This innovative process mitigates risks associated with the sterile biologics manufacturing. However, tight control of parameters is critical. The risk of contamination is always present throughout any pharmaceutical manufacturing pipeline. That risk is particularly acute in biologics fill and finish. For that reason, a growing number of biologic manufacturers are turning to novel aseptic (sterile) filling technologies; including blow-fill-seal (BFS), in which the container for an injectable biologic is formed, filled and sealed by automated machinery. Pharma manufacturers have long used BFS technology to fill ampules and other containers, for a wide range of solutions and other liquid dosage forms. However, BFS technology’s adoption is growing in the biologics sector; particularly for the filling of injectables such as monoclonal antibodies (mAbs), vaccines and other proteins. Because the BFS packaging process is automated, it eliminates many issues involved in more traditional fill-finish processes, such as the risk of breakage and inadvertent contamination. And since BFS is an aseptic process, it has proven particularly useful for biologics with high sensitivity to terminal sterilization procedures. This article summarizes the BFS process, along with several key advantages of adopting BFS technology in a biologic manufacturing pipeline. Blow-fill-seal streamlines several aspects of the fill-finish process for liquid biologics. In a conventional fill-finish process, the container (a glass vial or ampule, for example) must first be sterilized, after which it is filled and sealed. The risks of breakage and contamination are present throughout these three steps, necessitating extraordinary care on the part of all personnel who handle the biologic product and its container. The BFS process, on the other hand, proceeds rapidly and automatically, without the need for human intervention. BFS machinery begins by extruding thermoplastic resin into the final container’s [...]
The field has advanced considerably in recent years, but a number of key challenges remain. by Raymond E Peck, CEO of VxP Biologics Because injectable biologics are introduced directly into the body’s tissues, these formulations must be extraordinarily free from contamination of every kind. This requirement sets a high bar for the manufacturing of injectables. The demand for biologic injectables continues to grow. In 2015, the global injectables market was valued at $299.7 billion, with a projected compound annual growth rate (CAGR) of 6.9 percent over the next seven years. Even so, the US Food and Drug Administration (FDA) places extraordinarily strict restrictions on injectable formulations, demanding heightened attention to anti-contamination measures for manufacturing environments, equipment and personnel. These regulations mandate compliance with extensive guidelines for good laboratory practices (GLP) and good manufacturing practices (GMP), from the manufacture and packaging stages all the way to storage and distribution. In order to create safe, effective injectable biologics that comply with federal regulations, developers are turning increasingly to contract manufacturing organizations (CMOs) in the early stages of their pipelines. This article summarizes the current state of the injectable biologic industry, exploring several key challenges frequently confronted by developers and CMOs. Recent advances have helped streamline the manufacturing of injectable biologics. Pre-formulation of injectable biologics presents a variety of unique challenges. While the concept of injectable drugs dates back to 1855, the field of injectable biologic manufacturing has advanced considerably since the turn of the twenty-first century. The sterile (or aseptic) fill and finish process is now performed in a cleanroom, in which every workstation and piece of equipment is arranged to facilitate an uninhibited progression from filling, to lyophilization, to stoppering. High-efficiency particulate air (HEPA) [...]
