Multi-dose vial: difference between revisions
Diff·revision 18 → 19·21:15, 18 Apr 2025
Difference between revision 18 and revision 19 of Multi-dose vial. 5 lines changed; the page grew by 1,104 bytes.
| Revision 18 — 07:16, 10 Apr 2025 GHK_Gwendolen (talk) copyedit 11,251 bytes ±0 | Revision 19 — 21:15, 18 Apr 2025 ConsensusConal (talk) expand §The period after initial puncture 12,355 bytes +1,104 | ||
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| 53 | The phenolic preservatives illustrate that a preservative is not an inert additive. In insulin formulations, phenol and m-cresol bind at a specific site on the hexamer and shift the conformational equilibrium, and their presence is required for the physical stability of the formulation as well as for its preservation. Removing the preservative from such a product is therefore not merely a microbiological change.{{r|brange1993}} | 53 | The phenolic preservatives illustrate that a preservative is not an inert additive. In insulin formulations, phenol and m-cresol bind at a specific site on the hexamer and shift the conformational equilibrium, and their presence is required for the physical stability of the formulation as well as for its preservation. Removing the preservative from such a product is therefore not merely a microbiological change.{{r|brange1993}} |
| 54 | 54 | ||
| + | 55 | Conversely, benzyl alcohol has been reported to destabilise some proteins, promoting aggregation at concentrations within the preservative range. The interaction is protein-specific, and reports concern proteins rather than short synthetic peptides, for which the equivalent question appears not to have been systematically addressed.{{r|manning2010mdv}} | |
| + | 56 | ||
| 55 | === Preservative loss during use === | 57 | === Preservative loss during use === |
| 56 | Preservative concentration is not constant over a container's in-use life. Volatile preservatives such as chlorobutanol are lost to the headspace and through the closure; benzyl alcohol partitions into elastomer; and adsorption onto the stopper is documented for several preservatives. Compendial expectations accordingly include a preservative content specification at the end of shelf life, not only at release, and effectiveness testing is conventionally performed at the lower end of the specified range rather than at the target concentration.{{r|usp51,usp1381mdv}} | 58 | Preservative concentration is not constant over a container's in-use life. Volatile preservatives such as chlorobutanol are lost to the headspace and through the closure; benzyl alcohol partitions into elastomer; and adsorption onto the stopper is documented for several preservatives. Compendial expectations accordingly include a preservative content specification at the end of shelf life, not only at release, and effectiveness testing is conventionally performed at the lower end of the specified range rather than at the target concentration.{{r|usp51,usp1381mdv}} |
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| 71 | Periods are those tabulated in the 2023 revision of the chapter; the chapter is periodically revised and its earlier revisions differ in detail.{{r|usp797}} | 73 | Periods are those tabulated in the 2023 revision of the chapter; the chapter is periodically revised and its earlier revisions differ in detail.{{r|usp797}} |
| 72 | 74 | ||
| + | 75 | Three features of this framework are consequential. The single-dose periods depend on the air quality of the environment in which the container was entered, which is a recognition that the risk being managed is airborne and personnel-borne contamination during the entry itself. The multiple-dose period does not depend on air quality, because the preservative is doing that work. And the phrase ''unless the manufacturer specifies otherwise'' is not decorative: several products carry shorter in-use periods on their labels, and those govern.{{r|usp797}} | |
| + | 76 | ||
| 73 | == References == | 77 | == References == |
| 74 | {{reflist}} | 78 | {{reflist}} |
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| 80 | <ref name="fischer2010">Fischer GE, Schaefer MK, Labus BJ, et al. "Hepatitis C virus infections from unsafe injection practices at an endoscopy clinic in Las Vegas, Nevada, 2007–2008." ''Clinical Infectious Diseases'' 51(3):267–273 (2010).</ref> | 84 | <ref name="fischer2010">Fischer GE, Schaefer MK, Labus BJ, et al. "Hepatitis C virus infections from unsafe injection practices at an endoscopy clinic in Las Vegas, Nevada, 2007–2008." ''Clinical Infectious Diseases'' 51(3):267–273 (2010).</ref> |
| 81 | <ref name="brange1993">Brange J, Langkjaer L. "Insulin structure and stability." ''Pharmaceutical Biotechnology'' 5:315–350 (1993).</ref> | 85 | <ref name="brange1993">Brange J, Langkjaer L. "Insulin structure and stability." ''Pharmaceutical Biotechnology'' 5:315–350 (1993).</ref> |
| + | 86 | <ref name="manning2010mdv">Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. "Stability of protein pharmaceuticals: an update." ''Pharmaceutical Research'' 27(4):544–575 (2010).</ref> | |
| 82 | <ref name="ppmdv">PeptidePedia community reconstitution-practice tally, 2026 (self-reported; no sterility or preservative-effectiveness data; weak evidence — see [[Project:Sourcing_guidelines]]).</ref> | 87 | <ref name="ppmdv">PeptidePedia community reconstitution-practice tally, 2026 (self-reported; no sterility or preservative-effectiveness data; weak evidence — see [[Project:Sourcing_guidelines]]).</ref> |
| 83 | 88 |