The draft guidance, known as “Guidance for Industry Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products,” offers the agency’s opinions on cases where biopharma sponsors would need to justify excess volume in injectable vials.
“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,” the agency explains.
Deviations from the recommendations in USP General Chapter <1151> with regard to excess volume should be justified, the agency says, recommending justification by obtaining extractable content testing data, which is described in USP General Chapter <1> under Packaging, Determination of Volume of Injection in Containers, or other appropriately justified methods.
A variety of approaches may be considered acceptable for sample collection, for instance:
- For BLAs (biologic licensing applications): Lot release testing and/or collection from validation lots, using appropriate sampling and methods.
- For NDAs (new drug applications) and ANDAs (abbreviated new drug applications): One or more exhibit batches as part of the product development studies using appropriate sampling and methods.
The agency warns that “even when appropriately labeled, single-dose vials that contain significantly more drug than is required for a single dose may result in the misuse of the leftover drug product.” Similarly, the need to combine several single-dose vials for a single patient dose may lead to medication errors and microbial contamination.
The FDA adds that multiple-dose vials should contain no more than 30 mL of drug product except under specific and justified circumstances.
The agency says it may request justification when there are questions about the proposed labelled vial fill sizes in an application, and applicants should consider:
- 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; and
- 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.
This guidance also discusses the importance of appropriate packaging sizes for injectable drug products and recommends that labeled vial fill sizes be appropriate for the intended use and dosing of the drug.