Drug Stability: ICH versus Accelerated Predictive Stability Studies

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 degrees C +/- 2 degrees C/60% RH +/- 5% RH or at 30 degrees C +/- 2 degrees C/65% RH +/- 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 degrees C +/- 2 degrees C/65% RH +/- 5% RH (which is not necessary if this condition was utilized as a long-term one) and 40 degrees C +/- 2 degrees C/75% RH +/- 5% RH, respectively. Hence, the ICH stability testing for industrially fabricated medicines is rigorous and tedious and involves a long period of time to obtain preclinical stability data. For this reason, Accelerated Predictive Stability (APS) studies, carried out over a 3-4-week period and combining extreme temperatures and RH conditions (40-90 degrees C)/10-90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner. In this work, the conventional ICH stability studies versus the APS approach will be reviewed, highlighting the advantages and disadvantages of both strategies. Furthermore, a comparison of the stability requirements for the commercialization of industrially fabricated medicines versus extemporaneous compounding formulations will be discussed.

Automated summary

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the World Health Organization (WHO) have provided guidelines to unify stability standards for the European Union, Japan, and the United States. These guidelines aim to facilitate mutual acceptance of stability data for regulatory registration. ICH stability studies involve testing drug substances under various storage conditions to assess their thermal stability and sensitivity to moisture. Accelerated Predictive Stability (APS) studies have emerged as a more efficient approach to predict long-term stability by combining extreme conditions over a shorter period of time.