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During the lifecycle of a biopharmaceutical, occasions arise in which the facility and support organization responsible for ensuring that it is manufactured according to schedule, demand, and quality specifications must change, either in whole or in part. The reasons for this vary: some related to scale, some related to clinical development phase, some related to internal manufacturing capacity and program ownership. The industry has adopted the term technology transfer to describe these events. Many such situations have been discussed previously ( 1 , 2 , 3 , 4 ). Here, we discuss a scenario in which a product has been bought or licensed by another organization. Our perspective is mostly that of a buyer or licensee. We focus mostly on activities related to chemistry, manufacturing, and controls (CMC) because covering all the aspects of licensing a product in development would be too much for a single article. With no change in ownership involved, technology transfer commonly occurs under the control of...
The enabling value of monoliths was strongly in evidence at the 4th International Monolith Symposium, held 29 May – 2 June in the Adriatic resort city of Portoroz, Slovenia. Forty-seven oral presentations and 34 posters highlighted important advances in vaccines, gene therapy, phage therapy for infectious disease, and monoclonal antibodies, as well as continuing advances in the performance of monoliths themselves. As these fields advance in parallel, it becomes increasingly apparent that monoliths offer industrial capabilities substantially beyond traditional methods. Characteristics Monoliths are chromatography media cast as a single integrated unit. This is in contrast to porous particles packed in a column or membranes cut and configured to support practical use. The features that first brought monoliths to prominence were their abilities to maintain high resolution and capacity regardless of the flow rate and size class of the molecules they separate. Such features result from their unique architectu...
Biological therapeutics is one of the fastest growing segments of the pharmaceutical industry — so much in fact that the overall cell culture media and supplements market used in bioprocessing applications is reportedly near $800 million ( 1 ). An increasingly important trend in cell culture is risk reduction throughout the supply chain, including a stringent focus on key raw materials. Accordingly, the industry has increasingly adopted animal-component-free materials to mitigate concerns over safety, transmissible spongiform encephalopathies, and other contaminations. Until recently, such materials have been produced in mixed-use facilities, some with dedicated suites and/or equipment. But concerns over contamination have prompted a few forward-thinking companies to consider building or acquiring stand-alone processing plants. In August, I visited the new 95,000-ft 2 site of BD Biosciences–Advanced Bioprocessing in Miami, FL, the first fully dedicated animal-free, antibiotic-free (trademarked AF 2 ) CGM...
Methods and Materials Thanks to vendors large and small — such as Invitrogen ( www.invitrogen.com ), ProteoChem ( www.proteochem.com ), Sigma Aldrich ( www.sigmaaldrich.com ), Soltec Ventures ( www.soltecventures.com ), and Thermo Scientific Pierce ( www.piercenet.com ) — bioconjugation chemistry is a field of many options. For example, amine coupling of lysine amino-acid residues typically involves amine-reactive succinimidyl esters. Sulfhydryl coupling of cysteine residues uses a sulfhydryl-reactive maleimide. Photochemically initiated free-radical reactions offer broader reactivity. Most processes couple small molecules to proteins or proteins to one another (e.g., antibodies and enzymes). Other payload molecules include oligosaccharides, nucleic acids, synthetic polymers (e.g., PEG), and carbon nanotubes — each according to its own application. Technical challenges come along with these introduced downstream operations after proteins are purified — most particularly in the heterogeneity that they intr...
Peptides should be promising drug candidates. But their small size makes delivery difficult and gives them an extremely short in vivo half-life. They are often cleared by the kidneys or reticuloendothelial system only minutes after being administered, and they are susceptible to degradation by proteolytic enzymes. These problems could be solved by linking them to polyethylene glycol (PEG). Repeating chains of ethylene oxide (CH 2 CH 2 O), PEG molecules can be long or short and straight or branched. PEG groups are linked to a reactive group on a peptide molecule, usually lysine (can also be aspartic acid, glutamic acid, free cysteine, serine, threonine, the N-terminal amine, or the C-terminal carboxylic acid). Once linked to a peptide, each ethylene glycol subunit becomes tightly associated with two or three water molecules. This has the dual function of rendering the peptide more soluble in water and increasing its size. Kidneys filter substances according to their size, so adding PEG’s molecular weight a...
