Expiration dating period

The FDA guidelines establish, first, that the stabihty study protocol must describe how the stabihty study is designed and carried out and, second, the statistical methods to be used to analyze the data. The design of a stabihty study is aimed at establishing an expiration dating period. The expiration dating period is based on testing on a... 

Assuming a common slope with different intercepts for different batches, the expiration dating period is computed for each individual batch. The minimum of the expiration dating periods of the individual batches is the expiration dating period of the drug product. 

In summary, the null hypotheses for equality of slopes and intercepts are not rejected at the 0.25 significance level and, consequently, all batches are considered from the same population. Therefore, the expiration dating period can be computed by using model (45). 

The expiration dating period must be smaller than 38.11 months. Using the initial point %(0) = %ref - d = 38.11 - 8, the QNLS algorithm converges to xR = 32.801. Therefore, the expiration dating period for the underlying production batches is 32 months. 

Minimum Approach for Multiple Batches When the hypothesis for equality of slopes is rejected at the 0.25 significance level, the minimum approach should be implemented. This is because the degradation lines of individual batches cannot be considered the same since they have different degradation rates. In this situation the FDA guideline establishes that the overall expiration dating period has to ensure that the product will remain within acceptable limits regardless of the batch from which it comes. Thus, the shelf life for each batch is calculated and the expiration dating period is based on the lowest of all shelf lives. Mathematically, this can be expressed as... 

Since the minimum of all the expiration dating periods is the shortest shelf life among all batches, this estimate will provide a 95% confidence that the strength of the drug product will remain above the acceptable lower specification limit. 

Rules for Determining Shelf Life Once the analysis-of-covariance model has been identified, a set of rules for computing the shelf life must be implemented. This section describes the rules to follow to determine the expiration dating period for each of the nine representative models described in the previous section [8,11] ... 

CO The expiration dating period is computed separately for each batch and... 

Assuming a common slope and a common intercept for all batches, a single shelf life is computed as the expiration dating period of that package. 

Shelf Life (also referred to as Expiration Dating Period) — 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. 

A commitment should be included to conduct long-term stability studies through the expiration dating period, according to tlie approved protocol, on the first or first three (see text for details) production batches and to report the results in the annual reports. 

An extension of an expiration dating period based on (1) data obtained under a new or revised stability testing protocol that has not been approved in the application or (2) full shelf life data on pilot scale batches using an approved protocol. 

Addition of time points to the stability protocol or deletion of time points beyond the approved expiration dating period. 

Stability studies during the IND phase provide not only assurance of the quality of clinical trial material but also the basis for the drug product development program. Stability data are used to evaluate different formulations, methods of manufacture, and container-closure systems, as well as to determine storage requirements, expiration dating periods, and specifications. 

Extrapolation of data from one material to another must always be based on sound scientific principles and all available data. Even so, extrapolation always bears risk. To demonstrate that every batch of clinical trial material was within applicable specifications for the duration of its use in clinical studies, some firms test every batch of clinical trial material at expiry. This is especially valuable when an expiration-dating period was not based on real-time data for the precise clinical trial material in the precise container-closure used in the clinical trials. 

More protective container-closure systems generally allow a longer expiration-dating period. Since more protective systems are usually more expensive than less protective systems, these studies provide information for choosing the optimum balance between packaging costs and expiration dating period. 

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