [(g)(2)] is the total number of capsules in a serving. If a label instructs a person to consume 2 capsules, 3 times daily for a total of 6 capsules per day, only 2 capsules (a consumer unit) from each container would be used to make the composite sample. If the directions instructed a person to consume 1 capsule per day then only 1 capsule (a consumer unit) from each container would be used to make the composite sample.

A composite sample comprised of 12 servings is tested to determine the average nutrient content of the batch.

MISBRANDED PRODUCT REQUIREMENTS
21CFR PART 101.9 – Food Labeling (g)(3)

To determine if a batch is misbranded (unsuitable for distribution), the regulations have established the minimum nutrient content, based on type, which must be present in the composite sample, which represents the batch.

Sec.(g)(3) defines two classes of nutrients (ingredient/contents declared in the supplement facts panel):

  • Class I. Added nutrients in fortified or fabricated foods.
  • Class II. Naturally occurring (indigenous) nutrients.

21CFR PART 101.9 – Food Labeling (g)(4)

After segregating the Nutrients, the regulation specifies per Class the amount which must be present in the product when compared to the label.

The regulation states:
A food with a label declaration of a vitamin, mineral, etc. is deemed to be misbranded under section 403(a) of the FD&C Act unless it meets the following requirements:

  • Class I: The nutrient content of the composite is at least equal to the value for that nutrient declared on the label.
  • Class II: The nutrient content of the composite is at least equal to 80 percent of the value for that nutrient declared on the label.
  • The nutrient content does not fall below the stated label claim by a factor less than the variability generally recognized for the analytical method.

(Methods always have inherent variability, which is typically expressed as a percentage (%). It is [generally] established during method validation/verification and varies per method, analyte and product matrix. This variance is usually accounted for when calculating results or when comparing results to the acceptance criteria.)

When compared to the label values the average content of the composite sample must be at least:

  • 100% – Class I / Added Nutrients, or
  • 80% – Class II / Naturally Occurring, and
  • Within (scientifically established) method variability.

21CFR PART 101.9 – Food Labeling (g)(6)

The requirements allow for some content variance when compared to the label if the product was manufactured using current good manufacturing practices (cGMPs).

The regulation states:
“Reasonable excesses of a…

  • vitamin,
  • mineral,
  • protein,
  • total carbohydrate,
  • dietary fiber,
  • other carbohydrate,
  • polyunsaturated or monosaturated fat, or
  • potassium

…over labeled amounts are acceptable within current good manufacturing practice.”

CONCLUSION

To determine if a product is misbranded the FDA makes a composite sample by taking a serving from twelve bottles. This sample, which represents the batch, is based on the law of averages which simply states that a small population represents the larger population. Class I nutrients must be ≥100% of the stated label value and those nutrients specified above may be greater than the stated label value within a reasonable amou.

Because misbranding is determined through composite sampling and averages, statistically speaking the sample should be comprised of an equal number of both over and under-weight capsules. Therefore, if a weight range of 95% – 105% is used it is critical that 1) The average weight of a batch equals Target or greater, 2) Multiple samples are taken throughout the batch, and 3) A composite sample is made from those representative samples. If these three requirements can be met then, statistically speaking, the process should produce a batch suitable for distribution wherein all Class I nutrients are ≥100%

Dietary Supplements: Intended for Ingestion

Guest post by Sarah Eliason
October 19, 2014

ingestionIf you label your product as a dietary supplement, but claim that it can be consumed in any way other than oral ingestion, you may be at risk for a Warning Letter.

The Dietary Supplement Health and Education Act (DSHEA) defines a dietary supplement as a product that is “intended for ingestion.” Products cannot be labeled or marketed as dietary supplements if they use a delivery method that is not “ingestion” via an oral route.

What forms are allowed?

The typical forms—tablets, capsules, powders, softgels, gelcaps, and liquids—are allowed for dietary supplements. Other forms, like wafers or bars, can be considered dietary supplements, provided the form “is not represented as a conventional food and is not represented for use as a sole item of a meal or of the diet.” This means that the form may be considered a dietary supplement as long as it is not labeled or marketed to be used like a conventional food, or as a replacement for a conventional food.

What delivery methods are allowed?

The key word here is Ingestion. Ingestion via an oral route—swallowing into the stomach—is the only method of consumption for a dietary supplement.

What delivery methods are not allowed?

