The major multinational pharmaceutical companies, which were once considered traditional pharma companies, are now shifting their presence into biopharma on an unprecedented scale. However, with this comes growing pains. Looking at the industry growth and the complexities of biopharma development, it is no wonder that transformational developments are required to better equip laboratories and operations in biopharma.
The pharmaceutical industry is going through the revolutionary phase of moving from small molecule drugs to large molecule biological drugs. Biopharmaceutical sales alone have reached $218 billion (USD) in 2017, with a Compound Annual Growth Rate (CAGR) of more than 8%.1 This constitutes around 20% of total pharmaceutical sales and doubles the growth rate of conventional pharmaceutical industry.2 Biopharmaceutical drugs target disease pathways and provide superior efficacy and safety. Biologics also made the previously untreatable disease treatable. These key features have made the biologics widely accepted by the public, driving the demand for heavy investment in biopharma R&D. Biotechnology patents are increasing yearly at 25% growth rate. Currently, over a third of all new drugs in clinical trials are biologics and the success rate of biologics is higher than small molecule drugs. In a recent survey of global pharma lab managers, it is no surprise that 56% stated obtaining higher throughput and productivity in their laboratories is their primary goal, and 53% are looking to improve system efficiency.
The advancement of biotechnology opened the door to designing new types of therapeutic drugs to fight disease in a sophisticated manner. Biopharmaceutical products are diverse, including monoclonal antibodies, bi-specific antibodies, antibody-drug conjugates, fusion proteins, recombinant proteins, growth factors, hormones, synthetic immunomodulators, recombinant enzymes, vaccines, synthetic peptides, and oligonucleotides. Monoclonal antibodies (mAbs) and its derivatives have emerged as the largest group of biopharmaceuticals on the market. Monoclonal antibodies have been the major player in cancer therapy due to their specific targeting ability to cancer cells and their interaction with the immune system.
In recent years, researchers have expanded the mAbs development into bispecific mAbs and Ab-derived therapeutics in a variety of alternative formats. Bispecific antibodies are engineered to have two binding specificities, which can target multiple signal pathways and improve therapeutic function of the drug molecules. Another type of mAb derivatives are antibody-drug conjugates (ADCs), which are composed of a monoclonal antibody, a chemical linker and a biologically active drug or cytotoxic compound. ADCs combine both the specific and sensitive targeting capabilities of antibodies and the powerful cell-killing function of cytotoxic drugs. Several ADCs have been approved by the FDA in the last few years and many more are currently in clinical trials.
One of the main emerging areas from the last few years is CAR T-cell therapy, which is a form of immunotherapy that uses patient’s own blood with genetically modified T-cells to target specific cancer cells. CAR T-cell therapy genetically reprograms patients’ immune cells to attack cancer cells. With the FDA’s approval of CAR T-cell therapy in 2017, this type of cell therapy has offered patients a new way to fight cancer. Another cutting-edge technology is gene therapy with CRISPR/Cas9 technology as the key player. CRISPR/Cas9 edits genes by precisely cutting DNA and then letting natural DNA repair processes take over. It can disrupt, delete, correct or insert specific genes in the patient’s DNA. Gene therapy allows editing of the genetic information instead of targeting the proteins to cure disease. The possibilities of gene therapy hold much promise for cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Currently, gene therapy is only available in clinical trials.
Transitioning from conventional pharma to biopharma brings many challenges. Large biological drugs are complex and difficult to manufacture. Recombinant proteins are made using genetically modified living cells. Producing these molecules consistently at industrial scale is costly. Controlling the manufacturing conditions, and monitoring the cell growth and protein production are very important to the quality of drug products. The complexity of the biomolecules is also demonstrated by the variety of modifications on the molecule, including post-translational modifications, such as glycosylation, and degradation products, such as deamidation, oxidation, hydrolysis, and disulfide formation. These modifications could affect the efficacy and safety of the drug and needs to be closely controlled.
Denaturation and aggregation could also occur when the drug is exposed to various types of stress during production, shipment and storage. Denatured or aggregated protein species may lose efficacy and cause unpredictable immunogenicity or toxicity problems. Determining critical quality attributes and reliably monitoring them is a huge challenge. Many changes in critical quality attributes are subtle, which makes accurate analytical measurement crucial to the success of these assays. Furthermore, the demands from regulatory agencies for high quality drug products has put more pressure on the industry to incorporate new analytical technology for delivering better confidence in results and lower cost in manufacturing.
The fast-evolving biopharma industry has given immense opportunity for the analytical industry to innovate, implement and adapt advanced technologies to meet these challenges. Products and solutions must be user-friendly and provide accuracy and robustness for the biopharma customers, from drug discovery and development to QA/QC.
Across the board, transformational innovation is needed. Developments in new instrumentation, techniques, collaboration and processes are key areas that companies are looking at to better contribute to drug discovery processes. What is needed is innovation that delivers excellence across the pharmaceutical workflow, from formulation to QC, from cleaning verification to the application of tablet coatings. With it taking on average 10-15 years and $2.6 billion to develop a new medicine, instruments need to begin adding value the from the moment they are installed.
1. Mordor intelligence. Global biopharmaceutical market report. July 2018. https://www.mordorintelligence.com/industry-reports/global-biopharmaceuticals-market-industry
2. Otto, R., Santagostino, A. and Schrader, U., 2014. Rapid growth in biopharma: Challenges and opportunities. McKinsey & Company.