FDA Issues Draft Guidance for Repackaging Biological Products

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The draft guidance contains policies for drugs that are processed with additional manufacturing steps such as remixing, dilution, and repackaging.

Biological products for which there are no alternate strengths or dosage forms often need to be remixed, repackaged, or diluted depending on specific patient need, especially in the case of pediatric or ophthalmic use.  Because repackaging a biologic has the potential to negatively affect the safety or efficacy of a product, FDA released draft guidance on Feb. 19, 2015 explicating its policy on these activities by state-licensed pharmacies, Federal facilities, and outsourcing facilities specifically for when the actions are “not within scope of the product’s approved biologics license application (BLA)”. A product originator BLA contains information on product labeling and is submitted by entities that are engaged in drug manufacturing.

Failure to handle a biologic under aseptic conditions or using practices that “conflict with approved product labeling have led to product degradation resulting in adverse events associated with impurities in the product or lack of efficacy because the active ingredient has deteriorated,” according to the draft document.

The draft guidance only addresses biological products that have been licensed under section 351 of the Public Health Service Act (PHS Act). The guidance is also clear on what it does not cover, including products for which a marketing application can be or has been submitted under section 505 of the FD&C Act; biological products administered from original containers at point of care; oral dosages that are removed from larger containers and put into smaller containers by dispensing pharmacies; approved manipulations of a product within scope of a product’s BLA; repackaging of blood, blood components, vaccines, and cell- or gene-therapy products; products intended for animals; or products prepared at unlicensed facilities.

Specifically, the guidance addresses a hospital or health system pharmacy’s repackaging and transfer of drugs to other locations within the health system during an FDA shortage. FDA will not take action for violations of section 351 of the PHS Act or 502(f)(1) of the FD&C Act if a FDA-licensed biological product is mixed, diluted, or repackaged by a licensed pharmacist in a licensed pharmacy, Federal facility, or outsourcing facility after receipt of a valid prescription. The guidance also contained special instructions for product labeling and steps to take to ensure the biological product is within the beyond use date (BUD). Conditions for outsourcing facilities are described in detail in the guidance as well.

Importantly, a condition of the guidance is that a biological product is not sold or transferred to an entity other than the one that prepared the product. It says, “For purposes of this condition, a sale or transfer does not include administration of a biological product in a healthcare setting.” This could imply that oncology practices and other associated Accountable Care Act entities included within a health system would have access to repackaged biologics in the event of a shortage.


Another condition set in the guidance relates to prescription sets, which are described as “a vial or set of vials of premixed licensed standardized and non-standardized allergenic extracts for subcutaneous immunotherapy diluted with an appropriate diluent prepared according to instructions from a prescription or order by a licensed physician for an individual patient.” FDA will not take action, it says, on prescription sets prepared in accordance to the conditions outlined in the document.

Lastly, the guidance recommends each repackaging facility perform a growth promotion microbial challenge study “at least once” for each mixed, diluted, or repackaged product to ensure the microbial quality of a biological product.