When implementing Quality by Design concepts, the strategy for endotoxins testing should be based upon product and process understanding in combination with risk management to ensure consistent final product quality. The appropriate in-process testing should be used to evaluate the production process areas at risk of endotoxins formation or incursion. Many firms already have programs for monitoring incoming ingredients and components, including the processing water, for endotoxins contamination. The finished product release specification should be considered when determining in-process limits for each phase of manufacturing tested. For purposes of evaluating the relative risk of product contamination, quantitative testing may be preferable to limit testing to facilitate product quality trending and to identify and correct excursions before they exceed the specification and cause product failure. An endotoxins limit should be justified on a case-by-case basis, and will be evaluated as a part of each relevant marketing application or supplement.
