US FDA has issued a guidance on Allowable Excess Volume and Labeled Vial Fill Size in injectable drug and biological products. These norms are essentially issued to clarify the Center for Drug Evaluation and Research’s and the Center of Biologics Evaluation and Research’s recommendations to allow excess volume and labeled vial fill size in injectable drugs and biologics.
The new guidance discusses the importance of appropriate fill volumes for injectable drug products and recommends that labeled vial fill sizes be appropriate for the intended use and dosing of the drug product.
FDA states that the recommendations apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), as well as supplements or other changes to these applications for new packaging or other changes that may affect the fill volume.
According to Kaushik Desai, secretary, Indian Pharmaceutical Association (IPA), the new guidelines provide considerable clarity for manufactures and would prevent unpleasant discussions during audits by US FDA.
Injectable vial misuse, including unsafe handling and injection techniques, has led to vial contamination and an increased risk of blood-borne illness transmission between patients. Inappropriate excess volume and labeled vial fill sizes are two factors that may contribute to unsafe handling and injection practices by consumers and health care providers. FDA has been concerned about these issues and is publishing this guidance to clarify its regulatory requirements.
The United States Pharmacopoeia (USP) General Chapter on Injections provides that each container of an injectable product is filled with a volume that slightly exceeds the content indicated in the labeling. The excess volumes are meant to be sufficient to permit withdrawal and administration of the labeled volumes. FDA regulations at 21 CFR 201.51(g) provide that for drugs in ampoules or vials that are intended for injection, the declaration of net quantity of contents on the label is considered to express the minimum quantity of contents and further requires that variation should comply with the excess volumes indicated by USP.
But FDA is concerned when the excess volume in a vial is greater or less than the USP recommended amount without appropriate justification. Such excesses and deficiencies may result in medication errors and may lead to misuse of leftover drug product or pooling of vials to obtain a single dose. Therefore it devised a dedicated guideline on Allowable Excess Volume and Labeled Vial Fill Size in injectable drug and biological products.
Now FDA recommends that a drug product’s vial fill size should be appropriate for the labeled use and dosing of the product. The regulator could request justification when there are questions about the appropriateness of the proposed labeled vial fill sizes in an application. Therefore it has mandated now that single-dose vials should not contain a significant volume beyond what would be considered a usual or maximum dose.
Further, consumers and health care providers should not be routinely required to use more than one vial to administer a typical single dose of the drug product. Multiple-dose vials should contain no more than 30 ml of drug product except under specific circumstances, said the regulator in its guidance.