Manufacturing

eBook: Intensifying Processes for Monoclonal Antibodies

The commercial manufacturing success of monoclonal antibodies (MAbs) has become a touchstone of the biopharmaceutical industry. MAbs are so well established that they often are referred to as “traditional” biologics, and well-known MAb processing methods have become a model for processing of other “advanced” or “emerging” therapies. But MAb processing continues to advance as biomanufacturers seek ways to improve efficiencies, lower costs, and (most recently) increase sustainability of facilities. Drug makers are particularly interested in strategies for MAb process intensification.…

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…

Process Intelligence: Gene Therapy Case Study Shows That the Journey to Improved Capabilities Starts with One Step

The product development team at a gene therapy contract development and manufacturing organization (CDMO) was working on a high-priority drug-substance project for a key client. The material was crucial to that client’s early stage clinical trial, with an immediate value over US$500,000 to both the client and the CDMO. Unfortunately, the bioreactor used in the upstream process — a transfection unit operation for an adenoassociated virus (AAV) vector — had developed an intermittent problem that could force it to shut…

The CRISPR Saga (So Far)

Since January 2016 (with a brief interlude as described below), the Patent Trial and Appeal Board has been attempting to adjudicate the proper inventorship of CRISPR technology in (to date) six separate patent-interference proceedings. (Scientific “priority has been decided, for now, by the awarding of the Nobel Prize in Chemistry to Jennifer Doudna and Emmanuelle Charpentier in 2020; see the “Priority Claims” box). CRISPR-based gene editing was hailed as the “Breakthrough of the Year” in 2015 (1), and the scientific…

Partnerships Are Crucial to Getting Advanced Treatments to Market

New treatments and approaches for tackling serious diseases are being developed using cell and gene therapy (CGT). CGTs are adding a new dimension to the way patients with such conditions can be treated in modern healthcare. But these advanced treatments require complex research, development, and manufacturing processes. CGTs are related and to a degree interchangeable. However, gene therapies typically use some kind of genetic delivery system, (e.g., virus-based vectors) to treat a disease by replacing a malfunctioning gene or introducing…

Advancing Logistics for ATMP Manufacturing

Advanced therapy medicinal products (ATMPs) hold much potential for improving healthcare. They offer hope for treating or even curing patients. The biopharmaceutical industry has recognized the importance of making such therapies accessible to as many people as possible. To provide personalized ATMPs, biomanufacturers are shifting toward flexible, patient-centered production processes. A Paradigm Shift in ATMP Manufacturing Ex vivo cell and gene therapies are particularly promising approaches to personalized regenerative medicine. Thus, it is no surprise that the numbers of US…

Navigating New Options for Commercial-Scale Biopharmaceutical Production

Scalability remains a critically important topic for biopharmaceutical companies. For conventional protein products, the strategy once was straightforward: Drug makers would scale up, beginning with cultures in flasks and roller bottles to grow enough cells to inoculate laboratory-scale (often glass) bioreactors, then again to pilot- and commercial-scale, stainless-steel, stirred-tank bioreactors. At their highest volumes, such reactors can handle tens of thousands of liters of cells and growth media. If a drug developer did not have the requisite equipment to scale…

Boosting Yield and Preserving Quality: Increasing Production of Induced Pluripotent Stem Cells for Cell Therapy and Regenerative Medicine Applications

Induced pluripotent stem cells (iPSCs) are promising starting materials for several clinical and industrial applications in cell therapy production, drug discovery, and in vitro screening. But as I learned from Maxime Feyeux (cofounder and chief science officer of TreeFrog Therapeutics in Bordeaux, France), such cells are a relatively new option in the toolbox of cell therapy developers. Advanced-therapy products can require controlled proliferation and differentiation of millions or even billions of iPSCs depending on the clinical indication, he pointed out,…

Scaling AAV Production: Easing the Transition from Laboratory Scales to Commercial Manufacturing

Adenoassociated virus (AAV) has emerged as the leading vector for gene therapy delivery. Compared with options such as lentivirus and adenovirus, AAV exhibits a strong safety profile because it has low pathogenicity and requires a helper virus to replicate. AAV is also capable of long-term gene expression, and it can infect both dividing and nondividing cells (1–5). Developers of advanced therapies have found such advantages to be quite attractive. As of January 2021, two gene therapy products have gained US…

Mind the Gap: Managing Relationships Between Upstream and Downstream Intensification

Process intensification (PI) describes an integrated framework of strategies to maximize the output of a unit operation, a process, or an entire facility. By implementing PI strategies, biomanufacturers can accomplish their productivity goals by increasing production speeds and titers, reducing facility footprints, and cutting costs. Overall, such changes improve production efficiency and flexibility. Collectively, the biotherapeutic industry has made multiple advancements in intensifying upstream processing. PI strategies include using high-density cell banks, implementing seed-train intensification (n – 1 perfusion), and…