The Ins and Outs of Label Claim Testing

Label claim testing is no longer an option; rather it has become the law. At one time, it may have been considered a luxury expense only performed by large companies; but, the cGMP (current good manufacturing practice) regulation for the dietary supplement industry will affect all manufacturers, from million-dollar producers to small facilities. Primary label requirements include: statement of identity; quantity of contents; a supplement facts panel with 14 mandatory dietary ingredients; an ingredient list; name and address information for adverse event reporting; and a disclosure statement declaring the product has not been evaluated by FDA. Any claim made about a dietary ingredient requires it to be listed on the facts panel with an amount per serving and reference daily intakes (RDI). The new cGMPs were written to help prevent mislabeled quantities of ingredients, including extremely high overages and subpotency.

Quantities of unstable ingredients such as vitamins, enzymes, probiotics, etc., that are higher than label claims are a common problem in dietary supplements. This event usually occurs as buyers push to extend the shelf life of potential products, which subsequently places manufacturers in a tough predicament. They can either satisfy the demands or lose the business. Some manufacturers have circumvented this detail by increasing the amount of labile ingredients in a formulation sometimes up to 150 percent of label claim to guarantee an accurate label throughout the shelf life. There is no set limit on how much overage is allowed, but as more clinical data on dietary ingredients becomes available, this is likely to change. A good practice to follow in the meantime is to take into account the RDIs, review clinical literature for toxicology information and perform shelf-life studies to help focus on what ingredient amounts are required to overcome any degradation over the life of the product, which would result in subpotent quantities.

A more common mislabeled product is one in which the ingredient is found in lower amounts than claimed. The cGMPs require a product to contain 100 percent of a claim on a fortified ingredient, taking into account the deviation of the analytical testing method, and 80 percent on naturally occurring ingredients. There are a few facets of analytical testing to consider while guaranteeing continued label claim compliance. First, there may be various available methods, so choosing the most appropriate one is a big decision. Different methods can have different detection limits, deviations and limitations due to interfering substances in the product. Chondroitin testing is a prime example where selection of the USP CPC-titration method may give false high-recovery readings if the raw material was adulterated or simply based on other ingredients reacting with the reagents in the test. It was once considered the gold standard for testing and is still the only assay method for chondroitin in the USP; nevertheless, the AOAC enzymatic HPLC (high-performance liquid chromatography) method is a better choice due to the detection specificity for chondroitin (J AOAC Intern. 2007;90(3): 659-69).

It is important to point out that titrations are typically not optimal for finished products since there is a high potential for matrix interference. Moreover, many titrations are based on color changes that are difficult to determine with the vibrant products in the dietary supplement field. Chromatography is a more appropriate procedure, since it can first separate compounds of interest, and allow for various detection techniques.

Next, the manufacturer must share all details of the formulation with the analytical laboratory, as chemical composition can greatly affect extraction efficiency and final data. Microencapsulation/beadlet formation is an example where the active has been chemically altered in such a way to make the active more soluble in the finished product; however, this can prevent a routinely used extraction method from fully recovering 100 percent of the active, so the finished product would appear to be lower than label claim. Additionally, the form and units of the active used in the product and used to standardize the method must be known for final calculations.

Vitamin A is a good example of this scenario. Commonly used forms of vitamin A are retinol, retinyl palmitate and retinyl acetate. While all forms can provide a source for vitamin A activity, they are chemically different, and precautions to match up the retinol equivalents must be taken when calculating the final result. Moreover, beta-carotene may be used for vitamin A activity, which further imposes the need for the manufacturer and laboratory to cooperate. A common mistake made is when a manufacturer requests a standard vitamin A test on a product that was fortified with beta-carotene. In some cases, the standard vitamin A test does not recover beta-carotene, so the test would reveal undetectable levels of vitamin A. Ultimately, money is wasted on an unnecessary test and time is lost on resetting the sample to run the appropriate method.

Finally, instruments and methods used in the analytical laboratory have limitations on how much of a compound can be detected; this includes upper and lower detection limits. The laboratory must prepare the sample in such a way that the concentration of the ingredient falls within this range. Therefore, an expected value/label claim should be provided by the manufacturer to reduce unnecessary time and extra cost spent on performing multiple dilutions.

Label claim testing is not a matter to take lightly. Everyone involved should start preparation immediately, if not already in the process, as the deadlines for medium and small company cGMP compliance approach. The process of setting specifications will likely require lots of time performing accelerated and shelf-life studies, and this step is only the beginning of proving a manufacturing process is under control based on scientific evidence as required by the new law. After specifications are set, as with any manufacturing process, continued compliance must be demonstrated and label claim testing will be an integral component.

Cheri M. Turman, Ph.D., is the director of chemistry at Analytical Food Laboratories where she currently oversees daily contract testing as well as R&D of new testing procedures. Analytical Food Laboratories  provides independent, third-party chemical, microbiological, nutritional and physical analysis on an array of food, water, dietary supplements, cosmetic and additional services.