May 2011

Greater adoption of single-use systems in biomanufacturing is going to require downstream device innovation. To get there, over a third of the biopharmaceutical industry is demanding that suppliers innovate and develop new single-use purification devices, according to BioPlan Associates, Inc.’s annual survey of biopharmaceutical manufacturing capacity ( 1 ). Such new products would create exceptional opportunities for innovators. However, calls for new, more fully integrated single-use technologies and processes will require more adventurous innovation on the part of biomanufacturers and their suppliers. In our study, we evaluated 21 key areas of industry innovation (see the “Survey Methodology” box). Among more than 350 qualified biomanufacturers surveyed in 31 countries, the need for new disposable devices topped the list again in 2011 (Figure 1), and made up the largest individual grouping of new products. In addition, purification or separation products were the second most frequently mentioned groupi...

Fill–finish is the final operation in manufacture of sterile products (except for terminally sterilized products). This process requires sophisticated technology and machinery in a highly controlled, aseptic environment. Fill–finish assemblies must meet stringent requirements to ensure flow-path sterility and integrity, ensure operational safety and efficiency, and provide fill-volume accuracy to exacting requirements. Traditional fill–finish machinery comes as fixed systems comprising complex components that require assembly, cleaning and sterilization, disassembly, and material storage after filling is complete. Those operational steps allow for an open flow path, creating the possibility of contamination or sterility breach and subjecting operators to hazardous materials. Time-pressure and piston-pump systems are the predominant methods for dosing and filling. They require assembly, open flow paths, and validated clean-in-place (CIP) and/or steam-in-place (SIP) protocols to ensure a high probability of...

Where were you in 1987, and what were you doing? I’m not too embarrassed to say that I was beginning my last year of high school and paying far more attention to guitar lessons and writing my first novel than what I might eventually do for a career. Meanwhile, the US FDA was publishing a guidance document on process validation that the biopharmaceutical industry has relied on ever since. I’m willing to bet that quite a few readers of this issue weren’t yet working in the industry at that time either — and one or two could even have been in the New England crowd with me at a Def Leppard concert that year. A lot has happened since then in the United States: four different presidential administrations dealing with wars and major economic boom-and-bust cycles, a huge federal budget deficit turned into a surplus and then into an even larger deficit, the growth of the Internet from a niche military/academic application to a ubiquitous and vital personal and business tool, and the dawn of a new millennium. Bioph...

Single-use technology is being examined for implementation in an increasing number of steps in the biopharmaceutical manufacturing process. Some examples of currently available disposable components include filter capsules, tubing, connectors, and biocontainers (for storage, mixing, and bioreactors), as well as devices for chromatography and multipass tangential-flow filtration ( 1 , 2 ). This technology was first implemented in upstream and API downstream processes such as media and buffer preparation, followed by upstream bioreactors and mixers ( 3 ). The single-use trend has most recently shifted further downstream toward sterile formulation and filling operations ( 3 ). Vaccine manufacturers in particular are using disposable systems to streamline their final filling processes. Widely recognized benefits of single-use systems in biopharmaceutical manufacturing processes include elimination of cleaning/sterilization and associated validation; decreased operator exposure to product streams; and reduced ...

About a year ago, President Obama signed into law the highly publicized health care reform bill known as the Patient Protection and Affordable Care Act. This legislation included the new Biologics Price Competition and Innovation Act of 2009 (now a “biosimilar statute”). Before enactment of that biosimilar statute on 23 March 2010, no “abbreviated” regulatory approval system existed in the United States for biologics — unlike Europe, which has had a system since 2005, and unlike US generic drug approval under the Hatch–Waxman Act of 1984. Regarding a biologic product, applicants previously could pursue a nonabbreviated biologic license application (BLA) under the Public Health Service Act or a new drug application (NDA), a “§505(b)( 2 )” NDA, or an abbreviated new drug application (ANDA) (for approval of a generic drug) under the Food, Drug, and Cosmetic Act (FDC Act). The new statute created a pathway for Food and Drug Administration (FDA) approval of potentially “abbreviated” applications for biolog...

