Assess Biopharmaceutical Stability and Material Compatibility in IV Bags with QCM-D

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).

Stability of monoclonal antibodies in IV bag adminstration

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

Analyze adsorption of biologics to IV-bag materials to get an early indication of potential incompatibilities

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 (D_n/f_n) 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.

Experimental protocol

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:

• baseline in buffer, 1h
• mAb adsorption, 3h
• rinse with buffer, 2h

Results

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:

• The mAb exhibits similar binding affinity for both surfaces.
• The minimal difference between mAb uptake and rinse suggests that the mAbs bind strongly to both surfaces and remain attached after rinsing.
• The data reveal a slight difference in surface-saturation behavior, which may suggest somewhat different interaction mechanisms between the two surfaces.

Mechanistic insights

Plotting the acoustic ratio, ΔD/Δf, Fig. 2C, additional aspects and insights emerge:

• The low ΔD/Δf ratio observed on both surfaces suggests that the adsorbed layer is relatively rigid, potentially indicating that the protein is unfolded upon adsorption to the surface.
• Given the very similar acoustic ratios observed, we can conclude that the mAb layers formed on the LDPE and PP surfaces are comparable in film propreties such as, rigidity.

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.

Concluding remarks

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.

Using QCM-D to assess the protective effect of surfactant

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.