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Vial filling and stoppering (revision 2)

Old revision·04:14, 1 Nov 2024·SortKeySascha

This is an old revision of this page, as it stood at 04:14, 1 Nov 2024, saved by SortKeySascha with the summary state the difference between a validated shipper and an insulated box. It may differ substantially from the current revision, and any error it contains may since have been corrected.
Vial filling and stoppering
DeterminesFill mass, headspace, container integrity
Sequence for lyophilisateFill, partially stopper, dry, seat, cap
Failure mode of interestUnderfill; seal defects
Analytical method infobox · conventions

Vial filling and stoppering is the operation that transfers material into its final container and closes it. For a lyophilised product the sequence is distinctive: solution is filled, stoppers are seated only partially so that vapour can escape, the vials are dried in the chamber, and the stoppers are then pressed home before the vials leave it.[1]

Two attributes are set here and nowhere else. Fill mass determines how much material a purchaser receives — see Underfilling — and container closure integrity determines whether the contents stay dry and uncontaminated for the shelf life.[2]

Fill control

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Filling is volumetric or gravimetric. Volumetric filling meters a volume and relies on solution density; gravimetric filling weighs, in-process or in a sampling plan, and is more directly connected to the quantity of interest.[1]

Fill accuracy is specified as a tolerance and monitored during the run, since pump and valve behaviour drifts, and the in-process records are part of the batch documentation.[3] A deliberate overage above the label claim is ordinary and compensates for losses in reconstitution and withdrawal; it is not a defect. See Underfilling.

References

  1. ^ a b International Council for Harmonisation, Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (2000).
  2. ^ United States Pharmacopeia, General Chapter <1207>, Package Integrity Evaluation — Sterile Products.
  3. ^ ISO 9001:2015, Quality management systems — Requirements.