Upstream Development

A Decade of Product Development

    In 2004, the United States Food and Drug Administration (FDA) transferred regulation of many highly purified, “well-characterized” biopharmaceutical proteins from the Center for Biologics Evaluation and Research (CBER) to the Center for Drug Evaluation and Research (CDER), which until then had primarily regulated only synthetic, small-molecule drugs and chemical substances. The most novel/complex and the less-characterized biologics remained within CBER’s jurisdiction. This change complicated BPI’s mission somewhat. When the magazine was founded, we responded to questions from advertisers…

Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing

It’s official: The “Age of Cell Therapy” has arrived. A robust pipeline of cell therapies, with increasing numbers of both early- and late-stage clinical trials as well as FDA-approved commercial products that have entered the market already, strongly indicates that the cell therapy industry is poised to emerge as a distinct healthcare sector (1). Renewed investor interest and recent activity among major pharmaceutical companies suggest that this industry will rapidly develop the capability and capacity to be a highly competitive,…

A Decade of Bioreactor and Upstream Technologies

A high-quality product begins with efficient upstream process equipment. Ten years ago, manufacturers were still warming up to single-use bioreactors, which were mainly rocking-bag–based solutions. The benefits relating to cleaning and validation were clear, but their use as bioreactor vessels was still new, and stainless steel systems up to 20,000 L in scale were still needed. Today’s facilities are a hybrid of sophisticated single-use components and stainless steel equipment, the mechanisms of both having undergone improvement during the past decade.…

A Decade of Microbial Fermentation

Microorganisms play a vital role in modern life — with applications ranging from wine fermentation to biofuel production to solutions for complex mathematical problems (1). During the past decade, microbial fermentation for protein production reached a higher level of sophistication and wider adoption. When BPI was first published in 2003, the physical and biological characteristics of many microbial cells and the attributes of their fermentation processes were well known. Nonetheless, the economic environment at that time created immense pressure on…

A Decade of Process Development

    Our “manufacturing ” theme could be considered a sort of catch-all, encompassing much of what BioProcess International covers. You could argue that “the whole development process” is all about manufacturing biotherapeutics. But we instead consider this “pillar” of bioprocessing to include everything that isn’t strictly “upstream” (production) or “downstream” (processing) of biomolecules. Facility and supply-chain isssues come into play here, as do formulation and fill–finish (and of course, outsourcing). We discuss quality systems and their associated analytics in…

Designing the Ideal Bioreactor with Single-Use Technology

    Bioprocessing companies are hoping for a brighter future in biologics manufacturing that will include ever-higher titers of vaccines and therapeutic proteins grown in cell culture. It would also facilitate bioprocess operations without the recurring challenges that stem from process scale-up and human error. Moreover, that future would also comply with increasingly stringent regulatory and current good manufacturing practice (CGMP) requirements while providing better cost controls than we see today. How far away is this future? Perhaps not too…

Large-Scale, Insect-Cell–Based Vaccine Development

    Vaccines are among biotechnological products characterized by continuous growth over the past decade. According to a 2011 report, the global vaccine market is expected to reach US$34 billion in sales by 2013 (1). Much development can be ascribed to vaccine treatments for cancer, autoimmune, and infectious diseases (which have risen significantly) as well as the growing worldwide population and emergence of new pandemics. Although to date the main health impact of vaccines is still in disease prevention, the…

Scaling Up Stem Cells

    Cell-based products are becoming increasingly important as potential biotherapies. Cell therapy is predicted to have a huge impact on the healthcare sector over the coming decades. Stem cells, in particular, are investigated as potential treatments for a diverse range of applications (such as heart disease and metabolic and inflammatory disorders) in which they might be used to restore lost biological functions. The cell therapy industry is starting to mature. Several emerging companies are now supporting late-stage clinical trials,…

Strategies for Rapid Production of Therapeutic Proteins in Mammalian Cells

It is estimated that hundreds of new recombinant proteins and monoclonal antibodies (MAbs) enter preclinical and clinical development each year (1, 2). Concomitant global competition in biologics manufacturing has put immense pressure to shorten the time to market. Over the years, cells from various origins have been used for therapeutic protein production (2, 3,–5). One of the most economical choices is Escherichia coli, used to make proteins such as human insulin and growth hormone. But the bacteria have some serious…

Balancing the Statistical Tightrope

During one development meeting early in my industrial career, a process development group member asked me whether the value my group had reported in one result was okay to use. I confidently replied “Yes, it’s fine. It’s about 40, somewhere between 38 and 42. The other person raised his eyebrows. “About 40?” In response, I somewhat awkwardly mumbled “Yes, probably…about that” — an answer not met with full understanding, but rather concern. My answer hadn’t been incorrect. The result was…