As early as 1997, automation was ready to offer potential benefits to the bioprocess industry (
1
). Professor Bernhard Sonnleitner of the Zürich University of Applied Sciences’ Institute for Chemistry and Biological Chemistry suggested a “standard operating procedure” and pointed to the opportunities, requirements, and potential pitfalls of applying the principles of automation to bioprocess development and operations. If “boring and less interesting routine tasks” could “more efficiently and reliably be handed down to machines,” he explained, then personnel could “engage in more useful work.”
His proposal might be seen as a genesis of quality by design: First, measure everything that can be measured early on; then, determine which variables are most relevant and identify those that must be controlled/documented; and finally, collect data from the process and organize it according to those determinations. In just a few pages, Sonnleitner showed the way to developing what many practitioners now call profo...
Small, genetically engineered immunological constructs are being developed industry-wide for a growing range of in vivo applications. Examples include Fab, F(ab’)2, single-chain (sc) Fv, bis-scFV, diabodies, minibodies, and single-domain antibodies (
1
). Their small size potentially gives them access to tissues that are poorly accessible by intact antibodies; rapid clearance from blood and nontargeted tissues; lower immunogenic response; and eye-drop, inhalant, or oral administration.
We report here on purification of an affinity-matured, humanized, antiprostate stem-cell antigen (PSCA) minibody for first-in-human clinical studies. This minibody and an earlier chimeric version have demonstrated excellent high-contrast microPET imaging for PSCA-positive human prostate, pancreatic, and bladder cancers in animal models (Figure 1) (
2
). The overall structure is reminiscent of IgG, bivalent but only half the size. The “Fc region” is reduced to the Cγ3 domains and “Fab” to the variable domains (Figure 2). Alt...
+5This two-part article explores related tools and technologies that biopharmaceutical companies can leverage to build an efficient mechanism for capturing and delivering valuable information. In
BioProcess International’s
December 2009 issue, part 1 of the series focused on infrastructure selection and how hardware, software, and information systems form a kind of ecosystem (
1
). Simplicity, sustainability, and scalability can be achieved only when that trio is designed holistically. Part 1 further explored structured data capture and analysis tools, whereas this second half is dedicated to unstructured data capture and analytics. Part 2 concludes by focusing on how an integrated environment can be created to leverage on both structured and unstructured data, providing a single access window to enterprise information for end users.
A GMP/GLP Environment
Currently the major portion (estimated >80%) of the knowledge space within a biopharmaceutical organization exists in unstructured form (free-form text ...
Proteins can aggregate at any point during pharmaceutical manufacturing. Regulatory agencies pay special attention to aggregates that can enhance immune responses and cause adverse clinical effects and those that can compromise the safety and efficacy of a drug product. Biopharmaceutical companies have stringent quality control (QC) procedures in place to ensure that their final products are free of contaminants and defects, including protein aggregates. Trained QC inspectors, however, can typically see product defects or particulate material only as small as 50 m by visual inspection. If contaminants can be identified at this stage, then steps can immediately be taken to correct problems in the manufacturing process. Even when particles can be seen, visual inspection alone is not usually sufficient to identify them and determine their source.
Isolating and analyzing small particles may require specialized technical skills and analytical instrumentation that an in-house QC laboratory does not possess. Man...
For decades, the complexity of albumin has been researched extensively, yet many manufacturers and users of the protein have treated it more as a commodity. Because albumin has been readily available, suppliers and purchasers alike have frequently relied on more obvious measures of “purity” and other minimal release criteria to make their decisions. If a lot does not perform well in practice, the typical supplier’s response has been to investigate the manufacturing process for deviations, then correct them if found and make another lot. This is a costly strategy for both manufacturer and purchaser — especially if the “corrected” lot still doesn’t work. So what’s the answer? We can begin with an appreciation of albumin’s heterogeneity, then determine the effects of purification processes on its properties, and correlate those properties to the product application.
Albumin is the most abundant serum protein. It serves several functions in vivo: e.g., binding and transport of fatty acids, hormones, and metal...
Development of a recovery process for a fed-batch mammalian cell culture product involves several objectives: process scalability, robustness, maximizing product yield, elimination of subsequent purification steps, and low cost of goods. In an effort to achieve those objectives, we developed a three-stage primary recovery process to remove biomass and clarify the feed stream for downstream column chromatography (Figure 1). The initial stage involves removal of whole cells and larger cellular debris using a continuous disc-stack centrifuge. Depth filtration is the second stage, removing smaller particulates based on size exclusion and adsorption. The third stage consists of 0.2-µm filtration, which removes potential bioburden. To assist in process development, we are investigating innovative approaches to achieve better process control and maximize processing efficiency. Monitoring pressure in the depth filtration process step is one potential area for improving throughput and efficiency.
PRODUCT FOCUS: AL...
Downstream processing of biopharmaceuticals is costly and time-consuming, often involving multiple steps with significant time and energy expended on maximizing product quality and yield. Affinity chromatography is one of the simplest and most effective methods for purifying protein and peptide therapeutics, offering reduced process steps and therefore higher yields than nonaffinity methods can provide. Protein A is widely used for affinity purification of monoclonal antibodies (MAbs), Fc fragments, and Fc fusion proteins. But it is a challenge to find a protein A equivalent for nonantibody targets.
To be useful in bioprocess applications, an affinity medium must provide the specificity required to purify a product effectively while allowing elution conditions that preserve product structure and activity. It is also important that an affinity medium can withstand cleaning processes required for effective adsorbent cleaning to meet regulatory standards in therapeutics production.
To address these challenge...
+2 Antibody Development and Production is regarded as the most comprehensive event that delivers industry best practices across the spectrum of upstream and downstream processing. By attending, you will learn how companies are developing the latest molecular assessment approaches to optimize manufacturability and product quality and how they are applying smarter and faster tools for rapid process development. Industry leaders will assess the state of the industry and offer solutions to overcome the current capacity issues as they work towards their goals of lean manufacturing and facility optimization.
Featured presentations will demonstrate how to successfully integrate upstream and downstream processing and the integral role played by analytics as they develop the next generation of commercial processes. We will explore the impact of Quality by Design (QbD) and Design of Experiments (DOE) on process development as companies share results of the mock filings that have recently concluded with feedback from F...
If you have ever gotten frustrated trying to explain what you do at work to friends and family, we can relate. One of the greatest challenges perennially facing the biotech industry is the lack of public understanding of what biotechnology is and the many ways it contributes to a better world. A lack of solid public acceptance and support can make it all the more difficult to advance our advocacy efforts in the United States Congress and in state legislatures across the country.
The bright glare of science fiction films and TV shows skewed by fantasy often overshadows the reality of biotechnology’s contributions. Unfortunately, the average American cannot even define
biotechnology
, let alone appreciate the significant hope it creates for humanity. Educating the public about the existing benefits and future possibilities of biotechnology is imperative to dispel the fears and misinformation associated with it. National polling has consistently found that providing information on biotechnology results in a...
