Production and Analysis of Gene Therapies
The number of gene therapies in different stages of clinical trials is increasing, driving the need for innovative process and analytical strategies. Viral vectors (e.g., adenoassociated viruses and lentiviruses) are used for delivery of gene therapies, so their production and purification are critical for the success of gene therapies. In this featured report, authors project future capacity needs for viral vectors and discuss the importance of selecting the best platform for their manufacture and scalability. Authors also discuss approaches for assay development and testing strategies.
Technologies to Accelerate Speed to Market
Biomanufacturers are leveraging different solutions for compressing timelines to commercialization, including constructing efficient facility designs and implementing rapid manufacturing strategies. Alongside these approaches are the technologies and innovations being used at all process stages and scales. Biomanufacturing equipment suppliers have developed advanced process tools to meet the requirements for ever-decreasing times to market. This report presents some of those advancements.
Cell Line Development:
From Genome Editing to Media Adaptation
Cell-line development is more than just bioengineering. Every biomanufacturing process begins with transfection of recombinant genes into pools of cells — followed by a succession of screenings from which will emerge (ideally) a single progenitor cell of the new production cell line. But clonality is only part of the story. In this month’s featured report, we examine the latest advances in science and technology for transfecting, picking, screening, and adapting cell lines to the ideal conditions for producing therapeutic biomolecules as rapidly as possible. From new product modalities and biosimilars to continuous processing and serum-free media, the demands are high and the results can be rewarding.
Large-Scale Capacity Strategy
The biopharmaceutical industry is undergoing a paradigm shift in manufacturing. At the core of this evolution are definitions of scale and materials of construction. Options that at first seem mutually exclusive — multiuse, cleanable equipment based on stainless steel and single-use disposable equipment based on polymer films — actually could complement each other in combination approaches to large-scale manufacturing. In this featured report, authors from user and supplier companies review a number of strategies available for innovators and biosimilar developers making antibodies and their derivatives, other proteins, vaccines, gene and cell therapies, and beyond for the global biopharmaceutical market of the future.
Antibody Drug Conjugates
Cancer treatment is the primary application, so far, of antibody–drug conjugate product development. Lessons learned here will help companies expand this product modality into other areas. Authors in this featured report seek to characterize the current state of the ADC industry, science, and technology with an eye toward the future. They focus on process/manufacturing and product development issues, highlighting successes so far and potential for the future.
Smart(er) Facilities for Biomanufacturing
Forward-looking biomanufacturers continue to explore innovative strategies and new technologies to modernize their facilities. Leading-edge technologies in the Industry 4.0 evolution include smart sensors, predictive analytics, internet of things (IoT), cloud computing, digital twin simulations, and data lakes. In the featured report, Buytaert-Hoefen focuses on the key elements of data integrity. With assistance from the BioPhorum Operations Group, Beri et al. present one of the first discussions on the applications of robotics in bioprocessing. And Bower provides a new analysis of control chart limits and autocorrelation of data for continued process verification
Addressing Challenges in Formulation
Formulation increasingly is recognized as a crucial component in drug-product success. In this month’s featured report, Rentschler authors report on the results of a recent survey and case studies that elucidate the current state of the art; Merck authors describe analytical approaches to coformulated products, and BPI’s senior technical editor shares discussions on drug-product development with past authors and BPI conference presenters.
Manufacturing Strategies to Accelerate Speed to Market
Addressing manufacturing and technologies strategies to accelerate market entry is one of BPI’s highlighted themes for 2019. In partnership with our conference colleagues in Informa’s KNect365 division, this already has been a shared theme, reflecting the general goals of the industry and related advice from its regulators.
Biopharmaceutical Supply Chain: The Ins and Outs of Meeting Market Demand
From procurement and quality control of raw materials to distribution and safety of final products, the supply chain provides a framework within which process development, manufacturing, testing, and sales of biopharmaceuticals can function. This featured report includes articles from both sides of the story: from RoosterBio on stem cells as raw materials and from Biogen on final product stability.
