Ensuring the stability of monoclonal antibodies (mAbs) during IV bag administration is important due to the risk of aggregation and inactivation from weak interactions. By detecting and quantifying molecular adsorption and desorption early on in development, the risk of incompatibilities and late failure can be reduced. Here we present a case example where we used QSense QCM-D was used to analyze mAb adsorption on the IV-bag materials polypropylene (PP) and low-density polyethylene (LDPE).
Understanding and promoting the stability of monoclonal antibody, mAb is of paramount importance when administrating mAb using IV bags1. Physical instability promoted by weak interaction such as hydrogen bonding, hydrophobic and electrostatic interactions can lead to physical aggregation which can be extended to inactivation of mAb. Monoclonal antibody commonly needs a tailored formulation solution. Some components in this formulation are referred to as excipients. Excipients play a crucial role in stabilizing monoclonal antibodies during formulation development.
Surface induced stress can occur as the first step in the Lumry-Eyring2 model upon initial mAb surface-interaction. The mAb can then be converted and transformed into different states going from a native to unfolded and finally as a deactivated state. There are many factors that could contribute to this transformation with each step having its own time constant. The deceptively simple model, presented below can be extended to include several different steps going from native to deactivated mAb.
N ↔ U → D Lumry Eyring Model
Analyzing the adsorption of biologics and excipients to IV bag materials can provide an early indication of potential incompatibilities. QSense QCM-D analysis can be used to assess antibody adsorption, offering insights into when and why incompatibilities might occur and how to mitigate them.
In this study, we demonstrate the capabilities of QCM-D to measure mAb adsorption to polymer surfaces, such as polypropylene (PP) and low-density polyethylene (LDPE), used in IV bags. The focus was on the initial step in the Lumry-Eyring model, using the acoustic ratio (Dn/fn) to gain insights into the mAb layer properties upon initial interaction with IV bags. Notably, while surface interaction is a prerequisite for deactivation, it does not always lead to it.
The QCM-D sensors were coated with polypropylene (PP) or low-density polyethylene (LDPE) respectively, to replicate the material used in IV bags. The sample sequence was as follows:
The time-resolved QCM-D data, showned in Fig. 1, illustrates the dynamics of mAb interactions and enables analysis and comparison between different surfaces studied.
Figure 1. QCM-D data, ∆f and ∆D, showing time resolved mAb-surface interaction with the IV bag mimicking materials LDPE and PP.
Comparing the maximum Δf (Fig. 2A) and ΔD (Fig. 2B) responses in the mAb adsorption step, it is noted that:
Plotting the acoustic ratio, ΔD/Δf, Fig. 2C, additional aspects and insights emerge:
Figure 2. Comparison of the QCM-D data. A) Frequency shift, Δf, taken at mAb uptake and rinse step. B) Dissipation shift, ΔD, taken at mAb uptake and rinse step. C) Acoustic ratio, ΔD/Δf, taken at mAb uptake and rinse step.
Understanding and promoting the stability of monoclonal antibody, mAb is of paramount importance when administrating mAb using IV bags. By utilizing QCM-D analysis, we explored the adsorption dynamics of mAbs on polypropylene (PP) and low-density polyethylene (LDPE), commonly used in IV bags. Our findings revealed that mAbs bind strongly to both surfaces, with minimal differences in surface-saturation behavior, indicating distinct interaction mechanisms. The comparable acoustic ratios suggest similar rigidity in the mAb layers formed on both surfaces. These insights highlight the effectiveness of QCM-D as a tool for assessing material-biologic interactions, guiding the development of stable mAb formulations, and reducing the risk of late discovery of incompatibilities.
As an extension of the study, we analyzed mAb adsorption to PP and LDPE surfaces when co-formulated with a non-ionic surfactant. Download the white paper below to learn more about the study and how QSense QCM-D technology can be used to assess the stability and material compatibility of biopharmaceuticals.
Discover how QSense QCM-D technology reveals real-time cleaning insights. Join our webinar to enhance your cleaning strategies and efficiency.
Here we explain how Quartz Crystal Microbalance with Dissipation monitoring, QCM-D, works.
QSense QCM-D technology enables analysis of cleaning process dynamics, surface etching, and surface residual
Read about how and the QCM fundamental frequency matters in measurements
QCM-D was used to compare the potency and mechanisms of action of two different detergents in disrupting lipid membranes
Explore a case example of surfactant adsorption with QSense Omni, showcasing its performance and enhanced data quality.
Read about why it is important for the mass distribution on the QCM sensor to be even, and what the consequences are if it is not.
Learn more about the Sauerbrey equation and when it should be used.
Yousra is an Application Scientist at Biolin Scientific. She has a strong interdisciplinary research background and deep technical expertise in laboratory technologies, with a particular focus on surface science instruments. Holding a Ph.D. in Biology and Biochemistry, Yousra has extensive experience in diverse fields, including biomaterials, microbiology, and surface chemistry.