Release date- 15032017 - The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on FDA's revised draft Guidance for Industry 'Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.'
Re: Docket No. FDA-2014-D-1525-0357: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application; Revised Draft Guidance For Industry
The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on FDA's revised draft Guidance for Industry 'Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.'
BIO is the world's largest trade association representing biotechnology companies, academic institutions, state biotechnology centers, and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products.
I. General Comments:
BIO supports the FDA's issuance of the Revised Draft Guidance entitled, 'Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application' (Revised Draft Guidance). We remain firmly committed to the view that measures like those set forth in the Revised Draft Guidance, when finalized, represent critical steps forward in the effort to protect patients when biological products are handled in a manner that is inconsistent with their approved labeling and that could result in contamination or a lack of effectiveness.
BIO agrees that 'biological products are particularly sensitive to storage and handling conditions' and that 'diluting[,] mixing . . . or repackaging a biological product . . . is, in the absence of manufacturing controls, highly likely to affect the safety and/or effectiveness of the biological product.' Thus, BIO is pleased to see that FDA has responsively addressed many of the concerns raised in comments on the previous draft of the guidance. Specifically, BIO agrees that the following are among the minimum necessary conditions for attempting to safeguard the quality of a biologic removed from its approved container-closure system:
All repackagers must make a formal assessment of the suitability of the container closure used for the repackaged product. This assessment helps ensure that the repackaged container does not compromise the integrity of the biological product after it is repackaged.
State-licensed pharmacies and Federal facilities must complete repackaging in four hours or less. A four-hour in-process time for repackaging activities helps limit the risk for contaminating or destabilizing the repackaged biological product.
Outsourcing facilities should establish stability programs and conduct scientifically meaningful release testing. Stability testing is necessary to ascertain whether the mixed, diluted, and repackaged biologic will continue to meet critical quality attributes for the duration of the BUD, and release testing helps reduce the risk of releasing compromised or contaminated biological products that have been manipulated outside of the conditions set forth in their approved labeling.
Outsourcing facilities must ensure that biological products remain stable and maintain appropriate package integrity during the shipping process. This helps ensure end-to-end stability of the biological product so that it remains safe and effective upon reaching the patient.
There remain, however, several issues with respect to mixed, diluted, and repackaged biologics that BIO believes are not appropriately addressed in the Revised Draft Guidance or that would benefit from additional clarification or refinement. Prime among these is that the Revised Draft Guidance still fails to address the criticality of ensuring the sterility of the biological product's primary container closure and its secondary packaging, which is essential to patient safety.
 82 Fed. Reg. 4358 (Jan. 13, 2017).
 BIO Comments on Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application, Docket No. FDA-2014-D-1525, May 20, 2015 & Mar. 7, 2016.
 Revised Draft Guidance at 3 (Lines 100-06).
 Id. at 8 (Lines 299-300).
 Id. at 8 (Lines 307-10).
 Id. at 11 (Lines 373-75) & Appendices A-B.
 Id. at 19 (Lines 682-85).