Warranty or Waste

Storage at controlled room temperature (the earth is divided into four climate zones for this purpose), with sampling times in intervals of 3, 6, or 12 months. 

Storage under stress conditions according to ICH Guidelines,i.e. 25°C/60% RH, 30765% RH, or 40°C/75% RH (Conditions I, II, resp. Ill temperature controlled to within 2°C, relative humidity to within 5%), with sampling intervals of 2 weeks or 1 month. 

Storage in the same primary container as will be used on the market, e.g., blister strips for tablets or ovules, tubes for creams, or vials and ampules for injectables. 

During the development phase a series of laboratory or pilot-scale batches will be subjected to this stability program. As soon as the process is scaled up to production-size batches, the first few, and at least one per year thereafter will also go on stability. Submission is only possible if the product completes a minimal combination of tests, e.g., one full-size batch for 12 months and two reduced-size batches for 6 months 

Since full analyses are carried out, a lot of data are generated. Every parameter is reviewed for trends that signal product aging or outright decomposition of the active principle this can be as cosmetic in nature as discoloration or as potentially hazardous as buildup of toxic derivatives. If the drug substance is an ester, for example, hydrolysis, particularly if moisture penetrates the primary packaging material, will decompose the compound into its acid and alcohol components. From a pharmaceutical or medical viewpoint, even if there is no toxicity issue involved, this will result in a loss of bioavailability. Even this is to be avoided because subpotency introduces therapeutic uncertainty and can go as far as lethal undertreatment. 

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Manufacturers of hollow fine fiber elements usually require that the pretreated feedwater have an SDI of 3.0 or below In order for the element warranty to be effective. One manufacturer of spiral wound element requires that the pretreated feedwater have a turbidity of less than 1.0 turbidity unit to maintain the element warranty. As a general rule, if hollow fine fiber elements are to be used, the pretreated feedwater should have an SDI of 3.0 or less and, if spiral wound elements are to be used, an SDI of 5.0 or less. However, spiral wound elements have been used to recover municipal wastes with an SDI in excess of 5.0 after pretreatment. 

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