Download Small Volume Parenterals (SVP): Regulatory, Chemistry and

Small Volume Parenterals (SVP): Regulatory, Chemistry and
Toxicology Considerations
Scenario
Large US-based pharma/biotech company, by the name of “Megavac Bio” has
marketed a vaccine, “Prevent” since 1980 in the US, Europe, and Asia. Initially the
largest markets were the US and Europe but now Asia is the fastest growing market
and currently over 70% of units of Prevent are sold in Asia. Because of the market shift
and increasing domestic production costs, Megavac is going to close production in the
US and shift production to a contractor based in Asia. The drug formulation will remain
the same as well as the production process but the primary packaging components will
be changed. The current package is a 3mL glass vial (13mm finish) and a 13mm
rubber closure that is a blend of chlorobutyl and natural rubber. The new CCS will be a
3mL COC vial (13mm finish) and a 13mm bromobutyl rubber stopper. Both the COC
vial and rubber stopper will be made in Asia. The change to COC is being made to
reduce breakage during handling and to reduce the weight of the package. The rubber
is being changed because the current rubber formulation will not meet current
pharmacopoeial and extractables/leachables standards.
What packaging concerns should addressed by Megavac in making these changes?
1. Supply chain issues such as…
a. Packaging material quality and variability
b. Supplier contracts and Change Control issues
c. Finished component (vial & stopper) quality and variability including
composition and dimensional issues
2. Vaccine DP – CCS compatibility issues such as…
a. Particulates
b. Extractables/Leachables…chemical & toxicity issues. Rubber ingredients
such as metal contaminates, NR latex, PNAs from carbon black, and
sensitizers.
c. Water vapor and oxygen transmission through COC vial (not an issue with
previous glass vial).
SVP_Scenario.docx
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d. Migration of label adhesives/inks and other label materials through COC
vials into DP (not an issue with previous glass vial).
e. Migration of wooden pallet fungicide byproducts, such as 2,4,6tribromoanisole, into COC and rubber polymers.
SVP_Scenario.docx
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