Temperature excursion: difference between revisions
Diff·revision 49 → 50·16:44, 14 Dec 2025
Difference between revision 49 and revision 50 of Temperature excursion. 10 lines changed; the page grew by 1,287 bytes.
| Revision 49 — 14:34, 6 Dec 2025 HOMA_Hettie (talk) split overlong sentence 20,277 bytes +585 | Revision 50 — 16:44, 14 Dec 2025 CarryOverCai (talk) reorder sections to follow the class template 21,564 bytes +1,287 | ||
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| 128 | Two structural features of this sequence are worth noting. It is asymmetric in favour of rejection, because the burden is to show that quality is unaffected rather than to show that it is affected. And it depends at step 4 on data that exist only for products with a stability programme, which is why the sequence cannot be applied outside regulated distribution however carefully the temperature was recorded.{{r|ich_q1a}} | 128 | Two structural features of this sequence are worth noting. It is asymmetric in favour of rejection, because the burden is to show that quality is unaffected rather than to show that it is affected. And it depends at step 4 on data that exist only for products with a stability programme, which is why the sequence cannot be applied outside regulated distribution however carefully the temperature was recorded.{{r|ich_q1a}} |
| 129 | 129 | ||
| + | 130 | === What a stability-indicating assay is asked to demonstrate === | |
| + | 131 | A ''stability-indicating'' method is one shown to resolve the intact substance from its degradation products, so that a change in the assay result can be attributed to degradation rather than to variability. Demonstrating that property is a validation exercise, and the demonstration is conventionally made by forced degradation: the substance is deliberately stressed by heat, humidity, acid, base, oxidant and light, and the method is shown to separate and quantify what results, with mass balance accounted for.{{r|ich_q1a,manning2010}} | |
| + | 132 | ||
| + | 133 | After an excursion, such a method is asked to answer a narrow set of questions: | |
| + | 134 | ||
| + | 135 | * has the assay value for the intact peptide fallen relative to the pre-excursion result for the same lot; | |
| + | 136 | * have known degradation products increased, and specifically those expected from the stress applied — deamidation products after warm aqueous exposure, oxidation products after oxygen exposure, aggregate after freezing; | |
| + | 137 | * has any new peak appeared that was not present before and is not attributable to the method; | |
| + | 138 | * do orthogonal methods agree, since a single chromatographic method may be blind to a physical change that a size-exclusion or particulate method detects.{{r|manning2010}} | |
| + | 139 | ||
| 130 | == References == | 140 | == References == |
| 131 | {{reflist}} | 141 | {{reflist}} |