Since 2001, 39 Warning Letters mention products being marketed as dietary supplements that use delivery methods that are not “intended for ingestion”. These Warning Letters show that the following are not delivery routes for dietary supplements:

  • Oral or Sublingual absorption (claiming that a product bypasses the digestive tract and is absorbed from the mouth directly into the bloodstream)
  • Topical (including essential oils, sprays, creams, salves, ointments, wound dressings, skin patches, skin wipes, baths, and foot soaks)
  • Inhalation
  • Nasal spray or drops
  • Ear drops
  • Eye drops
  • Rectal
  • Vaginal
  • Subcutaneous injection

As long as companies come up with new delivery methods, the examples of types of violations will continue to expand. Remember that when marketing a dietary supplement, the only delivery method is oral ingestion. Conversely, when labeling and marketing a topical product, don’t add any information that would be considered representation as a dietary supplement or food (any mention of internal use, a Supplement Facts or Nutrition Facts panel, DSHEA disclaimer, etc.).

Visit the FDA Warning Letters page for a full list of “intended for ingestion” violations here.

The complete statutory definition of a dietary supplement is found in section 201(ff) of Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) can be found here.


Sarah Eliason is a Senior Research Scientist at Nature’s Sunshine Products, Inc. With 14 years of experience in the dietary supplement industry, she specializes in technical writing and technical review.

View Sarah’s LinkedIn Profile

AERs: Insurance Implications

Guest post by Greg M. Doherty, CPCU, ARM
August 27, 2014

An increase in adverse event reports raises product liability insurance disclosure requirements for supplement companies.

pills-helpIt was recently reported that the number of government mandated adverse events reports (AERs) connected to dietary supplements has risen for six consecutive years. AERs reflect hospitalizations, life-threatening illnesses, deaths and other serious adverse events that are connected to supplement consumption.

According to FDA statistics, adverse event reports for supplements submitted to the agency in 2008-2013 were:

  • 2013: 3,289
  • 2012: 2,844
  • 2011: 2,037
  • 2010: 1,014
  • 2009: 714
  • 2008: 687

Is this increase good news or bad news for the industry? It depends who you talk to. Critics of the industry say this is long overdue, saying that even the 2013 number is just the tip of the iceberg, and that more aggressive regulation is needed by FDA, including pre-market product approval, to get to the bottom of the quality and safety storm surrounding dietary supplement products.

Industry advocates say the increase is merely the slow-but-sure progress companies are making in the implementation of best practices, part of which is driven by FDA’s public focus on compliance with AER reporting in its cGMP inspections. These advocates are quick to add that data alone do not necessarily suggest that supplement products are getting more dangerous. Indeed, according to a U.S. Government Accountability Office (GAO) report on AERs released in March 2013, of the total number of supplement AERs received by FDA from 2008 through 2011, the agency established a “certain” relationship between the product and the reported health problem in only 3% of cases.

Product Liability Implications

What does all of this have to do with your product liability insurance?

When I first wrote about this topic four years ago, so few companies had ever reported an AER that they were off the radar of virtually every insurance broker and insurance company professing to be “experts” at nutraceutical product liability insurance. Now, with the soaring incidence of AERs going to FDA, the topic needs to be examined in a brighter light. The issue for supplement companies, in a word, is disclosure.

Why? Virtually every application for product liability insurance for nutraceutical companies includes a question that asks: “Is the applicant aware of any fact, circumstance or situation which one might reasonably expect could give rise to a claim that would fall within the scope of the insurance being requested?” Companies must ponder this question carefully before responding either “yes” or “no.” If a company is maintaining the required AER records, can the company in good faith answer “no” to that question? Hardly.

Two important mechanics about product liability insurance need to be understood. First, applications for this insurance must be completed each and every year to secure a renewal policy. So every year a supplement company must answer the aforementioned question, thus “refreshing” either the yes or no answer that was given a year earlier.

Second, the “claims made” nature of the insurance plays a role in understanding this complex issue. Under claims-made liability insurance, coverage is triggered by the date a claim is actually made against you, combined with prompt notification to your insurer of the claim. The insurer’s policy that is in force on the date you became aware and gave notice is the policy that must defend and settle the claim. One must understand—and this is the crux of the matter—that AERs do not constitute a “claim” as defined by most of the insurers; so an AER is in a kind of limbo status as to where coverage will be triggered, if and when the AER matures into a bona fide claim.

