November 17, 2014
A 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).
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…
- total carbohydrate,
- dietary fiber,
- other carbohydrate,
- polyunsaturated or monosaturated fat, or
…over labeled amounts are acceptable within current good manufacturing practice.”
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%