Bioassays: Technologies and Strategies for Optimization of Advanced Product Modalities
Bioassays are critical and essential components of ensuring the safety, potency, and efficacy of biologics. Designing an appropriate bioassay can take several weeks, even months to develop and validate. New platform technologies, statistical methods, and regulatory strategies are needed to improve development. The authors in this featured report on a novel high-throughput hepatoxicity screening method, a statistical approach to assessing bioassay variations, and an approach to characterizing bioactivity assays for antibody-drug conjugates.
Cell Line Development: Engineering the Workhorses of Bioprocessing
Advances in cell biology and associated technologies — from genetic engineering and nanotechnology to automation and data management — are changing the face of cell-line development in the biopharmaceutical industry. Seeing what’s possible, regulators are asking for more precision and better documentation on production cell lines than ever before. With an ever-intensifying desire for lowering the costs of development and manufacturing while speeding the progress of every biological candidate to market (or failure), companies are making new demands on their cell-line development groups to bring forth powerful, stable, high-expressing, and optimized cell banks as soon as possible. This featured report reviews the current state of the art of cell-line development, reports on recent discussions among experts in the field, and includes one specific case study illustrating some of the advancements being made.
BioProcess Theater at BIO 2018
Summaries and full videos of presentations, interviews, and panel discussions that took place at the BPI Theater @ BIO 2018. Focusing on emerging therapies and technologies enabled us to touch upon interconnected topics of interest to both BPI readers and the BIO exhibit-hall attendees. Speakers highlighted new manufacturing techniques that will enable faster speed to market for cell therapies, and flexible manufacturing environments to rapidly shift and produce a variety of biotherapeutic products at clinical and commercial scale. Read the summaries that appeared in our August 2018 Featured Report, and view the full presentation videos.
Bioreactors: Process Advances in Cell Culture and Fermentation
Achieving drug products that meet purity, efficacy, and quality standards depends first on cell culture quality and bioreactor performance. New analytical approaches, next-generation therapies, and innovative strategies for culture systems using a range of bioreactor types have led to a better understanding of upstream processes while reducing biopharmaceutical process/development time and costs.
Smart(er) Facilities: Automation and Innovation Can Take Bioprocessing to the Next Level of Intelligence
Today’s biomanufacturers need to be able to add capacity and capability quickly; provide increased supply service to customers on demand; and streamline the flows of personnel, traffic, utilities, and materials throughout bioprocess facilities. Companies need to be flexible enough to subtract capacity and retool quickly to produce new or different products. Future facilities are likely to be automated to some extent and use robotics in manufacturing. With personalized medicine on the rise, bioprocessors can benefit from colocation with academic research centers, laboratories, and clinics. Biofacilities should be designed to affect the environment as minimally as possible. And they would do well to be built with employees’ comfort in mind and serve as good neighbors in their local communities. It all comes down to a “smarter” approach. This featured report begins with a staff-written review, then includes end-user perspectives and supplier insights.
Cell Therapies: Technologies and Analyses to Advance Manufacturing
With several products in late-stage development, regenerative medicine is going mainstream. Even as some regulatory and manufacturing challenges are met, others arise. Expert contributors address topics such as supply chain and regulatory risk, cell culture technologies, economic considerations in cell therapy manufacturing, and manufacturing innovation lessons that can be derived from existing protein-based therapeutics.
Drug Product Fill and Finish: Challenges, Concerns, Compliance, and New Opportunities
Mainly based on the Drug Products track at the 2017 “BioProcess International Conference and Exhibition” in Boston, this report also includes a submitted case study and discussions from users and suppliers of fill–finish technology. BPI’s senior technical editor reports on the conference track. Presentations focused on predictive modeling, quality by design and process analytics, freezing–thawing and storage, endotoxin control, single-use technologies, analytics, and formulation. In addition, a new Pfizer case study examines single-use solutions for freeze–thaw of a vaccine. And experts address serialization, anticounterfeiting, and streamlining fill–finish operations.
Bioprocess Monitoring and Control: Leveraging Advanced Automation, Sensors, and Software
The need for advanced control strategies for bioprocessing and biomanufacturing is growing, and several manufacturers already have leveraged new automation and software solutions for bioprocess monitoring and control. In this Featured Report, authors discuss new approaches for process control that make use of increased computational power; advanced sensors, probes, and sampling technologies; and new software systems that can be applied to a wide range of operational modes (e.g., perfusion, continuous, and multicolumn platforms). Such technologies can be applied with single-use systems and within PAT and “machine learning” applications.
