Tools for the BioPharma Industry

Pharmaceutical Biotechnology

Pharmaceutical biotechnology is an increasingly important area of science and technology, and contributes to design and delivery of new therapeutic drugs, the development of diagnostic agents for medical tests, and the beginnings of gene therapy for correcting the medical symptoms of hereditary diseases.

Microorganisms have unique characteristics that make them irreplaceable, industry-friendly hosts, as they are the real workhorses for large scale production of an array of useful metabolites. Microorganisms have a high ratio of surface area to volume, which facilitates the rapid uptake of nutrients required to support high rates of metabolism and biosynthesis suitable for a variety of reactions. The microorganisms can be isolated from various ecological niches allowing them to be transplanted from nature to the laboratory flask and ultimately to the production scale fermenter, where it is capable of growing on inexpensive carbon and nitrogen sources and producing valuable compounds. With the development of recombinant DNA technology, microorganisms could be manipulated genetically with ease, to increase the production of the products.

Tools for the Bio/Pharma Industry:

Analytical testing, which deals with the characterization of raw materials and finished dosage forms, plays an important role in pharmaceutical manufacturing and all phases of drug development.

Developments in analytical instrumentation for pharma have largely been addressing three key trends over the past decade. The first is the significant rise in small-molecule generic drug development. This development has increased the requirement for instruments that offer performance-relevant measurements and/or high informational productivity for deformulation and the demonstration of bioequivalence (BE).

The second important trend is the shift toward continuous manufacturing (CM). The potential ease of scale-up of continuous processes and the ability to file on the basis of full-scale experimental data makes CM particularly interesting for pharma, but its realization relies on effective monitoring and automated control. Here, the ongoing transition of core analytical techniques to fully integrated, online implementation is enabling rapid progress.

Finally, in biologics, we’ve seen a growing awareness of the importance and power of orthogonality when it comes to probing the complex nature of the proteins. Identifying the optimal set of biophysical characterization techniques is crucial to comprehensively elucidate critical aspects of behavior, such as stability. Significant progress has been made in this area, and there is now growing awareness of how to complement traditional techniques with newer/less well-established ones, such as differential scanning calorimetry (DSC) and Taylor dispersion analysis (TDA), to maximize understanding and add value.

Recombinant therapeutic proteins from microorganisms:

Since the production of recombinant insulin in the late 70s, the emergence of molecular biology and biotechnology has enabled the biological fabrication of a long list of active therapeutic proteins. Today, recombinant DNA and hybridoma cell technologies are mainstream platforms to obtain most of the currently marketed protein drugs such as monoclonal antibodies, hormones, cytokines, and growth factors.

Over 200 protein drugs are expected to be available over the next few years to treat expanding human disorders such as diabetes, cancer, respiratory, cardiovascular and inflammation-related diseases, as well as other rare diseases. In fact, the global market for protein drugs already exceeds US $50 billion, with an average annual growth rate of almost 4%, according to BCC Research. Unfortunately, the costs of protein drugs are often extremely high. As a representative example, recombinant human Erythropoietin (EPO), which is used as treatment for anaemia due to kidney failure or anticancer treatments costs over 2 billion US $ per kg, probably being the most expensive existing substance today. Enzyme replacement therapies such as for lysosomal storage diseases (LSD) representing excess of 0.15 million $ per year per patient. Such high costs are partially explained not only by the investment in product development but also by the expenses associated to quality analysis and control.

Improving protein solubility represents a continuous challenge in the development of protein drugs. As a result, biopharmaceuticals still suffer from batch-to-batch conformational heterogeneity, a currently unavoidable disadvantage inherent to recombinant biological production. These drawbacks complicate the consideration of proteins as clinical drugs from the regulatory point of view. Moreover, proteins with therapeutic value often undergo posttranslational modifications necessary for the natural biological function.

Why Are Target–Protein Interactions Crucial in Drug Discovery?

Understanding protein–target interactions is crucial — we are talking about the difference between finding a lifesaving drug/therapy and wasting hundreds of millions of dollars developing a drug with the wrong mechanism of action.

A recent paper from Jason Sheltzer’s group showed that ten anticancer drugs undergoing clinical trials had a completely different mechanism of action from the one originally attributed to them. Briefly, when the protein targeted by each of the drugs was removed from cancer cells, the group expected the drugs to stop working. But what they found was that the drugs continued to work as normal and thus had to be working through off-target binding.

This is crucial because it means potentially there are many more drugs out there that are working through off-target binding; it also means that many other drug candidates that have previously been disregarded may have unrecognized promise. This problem is about to become even more acute as research expands into conditions with difficult targets like Alzheimer’s disease.

The way in which we discover the exact mechanism of action between proteins and potential drug candidates needs better technologies for characterizing on-target and off-target interactions We cannot discover new information relying solely on technologies that have fallen short for decades.

Biopharmaceutical Analysis

Organizations throughout the pharmaceutical and life sciences industry are increasing their investments in biopharmaceutical development. In this rapidly-evolving field, there is a widespread need for application-appropriate technologies. Strategic characterization technologies provide unique insights into the development potential of large molecule therapeutics. A first-line analysis of complex biotherapeutics that is rich with information can save significant time and development costs during production.

Mass spectrometry-based proteomics for absolute quantification of proteins from tumor cells:

Mass spectrometry-based proteomics allows profiling of protein expression on a genome-wide scale providing an important resource for the development of novel diagnostic and therapeutic targets. Advances in mass spectrometry have resulted in the development of a high definition MS (HDMS) technology with the data-independent acquisition (DIA) and ion-mobility function. As a result, the consistency of peptide identification and protein sequence coverage in complex biological samples has been substantially improved.