Label claims, pharmaceuticals

Ultimately the technical objective of an analytical procedure, which is included as part of a registration application for pharmaceuticals, is the responsibility of the analytical department. This objective is directly related to the regulatory objective as defined by the regulatory professionals. For example, the regulatory professionals require a means to quantitate an API in a finished pharmaceutical for release between 95-105% of label claim. This translates into a technical objective for the analytical chemist that involves the selection of an analytical technique and the development of a method that has the required accuracy and precision to meet the requirements for release. 

Many vitamins are quite stable under normal processing conditions and present little or no stability problems in finished pharmaceutical products. These include biotin, niacin, niacinamide, pyridoxine, riboflavin, and a-tocopheryl acetate. Others that can present problems are ascorbic acid, calciferol, calcium pantothenate, cyanocobalamin, fola-cin, and retinyl esters. Overages above label claim are customarily added to vitamin formulations as a means of maintaining the claimed level of each vitamin for the expected shelf life of the products. The percent overage for a particular vitamin such as L-ascorbic acid will vary... 

Poor values for linearity are usually the result when only production samples are used for development of quantitative calibrations. The low R values are a result of the narrow range of active concentrations due to the quality that is inherent in pharmaceutical processes. A typical pharmaceutical process gives samples that vary little from the nominal value. Typical ranges for tablet assays fall within a range of 97 to 102% of label claim. This 5% range, coupled with errors in the HPLC analysis, lead to a poor correlation line. In HPLC or UV/VIS spectroscopic methods, an R value approaching unity is common the U.S.P. recommends a value no lower than 0.995. A typical NIR linearity, based solely on actual production samples, is often closer to 0.8 than 1.0 due primarily to the narrow range. 

LC = Percentage label claim of active pharmaceutical ingredient (API) per tablet or capsule... 

Analytical method goals are often defined as method acceptance criteria for peak resolution, precision, specificity, and sensitivity. For instance, pharmaceutical methods for potency assays of an active pharmaceutical ingredient (API) typically require the following resolution >1.5 from the closest eluting components precision of retention time and peak area, <1-2% RSD and linearity in the range of 50-150% of the label claim. Other desirable characteristics include ... 

It should be noted that many of these parameters have pre-established confidence limit ranges that will capture the needs of the industry. For example, regulated pharmaceutical formulations may have a much more restrictive range than non-regulated nutritional supplements or herbal formulations. In the latter cases, method validation is often done for the support of label claims. Exact requirements should be derived directly from the organization involved. 

The potentially beneficial properties of antioxidants have been a common subject in the popular press. Such compounds have the ability to eliminate toxic free radical species in living systems. Antioxidants are claimed to have cytoprotective properties in the inhibition of cancer, heart disease, and various skin disorders, and are often simply labeled as antiaging. There is a host of benzofuran examples in the recent literature that find application in all of these areas as potential pharmaceuticals, cosmetics, and polymer stabilizers. 

Finally, the issue of information must be carefully noted. Companies have to ensure the quality of product information that they provide through labels package inserts, data sheets, advertising and promotional claims, and they must remember that information derived from the development and use of pharmaceutical products is not static as these change constantly. 

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