Facility Design/Engineering

Formulation, Fill and Finish of Lentiviral Vectors: Part 1 — Case Study in Facility and Process Design

Over the past few years, Oxford Biomedica Ltd. (OXB) has developed and implemented a fill–finish platform (“Oxbox,” Figure 1) at its viral vector processing facility in the United Kingdom. The facility includes four segregated bulk viral-vector drug substance (VS) suites, where closed systems and bioburden control processes apply, and two viral-vector drug product (VP) fill–finish suites that apply aseptic processing, with space for expansion by scale-out as product output demand increases. Segregated suites enable the facility to process different viral…

Aseptic Considerations in Formulation, Fill and Finish: Choosing Between Barrier and Isolator Technologies

Biological drug substances are constituent in a wide range of medicinal products with an even broader spectrum of applications. Those include autoimmune-disease treatments (e.g., for arthritis), vaccines, and recombinant therapeutic proteins (e.g., for cancer treatment). What such products all have in common is that they are manufactured using biotechnology and other cutting-edge technologies. Biologics are not as physically robust as their small-molecule counterparts. Hence, during biomanufacturing processes, these complex molecules present a number of challenges. Some of the typical shared…

Spontaneous Infection: Did You Leave the Back Door Open to Your Cultivation Suite?

Manufacture of biopharmaceuticals using mammalian cells inherently incurs a risk of viral contamination during cell cultivation. If introduced, viruses can infect and replicate in cells used to produce a therapeutic protein or vaccine. The consequences of such contaminations can be dramatic. Not only can a company lose contaminated batches, but it also faces potentially extensive root-cause investigations, facility cleanup efforts, and introduction of preventive measures. Until contamination issues are resolved adequately, production should not be resumed, and facility downtime brings…

Financial Benefits of Off-Site Prefabricated Cleanroom Infrastructures

Traditional cleanroom infrastructures, gypsum, or monolithic wall panels have been used in the past with varying success and benefit. One of the most often proclaimed benefits is the cost of those on-site built structures. Characteristically, the cost quoted at the beginning of a construction project seems to be attractive, but construction estimates are not better than ±50% at feasibility (preconcept) and ±25% at end of conceptual design. Given the above accuracy ranges, industry surveys establish that in most cases, the…

Four Design Factors Shaping Multimodal Cell and Gene Manufacturing

Cell and gene therapy manufacturing is about to hit a breaking point. The tension lies between increasingly diverse research pipelines and a tradition of dedicated facilities built for single-product, large-scale manufacturing. That incompatibility is widening as more cell and gene therapy products progress toward commercial production, forcing manufacturers to make a choice: either invest in major facility modifications and complex technology transfers to keep up or break from tradition and explore the potential of multimodal manufacturing. More than half of…

Toward the Point of Care: Flexibility and Decentralization Are Key to Making Autologous Therapies More Readily Available

Part of the advanced therapy medicinal products (ATMPs) class of therapeutics, cell and gene therapies (CGTs) can be either autologous, using the patient’s own cells, or allogeneic, using master banked donor cells. Global biotechnology company Orgenesis focuses on autologous therapies, with processes and systems developed for closed and automated processing that have been validated for regulatory-compliant production at the point of care for patient treatment. This technology could help overcome the limitations of traditionally cost-prohibitive CGT manufacturing methods that do…

Ask the Expert: Selecting the Right Buffer Management Strategy

Although buffers are among the simplest materials used in bioprocessing, they are critical to biopharmaceutical manufacturing success. Buffer preparation, storage, and handling can require significant investments in time, labor, equipment, and facility space. Jenny Dunker, MSc, and Alexander Troken, PhD (global product managers for customized bioprocess solutions and for process liquids and buffers, respectively, at Cytiva), delivered an “Ask the Expert” presentation on 30 March 2021 to explore strategies for intensifying buffer management. Available Options Biopharmaceutical manufacturers often prepare buffers…

Risk Considerations for Aging Pharmaceutical Facility Cleanrooms

Pharmaceutical facility cleanrooms are designed to reduce and control particle contamination and to minimize the ingress and retention of microorganisms. Such risks typically are easy to control in well-designed, modern facilities. But risk mitigation is more difficult in older facilities. There is no exact definition of what constitutes an aging facility (or what are sometimes euphemistically called legacy facilities). For example, a facility established 100 years ago to manufacture a simple tablet can continue to operate perfectly well with careful…

Total Global Capacity Finally Shows Improved Productivity

Since 2018, global bioprocessing capacity has grown from 16.5 million liters (1) to 17.4 million liters. Although output has continued to expand at around 12% overall, that rate represents a significant slowing in capacity growth as the industry moves toward greater productivity and efficiency. Trends that we have tracked in the BioPlan Associates annual report of biopharmaceutical manufacturing capacity and production (2) for over 17 years correlate with that finding. Titers are increasing; single-use technologies have reduced the need for…

Facilities Roundup: What’s Behind the Expansions?

In the early 2000s, the trade press was abuzz about an imminent “capacity crunch” in mammalian cell culture. Dire predictions of shortages were based on biopharmaceutical successes to that point, on bursting development pipelines, and on the lengthy timelines and high costs of assembling tens of thousands of liters of stainless-steel bioreactors and supporting infrastructure. Those predictions failed to anticipate several positive developments that would render doom-and-gloom scenarios moot. Notably, yearly improvements in protein titers for MAb processes already were…