Bioprocess Training: Strengthening Preparation for Biopharmaceutical Careers
This featured report continues BPI’s annual focus on biomaufacturing training by introducing some programs through which industry and academia are extending science to the production floor. After an introduction from NC State University’s Biomanufacturing Training and Education Center, articles from the United Kingdom (University College London) and the Netherlands (the Biotech Training Facility) describe two different approaches. The final article describes a collaborative program driven by a US government initiative that brings together many different perspectives from industry, academia, and beyond.
Emerging Therapies: Processing First-in-Class Biologics
According to a 2017 industry report, 74% of biopharmaceuticals currently in development (phase 1–3) are possible first-in-class medicines. They include regenerative medicines, conjugated monoclonal antibodies (MAbs), and DNA and RNA therapeutics. Some emerging therapies — such as antibody–drug conjugates (ADCs) and biobetters — have been more at the forefront of discussions than others, but all are poised to bring exciting changes to patient care. Authors and experts in this Featured Report discuss how meeting and optimizing specific process needs for those products will be imperative to keep pace with innovation.
BPI Theater @ BIO 2017
The 2017 BPI Theater @ BIO took place June 20-22 in San Diego CA and focused on two main themes: emerging therapies and emerging technologies. The BPI Theater provides convention attendees working and interested in biopharmaceutical research, development and manufacturing with a dedicated destination to meet, network, and experience the latest science and technology trends impacting bioprocessing. Summaries of the presentations were included in the July-August Featured Report, and full video presentations are available for on-demand viewing.
Continuous Processes: Disposables Integrate
Upstream and Downstream Processing
Perhaps the “hottest” buzzwords in biomanufacturing today are continuous processing and single-use technologies. They are closely related — as one is increasingly enabled by the other. Perfusion and other approaches have begun to blur the line between upstream and downstream processing (by performing certain separation/clarification duties as part of their function). And separations technology suppliers are offering solutions to the challenge of continuous drug-substance purification. Alongside a review of these advancements by BPI’s senior technical editor, contributed articles expand on continuous upstream/production methods and continuous downstream processing technologies.
Biosimilars: Tackling the
Technical and Regulatory Challenges
Biosimilar products have come about as a way to make biopharmaceuticals that are otherwise too costly available to a broader market. Like generic small-molecule drugs, they build on the success of licensed products. And although regulatory pathways allow biosimilar developers to bypass certain expensive testing, they are not generic drugs. Technical challenges remain a part of their development. This Featured Report contains an overview of those challenges and articles that dive into technologies that can help, regulatory hurdles that remain, and a look at the countries that are leading the way globally.
Who, What, When, Where, and Why?
Biopharmaceutical outsourcing has changed over the years. In this Featured Report the authors explore the increasing complexities of devising long-term business strategies, the importance of choosing between long-term partnerships or one-time/transaction-based projects; the assurance that adequate business support and technical capabilities exist on both sides of the relationships; and the criticality of navigating the uncertainties of working with different quality organizations. Issues that affect decisions to outsource include cost, converging quality systems, change management, and staff training/expertise (including statistical capabilities).
Cell, Gene, and Tissue Therapies:
Solutions for Expansion, Purification, and Engineering
Cell therapy bioprocessing has advanced from limited efforts in specialized laboratories and academic institutions to becoming part of the mainstream biologics industry, with hundreds of companies involved and 20 product approvals in the United States (and more elsewhere). This featured report takes a snapshot of the processing issues of today — manufacturing platforms, purification of viral vectors for gene therapy, three-dimensional bioprinting — and looks toward the future of this biologics market segment.
The Latest Advancements in Downstream Processing
As single-use technologies have grown in importance and acceptance, offering more solutions every year, their biggest challenges have come in downstream separation, purification, and processing that follows product expression in cell culture. Many technologies in downstream processing present technical and economic problems. Authors in this featured report delve into many of these issues and innovations. They discuss automation, depth filtration, continuous processing, alternatives to resin chromatography, and fill and finish technology.
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