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.…

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…

Meeting Lot-Size Challenges of Manufacturing Adherent Cells for Therapy

    Adherent cells such as adult primary cell lines and human multipotent (MSCs) and pluripotent stem cells (hPSCs) present a manufacturing challenge as lot sizes increase from 109 (billions) to 1012 (trillions) cells (1). Typically, manufacturing platforms are good for one log of expansion. So new methods will be required to achieve commercially relevant lot sizes. Traditional two-dimensional culture methods have been used to grow anchorage-dependent cell types. Although such methods are reliable and well defined, they are very…

Streamlining Cell Therapy Manufacture

    The cell therapy industry (CTI) is no longer a cottage industry; it is a distinct and sustainable component of the global healthcare sector (1). Today, CTI prospects are strong, with annual revenues exceeding US$1 billion/year, supported by improving investor sentiment and public support (1,–3). The next phase of CTI growth — toward a multibillion-dollar global industry — will depend on the biomanufacturing community innovating to meet growing market demands and providing products at affordable costs to healthcare payers.…