Guidance Goes After Overfilling of Vials, Ampules

The FDA wants manufacturers to better control the amount of excess drug or biologic they put in injectable vials and ampules to ensure proper patient dosing.

According to final guidance released last week, it’s okay for the volume of product to vary somewhat — adding a little extra can ensure that the patient gets the right amount of drug or biologic when it is transferred to a syringe, for example — but more than slight variations in amount of product should be justified.

The FDA considers the net quantity listed on the label to mean the minimum quantity of contents. Excess volume greater or less than the U.S. Pharmacopoeia’s recommended amount, without proper justification, could lead to medication errors, misuse of leftover drug product or combining vials to get a single dose, which could lead to contamination, the guidance says.

The guidance applies to NDAs, ANDAs, BLAs, as well as supplements or changes to those applications for new packaging or other changes that may affect fill volume.

Companies needing to fill a vial fuller than is recommended should refer to the USP’s General Chapter <1151> on injections, the FDA says. This means designing a product to “meet the label claim and acceptable overfill, and allow for correct dosing,” the guidance says.

Deviations from the USP should be justified using “extractable content testing data,” the agency adds. For BLAs, this should include lot release testing and batches that representative of the commercial process. NDAs and ANDAs should include samples from one or more batches.

The guidance, Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products, replaces a March 2014 draft version. Read it at www.fdanews.com/06-25-15-InjectableGuidance.pdf . — Kellen Owings