BIO, Pew Weigh FDA's Revised Draft Guidance on Mixing, Diluting or Repackaging Biologics

Regulatory NewsRegulatory News | 15 March 2017 |  By 

The Biotechnology Innovation Organization (BIO) and the Pew Charitable Trusts are offering their input on the US Food and Drug Administration's (FDA) recently revised draft guidance on mixing, diluting or repackaging biologics.

While both organizations say the revised draft guidance is a step in the right direction, BIO says several aspects of the guidance still raise concerns.


FDA first issued its draft guidance on mixing, diluting or repackaging biological products outside the scope of an approved biologics license application (BLA) in 2015 in order to detail the conditions under which pharmacists and outsourcing facilities could mix, dilute and repackage biologics.

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.

FDA acknowledges that there are 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."

In response to stakeholder concerns, FDA issued a revised version of the draft guidance in January 2017 that included new appendices detailing stability and release testing and provided additional flexibility to outsourcing facilities.

Comments on Revised Draft Guidance

In its comments, BIO says FDA's revised draft guidance addresses most of its concerns from the previous version.

However, BIO says it still has issues with some of the provisions, chief among them is that the revised draft guidance "fails to address the criticality of ensuring the sterility of the biological product's primary container closure and its secondary packaging."

According to BIO, the guidance should hold compounding pharmacies and outsourcing facilities to the same standards as manufacturers for ensuring both levels of packaging are sterile.

Additionally, BIO warns that outsourcing facilities may not be meeting GMP requirements. As such, BIO calls on FDA to prioritize inspections of outsourcing facilities that mix, dilute or repackage biologics.

For its part, Pew applauds FDA for providing more flexibility for outsourcing facilities to repackage biological products.

In its comments on the 2015 draft guidance, Pew raised concerns that limiting the beyond-use date (BUD)to five days would disincentivize outsourcing facilities from repackaging biologics.

In the revised draft guidance, FDA says it will allow outsourcing facilities to extend the BUDs for repackaged biologics based on the results of stability testing for each container-closure system, up to the expiration date of the product.

"The new draft guidance improves upon FDA's earlier proposal by providing compounders that comply with good manufacturing practices (GMP) the ability to set BUDs for repackaged biological products that are longer than the 24 hour limit in FDA's guidance where such extended dating is supported by testing," Pew writes. "This proposal strikes a reasonable balance between the practical advantages of longer dating and the need to ensure product sterility."


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