Blog 2018-01-03T03:29:05+00:00
2310, 2017

Flow Cytometry

By | October 23rd, 2017|Categories: Manufacturing, Research & Development|Tags: , , , |0 Comments

This powerful technique enables rapid identification and sorting of cells, streamlining the manufacture of many biologic pharmaceuticals. 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. The manufacture of biologic products often involves the generation of a variety of cells, including blood, bone, marrow and lymph; but not all these cell types will be [...]

1210, 2017

The Vero Vaccine Production Pipeline

By | October 12th, 2017|Categories: Research & Development|Tags: , , , |0 Comments

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. The Vero cell platform vaccine production technology is able to address many of these issues, providing a streamlined system for the rapid development of novel vaccines for emerging viruses. Vero has already proven effective in quickly developing vaccines to combat avian influenza, SARS, alphavirus, flavavirus, and other evolving viral threats. The platform’s key advantages lie in its rigorously validated pipelines for quickly generating, inactivating and purifying large batches of viruses, in order to rapidly produce safe, tested formulations ready for regulatory approval. This streamlined series of pipelines proceeds in five major stages: propagation of cells and viruses, replication, harvesting and inactivation, purification, and finally formulation and filling. The following is a more detailed breakdown and analysis of each of those five stages. The Vero platform’s upstream processing moves cells rapidly from propagation to inactivation. Following an initial period of cell culturing in roller bottles, the cells are passaged and expanded on microcarriers. This propagation and expansion takes place at three increasing scales of fermenter culture systems, leading to the generation of a final batch at the 6000-liter scale required for actual production of the host cells. Meanwhile, the target virus has been separately propagated to the necessary scale in a tiered virus bank system. This simultaneous [...]

510, 2017

Advanced Development and Manufacturing of Antibody Technologies (ADAMANT)

By | October 5th, 2017|Categories: Research & Development|Tags: , , , , , |0 Comments

This cutting-edge platform streamlines antibody development and optimizes production. Over the past several years, the US Food and Drug Administration (FDA) has rolled out its Medical Countermeasures Initiative (MCMi), aimed at establishing clearer regulatory pathways for medical products. The goal is for new vaccines (and other treatments) to gain regulatory approval more efficiently, so those cutting-edge treatments can be available in case of a medical emergency such as a regional pandemic. 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. Throughout the research and production stages, ADAMANT streamlines antibody development in all the following ways. ADAMANT aids in the selection of target antigens, CDRs, and V regions. When developing monoclonal antibodies (mAbs) and other antibodies for vaccines, biologic developers typically begin by selecting a target antigen, which will produce the desired response in the subject’s immune system. Once they’ve chosen a target antigen, developers then focus finding specific complementarity-determining regions (CDRs) on that antibody, where that antigen can bind. Next, they select cloned variable (V) regions corresponding to the desired effector functions, or design them by grafting V regions from multiple species’ antibodies together. In order to streamline all these processes, ADAMANT offers an array of powerful tools. The platform includes libraries of yeast and phage cells, organized by CDR, enabling researchers to quickly scan through CDRs for a wide variety of target antigens. It also includes tools for the design and selection of [...]

110, 2017

Vero Cell Platform Technology

By | October 1st, 2017|Categories: Research & Development|Tags: , , , , |0 Comments

The cell development platform has proven effective in the creation of a number of viral vaccines. 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 cell 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 Health Organization (WHO). Another new strain could [...]

2209, 2017

Upstream and Downstream Bioprocess Optimization

By | September 22nd, 2017|Categories: Analytical, Manufacturing|Tags: , , , , , , , |0 Comments

Improvements throughout the pipeline bring greater biologic yields, as well as higher quality. 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. The creation of a viral or bacterial vector, or a protein such as an mAb, involves a number of upstream steps, including the selection of host cells and expression vectors, as well as transfection and selection processes. In any of these steps (and often in several [...]

1909, 2017

Vector Development

By | September 19th, 2017|Categories: Manufacturing|Tags: , , , , , , |0 Comments

The creation, production and storage of viral vectors all pose highly unusual challenges. 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. 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. But despite these similarities between viral vectors and traditional biologics, vectors offer the unique challenge of being particularly delicate in [...]

