Gene therapy plays an increasingly significant role in the future of medicine. Process development and quality testing are yet in the focus of the international authorities. Today, due to their specific characteristics as non self-replicative viral vectors, adeno-associated viruses (AAVs) are a safe approach for delivering genes of interest.

Innovative companies face analytical challenges to find the most effective ways of process development and standardization. There is a broad range of important quality attributes for delivery vectors which need to be closely controlled for…

Antibody-Drug conjugates (ADCs) are an emerging class of biotherapeutics that hold enormous promise for effective targeted therapy in oncology and beyond. They combine the strengths of antibodies and small molecule drugs - high specificity and high potency - in a single format. ADCs consist of three elements: antibody, payload drug, and linker. The conjugation of payload and antibody via a linker is a critical aspect that defines ADC quality, safety and efficacy. The linker is designed to be stable in circulation but facilitate effective release of the payload at the site of action. Still,…

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 specific 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 efficiency of encapsulation of the genetic material into the viral capsid and is defined as the ratio of full to…

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…

Cell and gene therapies have the potential to provide long-term therapeutic efficacy, but their development is both risky and cost-intensive. Obtaining a better understanding of the specific structural attributes of vector proteins that influence clinical delivery and outcomes is essential for advancing both individual candidates and the platforms on which they are based.

Strategic application of advanced analytical techniques can help improve selection of candidates and guide development decisions, leading to a greater number of safer, more efficacious therapies successfully…

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…