SAMARTH PHARMA
Real-Time Stability Tests In real-time stability tests, a product is stored at recommended storage conditions and monitored for a period of time (ttest). Product will degrade below its specification, at some time, denoted ts, and we must also assure that ts is less than or equal to ttest. The estimated value of ts can be obtained by modeling the degradation pattern. Good experimental design and practices are needed to minimize the risk of biases and reduce the amount of random error during data collection. 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. It is also required that at least three lots of material be used in stability testing to capture lot-to-lot variation, an important source of product variability.1,2
The true degradation pattern of a certain product, assuming that it degrades via a first-order reaction, can be described as follows:
The observed result (Y) of each lot has a random component φ associated with that lot, as well as a random experimental error, ε.
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. Equation 2 is a nonlinear mixed model. Details on the estimation process are outside the scope of this paper.8,9
Let C represent a critical level where the essential performance characteristics of the product are within the specification. A product is considered to be stable when Y ≥ C. Product is not stable when Y < C, while Y < C occurs at ts. The manufacturer determines the value of C. The estimated time that the product is stable is calculated as
Here, a and d are the estimated values of the intercept and the degredation rate. The standard error of the estimated time can be obtained from the Taylor series approximation method and is used to calculate confidence limits. The labeled shelf life of the product is the lower confidence limit of the estimated time.8 Public safety is paramount, that is why we use the lower confidence limit. Lots should be modeled separately when lot-to-lot variability is large. More details on this issue are found in references 9 and 10.
We simulated data for three lots tested for a total period of 600 days (Table 1 and Figure 1). The product loses its activity as it ages, but it is considered to be performing within the specification until it reaches 80% of its activity (C = 0.8). The estimated lot-to-lot standard deviation is 0.000104, and the estimate of experimental error is 0.000262. Therefore, the shelf life of the product was determined to be 498 days. This represents the lower 95% confidence limit corresponding to the estimated time of 541 days.
Real-Time Stability Tests In real-time stability tests, a product is stored at recommended storage conditions and monitored for a period of time (ttest). Product will degrade below its specification, at some time, denoted ts, and we must also assure that ts is less than or equal to ttest. The estimated value of ts can be obtained by modeling the degradation pattern. Good experimental design and practices are needed to minimize the risk of biases and reduce the amount of random error during data collection. 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. It is also required that at least three lots of material be used in stability testing to capture lot-to-lot variation, an important source of product variability.1,2
The true degradation pattern of a certain product, assuming that it degrades via a first-order reaction, can be described as follows:
 |
The observed result (Y) of each lot has a random component φ associated with that lot, as well as a random experimental error, ε.
 |
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. Equation 2 is a nonlinear mixed model. Details on the estimation process are outside the scope of this paper.8,9
Let C represent a critical level where the essential performance characteristics of the product are within the specification. A product is considered to be stable when Y ≥ C. Product is not stable when Y < C, while Y < C occurs at ts. The manufacturer determines the value of C. The estimated time that the product is stable is calculated as
 |
Here, a and d are the estimated values of the intercept and the degredation rate. The standard error of the estimated time can be obtained from the Taylor series approximation method and is used to calculate confidence limits. The labeled shelf life of the product is the lower confidence limit of the estimated time.8 Public safety is paramount, that is why we use the lower confidence limit. Lots should be modeled separately when lot-to-lot variability is large. More details on this issue are found in references 9 and 10.
No comments:
Post a Comment