J Pharm Sci 2001; 90:1759-1766. Estimates of degradation rates, days of stability and 95% confidence limits. Find answers to commonly asked questions. This equation describes a relationship between temperature and the degradation rate as in Equation 4. If you wish to opt out, please close your SlideShare account. Rockville (MD); 1987. First, an acceleration factor, λ, is calculated as the ratio of the degradation rate at elevated temperature to the degradation rate at storage temperature.

Values above 60°C are not recommended. Experimental protocols used for data collection are called stability tests. Polymers are often kept at elevated temperatures, in order to accelerate chemical breakdown. Accelerated Shelf-life Test. Keep three batches for stability study at least for 1 year at one fixed temperature. 1. Arrhenius equation: Definition of rate constant k, the pre-exponential factor A, and activation energy. Lots should be modeled separately when lot-to-lot variability is large. However, since it can take up to two years to complete, the accelerated tests are often used as temporary measures to expedite drug introduction. Temperature is the most common acceleration factor used for chemicals, pharmaceuticals, and biological products because its relationship with the degradation rate is characterized by the Arrhenius equation. A model for parameter estimation and prediction of shelf life when temperature and pH are used as acceleration factors is given by Some et al.11. \text { Accelerated Aging Time }​ (A A T)=\frac{\text { Desired Real Time }(R T)}{Q_{10} ​ \scriptsize\left[\left(T_{A A}-T_{R T}\right) / 10\right]} Biopharmaceutical products in storage change as they age, but they are considered to be stable as long as their characteristics remain within the manufacturer's specifications. SHELF LIFE DETERMINATION BASED ON REAL TIME TESTING Another method which involves real time testing and statistical analysis, followed for determining shelf life. (Here, λ indicates this was evaluated from accelerated tests.) In addition to the prediction of product stability including colour, ASLT are useful for a number of other purposes, e.g. Testing should be performed at time intervals that encompass the target shelf life and must be continued for a period after the product degrades below specification. Whitepaper_Beschleunigte_Haltbarkeitstests_EN.indd. Clin Chem 1991; 37:398-429. Thus, the purpose of this paper is to provide an outline of the basic approaches to stability testing, as well as to create a foundation for advanced statistical modeling and shelf life prediction. The bracket method should not be confused with bracketing, which is an experimental design that allows you to test a minimum number of samples at the extremes of certain factors, such as strength, container size, and container fill.3,4,6 Bracketing assumes that the stability of any intermediate levels is represented by the stability of the extremes and testing at those extremes is performed at all time points.4, The Q-Rule states that the degradation rate decreases by a constant factor when temperature is lowered by certain degrees. Shelf life determination based on equivalence assessment. \begin{equation} VAT No: GB 6838559 76.© Copyright 2010-2020 Copyright 2010-2019 Medical Engineering Technologies Ltd. All rights reserved.Site designed and maintained by Go Vicinity Creative Ltd. How is vacuum decay used in pharma CCIT and packaging integrity testing? For example, cycles of heat and cold can simulate the effect of day and night for a few hours or minutes. Shelf life (t0.9) It is defined as the time necessary for the drug to decay to 90% of its original concentration. Statistics that test the appropriateness of this approximation are presented in literature. Although it is common to approximate these reactions with an exponential relationship, sometimes their degradation pattern needs to be modeled more precisely, and no shortcuts will suffice. J Biol Stand 1984; 12:195-206. Geneva; 2003. Choosing levels depends on the nature of the product and analytical accuracy, but other practical implications may be considered. (13) Magari R, et al. endstream endobj 3 0 obj <> endobj 6 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC]/Properties<>/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 7 0 obj <>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 8 0 obj <>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 9 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 10 0 obj <>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 11 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 12 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 13 0 obj <>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 14 0 obj <>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 15 0 obj <>/Font<>/ProcSet[/PDF/Text]>>/TrimBox[0.0 0.0 595.276 793.701]/Type/Page>> endobj 42 0 obj <>stream

Also, details on statistical modeling and estimation are outside the scope of the article, but we provide references to computer routines. Both α and δ represent the fixed parameters of the model that need to be estimated from the data, while φ and ε are assumed to be normally distributed with mean = 0, and standard deviations of σφ and σ.ε respectively.

(1) FDA.

Shelf stable and frozen products with a shelf-life of six months or more are good candidates for accelerated shelf life studies. (8) Tydeman MS, Kirkwood TBL. 19. Accelerated life testing is the process of testing a product by subjecting it to conditions (stress, strain, temperatures, voltage, vibration rate, pressure etc.) However, an understanding of the general principles of stability testing is necessary to apply these programs correctly and obtain appropriate results. Table 3. Data and trends are presented in Figure 2, with the estimates of degradation rates and days given in Table 2. 1. When most of the assumptions required to use the Arrhenius equation are not satisfied, comparisons to a product with a known stability is performed to assess shelf life. All rights reserved.



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