1409, 2017

BSL-3 Biologic Development

By | September 14th, 2017|Categories: Manufacturing|Tags: , , , , , |0 Comments

Advances in Biological Safety Level 3 technology offer advantages for agile biologic developers. Many types of biologics include live populations of organisms, some of which may be highly infectious in active form. Vaccines, in particular, often contain deadly bacteria and viruses in live but attenuated forms. The storage and processing of these dangerous organisms requires specialized laboratory facilities, where infectious agents can be handled securely, in accordance with the risk levels they pose. In fact, the US Centers for Disease Control (CDC), the Department of Agriculture (USDA) and the National Institutes of Health (NIH) all provide detailed parameters for the design and management of facilities where infectious agents will be stored and handled. These guidelines specify safety levels ranging from biosafety 1 to 4 (BSL-1 to BSL-4), depending on the degree and nature of the risks posed by a given biological agent. A facility with BSL-3 biocontainment precautions is both necessary and sufficient for the containment of “indigenous or exotic agents that may cause serious or potentially lethal disease through the inhalation route of exposure,” according to the CDC’s guidebook Biosafety in Microbiological and Biomedical Laboratories (BMBL). As the following analysis of the design of a typical BSL-3 lab will explain, these precautions are necessary for a wide range of reasons. A BSL-3 facility is designed to ensure the safety of workers and other community members. The top priority for any BSL-3 facility is to protect lab workers and the public from pathogens and toxins classified as Class III by the CDC. These facilities also also used to handle pathogens whose risk is unknown, or is currently being evaluated. To contain these pathogens and prevent the risk of infection from spreading, BSL-3 facilities are equipped [...]

309, 2017

Clinical Stage Products

By | September 3rd, 2017|Categories: Research & Development|Tags: , , , , , , , , |0 Comments

Emerging technologies offer exciting opportunities for the development of novel therapies. Although commercial sales are certainly a desirable target for pharmaceutical development, they’re far from the only reason to invest in new products. In a number of fields, pharma developers are partnering with contract manufacturing organizations (CMOs) to develop products designed specifically for clinical-stage trials. Clinical stage products can become profitable intellectual property, even as they advance the pharmaceutical field and provide new opportunities for innovation. Here are three of today’s most promising product categories for clinical stage pharmaceutical development. Monoclonal antibodies Also known as mAbs or moAbs, monoclonal antibodies are generated in clones of a cell, often from a human or rodent. They bind specifically to epitopes of the same antibody from which they’re generated. This property enables them to bind to specific antigens in a patient’s body, inducing or reducing an autoimmune response in target cells. For example, mAbs are used in a wide range of cancer treatments, binding to antigens present in cancerous cells, and triggering the immune system to attack those cells. In a reverse scenario, mAbs are used to treat autoimmune diseases like rheumatoid arthritis, ulcerative colitis and Crohn’s disease, by binding to receptor sites that suppress autoimmune responses. In a similar way, mAbs can be used to prevent the rejection of transplanted organs. Beyond this, mAbs can also be engineered to deliver a specific cytokine, radioisotope or toxin to specific cells, or even to activate specific receptors on a cell membrane. The range of mAbs used in clinical research and therapy has multiplied sharply in recent years. Advancing technologies such as polymerase chain reaction (PCR) toolkits enable engineers to design mAbs for specific targets, then grow them in the [...]

1108, 2017

Biologics Process Development

By | August 11th, 2017|Categories: Manufacturing|Tags: , , , |0 Comments

As the market expands, developers need support from expert contractors. A growing number of pharmaceutical development companies are partnering with contract manufacturing organizations (CMOs) to meet the global demand for biologics. This investment comes with good reason: as of 2016, the global biopharmaceutical market was valued at $192 billion, up from $176 billion in 2015, witnessing a staggering compound annual growth rate (CAGR) of 8.6 percent. Big pharma companies have expressed intense interest in the biologics market since 2008 or earlier. Major players such as Wyeth, Pfizer and Bristol-Meyers Squibb have all acquired smaller biotech firms and purchased large biomanufacturing facilities, as well as investing in enhanced capabilities for existing ones. As blockbuster biologic patents worth billions expire every year, the market remains ripe for firms able to move quickly and capitalize on their intellectual property (IP). In this highly competitive landscape, expert manufacturing capabilities are more crucial than ever. Few pharma developers possess these the in-house expertise necessary to ensure efficient manufacturing processes that produce minimal waste. However, some contract manufacturers offer exactly that level of expertise, providing significant advantages over in-house capacities. Here are some of the most critical reasons why biologic developers are partnering with CMOs. Contract manufacturing organizations offer strong technical expertise. Not all CMOs provide equal technical competency. Any developer planning to partner with a CMO should perform due diligence, auditing carefully for quality, consistency, cost-effectiveness and related factors. However, once a developer has found a trustworthy contractor, the benefits of that partnership can far exceed the capabilities of any in-house facility. Contract manufacturers typically offer equipment, facilities and trained teams for a wide range of processes that may be needed in the development and manufacture of pharmaceuticals. Some provide [...]