Abstract

Mr. Pratik Balasaheb Rokade*

ABSTRACT

There were more than 537 million people suffering from Diabetes mellitus in 2022, among which around 90% of cases is of type II Diabetes mellitus.[1] FDA guidelines and ICH guidelines emphasize need for stability testing data to comprehend the impact of environmental factors on the quality of Drug Substance (DS) and product over time. Understanding the stability of a molecule is crucial for making informed decisions regarding formulation, packaging, storage conditions, and shelf life. This knowledge is vital for regulatory documentation purposes. ICH along with WHO provide a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6AB) to maintain the standards of the formulations and facilitate the mutual acceptance of stability data for all regulatory authorities across the globe. In general all the guidelines for stability study, the API and Drug Product (DP) are tested in different storage condition For example: - Temperature (thermal stability) and Relative Humidity (sensitivity to moisture). For long-term (real time) stability testing, it is recommended to conduct tests for a minimum of 12 months at 30°C ± 2°C with 75% RH ± 5% RH. While accelerated testing should be carried out for a minimum of 6 months at 40°C ± 2°C with 75% RH ± 5% RH. The stability testing requirements set by the ICH for industrially formulated medicines are comprehensive and demanding.[2] They involve a lengthy duration to gather preclinical stability data, making the process rigorous and time-consuming. Accelerated Predictive Stability (APS) studies involve conducting tests over a duration of 3-4 weeks, incorporating extreme temperature and relative humidity (RH) conditions ranging from 40 to 90°C and 10 to 90% RH. These studies aim to provide predictive insights into the long-term stability of pharmaceutical products within a relatively short timeframe. The aim of these stability study is to forecast the degradation kinetics and, consequently, determine the shelf life of the product. Force degradation studies are conducted to identify the majority of degradation products and their degradation reactions associated with an active pharmaceutical ingredient (API). The principal degradation mechanisms encountered in pharmaceuticals are oxidation, hydrolysis, thermal degradation, isomerization, and photolysis.[3] According to a draft guidance, it is recommended to include the results of one-time Force degradation studies in Phase 3 Investigational New Drug (IND) submissions. The registration process for a New Drug Application (NDA) necessitates the inclusion of Force degradation study data, which comprises information on Force degradation products, degradation reaction kinetics, structural elucidation, mass balance, and drug peak purity, among other factors. A Force degradation study offers valuable insights into the degradation pathways of the active pharmaceutical ingredient (API), both in isolation and within the DP. It can help identify potential polymorphic or enantiomeric substances that may arise during degradation.