Facility Design/Engineering

Building Manufacturing Capabilities for Adenoassociated Virus Vectors: Key Considerations for Facility Design and Operations

Demand for gene therapies based on adenoassociated virus (AAV) vectors continues to exceed manufacturing capacity. Part of the imbalance stems from the growing number of AAV-based candidates that are advancing through clinical studies. Zhao et al. report that, in September 2021, researchers were enrolling participants for and/or conducting 137 trials for such products (1). As of August 2022, three AAV-based therapies have received commercial authorization in the United States and/or European Union, and other products have received conditional approval (2–5).…

A Plug-and-Produce GMP Plant for Cell and Gene Therapies Part 2: Rapid Deployment of a Commercial-Scale Facility

Extending the use of approved advanced-therapy medicinal products (ATMPs) to the tens of thousands of patients who could benefit from such treatment requires a 10- to 100-fold production scale-up. Given that each autologous ATMP batch yields one dose for one patient, expanding production throughput is not a question of boosting volume, but rather of amplifying single manufacturing runs. That is, scale-up is actually scale-out, and the dimensions of the ensuing endeavor extend beyond what occurs in the cleanroom. Coupled with…

A Plug-and-Produce GMP Plant for Cell and Gene Therapy — Part 1: Case Study in Modular Facility Design and Deployment

The use of approved advanced therapy medicinal products (ATMPs) remains limited despite their potential to address unmet medical needs. One example uses chimeric antigen receptor (CAR) T cells for treatment of refractory lymphoma (1). Typically, such medicinal products begin with cells that are harvested from a patient and genetically programmed to recognize and eliminate tumor cells upon reinfusion. Several cell therapies based on this and other technologies are approved for use in the United States, Europe, and China (2). Given…

BioProcess Insider Interview: Dr. Ger Brophy, Avantor

Moderator: Dan Stanton, Co-founder and Editor, BioProcess Insider. Featuring: Dr. Ger Brophy, Executive Vice President, Biopharma Production, Avantor. Avantor has expanded its biopharmaceutical capabilities significantly over the past year. In addition to opening facilities in The Netherlands and Massachusetts for manufacturing and distribution of single-use systems, respectively, the company has broken ground on sites in Ireland and Singapore. Avantor also acquired Masterflex, a manufacturer of peristaltic pumps and fluid-handling solutions. Brophy explained that such activity exemplifies Avantor’s efforts to increase…

BioProcess Insider Interview: James Park, Samsung Biologics

Moderator: Dan Stanton, Co-founder and Editor, BioProcess Insider. Featuring: James Park, Executive Vice President, Samsung Biologics. Samsung Biologics has established itself among the world’s largest CDMOs. It currently provides 364,000 L of bioreactor capacity, primarily in stainless-steel format, across three sites in Songdo, South Korea. Park reported that construction continues on a fourth facility. In October 2022, the plant will bring six 10,000-L bioreactors online for GMP production of recombinant proteins. A second construction phase is scheduled to add 12…

Reflections on the Evolution of Biopharmaceutical Manufacturing: A Virtual Roundtable with Scientists from Sartorius

As a trusted partner in the life-sciences industry, Sartorius has contributed significantly to the evolution of biopharmaceutical manufacturing. To reflect on the rich history of the industry, we arranged a virtual roundtable. Based on shared questions, we corresponded about what we considered to be the most important scientific, technological, and operational developments in the past 20 years of bioprocessing. We also reflected on the emergence of new modalities and how such products are likely to shape the future of the…

Challenging the Norms of Facility Design and Innovation

The past 20 years have spurred new technologies that enable flexible solutions to changing market demands. Small-scale tools, improved analytical methods, and innovative facility designs are among the notable breakthroughs. To enrich our understanding of the past 20 years of bioprocessing, BPI distributed questions to supplier companies. Below, Elyse Vlahos (director of process engineering at Genesis AEC) provides her perspective on innovation and future industry developments. Innovation and Regulations What have been the most important technical innovations over the past…

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…

Flexible Vaccine Manufacturing: Collaborations Bringing Localized Solutions

The COVID-19 pandemic has become the most recent reminder of how accessibility to drugs and vaccines depends heavily on geographical location and a country’s economic health. Some countries continue to lack the infrastructure, regulatory support, and trained workforce necessary for establishing a viable bioindustry. Unizima, part of the Univercells Group, is a team of experts, scientists, and engineers that partners with public and private companies and other organizations to help build biomanufacturing capabilities in low- and middle-income countries (LMICs). We…

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…