Biopharmaceutical Characterization

A biopharmaceutical is a therapeutic product created through the genetic manipulation of living things including, but not limited to, proteins and monoclonal antibodies, peptides, and other molecules that are not chemically synthesized, as well as gene therapies, cell therapies, and engineered tissues.

Biopharmaceutical characterization is a critical step of biopharmaceutical development and manufacturing. This emerging and exponentially growing class of drugs is characterized by an intrinsic complexity and heterogeneity, which drives the need for a deeper knowledge of the structural features that can have huge impact on the stability, efficacy, and safety of the final drug.

Different ways to characterize biopharmaceuticals and biotherapeutics

Biotherapeutics encompass drug products which are produced using biological means, including recombinant DNA technology. The biological molecules are diverse and currently encompass gene, protein, and oligonucleotide therapies and even combinations thereof.

There are several different technologies and modalities that comprise the biotherapeutic landscape. The most mature of these biologic drugs are monoclonal antibodies and protein-based biotherapeutics.

As for all other proteins, the analytical approaches for the characterization of protein-based biopharmaceuticals can be divided into bottom-up, middle-up, middle-down, top-down, and intact analysis.

Bottom-up, middle-up, and middle-down analyses imply a degradation of the sample and are usually performed through a chemical or enzymatic reaction to divide the molecule in smaller regions (peptides or subunits) that are easier to analyze, although the mixture complexity may increase.

Conversely, top-down and intact protein analyses involve the study of the biopharmaceutical in its intact form, with the only aid of MS fragmentation techniques (top-down). With this method, it’s easier to monitor those fragments or aggregates naturally present in the drug formulation, even though some of the low abundant or small modifications may be harder to monitor.

The choice in approach is determined by the question we need to answer in that specific analysis or at that specific step of the manufacturing process. However, oftentimes a combination of the two levels of analysis can provide a more comprehensive determination of product features.

Regarding gene- and nucleotide-based biotherapeutics, analytical approaches are yet to be full optimized and rapid progress is currently underway in their development.

Importance of biopharmaceutical characterization

Biopharmaceutical characterization is important because it allows scientists to monitor those features that ensure drug efficacy and safety. The characterization step allows manufacturers to improve biopharmaceutical production from the very early phases and to follow a Quality by Design approach — not only in the design of the biotherapeutics but also in the production process.

For example, some features may indicate cellular stress during upstream processing and monitoring allows for quick correction of the culture conditions, resulting in a better yield and an overall better quality of the product. For this reason, there is a growing interest in bringing analytical techniques closer to the bioprocess pipeline or even integrating them so that real-time monitoring of the critical features can improve both process and product.

Biopharmaceutical analytical testing

Biotherapeutics such as monoclonal antibodies, biosimilars, antibody-drug conjugates, and nucleotide-based therapies are increasingly important drug product classes. Most biotherapeutic drug products are fundamentally more complex than traditional chemically synthesized products, and are subject to modification events throughout development, manufacturing, and storage.

Well-designed characterization technologies provide unique insights which advance the development of biotherapeutics. Comprehensive characterization, allowing for full product understanding, can save significant time and development costs. Throughout process development and manufacturing, tools are required for reliable monitoring of product microheterogeneity to ensure drug safety and efficacy.

Our technology innovations have been specifically designed with the rapid pace and complex challenges of biotherapeutic development in mind. From early discovery through to delivery of a commercial product, we provide technologies to confidently answer your analytical questions, bringing life-changing biotherapeutics to the market faster than ever before.

Learn more based on your modality of choice: