![]() For example, the US Food, Drug and Cosmetics Act (FDCA) defines the term “Drug” as “articles recognized in the United States Pharmacopeia or National Formulary ”, without any clarification-either in the FDCA or USP/NF as to the amount of a particular article that would constitute a “product”. Somewhat surprisingly, an implementable definition of the term “product” is lacking from all standard-setting documents and even legal statutes, to the best of the authors' knowledge. This is an important question since it relates to how shelf life should be defined, which in turn guides how the data should be analyzed and how the results should be interpreted. A patient may think it is an individual dosage unit. ![]() An inspector may think it is the particular sample of units taken from the batch and placed on stability. The International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use guidance document Q1A(R2) ( 1) (ICH Q1A) defines shelf life as, “The time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label.” Although this is an accepted definition, a crucial-for-implementation first question that arises is: what is meant by “drug product”? A manufacturer may think it is the entire collection of individual units (e.g., tablets) released as one batch. ![]() Similar requirements are in place in the European Union and around the world. Since 1979, the Food and Drug Administration (FDA) has required that all prescription drugs have a shelf life (or expiration date) indicated directly on the container label. This work was conducted by the Stability Shelf Life Working Group of the Product Quality Research Institute. This approach, unlike a fixed-batch model, allows estimation of both within- and between-batch variability, and allows inferences to be made about the entire production process. For this strategy, a random-batch model is required. The choice of quantile translates to an upper bound on the probability that a randomly selected batch will be nonconforming when tested at the storage time defined by the labeled shelf life. Arguments are presented that for regulatory and statistical reasons the true product shelf life should be defined in terms of a suitably small quantile (e.g., fifth) of the distribution of batch shelf lives. The article also highlights a key missing element in the discussion of shelf life-a Quality Statement, which defines the quality standard for all key stakeholders. The article discusses various levels of “product” on which different stakeholders tend to focus (e.g., a single-dosage unit, a batch, a production process, etc.). These concepts are already in use, but not named as such. The five new terms that are necessary for a coherent discussion of shelf life are: true shelf life, estimated shelf life, supported shelf life, maximum shelf life, and labeled shelf life. Such comprehensive and common language is currently lacking from various guidelines, which confuses implementation and impedes comparisons of different methodologies. This article proposes new terminology that distinguishes between different concepts involved in the discussion of the shelf life of pharmaceutical products.
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