January 2008

Diagnostic tests originated at patients’ bedsides more than 3,000 years ago. However, over the past 200 years, diagnostics moved into laboratories as the tests became more complex. Now further technological advances are bringing these tests out of the laboratory and back to a near-patient environment. This change in procedure will save both lives and money. Know Faster, Act Faster Use of diagnostic tests principally falls into three categories. The first is long-term monitoring of chronic diseases (e.g., measuring glucose levels to control diabetes). The second is routine screening of a population for a particular condition; this can either provide a definitive diagnosis or indicate whether further, more expensive testing is advisable. The third is to provide definitive diagnoses when doctors believe that symptoms indicate a particular disease. A move from central laboratories toward point-of-care (PoC) testing will enable more diagnostic tests to shift from providing a diagnosis to providing routine scre...

IBC’s Antibody Development and Production is regarded by industry as a leading resource for process development scientists and engineers looking for the latest case studies on recent breakthroughs that help increase process efficiency and productivity. IBC has shared a unique partnership with industry experts delivering programs that present solutions to the ongoing challenges of developing and producing antibody-based therapeutics. Each year this event continues to evolve and explore new ways to accelerate speed to market and reduce cost with successful approaches to shortening timelines and streamlining workflows during early and late-stage development. IBC’s distinguished scientific advisory committee has designed a new and improved program for 2008 to examine multifaceted approaches to developing fast and efficient production processes while controlling product quality. In addition, several solution-based case studies will demonstrate new approaches in downstream processing that overcome the challenge...

Suspension-adapted Chinese hamster ovary cell (CHO-S) cultures are widely used in biotechnological production of recombinant proteins. In fact, such special cell lines have become the standard for this type of biopharmaceutical production ( 1 ). The reasons for that include their fast reproduction, high protein expression rate compared with other eukaryotic cells and, above all, the glycosylation patterns generated by the cells ( 2 , 3 ). PRODUCT FOCUS: Animal cell products (recombinant proteins) PROCESS FOCUS: Production and product development WHO SHOULD READ: Process and cell culture engineers, analytical personnel KEYWORDS: Process optimization, cell culture, PAT, laboratory scale, process control LEVEL: Basic Efficient production of correctly processed proteins requires optimized cultivation parameters. The SensorDish Reader (SDR) instrument from Precision Sensing GmbH of Regensburg, Germany ( www.presens.de ) offers a noninvasive online detection method that for the first time enables quantita...

Clone selection techniques used for development of stable, high-expressing recombinant cell lines suitable for robust fed-batch cell culture processes are critical for biopharmaceutical manufacturing. Basal media screening, feed development and addition strategies, and fed-batch bioreactor performance are all intimately tied to overall performance of the clones during scale-up. Serious issues can arise if a high-quality clone is not established, such as low or unstable protein yield and ineffective use of costly resources. PRODUCT FOCUS: Recombinant proteins PROCESS FOCUS: Production WHO SHOULD READ: Manufacturing, process development, analytical, and product development personnel KEYWORDS: Cell line development, medium optimization, cell screening LEVEL: Intermediate Cell Xpress clone selection technology combines high-speed image scanning and quantitation with high-speed laser manipulation that allows for in situ measurement of recombinant protein secretion of single cells, followed by laser-mediat...

Pichia pastoris is a species of methylotrophic yeast that is widely used for protein expression both in academia and the biotechnology industry. A number of properties make it suited for this task ( 1 ). Pichia has a high growth rate, and it can grow on simple, inexpensive media. It can also be grown in either shaker flasks or bioreactors, which makes it suitable for both small-and large-scale protein production. PRODUCT FOCUS: Yeast-expressed recombinant proteins PROCESS FOCUS: Production WHO SHOULD READ: Manufacturing and process development personnel KEYWORDS: Cell line development, seed cultures, Pichia pastoris , disposables LEVEL: Intermediate Growing P. pastoris to high densities is of great benefit when producing certain recombinant proteins. However, with high yield comes a high demand for oxygen. That in turn requires a culture vessel to deliver a large amount of oxygen to yeast cultures (that is, it must offer a high mass-transfer rate) if maximum densities are to be achieved. Single...

Extractables and leachables from disposable manufacturing systems must be addressed as part of process validation. Extractables are compounds that can migrate from a material into a solvent under exaggerated conditions of time and temperature. Leachables are compounds that actually do migrate into a drug product formulation under normal processing conditions. All materials have extractables and potentially have leachables. When properly evaluated, both are easily addressed and rarely lead to disqualification of a disposable component. PRODUCT FOCUS: ALL BIOLOGICS PROCESS FOCUS: MANUFACTURING WHO SHOULD READ: QA/QC, PRODUCT AND PROCESS DEVELOPMENT, ANALYTICAL, AND MANUFACTURING PERSONNEL KEYWORDS: PAT , ADVENTITIOUS AGENTS, REGULATORY COMPLIANCE, ENVIRONMENTAL CONTROL, MICROBIOLOGICAL TESTING LEVEL: INTERMEDIATE No specific standards or guidances reference extractables and leachables from single-use, disposable bioprocessing materials. But there are regulatory guidances and industry–regulatory coll...

Development and manufacturing of recombinant-protein–based vaccines has in the past few years become very similar to that of other well-documented and well-characterized biological drugs. For investigational vaccines, chemistry, manufacturing, and controls (CMC) information is critical for a successful regulatory filing. The process development and CGMP manufacturing of a recombinant protein drug is on the critical path toward clinical phase 1 dosing and safety studies as well as proof-of-concept clinical studies ( 1 , 2 ). However, resources invested in this process may be wasted if the methods and results are not sufficiently documented. PRODUCT FOCUS: Vaccines and recombinant proteins PROCESS FOCUS: Upstream and downstream process development WHO SHOULD READ: Manufacturing and process development, project managers and analytical personnel KEYWORDS: CELL LINE DEVELOPMENT, HOST-CELL PROTEIN ASSAY, PROCESS-RELATED IMPURITIES, PRODUCT-RELATED IMPURITIES, STABILITY, PAT LEVEL: INTERMEDIATE Here we de...

One of the earliest and most important decisions in a biopharmaceutical facility construction project is choosing a project execution strategy. This choice affects cost, schedule, and quality of the immediate project as well as further operations throughout the facility life-cycle. As technology and best practices evolve in the early 21 st century, many biopharmaceutical facility projects are integrating some form of modularization execution strategy to maximize predictable costs, schedules, and quality benefits. The modularization concept can manifest as prefabricated buildings, modular process skid systems and HVAC systems, and preengineered modular construction techniques. Here we focus on a preengineered modular construction project execution strategy adopted by Cook Pharmica for its new biotechnology active pharmaceutical ingredient (API) contract manufacturing facility in Bloomington, IN. This project won the 2007 Facility of the Year award for facility integration from the International Society fo...