The US Food and Drug Administration (FDA) last week finalized its guidance on repackaging drugs by pharmacies and registered outsourcing facilities and also issued a revised draft guidance detailing its policies on mixing, diluting and repackaging certain types of biological products outside of the scope of an approved biologics license application (BLA).
Final Guidance: Repackaging Drugs
In its final guidance, FDA lays out the situations where it does not intend to enforce certain federal regulations with regard to repackaging drugs by state-licensed pharmacies, federal facilities or registered outsourcing facilities.
The guidance also clarifies FDA's definition of repackaging, which the agency says is "the act of taking a finished drug product from the container in which it was distributed by the original manufacturer and placing it into a different container without further manipulation of the drug."
"If a drug is manipulated in any other way, including if the drug is reconstituted, diluted, mixed or combined with another ingredient, that act is not considered repackaging," FDA says.
Repackaging is done for a variety of reasons, including to meet specific patient needs and to reduce medication errors.
While FDA says that repackaged drugs are "generally not exempt from any of the provisions of the [Food, Drug, and Cosmetic Act] FD&C Act related to the production of drugs," including provisions related to premarket approval, misbranding and adulteration, the agency says it does not intend to enforce these provisions against state-licensed pharmacies, federal facilities or outsourcing facilities as long as they meet the criteria set out in the guidance.
The final guidance also removes a provision of the guidance discussing section 506F of the FD&C Act as amended by the Food and Drug Administration Safety and Innovation Act that exempted certain hospitals from registration requirements when transferring repackaged drugs within the same hospital network during a drug shortage, as section 506F was written to expire when FDA finalizes guidance on the matter.
Draft Guidance: Mixing, Diluting or Repackaging Biologics
Due to the unique properties of biologics, FDA says even minor manipulations of a product can result in safety or quality issues.
"Diluting or mixing a biological product with other components, or repackaging a biological product by removing it from its approved container-closure system and transferring it to another container-closure system, in, in the absence of manufacturing controls, highly likely to affect the safety and/or effectiveness of the biological product," FDA says.
However, the agency notes that there are a number of circumstances where it is appropriate to mix or dilute a biological product to meet specific patient needs. "For example, for some biological products there is no licensed pediatric strength and/or dosage form, so the product is diluted for use in pediatric patients."
While there are exemptions from certain federal regulations for compounded drugs under sections 503A and 503B of the Drug Quality and Security Act, these exemptions do not apply to biological products licensed under sections 351(a) or (k) of the Public Health Service Act.
As such, FDA says that any biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an "unlicensed biological product."
However, FDA says it "does not intend to take actions for violations of section 351 of the PHS Act or sections 502(f)(1) or 582 of the FD&C Act if a state-licensed pharmacy, a federal facility, or an outsourcing facility mixes, dilutes, or repackages a biological product" in accordance with the guidance.
FDA also clarifies that the guidance does not apply to radioactive biological products or to investigational new drugs being studied under a new drug application.
Final Guidance: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities
Revised Draft Guidance: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application