Revolutionizing Biotechnology
Why protein aggregation is important to measure
In biopharmaceuticals formulation development, aggregation of proteins is an unwanted outcome. Aggregation of therapeutic proteins is know to impact product efficacy, safety and immunogenicity.
Beginning in 1975 with the passage of USP <788>, monitoring particulate matter in parenteral formulations became a compendial mandate. Initially, this mandate was concerned primarily with foreign matter in these injectables such as rubber stopper pieces that might be introduced during the manufacturing process for small molecule drug products, due to the potential adverse effects in the blood system.
As large molecule therapeutics began being developed (starting in 1982 with Eli Lilly's Humulin), it was realized that these therapeutics were prone to aggregation, especially when encountering different types of stress as they moved through the supply chain. As a result, close monitoring of protein aggregation now became an additional requirement of USP <788>.
Using AIM for characterizing protein aggregation
Biologics QA/QC
AIM automates the process of quantifying protein aggregation with distinct advantages over other techniques:
- More sensitive than light obscuration
- Increased concentration versus standard Flow Imaging Microscopy (FIM)
- Ease of use via test plan implementation (SOPs)
- Self-contained, lower cost solution
Since AIM is an imaging-based solution, it allows you to get higher accuracy counts versus light obscuration, plus particle images which allow for classification of particle types. This is a key benefit, as the ability to classify particulates is critical in debugging process issues: what are the particles and where do they come from in the process?
This ability to differentiate protein aggregates (inherent) from other extrinsic and intrinsic particles such as silicone droplets, pieces of rubber stopper, glass shards, etc. is critical difference from compendial methods such as light Obscuration (LO), which can only count total particulates. For this reason, both the FDA and USP<1787> recommend using orthogonal methods (FIM) for verifying particle counts and particulate sources in biologics production.