Facility Design/Engineering

China’s First Digital mRNA Vaccine Facility: Leveraging Automation and Digitalization Solutions

Vaccines against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are designed to elicit immune responses that prevent recipients from getting — or becoming seriously ill or dying from — novel coronavirus disease (COVID-19). Two available COVID-19 vaccines are based on genetically engineered messenger RNA (mRNA). After administration, such molecules give muscle cells “instructions” for how to make target proteins — e.g., the SARS-CoV-2 spike (S) protein. Immune-system detection of those proteins prompts creation of neutralizing antibodies. Immediately upon delivery of…

Facing a Unique Challenge: Building an In-House Cell and Gene Therapy Manufacturing Facility During the Pandemic

In 2019, Expression Therapeutics (ET) obtained investigational new drug (IND) approval for its lead clinical product. The third-generation lentiviral vector (LV) expresses a bioengineered coagulation factor VIII to be used in an autologous hematopoietic stem- and progenitor-cell gene therapy for patients with severe hemophilia A. Like many other emerging biotechnology companies, ET’s initial strategy used reputable contract development and manufacturing organizations (CDMOs) for vector and cell manufacturing needs and a prominent clinical contract research organization (CRO) with extensive experience in…

Multimodal Facility Design for Cell and Gene Therapies

Cell and gene therapies (CGTs) are progressing rapidly through development pipelines and advancing through clinical trial phases. Manufacturing capacity will need to be sufficient when such products are approved for commercialization. Thus, biomanufacturers are seeking ways to leverage multimodal facilities. I spoke with Stephen Judd, who is principal process engineer for biologics and cell and gene therapy at DPS Group, an engineering and construction management consultancy. We talked about design considerations for multimodal facilities, how such facilities contribute to overall…

Elevating Your Pharmaceutical Facility to the Next Digital Plant Maturity Level

Pharma 4.0 technologies, offshoots from the Industry 4.0 model, focus on introducing new technologies for increased levels of digitalization within the pharmaceutical manufacturing industry. Many companies hesitate to embrace the Pharma 4.0 concept fully even though digitalization efforts are leading the way toward new levels of efficiency and productivity. The biopharmaceutical industry currently lags behind other industries in implementing digital technologies because of its rigorous and strict regulatory requirements. Adopting Pharma 4.0 tools and concepts benefits manufacturers by harmonizing the…

Robots in Biomanufacturing: A Road Map for Automation of Biopharmaceutical Operations

As BioPhorum authors stated in 2019, “It should come as no surprise to anyone familiar with biomanufacturing that current designs of bioprocess facilities as well as associated manufacturing spaces and support operations require excessive amounts of manual labor and manual interventions that lead to high labor costs and, consequently, total cost to supply” (1). Back then, a realization was starting to take hold in the biopharmaceutical industry that modern robotics showed great potential. However, a cohesive vision of their future…

Biologics Manufacturing Without the Big Bioreactors

Over the past few decades, the biotechnology industry has brought to patients a medical revolution with the most advanced medicine ever seen. Yet much of the world’s population cannot afford or get access to these breakthrough therapeutics. That is in part a consequence of the high associated costs of development and biomanufacturing, extended times for regulatory review and approval, and a lack of regional manufacturing and dependable supply chains (because of facility costs and a scarcity of expertise). The recent…

Scalability in Cell and Gene Therapy Facilities: How Today’s Developers Are Preparing for Tomorrow’s Commercial Success

Propelled by year after year of record-setting investments and regulatory approvals, cell and gene therapy (CGT) innovators are on track to revolutionize medicine by providing potential cures for many conditions. Now, CGT manufacturers must plan for a future beyond the production constraints of laboratories. What needs to happen now to prepare for a sustainable, commercially viable scale-up process in years to come? To answer that and other important questions about CGT production, my company, the CRB Group, surveyed more than…

Formulation, Fill and Finish of Lentiviral Vectors Part 2: Key Decisions and Risk Management

Over the past few years, Oxford Biomedica UK has developed and implemented its fill–finish platform at its 84,000-ft2 “Oxbox” manufacturing facility constructed in 2019. The first phase of development (45,000 ft2) houses four segregated suites for producing bulk viral-vector drug substance (VS) where closed systems and bioburden-control processes apply, and two fill–finish suites for viral-vector drug product (VP) in aseptic processing. The first of the fill and finish suites is expected to be approved in the first half of 2022.…

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…