Cosponsored by CASSS (an international separation society) and the FDA, the 23rd CMC Strategy Forum was held in Bethesda, MD, on 19–20 July 2010. For the third time, this forum explored the topic of quality by design (QbD) for biologics. The first such forum was held in July 2007 and focused on establishing a general understanding of QbD terminology and concepts. In July 2008, the second discussed approaches for submission of QbD data and associated regulatory implications. Building…
Analytical
Legacies in Bioprocessing
Bioprocessing is full of legacies. Our remote ancestors discovered fermentation: microbial magic that transformed fruit to wine and grain to beer. Building on the work of Edward Jenner and others, Edward Ballard systematically reinfected cattle to make vaccines. Louis Pasteur revolutionized both fermentation and vaccination by showing that different microbes caused fermentation and spoilage (saving wine and beer production from disastrous batch contamination), establishing the germ theory of disease, and using that knowledge to develop new vaccines against endemic infections.…
A Decade of Animal Cell Culture
Eukaryotic cells are fragile and finicky, requiring very specific culture conditions and nutrients to survive, grow, and be productive in an ex vivo environment. Even so, they have become vital to the biopharmaceutical industry’s ability to make complex biological products — overtaking yeast as a production system around 1990 and surpassing bacteria in the number of associated product approvals five years later (1). Since then, they have become even more useful, expanding their reach into the vaccine world. Mammalian cell…
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 Processing
About halfway through our first decade in publication, we became well acquainted with a new buzzword phrase in the biopharmaceutical industry: downstream bottleneck (1). This followed on the heels of a manufacturing capacity crunch that had been forecast shortly before BPI made its debut. Thanks to herculean efforts by upstream process and cell-line engineers, that crunch didn’t pan out. In its place, however, high-titer production moved the pressure downstream. Now separation and purification engineers were tasked with handling…
A Decade of Harvesting Methods
The preliminary separation of a protein of interest from a reactor “soup†of process impurities (e.g., cell debris, colloids, lipids) is the first step in a downstream process. It is also a primary step that introduces a significant risk of product degradation, bioburden concerns, or process errors, especially if a harvest method is not a good “fit†with a newly designed bioreactor (e.g., single-use) or fermentation vessel. In 2003, BPI’s first year, industry concerns revolved around potential capacity…
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…
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…
Sterilizing-Grade Filter Sizing Based on Permeability
Sterilizing filtration renders biotherapeutics free of biocontamination. In many cases, sterilizing-grade filters also reduce bioburden or facilitate closed or aseptic processing. They are used to filter active pharmaceutical ingredients (APIs), formulated bulk, cell culture media, buffer, additives, process intermediates, and so on. Such applications are often critical for ensuring a successful batch operations. Nonetheless, a significant amount of time and resources are typically not devoted to establishing filter sizing requirements for “simple†applications such as buffer filtration. Here,…
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 —…