USP <787> Subvisible particulate matter in therapeutic protein injections
USP chapter <787>, Subvisible Particulate Matter in Therapeutic Protein Injections, became official August 1, 2014 and provides specific guidance for protein-based formulations. Chapter <787> evolved to address the limitations of USP for therapeutic proteins and provides a smaller-volume testing framework to address proteinaceous particles and the immunological effects of a sub-10-µm particle load.
Application and scope
USP <787> requires pharmaceutical and biopharmaceutical manufacturers making injections and infusions follow rigorous rules regarding the quantity of particles present in final drug products. This regulation focuses specifically on the development of more costly protein formulations and the unique sensitivities inherent in producing protein-based therapeutics.
- Specifically for protein-based therapeutics (not all forms of injectable)
- Analysis of final dose & packaging
- Smaller test product volumes
- Smaller test aliquots
- Defines “inherent” form of particulate matter
- Describes prep and test methods
- Defines maximum particle burden limits
Although USP <787> focuses exclusively on protein-based formulations, there are a number of similarities between USP <787> and USP <788> (Particulate Matter in Injections) including:
- Primary method: Light Obscuration1
- Secondary method: Light Microscopy
- Minimum number of aliquots = 4
- Particle size thresholds >=10 & >=25 µm
- Particle limits:
- SVI: 6,000 & 600 per container
- LVI (>100 mL): 25 & 3 per mL*
*Larger test volumes must also pass a container test. No more than 6,000 counts at 10 microns and no more than 600 counts at 25 microns.
1 Should the primary method not be applicable (e.g., preparations with reduced clarity or increased viscosity), microscopic particle testing should be carried out.