Biotechnology is not simply about science or technology, process engineering or cell lines, corporations or regulations. It’s ultimately about the people involved in all these things — and about the people they hope to serve with their biotech aspirations. It’s about scientists and technicians, businessmen and medical professionals, patients and consumers, farmers and governments, all their lives touched in one way or another by the biotechnology industry — some admittedly more than others. Policy decisions made by legislators affect how companies can do their business. Ethical considerations affect what they do and how they communicate to the public about it. And ultimately, all these things affect how many people become interested in making biotechnology their career.
Bioethics
Two subjects that currently loom large in the bioethics arena, as far as most biotech companies are concerned, are genomics and clinical research. In Chapter One, we mentioned the regulatory aspects of clinical research conducted...
China’s business landscape offers enormous opportunity for both traditional foreign direct investments and newly hot foreign private equity (PE) and venture capital (VC) investments. The country’s economy has grown at an annual rate of nearly 9% for 25 consecutive years, and its growth is forecast to continue at an annual rate of 8% despite the current global economic crisis. Foreign investment in billions of dollars are continuing to flow into China. But the country’s explosive market growth also presents tremendous challenges. International companies must navigate a unique culture as well as an evolving legal and regulatory environment. Before capitalizing on the Chinese economy, foreign investors must give careful consideration to business structures and strategies, the regulatory landscape, and asset protection.
Developing a Product and Business Strategy
Regulatory Framework:
Before a foreign interest invests in China, careful analysis of the related product and technology is warranted. It is importa...
In the 1980s biotechnology began to transform medicine with the introduction of recombinant hormone treatments and “magic-bullet” drugs based on monoclonal antibodies. In the 1990s, protein kinases offered a key to cancer treatment, and gene therapies promised to address many diseases at their most basic, genetic level. The 21st Century has brought us stem cells, RNA interference, biomarkers, and predictive medicine. None of these things has supplanted the others; instead, they merely expand on the basic idea of biopharmaceuticals. The future of healthcare can be glimpsed in modern molecular medicine.
Biomarkers
The US FDA’s critical path initiative has put pressure on companies to find new and valid biomarkers in their pharmaceutical development. A
biomarker
was traditionally considered to be any specific physical trait used to measure or indicate the effects or progress of a disease or condition (wrinkles and hair loss, for example, were biomarkers of aging). But biotechnology has refined the concept ...
Eli Lilly’s 2001 annual report stated that “Xigris… will prove to be one of our industry’s genuine breakthroughs” (
1
). The company believed that its first-in-class drug “could help save one in five people who otherwise would die” from severe sepsis. One of the world’s oldest and most virulent killers, sepsis is the third most common cause of death for hospitalized patients in the developed world after heart disease and cancer. In the United States alone, 750,000 patients are hospitalized with severe sepsis each year. It is estimated that worldwide 1,400 people die each day from this condition, with up to 30% dying within one month of their diagnosis.
As sepsis progresses through a patient’s body, inflammation rapidly spreads, eventually shutting down organs and too often leading to death. Antibiotics are often administered, but it takes time for them to function while inflammation continues to spread. Lilly’s Xigris product (activated drotrecogin alfa), a biologic that acts as both an antiinflammatory a...
Calivin Coolidge, who served as president of the United States from 1923 to 1929, is often misquoted as saying “The business of America is business.” According to historians, however, what he really said was, “The chief business of the American people is business.” And he went on in the same speech to say, “Of course, the accumulation of wealth cannot be justified as the chief end of existence.” So the real Coolidge (as opposed to the caricature implied by the misquote) would have been impressed by the biotechnology industry, which was spawned in his home state of Massachusetts. Its business may be to make money, but that is certainly not the chief end of its existence. There are easier ways to make money, after all. But the people involved in biotech want to improve the quality of life on planet Earth — whether through health care, new energy, agriculture, or biomaterials and industrial biotechnology.
The new US president, Barack Obama, was elected on a platform of change during a time when not only the ...
Contract manufacturing is essential for early development of products by companies of all sizes, and it plays an important role in later production and testing. Product development is a complex process requiring manufacturing, optimization, and testing of candidate drugs, devices, combination products, and biologicals even before they ever reach the clinic. Contract manufacturing organizations (CMOs) provide services ranging from early product development and lead-candidate screening to process development, product manufacture, and testing.
Outsourcing of development, manufacturing, testing, preclinical, and clinical activities has sharply increased since the 1990s (
1
). The number and variety of such activities has changed, as well as the types of organizations that use contracted efforts. Gone are the days where only necessity (e.g., lack of equipment and skilled personnel for a given task) drove companies to outsource activities. Contracting of development and testing has proven to be cost effective e...
