Tag: <span>process development</span>

In the past 20 years, mammalian cell lines have been utilized to produce many viral veterinary vaccines. Cell lines such as baby hamster kidney (BHK)-21, Vero, and Madin Darby canine kidney (MDCK) are widely used because they help facilitate shorter manufacturing lead times and tighter process controls. As compared to other biotech products, viral vaccine manufacturing processes present some specific constraints linked to the cell substrates used. With the global veterinary vaccine market value predicted to be almost $7 billion per year by 2021[2], to remain competitively priced as well as profitable, bioprocess scientists are under pressure to develop methods for faster and more cost-efficient cell culture production. This has led to a shift from the use of expensive, two-dimensional T-flask and roller bottles to single-use, stirred tank bioreactors with microcarriers, or the adaptation of attachment-dependent cell lines such as BHK-21 for suspension culture. This requires time-consuming optimization and scale-up development experiments, which are real drawbacks. However, utilizing automated, single-use mini bioreactors as a scale-down model can enable more efficient use of time and optimization of media, feed, and culture conditions to de-risk upstream process development. In this article, single-use, mini bioreactors are evaluated to determine if they are geometrically comparable to benchtop bioreactors (both glass and single-use vessels) and pilot-scale, single-use bioreactors for effectively modelling mammalian cell culture at 2 L and 50 L scale…

Biologics Production

Many laboratories have utilized cell-free systems or prokaryotic systems designed to produce biological molecules with single polypeptide chains, limited folding requirements, and without glycosylation. The yeast systems are used to generate glycoproteins; however, their glycosylation profiles are vastly different from those of mammalian cells. Without significant glycoengineering, the yeast-produced recombinant glycoproteins may be unsuitable as therapeutic molecules. As such, the use of mammalian cells is still the preferred method to produce complex biological molecules…

Biologics Production

In order to move product development forward, the majority of biotech companies and academic institutions involved in cell-based therapies need new facilities in order to scale up production capabilities and comply with evolving regulatory requirements. Some institutions choose to use a contract manufacturing organization (CMO) to benefit from established expertise while others support their clinical development programs with their own dedicated production facility. The main challenges in establishing a dedicated pilot-scale production facility are described hereafter…

Manufacturing Regulatory

In today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases. More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products. Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success…

Biologics Production Manufacturing

In the last few years, we have seen many biotech products approved by FDA. These products have gained public awareness because of their ability to treat several debilitating diseases with very minimal side effects, and thereby impact the quality of life for many people. As a result, the biotech industry is constantly in the news for its successes and programs to develop new therapeutics for many unmet medical needs. Immunomedics, Inc., a New Jersey biotechnology company, recently completed an expansion project that included new bioreactor manufacturing suites and support laboratories. Building on the company’s existing headquarters site and fully integrating the new capacity into the existing operational facility, the project spanned two years and was completed in 2003…

Manufacturing

In today’s aggressive biopharmaceutical market, many drug discovery organizations, including both big pharmaceutical companies and small technology start-up companies, are outsourcing the development and manufacturing of their biopharmaceuticals to specialized contract manufacturing organizations (CMOs). Outsourced biopharmaceuticals range from those in early phase production to products that are well advanced down the development pipeline. As a result, there has been an expansion of CMOs that specialize in all aspects of biopharmaceutical manufacture, from process invention and development, through small-scale GMP production, to process validation and large-scale manufacture. The CMOs provide R&D services, quality function, and state-of-the-art good manufacturing practice (GMP) facilities needed for the production of biopharmaceutics. Using CMOs for biopharmaceutical process development and manufacture provides major cost savings by dispensing with the need to invest in experienced personnel and expensive manufacturing facilities…

Manufacturing

With the advent of the first gene therapy product to market, the industry faces the challenge of mass-producing high-purity viral particles and plasmids. The concept of manufacturing therapeutic genes rather than therapeutic proteins as marketable products is still in its infancy. Although manufacturers of biopharmaceuticals have decades of experience in the purification of proteins, virus and plasmid products pose unique challenges that cannot be addressed without some modifications to traditional, protein-based approaches…

Biologics Production Cell & Gene Therapy Viral Vectors

Total market share of biopharmaceuticals is estimated to increase from $33 billion now to more than $45 billion in 2007. These numbers are accounted for by the 64 products approved by European and US regulators and some of the 500 products currently under clinical evaluation. More than 2,000 products are in discovery and preclinical development. Monoclonal antibodies (MAbs) and recombinant glycoproteins constitute a major part of these new biotech leads. The estimated demands for MAbs alone are more than 6,000 kg per year in 2006. Currently, 16 MAbs are licensed by the U.S. Food and Drug Administration (FDA) for pharmaceutical use and more than 130 are in clinical trials. This fast-growing class of biotherapeutics is expected to reach worldwide sales of more than $15 billion per year in 2008. In the coming years, mammalian cell culture technology will remain the production system of choice for MAbs and other recombinant glycoproteins. Therefore, efficient, cost-effective production systems need to be in place to meet the demands…

Biologics Production Manufacturing

The Good Manufacturing Practices (GMPs) are becoming more and more familiar in biotechnology, and concepts such as quality assurance or validation are now part of the background of clinicians and researchers involved in clinical trials. A recent European Community directive (2001/20/CE) states that GMPs should also be applied to investigational medicinal products and not only to products on the market. Vector supernatant is a so-called Active Pharmaceutical Ingredient (API) and is subject to the same guidelines as traditional drugs produced by the pharmaceutical industry. This has a deep impact in the field of gene therapy because clinical trials are often run by small biotech companies or, at least in the first phases, by academic centers. The field is continuously developing and, according to the progress of the clinical studies, new processes are necessary to produce large-scale amounts of vector supernatant in a safe and reproducible way…

Manufacturing Viral Vectors

A growing number of separations‚Äô scientists and process developers are looking beyond protein A sorbents for capture and initial purification of monoclonal antibodies. A variety of strategic and operational goals have prompted examination of alternative immunoglobulin-selective sorbents. Most broadly, many workers wish to eliminate design considerations associated with leached protein A. Also cited is a preference for sorbents that can withstand stringent cleanup using 1 M sodium hydroxide. In some applications, it is desirable to avoid the low-pH elution conditions typically employed with protein A sorbents ‚ÄĒ conditions that can foster aggregate formation. In still other cases, the target antibody may bind poorly to protein A. Finally, there may be interest in evaluation of immunoglobulin-selective sorbents less costly than protein A sorbents…

Biologics Production