Public and private healthcare providers are under increasing pressure with the demand for better quality drugs and cheaper healthcare on the rise. However, rising costs and time scales for bringing new drugs to market suggest that challenging times are ahead for many pharmaceutical companies.

Current trends in US healthcare indicate that almost half of the hospitals across the country have seen a >20% drop in income. With an additional drop in financial donations, many hospital staff budgets are being cut, and some clinical development programs are getting postponed. Recent figures further support the need for change. Some 22% of chronically ill adults report serious problems with their treatments that can lead to issues of patient noncompliance. The increasingly aging population adds further pressure on pharmaceutical companies to deliver improved healthcare in new therapeutic areas. Although this demographic shift creates new markets, it also spurs new lower-cost competition.

These downward trends in the healthcare sector highlight the need for innovative solutions that provide less-expensive drugs and more effective treatments. In the worldwide pharmaceutical industry, only the market for biopharmaceuticals has seen double-digit growth. By 2006 this market was worth $76 billion, it almost doubled to $125 billion in 2008, and it is predicted to reach $203 billion by 2015 (1,2). However, a new biopharmaceutical typically takes eight to 12 years to bring to market at an average cost of $100–200 million. So the pharmaceutical industry must rethink efficiencies to reduce those costs and ensure quicker turnaround times to deliver more economical and efficient products.

The bioindustry’s current requirement is to find ways to produce better quality products and maintain regulatory compliance while reducing overall costs and the time taken to bring new drugs to market. Biomanufacturing processes have seen major developments and improvements as a result. The introduction of innovative technologies and products is helping to drive efficiencies across the drug lifecycle.

New Technologies Address Old Challenges

Many biopharmaceutical organizations rely on mammalian cell-based expression systems as their production platform. Serum-free media are commonly used to culture those cells, often in conjunction with animal-derived supplements such as transferrin, albumin, or insulin-like growth factors to enhance growth and productivity. Animal-derived ingredients constitute an intrinsic safety risk, primarily through potential contamination of adventitious agents in the final drug product. Consequently, regulatory authorities enforce strict quality controls on all such products and their use in biopharmaceutical manufacture. Pharmaceutical companies are thus looking for alternatives.

Development of animal-free recombinant transferrin, albumin, or insulin-like growth factors is an example of how innovation has helped biopharmaceutical companies bypass some regulatory obstacles. These recombinant protein supplements are chemically defined and free from the risk of infecting patients, which alleviates many regulatory concerns traditionally linked with animal-derived protein supplements. Animal-free supplements have been developed specifically for use in large-scale mammalian cell culture and are now readily available.

The industry is also investigating the benefits of nonmammalian expression systems that offer additional benefits such as faster production timelines in simpler, chemically defined growth media. For example, certain microbes offer a rapid production process, can be cultured without animal- or human-derived materials, are versatile, and have broad product applicability. Because of the genetic simplicity of these organisms relative to animal cells, they can be genetically manipulated to optimize production of recombinant proteins without negatively affecting product quality. A number of systems and platforms — such as Saccharomyces cerevisiae, Picchia pastoris, Pseudomonas fluorescens, and Corynebacterium glutamincum — offer solutions to some regulatory issues while reducing the timelines for bringing a new biotherapeutic to market or clinical trials.

Protein therapeutic developers face several other challenges, such as overcoming poor protein half-life and bioavailability. Such issues lower efficacy, which can cause high peaks or low levels of the drug in patients, potentially leading to unwanted side effects and limitations of the therapeutic benefit and requiring higher and more frequent doses. These are not only problems for patients, but they create additional strain on manufacturing capacities and ultimately incur higher treatment costs (Figure 1).

Certain products and technologies have been shown to manage those difficulties. Protein half-life can be extended through the application of single-step protein expression solutions such as albumin fusion. This technology enhances the stability of a recombinant protein and improves associated downstream purification efficiencies for significant cost savings. Drug stability improvements and increased protein half-life ensure more cost-effective treatments by reducing the dosages required and their frequency of administration.

The Future Requires …

Protein therapeutics are predicted to be one of the most medically beneficial areas of drug development in the future. However, innovations related to efficiency improvements can be driven only by ongoing dialog between pharmaceutical companies and providers of those solutions. Trends for the future indicate that people are living longer, and the demand for better quality healthcare for an aging population is being addressed through such cooperation.

Collaborative relationships are already being used to develop improved treatments for type II diabetes, Alzheimer’s disease, and hepatitis C. For example, Novozymes’ abufuse technology extends the efficacy and half-life of Syncria (glucagon-like peptide-1 from GlaxoSmithKline and Human Genome Sciences) and the half-life of HGSI’s Zalbin interferon for hepatitis C. A measles—mumps–rubella II (MMR-II) vaccine manufacturing process uses Novozymes’ Recombumin product to enhance process performance as well as the final vaccine formulation. Several partnerships are also ongoing in other treatment areas including cancer research and ophthalmic care.

As the demand for better quality and more effective drugs increases, new approaches such as pharmacogenomics must be investigated. Development of personalized medicines aims to identify patients who are considered to be “at risk” of developing common conditions such as heart disease or diabetes. Rather than using family history to predict potential illness, doctors would analyze a patient’s genetic make-up to predict susceptibility to future illnesses — and even the potential to respond to certain types of treatment. Many people hope that advances in predictive and personalized medicine will lead to new approaches in diagnosis, drug development, and therapy tailored to each individual. The ability to personalize doses at the most appropriate levels for a given patient would lead to more effective and safer treatments.

Innovators Lead the Way

The healthcare industry is under pressure. This is certainly a time of financial uncertainty for many businesses. But the exciting partnerships we see developing across the biopharmaceutical industry are leading to new products and solutions that will help drive efficiencies and improvements in many aspects of the drug life cycle — from discovery to drug delivery (Figure 2).

Biotechnology companies have experienced the benefits of this new approach and are actively seeking to develop new relationships with the providers of innovative technological solutions. With budgets tightening across the industry, these relationships can help to improve the quality and effectiveness of new drug products while reducing the time and cost involved in bringing them to market through purposely engineered recombinant products and technologies. Those address many areas of concern for the biopharmaceutical industry, including regulatory issues and process/product efficiencies, which in turn can lead to manufacturing cost reductions.

Interesting times are ahead for the industry, and innovation is a key factor for driving efficiency. Successful companies will be the ones that can best anticipate the needs of tomorrow.

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