Mixing, Diluting, or Repackaging Biological Products - FDA Draft Guidance

Recommendation

7/8 May 2024

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Regulatory Requirements and Practical Implementation

In February, the FDA published a new draft guidance on "Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application". Background is the reality that sometimes certain licensed biological products may need to be mixed or diluted in a way not described in the approved labelling for the product to meet the needs of a specific patient. For example, if there is no licensed pediatric strength and/or dosage form for the product defined and licensed, it must be diluted for use in pediatric patients.

But biological products are mostly complex in their structure, or they are a combination of compounds or possibly have living entities. That's why they are normally very sensitive for any manipulation in their manufacturing process as well as in terms of storage and packaging. Accordingly, 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, is, in the absence of manufacturing controls, highly likely to affect the safety and/or effectiveness of the biological product.

Within this draft document, FDA shows their policy regarding the mixing, diluting, and repackaging of certain types of biological products that have been licensed under section 351 of the Public Health Service Act (PHS Act) when such activities are not within the scope of the product's approved biologics license application (BLA) as described in the approved labelling for the product.

But for the use of this guidance document, it must be considered, that FDA defines the following exceptions, which the document does not address: 

• "Biological products not subject to licensure under section 351 of the PHS Act (i.e., biological products for which a marketing application could properly be submitted under section 505 of the FD&C Act (see section 7002(e) of the Affordable Care Act)). The repackaging of biological products not subject to licensure under section 351 is addressed in a separate draft guidance document. 
• Products intended for use in animals. FDA will consider addressing this issue in a separate guidance document. 
• Mixing, diluting, or repackaging biological products (other than allergenic extracts) by entities that are not state-licensed pharmacies, Federal facilities, or outsourcing facilities;  and preparation of allergenic extracts by entities that are not state-licensed pharmacies, Federal facilities, outsourcing facilities, or physicians (See additional information in section III.A. of this draft guidance document). 
• Removing a biological product from the original container at the point of care for immediate administration to a single patient after receipt of a patient-specific prescription or order for that patient (e.g., drawing up a syringe to administer directly to the patient). FDA does not consider this to be "repackaging," for purposes of this guidance document. 
• Upon receipt of a patient-specific prescription, a licensed pharmacy removing from one container the quantity of solid oral dosage form biological products necessary to fill the prescription and placing it in a smaller container to dispense directly to its customer. 
• Mixing, diluting, or repackaging a licensed biological product when the product is being mixed, diluted, or repackaged in accordance with the approved BLA as described in the approved labelling for the product. FDA considers this to be an approved manipulation of the product. 
• Mixing, diluting, or repackaging of blood and blood components for transfusion, vaccines, cell therapy products, or gene therapy products The guidance  does not alter FDA's existing approach to regulating the collection and processing of blood and blood components. In addition, FDA intends to consider regulatory action if  licensed vaccines, cell therapy products, and gene therapy products are subject to additional manufacturing, including mixing, diluting, or repackaging, in ways not specified in the product's approved BLA as described in the approved labelling for the product."

For more details, please see the complete Draft Guidance entitled "Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application".