Biotherapeutic Reformulation Achieved Through Extended Particle Analysis

Biotherapeutic Reformulation Achieved Through Extended Particle Analysis

Proteinaceous particles in parenteral drugs pose an immunogenic risk. These formulations are therefore rigorously characterized for optimal conformational and colloidal stability of the drug molecule. As such, they undergo thorough analysis of biophysical descriptors and extended particle characterization to ensure a safe and stable product is delivered to market with a shelf life of about two years. In this post, we summarize a recent paper by Mattison et al. (2018) published in BioProcess International on how they successfully reformulated biotherapeutics by using quantitative stability predictors and descriptors. 

FlowCam collage of protein aggregate particles from Mattison et al studyFlowCam collage of silicone oil droplets from Mattison et al studyMattison et al. sorted images based on morphology to distinguish between silicone oil droplets (pre-filled syringe lubricant) and proteins. Credit: Mattison et al., 2018. 

Different methodologies are used to characterize the liquid protein formulations to measure biophysical descriptors and perform extended particle characterization. An article by Mattison et al. (2018) describes how they rationally achieved the reformulation of a biotherapeutic product based on biophysical stability predictors and descriptors as measured by the initial product ("formulation A") and the reformulated product ("formulation B").

Such predictors and descriptors included:

  1. diffusion interaction parameter (kD) as measured by dynamic light scattering,
  2. second virial coefficient (B22) as measured by static light scattering,
  3. effective protein charge (ZEff), and
  4. melting and onset aggregation temperatures (TM and TOnset). 

The formulations were also characterized using flow imaging analysis (FlowCam) for the quantification of subvisible particle count and morphology. Additionally, the FlowCam was used to sort images based on morphology, enabling the differentiation and separate analysis of amorphous, proteinaceous particles, from round silicone oil droplets used in the prefilled syringe lubricant. 

To learn about their method for liquid protein formulation characterization, you can access the full article here.  

Citation: 
Mattison, K., Mehtala, J., Taddei, M., Cheung, J., Gutka, H. 2018. Rational Design of Liquid Protein Formulations: Application of Biophysical Stability Predictors and Descriptors to Reformulate Biotherapeutics. BioProcess International, 16(5) pp. 32-42. 

Post Topics

Related Posts

Nurse with IV bag and patient in the background
Monitoring Subvisible Particle Formation in Infusion Bags Exposed to Stress Conditions
Agitation during transportation is one of the most ubiquitous stress conditions to which therapeutic protein formulations and other biotherapeutic …
Read Post
FlowCam images of IVIG proteins before and after drop shock
Study Uses FlowCam to Investigate Effects of Diluent and Silicone Oil on Particulate Formation in IV Bags
Protein aggregation is a major concern for biopharmaceuticals in post-production. Subvisible particles that form due to routine handling compromise …
Read Post
Need Supplies?

Find supplies and spare parts for your FlowCam instrument or ask for a quote. 

Order Now

Need Help?

Get technical support and application help. Request training or preventative maintenance.


Submit a Support Ticket

Need Information?

Check out our knowledge base including white papers, application notes, technical notes, and videos.

View Resources