In the rapidly developing field of gene therapy, adeno-associated virus (AAV) represents one of the
most prominent and promising platforms for therapeutic application. Different serotypes of AAVs have demonstrated preferences for targeting specifific tissues and represent an auspicious approach for delivering genetic information into patients. A critical quality attribute (CQA) of AVVs is their capsid loading because it influences dose and purity. Capsid loading reflects the effificiency of encapsulation of the genetic material into the viral capsid and is defifined as the ratio of…

The focus is on two specific applications of advanced Mass Spectrometry (MS) for the development of complex biologics. These applications include mapping of disulfide linkages of complex biologics and the application of advanced MS for Critical Quality Attribute (CQA) mapping of a biologic in vivo.

Higher order structure (HOS) is a CQA because it reflects both CMC/process consistency and functional integrity of the biologic drug product. Most biologic therapeutics contain Cys and disulfide bonds (DSBs) and are known to play critical roles in the structural stability and…

The strategic use of advanced analytics is an essential element in today’s early-stage product selection and development. This is particularly true for more complex biologics and emerging modalities such as gene therapy, gene editing, and structurally complex conjugated and fusion biologic products.

Temperature-induced unfolding of monoclonal antibodies and other therapeutic proteins, analyzed by differential scanning calorimetry (DSC) is an indispensable tool for the identification of the candidates with the lowest tendency to denature or of the formulations that increase stability. These decisions usually take into account the thermodynamic stability, represented by the melting temperature (Tm) of the protein and enthalpy of unfolding, derived from equilibrium thermo-dynamic analysis. However, the temperature induced denaturation of proteins is rarely reversible and equilibrium…

Protein-based drugs are characterized with a plentitude of different analytical approaches and methods. Each of these methods provides insight into a certain aspect of the molecule. For example, capillary Gel Electrophoresis (cGE) provides detailed information about the relative impurity content and the purity of an analyte. Especially for low molecular weight species, cGE shows high resolving power and a reproducible relative quantification.

One of the key aspects is not simply just to quantify the different detected signals but also to identify if they originate from the drug…

Host Cell Proteins (HCP) are critical quality attributes and must be monitored during the manufacturing processes by an adequate control strategy.

Protagen Protein Services (PPS) developed an approach for qualitative and quantitative control of HCPs applying shotgun LC-MS. This approach enables us to gain knowledge about HCP level, clusters and species and allows for risk assessment in HCP control.

In this webinar, experts from PPS will discuss the USP and DSP parameters of four different biopharmaceutical products, two different process variants, and one mock…

The development of a biopharmaceutical consists of R&D, CMC manufacturing and clinical trial phases. The quality of the biopharmaceutical product and its assessment via biophysical and biochemical analysis are essential components of this process. The requirements for the protein content determination method are thus very strict, and there is an eminent need for high precision and accuracy. We present a concept for developing, qualifying and validating a precise, accurate and robust method for protein content determination, one that can be adapted to the specific requirements of the product…

Target engagement is a critical factor in drug efficacy. Understanding and controlling how drug candidates interact with their expected targets can be enhanced using combined profiling approaches, specifically high-resolution analyses that provide details about the interaction. Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) and Native Mass Spectrometry (Native MS) are powerful, information-rich approaches that are increasingly used for binding site profiling and analysis of stoichiometry.

Host cell proteins (HCPs) are impurities present in all therapeutics derived from biological sources, and as a critical quality attribute (CQA), they must be characterized in detail and controlled through the manufacturing process and in the final drug product.