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,…
Manufacturing
Implementation of Single-Use Technology in Biopharmaceutical Manufacturing
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…
Formulation Effects on Opalescence of a High-Concentration MAb
Monoclonal antibodies (MAbs) are increasingly formulated at concentrations >100 mg/mL as a means to deliver a high dose in a low volume (1,2). Such high-concentration solutions are commonly opalescent (3,4), an undesirable characteristic of biopharmaceutical products for several reasons. Although it may be only aesthetic, opalescent products are not considered pharmaceutically “elegant.†Of more serious concern, opalescence may be a precursor to aggregation and indicate a propensity toward decreased product stability or quality. The term opalescent refers to…
Industrializing Stem Cell Production
Stem cells have potential as a readily available, consistent source of many differentiated cell types. This unique property can be leveraged both for therapeutic purposes and for facilitating and improving a number of drug discovery and development processes. Large-scale, “industrialized” production of human stem cells in tightly controlled conditions will be required to deliver the quantity and quality of cells needed to support clinical trials and drug discovery development activities (Figure 1). Achieving this level of production while meeting rigorous…
Minimizing the Environmental Footprint of Bioprocesses
Part 1 of this two-part article introduced the need to reduce the environmental footprint of bioprocesses and evaluated the impact of solid-waste disposal. Part 2 continues by describing the effects of the remaining elements of the bioprocess footprint: wastewater, electricity, and air emissions. Wastewater Process Waste Streams: Generally, raw materials to produce and purify biopharmaceuticals fall into one of the following categories: inorganic/organic salts, sugars/polyols, trace elements, vitamins, amino acids, surface active agents, or complex (undefined)…
Increasing Biopharmaceutical Quality Through Packaging Partnerships
Containers and administration devices are integral to the safety and efficacy of biopharmaceutical therapies and must be key considerations for all new drugs coming on the market. By partnering with packaging manufacturers early in development, biopharmaceutical manufacturers can increase efficiencies in their production processes while gaining expert advice and counsel throughout a drug’s lifecycle. Such an alignment can also improve product quality, enhance regulatory compliance, and contribute to the overall state of control by preserving biopharmaceutical stability, ensuring sterilization, and…
Sequence Variant Analysis Using Peptide Mapping By LC–MS/MS
Monoclonal antibodies are usually expressed in mammalian cell lines and are produced in several variants known as isoforms (1,–2). Microheterogeneity can result from posttranslational and enzymatic modifications as well as those caused by processing, alteration, storage, and incorrect translation of the target protein (1,3). Common sources of heterogeneity include Fc glycosylation, partial carboxypeptidase processing of heavy-chain (HC) C-terminal lysine residues (4), deamidation or isomerization (5), Fc methionine oxidation, hinge-region fragmentation (6), aggregation, and sequence variants. Sequence variants are…
Manufacturing Convergence Technologies
Many regenerative medicine products represent a convergence of pharmaceutical, biologic, and medical device technologies. Although such products could have a great impact on medicine, they often pose significant challenges for their developers, requiring companies to incorporate competencies from several technology sectors. By addressing commercial regulatory and manufacturing challenges at an early stage in product development, these companies are more likely to succeed in reaching their commercial goals. Exact regulations governing the manufacture of a convergent technology — or…
Containment of High-Potency Products in a GMP Environment
Many modern medicines are highly potent, with only tiny doses required to achieve a therapeutic effect. But a nanomolar medicine poses extra hazards during manufacturing, whether the product is a biologic or a small molecule. These issues have to be evaluated and addressed in the design of a manufacturing facility for such products. Not only is it vital that the product not become contaminated, but employees and the general public must be protected from the product. Exposure to just a…
Building Regulatory Compliance for Personalized Medicine
Regulatory compliance is the means by which biopharmaceutical companies bring new medicines to market. But as we embark on developing and bringing to market more complex, more personalized medicines in the 21st century, we are about to find that our most experienced sources of compliance know-how and intelligence are getting ready to leave for the comforts of retirement. Demographics are working against the biopharmaceutical industry. Survey Results A 2006–2007 survey by the University of Southern California…