Control of sub-visible particles in samples of recombinant proteins and mAbs

Regulatory expectations for the control of particles have increased significantly over the last decade. Orthogonal methods are required to monitor aggregates and particulate matter in the range of 0.1-10um. Factors that can give rise to particles at different process stages are numerous. Below are some examples:

Extrinsic particles arising from the manufacturing process

• Shear forces from pumps
• Rubber fragments, e.g. from tubings
• Leachables from disposable technology
• Buffer and excipients
• Silicon oil from syringes

Intrinsic particles due to non-optimized conditions

• Protein  aggregates