Multi-dose vial: difference between revisions
Diff·revision 9 → 10·05:19, 6 May 2025
Difference between revision 9 and revision 10 of Multi-dose vial. 17 lines changed; the page grew by 2,480 bytes.
| Revision 9 — 14:45, 23 Apr 2025 SyringeSybille (talk) expand §Definition and compendial basis 12,489 bytes +1,238 | Revision 10 — 05:19, 6 May 2025 SecondarySrc_Seb (talk) copyedit 14,969 bytes +2,480 | ||
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| 1 | {{Infobox concept | 1 | {{Infobox concept |
| 2 | | name = Multi-dose vial | 2 | | name = Multi-dose vial |
| + | 3 | | subtitle = Multiple-dose container | |
| 3 | | image = vial.svg | 4 | | image = vial.svg |
| 4 | | caption = Repeated penetration of a single closure is the defining feature, and the source of both the preservative requirement and the coring risk. | 5 | | caption = Repeated penetration of a single closure is the defining feature, and the source of both the preservative requirement and the coring risk. |
| ⋮ | ⋮ | ||
| 13 | | Methylparaben with propylparaben = approximately 0.18% with 0.02% w/v | 14 | | Methylparaben with propylparaben = approximately 0.18% with 0.02% w/v |
| 14 | | Thimerosal = 0.003–0.01% w/v; largely withdrawn | 15 | | Thimerosal = 0.003–0.01% w/v; largely withdrawn |
| + | 16 | <!-- Governing chapters --> | |
| + | 17 | | Container definitions = USP <659> | |
| + | 18 | | Antimicrobial effectiveness = USP <51> | |
| + | 19 | | Sterile compounding = USP <797> | |
| + | 20 | | Closure self-sealing and fragmentation = USP <381> | |
| 15 | }} | 21 | }} |
| 16 | {{hatnote|For the container itself and its materials, see [[Vial]]. For the dating of an opened container, see [[Beyond-use date]].}} | 22 | {{hatnote|For the container itself and its materials, see [[Vial]]. For the dating of an opened container, see [[Beyond-use date]].}} |
| ⋮ | ⋮ | ||
| 56 | 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}} | 62 | 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}} |
| 57 | 63 | ||
| + | 64 | {{note|A preservative suppresses growth of organisms introduced during use. It does not sterilise a contaminated preparation, does not act instantaneously, and is ineffective against blood-borne viruses. Contamination of a vial with blood via a reused syringe is not addressed by any preservative.}} | |
| + | 65 | ||
| 58 | === Preservative loss during use === | 66 | === Preservative loss during use === |
| 59 | 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}} | 67 | 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}} |
| ⋮ | ⋮ | ||
| 76 | 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}} | 84 | 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}} |
| 77 | 85 | ||
| + | 86 | Infection-control guidance from the Centers for Disease Control and Prevention adds a practice dimension that the compendial rule does not address. Its recommendations are that a multiple-dose vial be dedicated to a single patient wherever possible; that vials be entered with a new sterile needle and syringe on every occasion; that a vial be discarded if sterility is compromised or questionable regardless of its date; and that vials entered in an immediate patient-treatment area be discarded at the end of the procedure rather than retained.{{r|cdc_injection}} | |
| + | 87 | ||
| + | 88 | == Repeated entry: coring and closure integrity == | |
| + | 89 | Each penetration of an elastomeric closure creates a channel that reseals by elastic recovery. The closure's ability to do so repeatedly is a specified property, tested compendially by the self-sealing test in USP <381> and the corresponding European Pharmacopoeia chapter: a defined number of penetrations is made and the container is then examined for leakage.{{r|usp381mdv,pheur329mdv}} | |
| + | 90 | ||
| + | 91 | Resealing is not unconditional. Its reliability falls with the diameter of the needle used, with repeated penetration through the same point, and with damage to the elastomer surface. A closure penetrated twenty times with a 30-gauge needle at varied points is in a different condition from one penetrated twenty times with a 21-gauge needle at one point, and the compendial test — performed with a specified needle and technique — characterises the closure rather than any particular pattern of use.{{r|usp381mdv}} | |
| + | 92 | ||
| 78 | == References == | 93 | == References == |
| 79 | {{reflist}} | 94 | {{reflist}} |
| ⋮ | ⋮ | ||
| 81 | <ref name="usp51">United States Pharmacopeia, General Chapter <51>, "Antimicrobial Effectiveness Testing". USP–NF, current revision.</ref> | 96 | <ref name="usp51">United States Pharmacopeia, General Chapter <51>, "Antimicrobial Effectiveness Testing". USP–NF, current revision.</ref> |
| 82 | <ref name="usp797">United States Pharmacopeia, General Chapter <797>, "Pharmaceutical Compounding — Sterile Preparations", 2023 revision.</ref> | 97 | <ref name="usp797">United States Pharmacopeia, General Chapter <797>, "Pharmaceutical Compounding — Sterile Preparations", 2023 revision.</ref> |
| + | 98 | <ref name="usp381mdv">United States Pharmacopeia, General Chapter <381>, "Elastomeric Closures for Injections", including self-sealing and fragmentation tests. USP–NF, current revision.</ref> | |
| 83 | <ref name="usp1381mdv">United States Pharmacopeia, General Chapter <1381>, "Assessment of Elastomeric Components Used in Injectable Pharmaceutical Product Packaging/Delivery Systems" (informational). USP–NF, current revision.</ref> | 99 | <ref name="usp1381mdv">United States Pharmacopeia, General Chapter <1381>, "Assessment of Elastomeric Components Used in Injectable Pharmaceutical Product Packaging/Delivery Systems" (informational). USP–NF, current revision.</ref> |
| + | 100 | <ref name="pheur329mdv">European Pharmacopoeia, general chapter 3.2.9, "Rubber closures for containers for aqueous parenteral preparations, for powders and for freeze-dried powders", including the fragmentation test.</ref> | |
| 84 | <ref name="cdc_injection">Centers for Disease Control and Prevention. ''Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care'', and associated injection-safety questions and answers on multi-dose vials.</ref> | 101 | <ref name="cdc_injection">Centers for Disease Control and Prevention. ''Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care'', and associated injection-safety questions and answers on multi-dose vials.</ref> |
| 85 | <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> | 102 | <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> |