Manufacturing

In the Information Technology Zone

Successfully driving your global business requires vigorous, secure information exchange within your facility, from site-to-site, and with your partners and contract service providers. Tools to capture data in real time support decision making and enable companies to manage volumes of historical data needed for regulatory submissions. Software is available for data mining, managing clinical trial networks, and assessing toxicology data (among many other things). Information technologies in the biotechnology industry facilitate development and delivery of new therapies and diagnostics, improvements…

Development of an Antibody Screening Assay for Selection of Production Cell Lines

Biopharmaceuticals such as recombinant monoclonal antibodies (MAbs) account for a significant proportion of all new drugs (1,2,3). Although manufacturing site capacities have expanded and process efficiencies have improved greatly, there is still some concern the current biomanufacturing capacity worldwide might not meet increasing market demands (1, 2). PRODUCT FOCUS: RECOMBINANT PROTEINSPROCESS FOCUS: PRODUCTION PROCESS DEVELOPMENTWHO SHOULD READ: QA/QC, PROCESS DEVELOPMENT, AND ANALYTICAL PERSONNELKEYWORDS: CELL LINE DEVELOPMENT, SCREENING ASSAY, MONOCLONAL ANTIBODIES, FC PROTEINS, CHO, IGG, HTRF, ANTIBODY TITER, CELL LINE PRODUCTIVITY,…

Cell Cultivation Process Transfer and Scale-Up

The introduction of therapeutic monoclonal antibodies (MAbs) has greatly revolutionized therapies for several cancer immune disorders (1,2,3,4,5). Benefits to patients have been substantial, translating into both increased life expectancy and improved quality of life. Currently, twenty-one therapeutic MAbs are registered for marketing in the United States, with the introduction of several more expected in the coming years (6,7,8,9,10,11). PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: Technology transfer (production) and analytical methods developmentWHO SHOULD READ: PRODUCTION AND PROCESS DEVELOPMENT, MANUFACTURINGKEYWORDS: IGF-1R, EXPRESSION, TECH…

Throwing a Flag at Biosimilars

PHOTO COURTESY OF ROGER LUNDBLAD (PICTURED). When I officiated at high school (US) football, I learned a lot from the experience. Contrary to popular opinion, there are rule books referees study. However, although the rule book is modest in size, the case book for interpretations is large. This brings me to the topic of generic or follow-on biologicals and biosimilar products for which there will be rules, and the interpretations will be many. Continuing with the US football analogy, the…

Variables Affecting Titer and Long-Term Stability of Virus Stocks

Assurance that monoclonal antibody (MAb) therapeutics produced using large-scale animal cell culture are free of adventitious agents is based on three complementary approaches. First, a master cell bank is extensively characterized to demonstrate its freedom from adventitious agents. In addition, end-of-production cell culture material is tested and demonstrated to be free of adventitious contaminants. Finally, the viral clearance capacity of a purification process is assessed using model viruses. PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: PURIFICATIONWHO SHOULD READ: MANUFACTURING, PROCESS DEVELOPMENT, REGULATORY…

Construction and Start-Up Costs for Biomanufacturing Plants

All bioproducts heading to commercialization go through a rigorous process that includes research and development, proof of concept, and validation studies. Furthermore, the fabrication process of a biological product is very different from that of a classical (synthetic small-molecule) pharmaceutical. That’s not only because of specific characteristics and requirements of the molecular entities involved, but also environmental considerations and specific issues related to human health and safety. Such differences are reflected in the cost drivers of approved manufacturing plants. Herein…

Proteomics Technology Applied to Upstream and Downstream Process Development of a Protein Vaccine

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…

Integrating Modular Design–Build Execution Strategies into Biotech Projects

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 21st 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…