Clinical studies serve as a bridge between biopharmaceutical laboratories and the patients who need therapies. Drugs need to be tested in small populations before they are made available to the world at large. In a 2006 interview with
BioProcess International
, editorial advisor Michiel Ultee (vice president of Process Sciences for Laureate Pharma) said, “Until your product is tested in humans — and shown to be safe and to have some efficacy — then you really don’t have much of a claim, and you don’t really have high odds of making it to the marketplace.”
Clinical Research, Clinical Trials
Before human testing begins, companies file paperwork with the appropriate regulatory authorities. In the United States, an Investigational New Drug (IND) application is filed with the FDA through either its drug or biologics center (CDER or CBER). Elsewhere a variety of documents are filed with other agencies. In Europe, for example, a clinical trial application must be filed with the “Competent Authority” of the memb...
In biopharmaceutical manufacturing, the disposal of solid waste from single-use systems is becoming an increasingly important issue. The new focus is driven by several major factors including a broadening range of disposable technologies enabling, in some cases, the installation of completely disposable multistage systems; improved scalability of single-use components offering production capacities to thousands of liters; and the environmental impact of waste disposal. The latter concern includes not only regulatory and cost constraints, but also the need for users to implement a responsible approach for environmental sustainability.
PRODUCT FOCUS:
ALL BIOLOGICS
PROCESS FOCUS:
MANUFACTURING
WHO SHOULD READ:
PROCESS DEVELOPMENT, FACILITIES MANAGEMENT, AND MANUFACTURING
KEYWORDS:
DISPOSABLES, DISPOSAL, ENVIRONMENTAL IMPACT, SINGLE-USE TECHNOLOGY
LEVEL:
BASIC
Figure 1:
Environmental impact can and should be part of the single-use equation.
All those factors must be balanced against the potential benef...
No segment of the biotechnology industry has received more public scrutiny than agricultural biotech — except maybe its application to food. And none has been subject to more “hype” and high hopes for instant results than biofuels. By contrast, industrial biotechnology seems almost invisible to the public at large. In general, the more immediate the effects on consumers, the more likely they are to pay attention and either laud or loathe the associated technology.
The general public doesn’t know anything about the economics of large-scale farming or agriculture’s decades-long dependence on herbicides and pesticides, and people don’t much care whether a farmer loses a crop when they can get whatever they want from someone else. And even though consumers ultimately benefit from improved industrial processes, they don’t think about them unless they’re watching an episode of “How It’s Made” on the Discovery Channel. Understanding is never guaranteed — and it is the vital key to public acceptance as well as th...
Use of automated liquid handling equipment for rapid testing and reproducible screening of thousands of molecules, cells, and compounds has become an essential component of life-science laboratories across the globe. Along with an increase in such use, transferred volumes have shrunk, as demands increase on transfer accuracy and precision when aspirating, diluting, dispensing, mixing, and washing. Automated liquid handlers are generally used to increase the productivity and repeatability of volume transfer, but as discussed here, they are still prone to error. So it is important to understand how some errors can be recognized and prevented to maintain liquid handling quality assurance, especially when transferring critical reagents.
PRODUCT FOCUS:
BIOLOGICS AND OTHER PHARMACEUTICALS
PROCESS FOCUS:
PRODUCT AND PROCESS DEVELOPMENT
WHO SHOULD READ:
QA/QC, R&D, AND ANALYTICAL PERSONNEL
KEYWORDS:
ASSAY DEVELOPMENT, HIGH-THROUGHPUT SCREENING, AUTOMATION
LEVEL:
BASIC
Because concentrations of biological and...
Biotechnology truly is global, with some form of the industry in progress on every continent but Antarctica. Countries such as Brazil are even outpacing Europe and North America in the advancement of biofuels technology. But as in the developed world where this industry began, we see other countries looking first and foremost to the medical applications of biotech — because historically that’s where the money has been. Some countries are building their own fully integrated bioindustrial sectors.
Economic development of life-science businesses is based on the development of bioclusters in which new biotech companies can develop. Many such clusters are specializing in one aspect of the industry to work in synergy with other complementary clusters — especially when one local company reaches the point at which its capabilities become a competitive asset. This requires a “critical mass” of activities to create a self-sustaining biocluster model that assures cost savings, quality adaptability, and flexibility t...
The ultimate goal of recombinant fermentation research is cost-effective production of desired proteins by maximizing volumetric productivity (to obtain the highest amount of protein in a given volume in the least amount of time). Bioprocessing for recombinant proteins using genetically modified organisms requires a stable, high-yielding recombinant culture, a highly productive fermentation process, and cost-effective recovery and purification procedures.
