Substantiating label claims can be a daunting process, but testing is always a good place to start. Knowing exactly what is in the supplement bottle is paramount, and recent FDA warning letters confirm this. FDA requires that products have specifications and that those specifications are met. Following 21 CFR part 111 for dietary supplement products, the rules make it clear that testing is required. An FDA warning letter from Jan. 17, 2017 cited Unique Encapsulation Technology for specification issues.
“You failed to establish product specifications for the purity and strength of the finished batch of the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.70(e)," FDA wrote. “Specifically, your finished product specifications for the (b)(4) product do not include a specification for the product’s label declaration of containing 95 percent of curcuminoids nor do they include a specification for the presence of essential oils of turmeric rhizome."
Testing the finished product to prove label claims is a critical step in the quality control (QC) process. Additionally, each step in the manufacturing process must be monitored and maintained to ensure the finished product will meet specifications when tested. When the goal is to make quality finished products, brands must start with quality raw ingredients. Testing the raw ingredients will ensure they are what is expected. Test results will also give accurate information to calculate the blend to meet finished formula specifications. When testing is conducted from start to finish during the manufacturing process, the finished product should meet label claims. But what happens if a brand has taken every appropriate step, and the finished product does not meet label claims?
Unfortunately, this can occasionally occur, and an investigation will need to be completed to determine the root cause, as there could be many reasons the finished product does not meet specifications. For example, an error in the manufacturing process or matrix interference can cause this. Using batch records, quality checks, test records and other resources throughout the investigation can help a brand identify and solve the problem. For instance, if all batch records and manufacturing data look fine, the brand owners can troubleshoot the testing to see what issues could arise causing a finished product to not meet label claims.
When troubleshooting, the test method needs to be evaluated. For example, many U.S. Pharmacopeia (USP) methods are designed for raw material testing, so if a brand is trying to use a raw material method on a blend, it’s probably not the best method for the matrix. Also, many methods for pharmaceutical products are for single-ingredient products, and are like raw material methods. In the dietary supplement industry, manufacturers use multiple ingredients in a one-dose form. When blending botanicals, vitamins, minerals, probiotics, enzymes and other ingredients in one capsule, matrix interference issues can occur. If the test method uses ultraviolet-visible spectrophotometry (UV-Vis) detection, this will give a reading for any ingredient that is measured at the same UV wavelength. For this reason, UV-Vis type methods are generally used for single-ingredient or raw material-type testing and for blends that have ingredients with unique UV-Vis wavelength absorbance.
Similar issues can occur with high-performance liquid chromatography (HPLC) or other chromatography type methods. FDA recognizes these testing limitations, and the CFR does have a clause in 111.75 4(d) (1) that allows the manufacturer to “exempt one or more product specifications from verification requirements." This must be documented to show “there is no scientifically valid method for testing." Completing the documentation process requires additional testing to prove what can and cannot be tested in the finished product. In some cases, these blends may need method development and validation work to be able to accurately quantify the active marker compounds for that product. Eventually, it may be determined that the product can be tested once the correct sample prep and analysis steps are resolved.
For other products, creating a lab blend or small batch of the exact formula can be helpful in finding out if there is a matrix interference problem. Here is an example: The USP method, FIP Lipase, is a pH-based titration. If a product is an enzyme blend that also contains an acidic ingredient such as lemon grass, the enzyme method may have interference from the lemon grass pH. To prove this theory, a lab blend could be made to purposefully exclude the ingredient that is thought to be causing the interferencein this case, the lemon grass. Testing the blend with and without the interfering ingredient will be necessary to compare results. If the blend without the ingredient in question tests to specification, the researchers have proven matrix interference caused the out-of-specification result. The testing data gives proof matrix interference caused the finished product to not meet label claims. This provides the documentation needed for exemption of this test in the future, and is invaluable during an audit or FDA inspection. This provides conclusive information to answer the difficult questions about why certain tests are not being completed on the finished product.
If after completing these additional steps to find the root cause, the finished product still does not meet label claims, the determination may be made that the product will need to be reprocessed. However, this conclusion can be costly. These examples show an investment needs to be made in testing and research throughout the manufacturing process to prove the quality and potency of a product.
While label claim testing is just one part of QC, many other tests are needed to make sure the product is not contaminated with heavy metals, microbiological counts or tainted substances. QC can be complicated, but with the correct processes in place and monitoring with testing, manufacturers can make quality products that meet label claims and are safe for consumersand, safe products for consumers should always be the main goal.
Tammy Blakemore is general manager at SORA Labs, a third-party dietary supplement testing lab that specializes in enzyme testing.