The correct choice of sterilized packaging is crucial, as is regulatory compliance. by Raymond E Peck, CEO of VxP Biologics While the potency and efficacy of active pharmaceutical ingredients (APIs) remain crucial in biologics manufacturing, the packaging of those drugs is equally critical in ensuring safety and stability. A wide variety of packaging types abound on the market, including options that range from flexible pouches and wraps, to pre-fillable inhalers and syringes, to blisters and clamshells. As consumers’ healthcare awareness increases worldwide, and measures for infection control continue to develop, spending on biologic drugs is on the rise, providing significant impetus for expansion in the manufacture of sterile biologic packaging. Meanwhile, the US Food and Drug Administration (FDA) has recently rolled out new guidelines for the labeling of sterilized packaging, heightening the demand for packaging that complies with federal regulations. A growing number of packaging manufacturers are responding to all these demands, by incresing their investments in the development and manufacturing of sterilized packaging for biologic drugs. This product category is growing rapidly: a 2014 MarketsAndMarkets forecast predicts that the sterile medical packaging equipment market will experience a compound annual growth rate (CAGR) of 8.8 percent, rising to $6.93 billion within the next five years. This article offers a brief overview of the sterile packaging market as of 2017, particularly as this industry relates to biologic pharmaceutical manufacturing. Sterile packaging is critical for safe storage, transport and administration of biologic drugs. The sterility of biologic packaging is perhaps its most vital attribute. Aside from the necessity of durability and ease of use, the sterility of this packaging is perhaps its most vital attribute; particularly in biologics manufacturing, where the risk of inadvertent contamination [...]
This powerful technique enables rapid identification and sorting of cells, streamlining the manufacture of many biologic pharmaceuticals. by Raymond E Peck, CEO of VxP Biologics In the manufacture of many types of biologics, flow cytometry is a crucial tool for identifying, analyzing and sorting cells. This technique can provide a wide range of data points about cells’ physical and chemical attributes, including their volume, cytoplasmic granule content, and even nuclear structure. The underlying principle is to label cell components with fluorescent dye (typically carboxyfluorescein succinimidyl ester, or CFSE), then use a hydrodynamically focused stream of fluid to shuffle those cells in single file across the beam of a laser. The laser excites fluorescence in the dye, emitting light at a longer wavelength than that of the source. By emitting laser light at varying wavelengths, the cytometer sends a combination of scattered and fluorescent light back to its detectors, providing data which is then analyzed by computer software to provide information about many properties of each cell. As complex as the procedure is, the detector and software are powerful enough to perform it thousands of times per second. With a combination of Forward Scatter (FSC) detectors in front of the stream, and Side Scatter (SSC) detectors perpendicular to it, the cytometer enables engineers not only to classify thousands of individual cells in a matter of seconds, but also to track their proliferation, apoptosis, and other cell cycle properties. Flow cytometry can aid in all the following applications within a biologic manufacturing pipeline. A flow cytometer can help identify, quantify, and sort thousands of cells per second. Flow cytometry can be used to track cell proliferation and interaction. The manufacture of biologic products often involves [...]
The Vero platform’s upstream and downstream processing stages are designed for maximum efficiency and safety, as well as purity of the final product. Despite many recent advances in vaccine development technology, the actual process of bringing new vaccines to the clinical trial stage often remains cumbersome and slow. Even the most elaborate recombinant technologies and vector systems may not integrate smoothly into an existing manufacturing pipeline, and inefficiencies and safety issues may emerge at any step of the process.
To help accelerate MCM development, VxP Biologics has developed its Advanced Development and Manufacturing of Antibody Technologies (ADAMANT) platform. This platform integrates cell libraries, region design and selection techniques, and formulation standards into a high-throughput production format. By optimizing and standardizing antibody design and production, ADAMANT helps biologic developers bring new antibody candidates to the clinical trial stage more rapidly.