Escherichia coli
has been a widely used host for expression of recombinant proteins (
1
). Its advantages lie in the enormous data available on
E. coli
cell biology and fermentation process development, as well as its ability to produce large quantities of recombinant proteins cost effectively. Early successful production of insulin by Eli Lilly (
www.lilly.com
) and bovine growth hormone by Monsanto Corporation (
www.monsanto.com
) validated the versatility and economic potential of
E. coli
-based therapeutic protein production. Although it cannot ...
+1As new medicines, vaccines, biomaterials, and biofuels move through development, companies often face some of their toughest hurdles in moving from benchtop to production-scale processes. These are not only technological, but as technology advances it becomes more difficult to find experienced talent to make use of it. Some regional endeavors, such as the National Biomanufacturing Centre in the United Kingdom and the Massachusetts Biomanufacturing Center in the United States are pooling skills and resources to help companies overcome the technical and workforce challenges in developing the biomanufacturing capabilities these new products require.
Emerging companies face tremendous obstacles in transitioning from research to development organizations, when bioprocess scale-up issues often take them by surprise. Few contract manufacturers specialize in helping small, early stage companies make such a transition because most prefer to focus instead on more mature and experienced clients that are, quite frank...
For 2009, TIDES renews its focus on science. The agenda was put together by leaders in oligonucleotide and peptide development and manufacturing. The result is a program with novel, in-depth scientific data in each presentation. The agenda once again includes comprehensive coverage of drug candidates in development; new strategies for formulation and delivery; and the latest in regulatory updates, quality initiatives, process and analytical development, and manufacturing. This allows you the opportunity to benchmark your progress against that of your peers, advance your program, and meet new collaborators.
This is
the
place to meet key players in oligonucleotide and peptide drug development and manufacturing as well as raw material and equipment supply. At one venue, you can hear from all leading pharmaceutical and biotech companies developing peptide and oligo drugs and diagnostics, and you can consult with all the important suppliers of products and services in the exhibit hall.
PRECONFERENCE COURSES
By far the most successful applications of biotechnology have been in the medical field. The vaccine industry is undergoing a complete transformation thanks to biotechnology. And cutting-edge research is giving us whole new ideas about disease therapy using nucleic acids and regenerative medicine.
Proteins and Other Therapeutics
Cancer has been a primary target for many MAb “magic bullets” and a major research area for life scientists over the past quarter-century. Oncologists have identified ∼200 cancers that affect human beings, some more dangerous than others, some more treatable. The newest mechanisms of action in oncology research include oxidative stress, epigenetics, cancer metabolism, and enzyme inhibition. Some of these are already being tested in clinical trials.
RNA Rx:
Gene therapy is based on DNA, but RNA therapy may be the next step. Recent discoveries reveal additional possibilities to target human diseases using treatments such as microRNAs and small RNA-induced gene activation (RNAa).
Re...
Point-of-Use Filtration
Product:
SFE filter cartridges with -222 O-ring adapters
Application:
Small-batch processing of liquids and gases
Features:
New high-performance, small-flow–element filter cartridges with optional -222 O-ring adapters come in 2.5-in. (6.4-cm) or 5-in. (12.7-cm) lengths. They are designed for point-of-use filtration and small-batch processing of liquids and gases with flow requirements <3 gpm (11 L/min) or 60 scfm (102 Nm
3
/hr). These pleated small-area filters provide excellent chemical compatibility and low extractables. They offer a range of media and 0.04–99.00 µm filtration ratings for prefilters in glass and polypropylene microfiber and membranes in PES, PVDF, polypropylene, and PTFE.
Contact Meissner Filtration Products, Inc.
www.meissner.com
Single-Use Tubing
Product:
DAFPA sets
Applications:
Aseptic or sterile processing
Features:
Flexicon offers single-use tubing sets, each supplied complete with a validation package. The DAFPA (disposable aseptic fluid path) sets...
The global vaccine industry has undergone a dramatic and well publicized rebirth. Near the end of the 20th century, it faced an uncertain future with increased pricing pressures and liability challenges for marketed vaccines. Many long-standing members of the industry chose to scale back their R&D efforts or abandon them altogether. Today, however, the landscape has changed. Because of a confluence of positive factors (advancements in science and technology, greater appreciation for the role of vaccines as antibiotic resistance increased, and documentation of the true public health benefits of vaccines), major pharmaceutical and start-up companies are reinvesting significant resources into vaccine discovery.
Perhaps just as significant has been the demonstration of the commercial possibilities of newly introduced vaccines such as Wyeth’s Prevnar pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein), the first to achieve “blockbuster” status in the industry. Through routine use, annual sales ...
