Scale Up

How to implement a risk-based approach to eliminating viruses.

A review of some recent contributions in process chromatography.

Best methods to maximize product yield and membrane lifetime to enhance a tangential flow filtration process.

A discussion of past achievements and future expectations of recombinant protein production yields from mammalian cells.

With a variety of recombinant, animal-free, defined protein supplements such as growth factors, transferrin, and albumin entering the market, the biopharmaceutical industry now has innovative and safer alternatives to serum and other animal-derived supplements.

Gene fusion tags can improve the yield and solubility of many recombinant proteins. This article discusses the most popular fusion tags and the proteases used to remove them, with special reference to recently introduced technologies.

Using chemically defined feeds with CHO cell lines not only eliminates the variability associated with using plant hydrolysates, but could also improve the productivity of biopharmaceutical protein manufacture and help move therapeutic proteins into clinical trials more rapidly.

Recombinant protein and plasmid DNA production using microbial expression systems is the cornerstone of many biologics manufacturing processes. HCD methods are commonly used for these processes because of the advantages they provide.

Process-modeling tools can ensure smooth tech transfer.

A comparison of primary harvest techniques.

Disposable technologies that mimic the conventional stainless-steel bioreactor will be most readily adopted

Manufacturing challenges surround the use of IgM monoclonal antibodies, but these can be overcome with current technology.

An alternative approach to traditional Protein A schemes is comparable in overall efficiency, product recovery, and quality.

The future of therapeutic MAbs lies in the development of economically feasible downstream processes.

If certain engineering challenges can be addressed, precipitation may prove to be a valuable tool for antibody purification.

When platform processes are applied to fusion molecules, innovation and flexibility are needed.

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

Design space concepts are key to a successful technology transfer.

A solution for the problems of a "bag in a can" system would be a fully jacketed and insulated container, similar to a traditional freeze tank.

Low-pressure process chromatography could not have developed without immense efforts to resolve scale-up issues in both column design and matrix stability.

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.

Small biotechnology companies often need guidance during the development of new therapies-particularly when it comes to manufacturing.

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

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.

These articles encapsulate the past, present, and possible future of process-scale chromatography in biopharmaceutical production.

This article shows how Probabilistic Tolerance Intervals of the form, "We are 99% confident that 99% of the measurements will fall within the calculated tolerance limits" can be used to set acceptance limits using production data that are approximately Normally distributed. If the production measurements are concentrations of residual compounds that are present in very low concentrations, it may be appropriate to set acceptance limits by fitting a Poisson or an Exponential Distribution.

Development reports document process development and support the design of validation experiments, yet in many firms training is not provided nor are expectations established. This article describes how project managers can help scientists master the art of report-writing.

Capital investments in production plants represent a significant portion of the cost of new recombinant drugs

Extra column effects must be accounted for to make a valid comparison