USP <787> Subvisible Particulate Matter in Therapeutic Protein Injections will be published for public comment before year-end. This chapter discusses strategy and methods for characterization of the protein aggregates and particles in biotherapeutics. While initial limits for subvisible particles will likely be the same as in USP<788>, there may be a requirement to monitor (but not report) particles less than 10µm.
Included in the chapter is guidance concerning injectables that typically have inherent particulate burden i.e. those with adjuvants, or high protein concentrations prone to aggregation. Such preparations typically would not meet guidelines using standard particulate testing procedures such as light obscuration. In these cases, it is anticipated that regulators will be looking at manufacturing processes to ensure that particulate contamination is avoided wherever possible and that the finished product is fully described and defined in terms of the expected particulate load in product submission documents. This biologics specific chapter includes considerations of smaller volume, appropriate sample handling and a focus on protein aggregates rather than just extrinsic and intrinsic particles.1
The chapter outlines multiple analytical procedures for the measurement and characterization of particulates, with the intention to help ensure patient safety by preventing the acceptance of products that contain particles that may cause capillary occlusion.2
No one should be surprised that more examination and record keeping is being required of particulates in biologics. When it comes to particulate, less is more! We can help you reduce extrinsic particulate from containers. With USP <788> certified PharmaTainer bottles and carboys. Consider also the particulate levels in containers of adjuvant and other materials used in your product, they contribute, too!
1 Narhi, Linda and Satish Singh, Update on the status of the USP chapters revisions <787>, <1787> and the stimulus article, Protein Aggregation and Biological Consequences Focus Group Newsletter, (PABC-FG) (AAPS), March 2013 v 4 no. 1.
2Particles in Parenterals: Visual Inspection Systems & Root Cause Analysis conference, Vienna, Austria; 7-8 May 2013