Parenteral drug products sampling

For liquid or semisolid drug products such as parenterals, emulsions, suspensions, dermal creams, etc., the issue of "direct exposure" is not clearly addressed and can be somewhat confusing. The ICH guideline states, "Where practicable when testing samples of the drug product outside the primary pack, these should be presented in a way similar to the conditions mentioned for the drug substance."... 

Therefore, admixture studies are performed on parenteral drugs with commonly used intravenous diluents. Studies are performed by preparing admixtures of the drug product with various diluents in an appropriate type of flexible intravenous bag. Initial samples are taken for analysis before the bags are stored in temperature-controlled stability chambers. Subsequent samples may be pulled at 6-, 12-, 24-, 48-, and 72-h time points. The analytical tests commonly performed include visual appearance, pH, and HPLC assay. Degradation products are not commonly tested unless the method has been previously evaluated for specificity and stability-indicating ability with a particular intravenous diluent. This is necessary because there may be differences in the stability profile of the product in its original formulation compared to the admixture solution. Formation of any particulate matter is detected by visual... 

The production of freeze-dried pharmaceuticals (and other products) is of paramount importance since many drugs, used in parenteral products, are freeze-dried powders intended for reconstitution in aqueous solvent prior to administration. Control of the freeze-drying conditions is important in producing a usable product and to allow drying of the sample. Residual water may result in drug degradation and conversion of a glassy state to a crystalline... 

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