Despite the advantages of presterile, single-use technologies, mixing is one of their most complex applications. Industry has been progressing toward using single-use bag technologies rather than traditional methods of stainless steel tanks and grades A/B processing because of the positive aspects they impart to end users, including a reduced potential for contaminants, cleaning, sterilization, and capital. These technologies offer simplicity and flexibility ( 1 ). However, using them for an operation such as mixing can add processing challenges. For example, solutions in soft-walled bags do not always behave according to typical fluid dynamics as they would in rigid, cylindrical vessels. Here we review scalability, design considerations, and testing approaches and outline some studies we performed in the early development of small-scale single-use mixing systems for suspensions using the limited technologies currently available. PRODUCT FOCUS: ALL BIOLOGICS, INCLUDING VACCINES PROCESS FOCUS: PRODUCTION, ...
The increasing application of single-use components and systems in bioprocessing represents one of the most significant changes in biopharmaceutical manufacturing in recent times. Driven by various factors such as improved efficiency, flexibility, and economics, this trend also presents specific challenges to end users. In one industry review by Langer, extractables and leachable compounds from disposable components were considered by end users to be a major area of potential concern regarding safety, efficacy, and stability of the pharmaceutical product ( 1 ). In a more recent survey by the Bio-Process Systems Alliance (BPSA), however, extractables and leachable compounds were considered by only 13% of respondents to be a barrier in integrating single-use technologies into existing or new processes ( 2 ). The apparent change in thinking may be due, in part, to an increased amount of information available in published case studies, reviews, and industry guides such as those issued by BPSA ( 3 , 4 ) coveri...
At every stage of biopharmaceutical development, efficient and cost-effective protein production is critically important to maintaining the economic viability of both a product and the company developing it. Biopharmaceuticals have significantly evolved through recent protein engineering advances, resulting in highly complex, novel proteins dominating the development pipeline. Such proteins are by definition very difficult to express in a soluble and active form. The success of these products depends on accessing a platform that rapidly produces high-quality, properly folded, active protein while ensuring seamless scale-up to maintain economic viability of each product throughout development and commercialization. The three primary sources of value that can be derived from a robust expression are The Pf &ebar;nex Expression Technology system uniquely addresses all three of these areas. However, here we focus on only one aspect of the value proposition: large-scale process economics. PRODUCT FOCUS: AGLYC...
Microbiological Testing Product: GeneDisc specified microorganisms assay Applications: Compendial testing Features: Pall’s GeneDisc specified microorganisms assay is part of its GeneDisc rapid microbiology system based on real-time quantitative polymerase chain reaction (qPCR) technology. Performed using a GeneDisc plate, this rapid assay detects six key indicator microorganisms used in several compendial tests. Users can simultaneously distinguish multiple organisms, obtaining results within two hours (rather than two days with traditional methods) after relevant sample preparation, depending on type of assay performed. Contact Pall Corporation www.pall.com Fluid Control Product: 2000 INOX valves Applications: Stainless steel piping Features: Pneumatically operated 2000 INOX angle seat valves from Bürkert have a pneumatic piston actuator and a two-way valve body. Both parts are manufactured from stainless steel 316L for use with media at temperatures of ≤180 °C. The material protects against corros...
Join us for the week and you will Discussion forums will provide uncensored insights on some of the industry’s most pressing concerns: What are we doing with our idle capacity? Can we create a consortium for small and large companies to deal with overcapacity as a community? What are phase-appropriate approaches to support exploratory investigational new drug (IND) applications? Keynote Presentations “OBP’s Pilot Program for QbD: Initial Results and Next Steps” by Patrick Swann (deputy director of the division of monoclonal antibodies at FDA/CDER’s Office of Biotechnology Products) “Risk-based Approaches to Process Understanding and Manufacturing Control” by Mansoor A. Khan (director of the division of product quality research at FDA/CDER/OPS/OTR) “Generation and Characterization of Novel Mono- or Multi-Specific Therapeutic Proteins for Oncology and Autoimmune Diseases” by Kendall Mohler (senior vice president of research and development at Trubion) “Process Validation Moves Forward: A Global Evolution o...
Looking ahead to next year’s tax season, you can maximize the benefits of available US tax credits and incentives. A powerful incentive known as the research and development (R&D) tax credit is available at federal and state levels to help companies recover a significant amount of their R&D costs. Organizations that qualify for the credit range from small farming collectives investing in improved livestock breeding methods to pharmaceutical and medical device companies developing new products. The key factor is identifying research projects and activities and their related wages, supplies, and outside contractor costs to meet a four-part test under Section 41 of the US Internal Revenue Code. This credit has been available since 1981, but the definition of qualified activities has changed significantly. In the past, the key barrier to the credit required that research be “revolutionary” in nature or advance the technical knowledge of a given industry. Now the requirement is merely that research activity ...