Upstream Processing

A comprehensive process and analytical transfer package can speed up your product's time to market and save costs.

Two case studies illustrate a systematic approach.

The use of disposables has changed significantly in the biopharmaceutical industry.

Chinese hamster ovary (CHO) cells are used extensively in the biopharmaceutical industry to produce recombinant proteins that require post-translation modification for full biological functionality. Optimization of culture conditions for recombinant CHO cell lines presents challenges in light of the diverse nutritional requirements observed with different clonally derived cell lines.

Design space concepts are key to a successful technology transfer.

An overall increasing proportion of future product approvals will be engineered in some way, either directly or indirectly.

SAFC (St. Louis, MO), a member of the Sigma-Aldrich Group, has announced a $29-million investment to significantly expand its drug substance capabilities in high-potency biologics at the Sigma-Aldrich facility in Jerusalem, Israel

Regulatory agencies have evolved along with the biotechnology industry to define quality standards.

Favrille, a San Diego-based biopharmaceutical company, is one of a handful of firms on the forefront of personalized medicine. Because personalized treatment is tailored to an individual's biology, it has the potential to be far more effective than current approaches to disease management.

It is commonly believed that technologies in the next 10–15 years will enable sequencing an individualized human genome for less than $1,000. With innovations like these, the twenty-first century will certainly belong to biotechnology. From an industrial standpoint, the discovery of therapeutic molecules and the development of cell lines and processes to produce these molecules will be of paramount importance. This article describes various approaches that have been prevalent in the industry or are likely to be used in the future for generating cell lines with desirable traits and developing high titer cell culture processes.

It became a strategic imperative to find a better, more efficient way to manufacture our products. To continue with the status quo was untenable.

In one series of experiments, the glycosylation site of IgG1 was removed and an IgA glycosylation site was introduced-resulting in a total loss of biological function.

Multivariate data analysis can help biotech manufacturers deepen their process understanding.

In analyzing the industry's current challenges, let's be careful before extrapolating about what they mean.

There were notable approvals in nonparenteral delivery systems and biosimiliars in 2006.

From the earliest days of the biotechnology industry, companies have grappled with the complexities of making innovative biopharmaceuticals on a large scale. Success in manufacturing begins with process science, since biotech production requires perfection in maintaining living organisms in a sterile environment under controlled physiological conditions. But unless companies can solve the challenge of planning for and managing manufacturing capacity, they will not be able to achieve the full potential of promising biotech products.

SemBioSys Genetics, Inc. (Calgary, Canada, www.sembiosys.com) announced that it has successfully produced commercial levels of apolipoprotein AI and its variant apolipoprotein AI(Milano), collectively referred to as Apo AI, in safflower seed lines.

For pandemic vaccine processing, single-use filter cartridges and membrane chromatography technologies could offer significant time- and cost-reduction advantages.

With the advent of high-resolution mass spectrometers and highly sensitive MS instruments, vaccine characterization has entered a new phase.

In animal studies, we have demonstrated that the dose of an injected H5N1 vaccine candidate can be significantly reduced by using a skin patch containing E. coli heat-labile enterotoxin (LT) applied over the injection site. LT-activated epidermal Langerhans cells migrate to the nearby draining lymph node and enhance the immune response to the injected antigen. A dry patch formulation has been optimized as a dose sparing strategy for pandemic flu and other vaccines. Iomai Corporation has developed a proprietary stabilizing formulation for the patch that allows use and storage at ambient temperature. The patch withstands temperature extremes during shipment, and is suitable for stockpiling.

For many cell-based vaccines, the precursor monocytes or CD34+ cells are cultured with cytokines to obtain dendritic cells, which are very potent antigen-presenting cells (APCs).

The recent growth in the vaccine market has led to renewed interest in using adherent human cell lines for vaccine production. Traditionally, small-scale adherent cell line production has been carried out in roller bottles or T-flasks. Over the past few years, however, a number of companies have found multi-tray disposable bioreactors an effective method for producing high-quality drug products using adherent cells. These disposable, expandable systems have also facilitated scale up from laboratory to clinical-scale.

Vaccines against strains originating from avian flu may achieve poor yields in egg-based systems. Consequently, both public and private interest in alternative systems is high.

Any endpoint considered appropriate to support approval, whether a surrogate or a clinical endpoint, must be supported by substantial evidence of effectiveness.

Like the egg-based vaccine production process, producing a vaccine under cGMP conditions using mammalian cells can be a lengthy process, taking a minimum of six to 12 months.