This cell development platform has proven effective in the creation of a number of viral vaccines. by Susan Thompson, Technical Director at VxP Biologics Recent years have witnessed a significant amount of innovation in technologies for the development of novel vaccines. These technologies include new vector systems for delivering attenuated vaccines, recombinant technologies for generating virus-like particle (VLP) vaccines, and a range of other tools for the manipulation of DNA and mRNA. However, even these evolving techniques may not enable the development of new vaccines to proceed rapidly enough to contain emerging viral threats. In order to stop global epidemics before they spread beyond control, a platform for the rapid generation of inactivated whole virus vaccines is a critical asset. The Vero cell platform vaccine production technology addresses precisely this need. Vero’s unique pipeline streamlines the inactivation, harvest and purification of large batches of viruses within robust safety margins, at reasonable costs. The platform has already been utilized to rapidly generate novel vaccines for several viral epidemics, and is currently being used in the development of other inactivated viral therapies. The following cases demonstrate the effectiveness of the Vero platform in enabling the rapid development of new vaccines. The Vero platform has proven effective in rapidly developing novel influenza vaccines. Avian influenza is a particularly virulent form of the influenza A virus. Since 2003, more than 50 countries have suffered outbreaks of various strains of avian flu, including H5N1 and H9N2. The 2009 outbreak of the H1N1 strain gave the virus a high media profile in the US. And in 2013, a strain known as H7N9 appeared in China, presenting an unusually high fatality rate and demanding rapid action on the part of the World [...]
Improvements throughout the pipeline bring greater biologic yields, as well as higher quality. by Raymond E Peck, CEO of VxP Biologics Bioprocessing is the production of natural or genetically manipulated cells (or other organic parts). In the field of biologic pharmaceuticals, bioprocessing is used to generate proteins like monoclonal antibodies (mAbs), as well as viral vectors for the transmission of targeted gene therapies, and many other cutting-edge therapies. However, bioprocesses have long been known to tend toward inefficiency and high costs. In large part, this is due to the nature of the processes themselves: generating, harvesting and storing sizable quantities of proteins or cells will inevitably result in some lost product. Even so, bioprocesses can be analyzed and re-engineered to increase their efficiency, as well as the concentration, yield and quality of the final products. These improvement-oriented analyses divide bioprocessing into upstream and downstream components. While upstream bioprocessing deals with early cell isolation, cultivation and banking in preparation for harvesting, downstream bioprocessing involves separating the resulting biomass, cell disruption, concentration, and other sub-processes concerned with isolating and concentrating the desired biologic product. As a growing number of pharmaceutical developers compete to bring new biologic therapies to the clinical trial stage, and eventually to market, optimization of both upstream and downstream bioprocessing is essential for cost-effectiveness and effective competition in the marketplace. The following analysis breaks down some of today’s key concerns in the optimization of upstream and downstream bioprocesses. Upstream bioprocessing optimization focuses primarily on boosting production. Vero has already proven effective in quickly developing vaccines to combat avian influenza, SARS, alphavirus, flavavirus, and other evolving viral threats. The creation of a viral or bacterial vector, or a protein such as an mAb, [...]
The creation, production and storage of viral vectors all pose highly unusual challenges. by Susan Thompson, Technical Director at VxP Biologics Traditional viral vaccines use attenuated or inactivated forms of viruses to trigger and “train” the body’s immune responses. In recent years, however, pharmaceutical developers have also begun to use viruses as vectors to deliver an increasing range of targeted gene therapies. These therapies use strands of DNA to add or edit genes in specific cells, offering the potential to treat a wide variety of inherited ailments, as well as metabolic, neurological and cardiovascular diseases. The number of gene therapy products currently in clinical or commercial development exceeds 400, while the number of products in preclinical development is at least 1,700. In fact, a recent market report by Roots Analysis estimates that the worldwide market for viral vectors (along with related technologies such as plasmid DNA manufacturing) will achieve a compound annual growth rate (CAGR) of 17 percent over the coming decade, to reach at least $1 billion. The following analysis explores some of the most common challenges associated with vector development, along with several of the ways in which contract manufacturing organizations (CMOs) are assisting with those challenges throughout the development stage. The fragility of viral vectors often creates significant development challenges. The fragility of viral vectors often creates significant development challenges. Like monoclonal antibodies (mAbs) and other conventional biologic pharmaceuticals, vectors are generated in bioreactors, then harvested and purified downstream through processes like depth filtration and chromatographic separation. These processes must be characterized and analyzed by the CMO and/or the developer, in order to validate the results at each stage and ensure that effective lots are produced on a consistent basis. [...]