Leachables studies can also be perf

Leachables studies can also be performed early in the drug product development process (e.g., preclinical stage) in order to facilitate the selection of packaging components and their materials of construction. Such leachables studies are particularly useful for certain “high-risk” dosage forms (see Table 1) where selecting appropriate packaging components and materials of construction is critical. A variety of packaging components and materials of construction can be evaluated at the same time and drug product leachables profiles determined and evaluated for each configuration. For primary packaging systems orcombination drug/device products this can be accomplished by using either the drug product formulation or a placebo formu- lation in contact with the proposed packaging system. In the latter case, the placebo formulation can be considered as a simu- lating solvent to characterize extractables as probable leachables (see Simulation Studies). In either case, the leachables study conditions (i.e., time, temperature, etc.) should be based on conditions that are relevant for either the use-life or shelf-life ofthe drug product. Preclinical development stage leachables studies can be designed in a systematic way in order to support QbD processes and principles. It is important to also note that during early stage drug product development for high-risk dos- age forms, leachables characterization is recommended for any drug product batches that are used as test articles in any defin- itive toxicology or clinical studies. For “low-risk” dosage forms (e.g., solid orals, topical powders) leachables studies conducted throughout development might be appropriate in order to assess, and thereby avoid, problems with packaging systems that might appear either in later stage development or marketed product.