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Temperature excursion: difference between revisions

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11An excursion is defined relative to a label, not to an absolute temperature. Because compendial definitions of controlled cold and controlled room temperature build permitted excursion bands into the definitions themselves, a departure from the nominal range is not automatically an excursion in the regulatory sense; a product labelled for storage at 2–8 °C that reaches 15 °C for an hour may remain within its labelled conditions, whereas the same profile applied to a product labelled for frozen storage would not.{{r|usp659}}11An excursion is defined relative to a label, not to an absolute temperature. Because compendial definitions of controlled cold and controlled room temperature build permitted excursion bands into the definitions themselves, a departure from the nominal range is not automatically an excursion in the regulatory sense; a product labelled for storage at 2–8 °C that reaches 15 °C for an hour may remain within its labelled conditions, whereas the same profile applied to a product labelled for frozen storage would not.{{r|usp659}}
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+13Assessment proceeds from three quantities: how far outside the range the product went, for how long, and how much such exposure it has already accumulated. Duration and magnitude are combined through the '''mean kinetic temperature''', a degradation-weighted average that gives disproportionate weight to warm intervals and can exceed the permitted range even when the ordinary time-weighted mean does not. Cumulative accounting matters because a product that has spent three separate periods outside its range has consumed three portions of whatever stability margin the manufacturer's programme established.{{r|haynes1971,usp1079}}
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13== Definition and framing ==15== Definition and framing ==
14Distribution and compendial guidance treat an excursion as a deviation requiring investigation. The European good distribution practice guidelines require that deviations be recorded and their effect on quality evaluated, and that product not be released for further distribution until that evaluation is complete. WHO model guidance takes the same approach and adds the concept of a stability budget: the total permitted exposure outside labelled conditions, allocated across the product's life, against which each event is charged.{{r|eugdp2013,whotrs961}}16Distribution and compendial guidance treat an excursion as a deviation requiring investigation. The European good distribution practice guidelines require that deviations be recorded and their effect on quality evaluated, and that product not be released for further distribution until that evaluation is complete. WHO model guidance takes the same approach and adds the concept of a stability budget: the total permitted exposure outside labelled conditions, allocated across the product's life, against which each event is charged.{{r|eugdp2013,whotrs961}}
26<ref name="usp659">United States Pharmacopeia, General Chapter <659>, "Packaging and Storage Requirements". USP–NF, current revision.</ref>28<ref name="usp659">United States Pharmacopeia, General Chapter <659>, "Packaging and Storage Requirements". USP–NF, current revision.</ref>
27<ref name="usp1079">United States Pharmacopeia, General Chapter <1079>, "Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products" (informational). USP–NF, current revision.</ref>29<ref name="usp1079">United States Pharmacopeia, General Chapter <1079>, "Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products" (informational). USP–NF, current revision.</ref>
+30<ref name="haynes1971">Haynes JD. "Worldwide virtual temperatures for product stability testing." ''Journal of Pharmaceutical Sciences'' 60(6):927–929 (1971).</ref>
28<ref name="whotrs961">World Health Organization. "Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products." ''WHO Technical Report Series'' No. 961, Annex 9 (2011).</ref>31<ref name="whotrs961">World Health Organization. "Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products." ''WHO Technical Report Series'' No. 961, Annex 9 (2011).</ref>
29<ref name="eugdp2013">European Commission. ''Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use'' (2013/C 343/01).</ref>32<ref name="eugdp2013">European Commission. ''Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use'' (2013/C 343/01).</ref>