June 2012 Supplement

A Decade of Formulation

    Although no biopharmaceutical pills are yet on the horizon, formulation and delivery have advanced over the past 10 years. Formulators have new biophysical technologies and new product types (such as protein–drug conjugates) to work with. The most important issues haven’t changed much, though — from aggregation to stability, freezing to freeze-drying — although the FDA’s quality by design (QbD) initiative changes the strategies used to address them. Fragile proteins and other biologically sourced macromolecules need protection to achieve…

A Decade of Fill–Finish and Packaging Solutions

    In 2003, BPI’s first year of publication, the Food and Drug Administration released a draft of its updated guidelines on aseptic processing. In it, the agency included the statement, “A well-designed positive pressure isolator, supported by adequate procedures for its maintenance, monitoring, and control offers tangible advantages over classical aseptic processing, including fewer opportunities for microbial contamination during processing” (1).That kind of statement, seemingly approving one technology over another, was unprecedented in an FDA guidance and perhaps an…

A Decade of Biomanufacturing

    The biopharmaceutical industry is emerging from four years of economic challenge in a very healthy state. Process improvements over the past decade have played a major role in keeping the industry healthy. Earlier this decade, most companies were more concerned about quickly getting their drug products to market than about strategically controlling costs of operations. But according to my group’s recent study, this has changed in most areas of manufacturing. In fact, although this year companies reported overall…

A Decade of Filtration

    Filtration is just as vital to bioprocessing as chromatography — and arguably even more so. Filters are not only used as downstream unit operations in themselves, but also in support of nearly every other step in bioprocessing. Gas or liquid filters ensure the quality of incoming air and feeds for cell culture operations, clean the circulating media in perfusion processes, aid in harvest clarification, and remove buffers from chromatographic eluate after chromatography columns. They are used in formulation…

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 Production

Single-use technology has arguably been the biggest “story” of the past 10 years in bioprocessing. And for many people, implementation of disposable elements began soon after the turn of the century with a bioreactor (1, 2), first developed by Wave Biotech in 1996, now a mainstay of many upstream process development laboratories and sold by GE Healthcare. BPI identified the significance of such technologies early on, making them the subject of a supplement in its second year. By the fourth…

A Decade of Characterization

    Over the past 10 years, the biopharmaceutical industry has placed increasing pressure on analytical laboratories, whose work is more important to the success of biotherapeutic products than ever before. Nearly concomitant with the appearance of BPI on the scene, the US Food and Drug Administration put forth its final report on the 21st century good manufacturing practice initiative, which in changing how regulators would review product applications, changed how companies must approach them (1). The guiding principles —…

A Decade of Change

Allen Roses, former worldwide vice president for genetics research and pharmacogenetics at GlaxoSmithKline, raised eyebrows in 2003 when the newspaper The Independent quoted him as saying that the vast majority of drugs — more than 90% — work in only 30 or 50% of the people. “I wouldn’t say that most drugs don’t work,” he said. “I would say that most drugs work in 30 to 50 percent of people.” Though the newspaper characterized this as an “open secret within…

A Decade of Chromatography: A Powerful Technology Reasserts Itself

    Chromatographic separations are vital both to the analysis of biological macromolecules and to their manufacturing. When properly applied, chromatography provides exquisite specificity in separating different molecules from solution based on their size, electrical charge, or other physicochemical properties. Large liquid chromatographic (LC) columns remove host-cell nucleic acids, endotoxins, viruses, and process intermediates from harvest material. Combine high-pressure liquid chromatography (HPLC) with mass spectrometric (MS) or ultraviolet–visible (UV–vis) spectroscopic detection, and you can qualify and quantify macromolecules in such…