Temperature excursion: difference between revisions
Diff·revision 18 → 19·17:50, 20 Oct 2025
Difference between revision 18 and revision 19 of Temperature excursion. 2 lines changed; the page grew by 491 bytes.
| Revision 18 — 16:48, 6 Oct 2025 FmocFrancis (talk) add the stopper material, since it affects moisture ingress 17,652 bytes +341 | Revision 19 — 17:50, 20 Oct 2025 ITT_Imelda (talk) rm the shipping recommendation — that is advice, not description 18,143 bytes +491 | ||
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| 107 | Real products depart from the single-pathway model in documented ways. Peptide degradation proceeds by several routes with different temperature dependences — [[deamidation]] of asparagine, [[Methionine oxidation|oxidation]] of methionine, backbone hydrolysis, disulfide exchange, and physical [[Peptide aggregation|aggregation]] — so the apparent activation energy of total degradation changes with temperature as the dominant route changes. Extrapolation from accelerated conditions to real storage is therefore reliable only over a limited range, which is why ICH stability programmes require long-term data at the labelled condition and treat accelerated data as supporting rather than substituting.{{r|ich_q1a,manning2010}} | 107 | Real products depart from the single-pathway model in documented ways. Peptide degradation proceeds by several routes with different temperature dependences — [[deamidation]] of asparagine, [[Methionine oxidation|oxidation]] of methionine, backbone hydrolysis, disulfide exchange, and physical [[Peptide aggregation|aggregation]] — so the apparent activation energy of total degradation changes with temperature as the dominant route changes. Extrapolation from accelerated conditions to real storage is therefore reliable only over a limited range, which is why ICH stability programmes require long-term data at the labelled condition and treat accelerated data as supporting rather than substituting.{{r|ich_q1a,manning2010}} |
| 108 | 108 | ||
| + | 109 | Aggregation is the clearest departure. It is frequently nucleation-dependent, so it exhibits a lag phase and then accelerates, and its rate may be non-monotonic in temperature because the conformational states that aggregate are populated over a limited range. A short excursion that nucleates aggregation can produce consequences that continue to develop after the temperature has been restored, which no rate constant evaluated at the excursion temperature will capture.{{r|manning2010}} | |
| + | 110 | ||
| 109 | === Freezing and interfacial damage === | 111 | === Freezing and interfacial damage === |
| 110 | Cooling a liquid formulation below its freezing point subjects the solute to several distinct stresses, none of which is described by the Arrhenius relationship. Ice formation concentrates the remaining solution — freeze concentration — raising solute and salt concentrations by as much as an order of magnitude and shifting pH where buffer components crystallise selectively. It creates a large ice-water interface at which peptides and proteins adsorb and may unfold. And it may bring the system through a temperature range in which cold denaturation occurs.{{r|bhatnagar2007}} | 112 | Cooling a liquid formulation below its freezing point subjects the solute to several distinct stresses, none of which is described by the Arrhenius relationship. Ice formation concentrates the remaining solution — freeze concentration — raising solute and salt concentrations by as much as an order of magnitude and shifting pH where buffer components crystallise selectively. It creates a large ice-water interface at which peptides and proteins adsorb and may unfold. And it may bring the system through a temperature range in which cold denaturation occurs.{{r|bhatnagar2007}} |