Shelf-life, drug product

Chemical stability under a variety of macro- and microenvironmental conditions is a highly critical property determining the expected shelf life of products. The stability of the bulk solid and in solution must be studied, whereby the influence of environmental factors (pH, temperature, humidity, oxygen, light) and including the presence of various excipients on drug stability must be established. 

The guideline on impurities in new medicinal products parallels the drug substance text, but the designated thresholds concern only degradation products. The thresholds should be applied to the product at the end of its shelf-life, as that is when the greatest level of degradation is expected to have occurred. 

Various drugs are known to exist in different polymorphic forms (e.g., cortisone and prednisolone). The rate of conversion from a metastable into the stable form is an important criteria to be considered with respect to the shelf life of a pharmaceutical product. Polymorphic changes have also been observed during the manufacture of steroid suspensions. When steroid powders are subjected to dry heat sterilization, subsequent rehydration of anhydrous steroid in the presence of an aqueous vehicle results in the formation of large, needle-like crystals. A similar effect may be... 

It has now been established beyond any reasonable doubt that quality of a drug product cannot simply be ensured by inspection or analysis, but a control system has to be built into, from the very beginning of manufacture of a drug. Besides effective quality control measures exercised in every aspects of production including environment, screening of raw materials, process controls, intermediate shelf-life of finished products the most important aspect is to assess the bioavailability of the active principle. 

---