Comparison of Shelf Life Estimates Generated by ASAP prime TM with the King-Kung-Fung Approach. Juan Chen 1 , Sabine Thielges 2 , William R. Porter 3 , Jyh-Ming Shoung 1 , Stan Altan 1. 1 Nonclinical Statistics and Computing, Janssen R&D 2 BE Analytical Sciences and COES, Janssen R&D
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Juan Chen1, Sabine Thielges2, William R. Porter3, Jyh-Ming Shoung1, Stan Altan1
1Nonclinical Statistics and Computing, Janssen R&D
2BE Analytical Sciences and COES, Janssen R&D
3Peak Process Performance Partners LLC
Named for Svante Arrhenius (1903 Nobel Laureate in Chemistry) who established a relationship between temperature and the rates of chemical reaction:
Where kT= Degradation Rate
A = Non-thermal Constant
Ea= Activation Energy
R = Universal Gas Constant (1.987 cal/mol)
T = Absolute Temperature
A humidity term with coefficient B is introduced to account for the effect of relative humidity on rate parameter.
humidity sensitivity factor
gas constant (1.987cal/mol)
King-Kung-Fung (KKF) model is widely used for analyzing accelerated stability data
Let T =298oK (25oC)
H = 60
The ASAPprimeTMcomputerized system is a computer program that analyzes data from accelerated stability studies using a 2-week protocol accommodating both temperature and humidity effects through a extended Arrhenius model.
The program makes a number of claims:
These claims require careful statistical considerations of the modeling strategies proposed by the developers.
Our objective is to evaluate the first two claims in relation to widely accepted statistical approaches and considerations.
Data SD Hierarchy:
1. Calculate from replicate data , if >LOD
2. User-defined SD (fixed) or RSD, if >LOD
3. Default 10%RSD, if >LOD
Pairs of lnK at 50C and 60C form 49 regression lines across 1/T with slopes (=Ea/R) and intercepts (lnA)
ASAP Probability statement about lnK and SL at 25C
ASAP generally underestimated lnA.
Standard errors of Ea are affected by user specified SD, and are generally larger than KKF estimates.
ASAPunderestimated B for data HHH and HLH, and overestimated B for LLL.
Standard errors of B are affected by user specified SD, and are generally larger than KKF estimates.