Abhinav A. Shukla

Single-use disposable technologies for biopharmaceutical manufacturing

The manufacture of protein biopharmaceuticals is conducted under current good manufacturing practice (cGMP) and involves multiple unit operations for upstream production and downstream purification. Until recently, production facilities relied on the use of relatively inflexible, hard-piped equipment including large stainless steel bioreactors and tanks to hold product intermediates and buffers. However, there is an increasing trend towards the adoption of single-use technologies across the manufacturing process. Technical advances have now made an end-to-end single-use manufacturing facility possible, but several aspects of single-use technology require further improvement and are continually evolving. This article provides a perspective on the current state-of-the-art in single-use technologies and highlights trends that will improve performance and increase the market penetration of disposable manufacturing in the future.

The need for innovation in biomanufacturing

489 immediately on the welfare of subjects and the interpretability of trials. Moreover, these studies have a structure similar to controlled clinical trials and are unlike basic science (which has a more exploratory structure). Third is the question of cost. Registries entail administrative costs (the 2007 budget for clinicaltrials.gov (http://clinicaltrials.gov/) was

Evolving trends in mAb production processes

3 million) and compliance expense for investigators. Well-documented flaws in reporting and compliance with trial registries would likely be recapitulated in preclinical registries10. Would benefits outweigh costs? Without a proper cost-benefit analysis or a specified registry architecture, we cannot provide an unequivocal answer. We do not underestimate the technical, economic, political and logistical challenges of incentivizing good preclinical disclosure. Nevertheless, models less costly than clinicaltrials.gov might be explored, such as those used to promote deposition of genomic and microarray data. High-impact biomedical journals, for example, might encourage good disclosure practices by requiring authors of trials or preclinical experiments to include a sentence stating that complete summary preclinical evidence has been deposited in a public database. Funding agencies might consider mechanisms, like those used for prospective protocol review in gene transfer trials, to encourage researchers at publicly funded institutions to deposit supporting preclinical evidence. Trial registries began with a series of modest steps that afforded opportunities to test and refine models. Initially, registries incorporated only publicly sponsored studies. Research agencies and drug regulators then convened working groups to establish data elements for inclusion. Only later did journals and legislation establish rules that significantly incentivized good disclosure practice11. Implementation of preclinical registries should follow a similar course of iterative refinement. In recent years, various funding bodies have signaled their commitment to clinical translation by creating new support and mechanisms for research. To better meet the potential of these programs while enhancing protections for volunteers, we urge funding agencies, journals, foundations and academic institutions to devise policies that promote registration and reporting of preclinical results.

Evolution of mAb Downstream Process Platforms

Abstract Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing have arisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non‐chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes.

Innovation in biomanufacturing: the only way forward

Monoclonal antibody (mAb) therapeutics have formed and continue to form the vast majority of biopharmaceutical company pipelines today with a number of remarkable commercial successes. The advent of mAbs as therapeutics has been greatly aided by a process platform approach that has enabled rapid development and manufacturing for this class of drugs. Downstream process platforms for mAbs first evolved over a decade ago and have had a significant impact on the time and resources spent in process development. This article describes some of the platform approaches first used in the biopharmaceutical industry and how those platforms have evolved over the last decade based on needs as well as newly available technology. We also describe the advent of next-generation mAb-based constructs and the creation of possible platforms for those moieties.