Temperature excursion: difference between revisions
Diff·revision 14 → 15·04:04, 28 May 2025
Difference between revision 14 and revision 15 of Temperature excursion. 27 lines changed; the page grew by 3,135 bytes.
| Revision 14 — 14:13, 22 May 2025 TirzTaxonomist (talk) add confidence interval 6,150 bytes ±0 | Revision 15 — 04:04, 28 May 2025 ArchiveBot (talk) bot: normalise citation format 9,285 bytes +3,135 | ||
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| 5 | | Summary statistic = Mean kinetic temperature | 5 | | Summary statistic = Mean kinetic temperature |
| 6 | | Disposition outcomes = Release, shortened dating, or rejection | 6 | | Disposition outcomes = Release, shortened dating, or rejection |
| + | 7 | <!-- Arithmetic conventions --> | |
| + | 8 | | Assumed activation energy = 83.144 kJ·mol⁻¹ | |
| + | 9 | | Corresponding ΔH/R = 10,000 K exactly | |
| + | 10 | | Rate multiplier per 10 K near 25 °C = approximately 3 | |
| + | 11 | | Applicable to freezing damage = No | |
| 7 | }} | 12 | }} |
| 8 | 13 | ||
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| 13 | Assessment 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}} | 18 | Assessment 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}} |
| 14 | 19 | ||
| + | 20 | The evidence that makes a disposition possible is the product's own stability data, generated under the conditions specified in ICH Q1A(R2) and supplemented where necessary by deliberate stress studies. A product with no such programme — which includes essentially all peptides distributed for research use — cannot have an excursion assessed in this sense, because there is nothing against which to compare the exposure.{{r|ich_q1a}} | |
| + | 21 | ||
| 15 | == Definition and framing == | 22 | == Definition and framing == |
| 16 | Distribution 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}} | 23 | Distribution 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}} |
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| 28 | {{note|The label is the reference. Two vials of chemically identical peptide, one supplied as a licensed medicine and one as a research chemical, may experience the same profile and be subject to entirely different assessments, because only one of them has labelled conditions established by a stability programme.}} | 35 | {{note|The label is the reference. Two vials of chemically identical peptide, one supplied as a licensed medicine and one as a research chemical, may experience the same profile and be subject to entirely different assessments, because only one of them has labelled conditions established by a stability programme.}} |
| 29 | 36 | ||
| + | 37 | == Labelled allowances and in-use periods == | |
| + | 38 | Modern labels for injectable incretin therapies do not state a single storage condition; they state a cold-storage condition for the unopened product and a permitted period at higher temperature, either before first use or after it. These allowances are excursion tolerances that have been established by stability testing and written into the label, which converts what would otherwise be a deviation into ordinary use. | |
| + | 39 | ||
| + | 40 | |+ Storage and in-use allowances stated in manufacturers' prescribing information | |
| + | 41 | | !Product | Storage before first use | Permitted period at higher temperature | | |
| + | 42 | |---|---|---| | |
| + | 43 | | Semaglutide, weekly injection (Ozempic) | 2–8 °C | After first use, 56 days at 2–8 °C or at 15–30 °C | | |
| + | 44 | | Semaglutide for weight management (Wegovy) | 2–8 °C | Up to 28 days at 8–30 °C before use if required | | |
| + | 45 | | Tirzepatide (Mounjaro) | 2–8 °C | Up to 21 days at not above 30 °C | | |
| + | 46 | | Dulaglutide (Trulicity) | 2–8 °C | Up to 14 days at not above 30 °C | | |
| + | 47 | | Liraglutide (Victoza) | 2–8 °C | After first use, 30 days at 15–30 °C or 2–8 °C | | |
| + | 48 | ||
| + | 49 | Allowances are as stated in the respective prescribing information and differ between jurisdictions; the figures above follow United States labelling and are cited to the labels rather than to secondary summaries.{{r|pi_ozempic,pi_wegovy,pi_mounjaro,pi_trulicity,pi_victoza}} | |
| + | 50 | ||
| 30 | == References == | 51 | == References == |
| 31 | {{reflist}} | 52 | {{reflist}} |
| ⋮ | ⋮ | ||
| 33 | <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> | 54 | <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> |
| 34 | <ref name="haynes1971">Haynes JD. "Worldwide virtual temperatures for product stability testing." ''Journal of Pharmaceutical Sciences'' 60(6):927–929 (1971).</ref> | 55 | <ref name="haynes1971">Haynes JD. "Worldwide virtual temperatures for product stability testing." ''Journal of Pharmaceutical Sciences'' 60(6):927–929 (1971).</ref> |
| + | 56 | <ref name="ich_q1a">International Council for Harmonisation, ''Q1A(R2): Stability Testing of New Drug Substances and Products'' (2003), read with ''Q1E: Evaluation for Stability Data'' (2003).</ref> | |
| 35 | <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> | 57 | <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> |
| 36 | <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> | 58 | <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> |
| ⋮ | ⋮ | ||
| 38 | <ref name="bhatnagar2007">Bhatnagar BS, Bogner RH, Pikal MJ. "Protein stability during freezing: separation of stresses and mechanisms of protein stabilization." ''Pharmaceutical Development and Technology'' 12(5):505–523 (2007).</ref> | 60 | <ref name="bhatnagar2007">Bhatnagar BS, Bogner RH, Pikal MJ. "Protein stability during freezing: separation of stresses and mechanisms of protein stabilization." ''Pharmaceutical Development and Technology'' 12(5):505–523 (2007).</ref> |
| 39 | <ref name="matthias2007">Matthias DM, Robertson J, Garrison MM, Newland S, Nelson C. "Freezing temperatures in the vaccine cold chain: a systematic literature review." ''Vaccine'' 25(20):3980–3986 (2007).</ref> | 61 | <ref name="matthias2007">Matthias DM, Robertson J, Garrison MM, Newland S, Nelson C. "Freezing temperatures in the vaccine cold chain: a systematic literature review." ''Vaccine'' 25(20):3980–3986 (2007).</ref> |
| + | 62 | <ref name="pi_ozempic">Novo Nordisk. ''Ozempic (semaglutide) injection'' — United States prescribing information, current revision, section on storage and handling.</ref> | |
| + | 63 | <ref name="pi_wegovy">Novo Nordisk. ''Wegovy (semaglutide) injection'' — United States prescribing information, current revision, section on storage and handling.</ref> | |
| + | 64 | <ref name="pi_mounjaro">Eli Lilly and Company. ''Mounjaro (tirzepatide) injection'' — United States prescribing information, current revision, section on storage and handling.</ref> | |
| + | 65 | <ref name="pi_trulicity">Eli Lilly and Company. ''Trulicity (dulaglutide) injection'' — United States prescribing information, current revision, section on storage and handling.</ref> | |
| + | 66 | <ref name="pi_victoza">Novo Nordisk. ''Victoza (liraglutide) injection'' — United States prescribing information, current revision, section on storage and handling.</ref> | |
| 40 | 67 | ||
| 41 | {{DEFAULTSORT:Temperature excursion}} | 68 | {{DEFAULTSORT:Temperature excursion}} |