Cold chain: difference between revisions
Diff·revision 29 → 30·08:26, 3 Nov 2024
Difference between revision 29 and revision 30 of Cold chain. 14 lines changed; the page grew by 1,676 bytes.
| Revision 29 — 13:13, 26 Oct 2024 CDMO_Caradoc (talk) replace primary source with the review 11,453 bytes ±0 | Revision 30 — 08:26, 3 Nov 2024 OralSemaOswin (talk) attribute range as a review estimate per talk 13,129 bytes +1,676 | ||
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| 1 | {{Infobox concept | 1 | {{Infobox concept |
| 2 | | name = Cold chain | 2 | | name = Cold chain |
| + | 3 | | subtitle = Temperature-controlled distribution | |
| 3 | | image = cold-chain.svg | 4 | | image = cold-chain.svg |
| 4 | | caption = A cold chain is a series of custody transfers, each of which is a candidate point of failure and each of which is expected to leave a temperature record. | 5 | | caption = A cold chain is a series of custody transfers, each of which is a candidate point of failure and each of which is expected to leave a temperature record. |
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| 66 | The vaccine vial monitor deserves separate mention because it is attached to the individual container rather than to the shipment, and therefore survives every custody transfer. It is a heat-sensitive label whose inner square darkens progressively; when it matches or exceeds the reference ring the vial is not to be used. Its limitation is definitional: it responds to heat and not to freezing, so a vial that has been frozen presents an unchanged monitor.{{r|kartoglu2014}} | 67 | The vaccine vial monitor deserves separate mention because it is attached to the individual container rather than to the shipment, and therefore survives every custody transfer. It is a heat-sensitive label whose inner square darkens progressively; when it matches or exceeds the reference ring the vial is not to be used. Its limitation is definitional: it responds to heat and not to freezing, so a vial that has been frozen presents an unchanged monitor.{{r|kartoglu2014}} |
| 67 | 68 | ||
| + | 69 | {{figure|cold-chain|A cold chain as a series of custody transfers. Each handover is a point at which monitoring may be interrupted and at which responsibility for the record changes.}} | |
| + | 70 | ||
| 68 | === Calibration and traceability === | 71 | === Calibration and traceability === |
| 69 | A temperature record is only as good as the calibration of the instrument that produced it. Compendial guidance on monitoring devices expects calibration traceable to a national metrology institute, at intervals appropriate to the device, and at points within the range of interest rather than only at ambient temperature. A logger calibrated at 25 °C and used at 5 °C may carry an error larger than its stated accuracy.{{r|usp1118}} | 72 | A temperature record is only as good as the calibration of the instrument that produced it. Compendial guidance on monitoring devices expects calibration traceable to a national metrology institute, at intervals appropriate to the device, and at points within the range of interest rather than only at ambient temperature. A logger calibrated at 25 °C and used at 5 °C may carry an error larger than its stated accuracy.{{r|usp1118}} |
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| 73 | Traceability of the record itself is a separate question from calibration of the sensor. A record that cannot be tied to a specific consignment, with the times of custody transfer identified, cannot be used to attribute an excursion to a stage of the chain, which is the purpose for which such records are chiefly wanted.{{r|eugdp2013}} | 76 | Traceability of the record itself is a separate question from calibration of the sensor. A record that cannot be tied to a specific consignment, with the times of custody transfer identified, cannot be used to attribute an excursion to a stage of the chain, which is the purpose for which such records are chiefly wanted.{{r|eugdp2013}} |
| 74 | 77 | ||
| + | 78 | == Mean kinetic temperature == | |
| + | 79 | Cumulative thermal exposure cannot be summarised by an arithmetic mean, because degradation rate rises exponentially with temperature. Time spent warm contributes disproportionately, and an average conceals it. The conventional summary statistic is the '''mean kinetic temperature''', introduced by Haynes in 1971: the single constant temperature that would produce the same extent of degradation, over the same period, as the varying profile actually experienced.{{r|haynes1971}} | |
| + | 80 | ||
| + | 81 | For a series of intervals of duration ''t''<sub>i</sub> at absolute temperatures ''T''<sub>i</sub>, the mean kinetic temperature is | |
| + | 82 | ||
| + | 83 | {{math|T_{MKT} = (ΔH/R) ÷ [ −ln( Σ t_{i} e^{−ΔH/(R T_{i})} ÷ Σ t_{i} ) ]}} | |
| + | 84 | ||
| + | 85 | where ΔH is an assumed activation energy and R the gas constant. Compendial practice takes ΔH as 83.144 kJ·mol⁻¹, chosen so that ΔH/R is exactly 10,000 K, which simplifies hand calculation and is the value used throughout this wiki.{{r|usp1079,haynes1971}} | |
| + | 86 | ||
| 75 | == References == | 87 | == References == |
| 76 | {{reflist}} | 88 | {{reflist}} |
| 77 | <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), with associated technical supplements.</ref> | 89 | <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), with associated technical supplements.</ref> |
| 78 | <ref name="usp659">United States Pharmacopeia, General Chapter <659>, "Packaging and Storage Requirements". USP–NF, current revision.</ref> | 90 | <ref name="usp659">United States Pharmacopeia, General Chapter <659>, "Packaging and Storage Requirements". USP–NF, current revision.</ref> |
| + | 91 | <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> | |
| 79 | <ref name="usp1118">United States Pharmacopeia, General Chapter <1118>, "Monitoring Devices — Time, Temperature, and Humidity" (informational). USP–NF, current revision.</ref> | 92 | <ref name="usp1118">United States Pharmacopeia, General Chapter <1118>, "Monitoring Devices — Time, Temperature, and Humidity" (informational). USP–NF, current revision.</ref> |
| + | 93 | <ref name="haynes1971">Haynes JD. "Worldwide virtual temperatures for product stability testing." ''Journal of Pharmaceutical Sciences'' 60(6):927–929 (1971). The origin of the mean kinetic temperature calculation.</ref> | |
| 80 | <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> | 94 | <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> |
| 81 | <ref name="hanson2017">Hanson CM, George AM, Sawadogo A, Schreiber B. "Is freezing in the vaccine cold chain an ongoing issue? A literature review." ''Vaccine'' 35(17):2127–2133 (2017).</ref> | 95 | <ref name="hanson2017">Hanson CM, George AM, Sawadogo A, Schreiber B. "Is freezing in the vaccine cold chain an ongoing issue? A literature review." ''Vaccine'' 35(17):2127–2133 (2017).</ref> |