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Multi-dose vial: difference between revisions

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Revision 12 — 21:43, 8 Mar 2025
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5| Requirement = Antimicrobial preservative, with effectiveness demonstrated5| Requirement = Antimicrobial preservative, with effectiveness demonstrated
6| Default period after initial puncture = 28 days, unless otherwise specified6| Default period after initial puncture = 28 days, unless otherwise specified
+7<!-- Preservatives in injectable use -->
+8| Benzyl alcohol = 0.9–2.0% w/v
+9| m-Cresol = 0.15–0.32% w/v
+10| Phenol = 0.25–0.5% w/v
+11| Methylparaben with propylparaben = approximately 0.18% with 0.02% w/v
+12| Thimerosal = 0.003–0.01% w/v; largely withdrawn
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13The 28-day convention is frequently misread as a statement about chemical stability. It is not: it derives from the antimicrobial effectiveness of preserved formulations and from infection-control practice, and it is independent of whether the active substance remains within specification. A preparation may be chemically stable for a year and still be discarded at 28 days, and a preparation may lose potency well before 28 days despite its preservative performing perfectly.{{r|usp797,cdc_injection}}19The 28-day convention is frequently misread as a statement about chemical stability. It is not: it derives from the antimicrobial effectiveness of preserved formulations and from infection-control practice, and it is independent of whether the active substance remains within specification. A preparation may be chemically stable for a year and still be discarded at 28 days, and a preparation may lose potency well before 28 days despite its preservative performing perfectly.{{r|usp797,cdc_injection}}
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+21Documented outbreaks of blood-borne and bacterial infection traced to multiple-dose vials have been reported repeatedly, almost always from practices that reuse a syringe or needle to re-enter a vial rather than from failure of the preservative itself. This distinction — between the container as a vector and the container as a reservoir — shapes the infection-control guidance and explains why that guidance concentrates on the syringe.{{r|fischer2010,cdc_injection}}
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15== Definition and compendial basis ==23== Definition and compendial basis ==
16USP <659> distinguishes several container categories, and the distinctions govern labelling and use.24USP <659> distinguishes several container categories, and the distinctions govern labelling and use.
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22The requirement for a preservative in a multiple-dose container appears in the general requirements for injections, and the demonstration of effectiveness is by the antimicrobial effectiveness test in USP <51>. That test challenges the formulation with specified organisms — ''Staphylococcus aureus'', ''Pseudomonas aeruginosa'', ''Escherichia coli'', ''Candida albicans'' and ''Aspergillus brasiliensis'' — and requires defined log reductions at defined intervals over 28 days. For injectable products the criteria are the most demanding of the product categories the chapter defines.{{r|usp51}}30The requirement for a preservative in a multiple-dose container appears in the general requirements for injections, and the demonstration of effectiveness is by the antimicrobial effectiveness test in USP <51>. That test challenges the formulation with specified organisms — ''Staphylococcus aureus'', ''Pseudomonas aeruginosa'', ''Escherichia coli'', ''Candida albicans'' and ''Aspergillus brasiliensis'' — and requires defined log reductions at defined intervals over 28 days. For injectable products the criteria are the most demanding of the product categories the chapter defines.{{r|usp51}}
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+32The 28-day duration of the test and the 28-day default period after puncture are related but not identical claims. The test demonstrates that the preservative system suppresses growth of a substantial deliberate inoculum over 28 days under laboratory conditions; the use period is a practice rule informed by that demonstration. Guidance is explicit that a manufacturer may specify a shorter period, and that a shorter period so specified governs.{{r|usp797,usp51}}
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24== Antimicrobial preservatives ==34== Antimicrobial preservatives ==
25Preservatives used in injectable products are a small set, constrained by systemic toxicity at the concentrations required, by compatibility with peptides and proteins, and by the pH range over which they remain active.35Preservatives used in injectable products are a small set, constrained by systemic toxicity at the concentrations required, by compatibility with peptides and proteins, and by the pH range over which they remain active.
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43<ref name="usp797">United States Pharmacopeia, General Chapter <797>, "Pharmaceutical Compounding — Sterile Preparations", 2023 revision.</ref>53<ref name="usp797">United States Pharmacopeia, General Chapter <797>, "Pharmaceutical Compounding — Sterile Preparations", 2023 revision.</ref>
44<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>54<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>
+55<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>
45<ref name="brange1993">Brange J, Langkjaer L. "Insulin structure and stability." ''Pharmaceutical Biotechnology'' 5:315–350 (1993).</ref>56<ref name="brange1993">Brange J, Langkjaer L. "Insulin structure and stability." ''Pharmaceutical Biotechnology'' 5:315–350 (1993).</ref>
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