The increasing adoption of single-use technology in biopharmaceutical, vaccine, and cell therapy production is one indication that such technology has moved far beyond its novelty stage. Arguably, this is the preferred technology of newly developed processes. Benefits have been well documented in journals and conference presentations and have led the industry to form the Bio-Process Systems Alliance (BPSA). One current need is for process sensors that offer the same convenience as disposable bags, tubings, and filters being used. An ideal complementary sensing technology can offer the same or better quality of measurement as more traditional, reusable sensing technology and be read locally and/or integrated to control systems and higher level data acquisition systems. Addition of process monitoring and control to a bioprocess operation lends itself to easier adoption of the FDA’s quality by design (QbD) initiative, which emphasizes achievement of product quality though process understanding, monitoring, a...

The world loves a winner, and no one wants to be linked to a failed endeavor that could stall or otherwise negatively affect his or her career. If you’re reading this magazine, you’ve probably been inspected or audited by regulators and/or customers at some point. Consider for a moment that regulatory inspections and corporate audits are somewhat like a high-school football game, one that regulated companies are obliged to play whether they want to or not. This game is always played on the inspected party’s “home field” and the auditors/inspectors are always the visiting team, but there is no home-team advantage. The date and time of the game is dictated by the visitors for their advantage, and the specifics and the length of play are entirely at their whim. Furthermore, the visiting team is allowed without announcement to bring as many players as they want to “the game” and wander through the home field without disclosing the specifics of their agenda until well after they have collected needed informati...

The biopharmaceutical market accounts for about 20% of the total market for pharmaceuticals, but its share continues to increase because of double-digit compound annual growth rates leading to projections that by 2014 eight of the top 10 best-selling drugs will be biologics ( 1 ). The industry faces many challenges and opportunities, as Jim Davies of Lonza Biologics explained to me: “Biomanufacturers have to contend with what is at present a dynamic technical and commercial landscape. Industry consolidation continues to occur as large pharmaceutical companies look to small biotechs to strengthen their product pipelines. Production of biologics has become a global enterprise, with new manufacturing hubs such as Singapore and South Korea developing in the Asia–Pacific region. There is a lot of interest in the biosimilars market at the moment, for which the cost of goods is likely to play a more significant role in commercial success relative to innovator molecules. Adoption of single-use processing technolo...

Spending is up, the global economy is slowly getting back on track, and the biopharmaceutical industry continues to roll along at double-digit growth. Productivity has been the primary industry focus over the past few years, and it remains a hot topic. Companies are aggressively going after the bottlenecks to their efficiency, and now they’re opening their wallets to fix what’s broken. One of the biggest productivity fixes today centers on improved single-use devices and systems. They top a long list of product innovations that biomanufacturers demand today. According to our just-completed Eighth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, innovative products are needed especially in downstream purification. Biomanufacturers are willing to pay for a wide range of product improvements. Their wish list includes single-use purification systems, for which 37.9% of the biopharmaceutical industry has indicated it needs more innovative devices. The demand for disposable...

Orthogonal methods for assuring robust downstream purification are critical to today’s demanding downstream process industry. Regulatory scrutiny on the immunogenic propensity of drugs has increased and broadened over the past two decades. Although immunogenicity can come from a number of sources, common concerns include host-cell proteins and aggregates. Constantly lurking in the background are other issues such as viral clearance, DNA levels, and so on. Those problems can be addressed simultaneously with the mixed-mode chromatographic support known as ceramic hydroxyapatite (e.g., Bio-Rad’s CHT product) or hydroxylapatite. It offers unique selectivities and often separates biomolecules that appear homogeneous using other chromatographic methods. The diverse binding capabilities of ceramic hydroxyapatite for host-cell proteins, leached protein A, antibody dimers and aggregates, nucleic acids, and viruses allow its use at all stages from initial product capture through final polishing. Recent advances in ...

Shaker–Incubator Product: Multitron II system with shaker-bag option Applications: Cultivation of mammalian, insect, or plant cells Features: A Multitron II unit (50-mm orbit) with shaker-bag option enables 1- to 10-L cell cultures in disposable bags. Direct gassing of air or air–CO 2 mix provides pH stability, and media temperature is controlled by air inside the incubator chamber. Up to three 2-L or two 10-L bags, or one 20-L bag from a number of manufacturers can be accommodated. The system also works for flasks after a slide-out tray exchange. Contact ATR, Inc. http://www.atrbiotech.com Activated Carbon Filters Product: Stax AKS filter capsules Applications: Clarification and prefiltration, scale-up, and downstream process development Features: Stax disposable depth filter capsules incorporating Seitz AKS media streamline the activated-carbon filtration process in pharmaceutical manufacturing to a single step. This reduces overall process time, increasing product yield and making activated carb...