16-18 March 2021
If a liquid is withdrawn from a vial by means of a syringe, remains of the liquid stay in the vial or on its walls. Since it is nearly impossible to extract 100 % of the liquid but the dosage has to be correct, nevertheless, vials usually are slightly overfilled. A vial with a dosage of 1 ml might for example contain 1.1 ml. The FDA has two points of concern: on the one hand some manufacturers fill up to much or not enough drug products without sufficiently justifying this which may result in medication errors. On the other hand the leftover of several vials with excess volume could be pooled to obtain a further dose which could lead to microbial problems.
The intention of the new guidance is to show when such excess volumes should be justified. The FDA recommends to comply with the excess volume recommendations for injectable drugs that appear in the US-American pharmacopoeia USP General Chapter <1151> "Pharmaceutical Dosage Forms". All deviations therefrom must be justified. For this justification it should be proceeded according to USP General Chapter <1> "Packaging, Determination of Volume of Injection in Containers". The Guidance also addresses labelling. The excess volume should not be indicated on the label. The FDA describes the use of the appropriate packaging sizes depending on the intended use as essential point. Single-dose vials, for example, that are designed for injection in a single patient should never contain so much excess volume that the leftover might be pooled to receive a new dose. Multiple-dose vials should not exceed the volume of 30 ml in order to minimize vial septum punctures, which will reduce the risk of microbial contamination.
You can find the draft for the new Guidance Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products on the FDA homepage. The deadline for comments is 90 days.