So what are the possible consequences of answering the question incorrectly? Quite simply, if a lawsuit arises out of a previously documented AER incident, the insurance company will surely deny the claim once it discovers (and it will) the AER was documented in the company’s files, and not properly disclosed. The insurance company will allege fraud for inducing it to issue a policy based on concealed information. It will not only deny the claim, but most likely will seek to rescind the policy in its entirety. We have seen this happen.

Thus, AER requirements have introduced a new necessity to disclose such events to a product liability insurance company when applying for coverage, or risk claim denial when a claim is made—as unlikely as statistics make that possibility seem (remember the 3%).

The Other Side of the Coin

So you have followed the advice of your expert insurance broker and reported one or a handful of AERs to your insurer, with the full expectation that this disclosure will keep you out of trouble. What‘s next?

The unfortunate truth is that at the present time, the majority of the insurers offering product liability insurance to the industry do not understand the subject of AERs. What we have generally witnessed is that when they see an AER, they view it as a potential claim against them, rather than an incident that might give rise to a claim against them at a later date (again, remember the 3%). This lack of understanding restricts the number of insurers willing to offer a company with AERs the coverage they desire. Other times, we have seen the insurer significantly raise the client’s premium in anticipation of the reported AER to turn into a real claim.

One insurer has introduced an endorsement to its policy that states it acknowledges a reported AER will be a “covered claim” if it is made in the future, subject to underwriting the AER with available information. The problem, however, is that AER reports are often sketchy at best, offering very little detail as to the facts of the report. Recently, a client of this insurance company disclosed an AER, had the company agree to “cover” it via the special endorsement, and raised the premium rate by 35%.

In conclusion, the slippery slope of AERs and your product liability insurer is getting even more slippery with the increased reporting of adverse events. Be very careful or you may find out that your coverage has been voided at the worst possible time—after a lawsuit has been filed against you!


Greg Doherty is a commercial insurance broker with Bolton & Company Insurance Brokers and Employee Benefits Consultants, Pasadena, CA. He is the Executive Vice President and Managing Director of the Dietary Supplement Practice Group for the firm, which specializes in the nutritional product and dietary supplement industries, including but not limited to contract manufacturers, raw materials suppliers, distributors/retailers. Mr. Doherty has four decades of experience as a broker, focusing solely on the dietary supplement industry for the last 12 years. He can be reached at gdoherty@boltonco.com; Website: www.boltonco.com Phone: (626)535-1409.

Label Review Tools Part I

By Curtis Walcker, M.S.
August 10, 2014

toolsIf you are a frequent reviewer of dietary supplement labels, you have probably found that your speed and efficiency increase when you have your “tools” readily accessible. This month we have prepared a two-part series focusing on a selection of the important tools of our trade. If you are not currently using some of these, we help direct you to where you may find them.

Tool #1 – The regulations and guidance documents

These can be located on the FDA’s website. One of the best ways to use the regulations and guidance documents is to bookmark them in your browser. When a label issue arises, you can go straight to the page(s) to look for the answer. Many of the documents are large, so effective word searching is essential to make the task a breeze. The more you access these documents, the quicker you will be able to pinpoint specific regulations.

Tool #2 – A calculator

But not just any calculator – a percent Daily Value calculator. If you are currently using a regular calculator for determining your declarations, you are wasting far too much time. Using a program such as Microsoft Excel, you can create your own spreadsheet, where you can enter in the label values for nutrients and it will give you the percentages. A proper and efficient one will be built so that all of the nutrients are already in the order that they must be declared on the label, the correct nomenclature is used, the defined units of measure are used, and the numbers are automatically rounded to the nearest whole percentages. Not up to building one or just need a better one? Download one that can do all of the above for free here.

Tool #3 – The FDA Warning Letters

If you currently are not reviewing the FDA Warning Letters to dietary supplement companies posted each week, you are truly missing out on one of life’s great pleasures. Not only can they be entertaining, they can also expose you to regulations you may not have been aware of, remind you of regulations you have forgotten about, and help you gather regulatory intelligence regarding trends in what the FDA is looking at. The Warning Letters are a great tool for continually self-auditing your own skills and improving your label review expertise. Visit the FDA Warning Letters page to access past Warning Letters and sign up for e-mail updates so you never forget. Access and cite these when needing to support your assessments and edits.

2013 FDA Warning Letters Summary

By Curtis Walcker, M.S.
May 1, 2014

2013 Infographic

 

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