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

Rx-360 has released a summary regarding Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products.

FDA recently issued the final guidance "Allowable Excess Volume and Labeled Vial Fill SIze in Injectable Drug and Biological Products".  This guidance clarifies the FDA regulatory requirements and recommendations pertaining to allowable excess volume in injectable vials and describes when justification is needed for a proposed excess volume in these injectable drug products. This guidance also 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.

The guidance addresses withdrawable volume and labeled vial fill size for injectable drug products that are packaged in vials and ampules, including products that require reconstitution. It does not address injectable drug products in other packaging types (e.g., prefilled syringes, intravenous infusino bags) or noninjectable products.  The recommendations in the guidance apply to NDAs, ANDAs, BLAs, and supplements or other changes to these applications for new packaging or other changes that may affect the fill volume.  Note that the guidance does not specifically address either legacy products or variable dosing from single-use vials.

The guidance states that for all application types, the applicant should communicate with FDA early in the drug development process about the vial size and unique excess volume concerns. The guidance also recommends communicating with FDA as outlined in existing recommendations related to communication with sponsors/applicants, including the Guidance for Review Staff and Industry Good Review Management Principles and Practices for PDUFA.

The guidance also states that the drug product's vial fill size should be appropriate for the labeled use and dosing of the product. When deciding what is appropriate, the following should be considered:

•  Single-dose vials should not contain a significant volume beyond what would be considered a usual or maximum dose for the expected use of the drug product. Note that the guidance indicates that a specific quantitative volume of remaining drug product considered 'significant' cannot be specified, volumes remaining that could provide a second dose, or would encourage pooling for a second dose, would be considered excessive.

•  Consumers and/or 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.

To view or download the FDA Guidance, click here.