Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products

In June, 2015, FDA issued a CDER/CBER guidance document on FDA’s current thinking on allowable excess volume and labeled vial fill size for injectable drugs and biologics.  The guidance is only 5 pages long and discusses the need to comply with current USP requirements for excess volume and the need to provide justification through extractable content testing data (USP Chapter <1> under Packaging, Determination of Volume of injection in Containers).  General fill volume should be based on what is considered a usual or maximum dose for the expected use of the drug product.  FDA is requesting that users of the drugs or biologics not be required to use more than 1 vial to administer a typical single dose of drug product.  For multi-dose vials, no more than 30 mL of drug product should be filled in the vial.

If excess volume is added to the drug product, it should be described in the CTD section 3.2.P.1 and should be justified with the appropriate studies.

Overfill is not the same as overage, the latter being an amount of drug substance in excess of the label claim.  This is further discussed in the ICH Guidance for Industry, Q8(R2), Pharmaceutical Development.

Download the guidance here.