Manufacturing

Biosimilarity Assessments: The Totality of Evidence Framework

Biosimilars are evaluated through comparisons with their reference products using abbreviated pathways that have evolved significantly over the past few years. Scientists and regulators now accept that some quality attributes can vary from batch to batch over a product’s lifecycle, even for reference products. Moreover, reference and similar biotechnology products can show differences in noncritical quality attributes but still demonstrate comparable efficacy and safety (1). Here we describe a similarity assessment approach that is also applicable to comparability of lifecycle…

Embedded Particles in Single-Use Bags: Risk to Bag Integrity and Drug Product Purity, or Only a Cosmetic Defect?

When using single-use systems (SUS) to process biopharmaceuticals, preventing drug product contamination from extractables and leachables (E&Ls) and embedded particulate matter (gel particles) in the polymer films used to make bioprocess bags is critical. Using a pressure burst test to assess film integrity, Sartorius Stedim Biotech’s Klaus Wormuth and colleagues compared Flexboy and Flexsafe samples with gel-particle-free materials to assess their potential for contamination. The results showed that only large (2–4 mm2) gel particles affected the burst test results, concluding…

Toward Standardized Sample Collections: UK Government Seeks to Expand Cell and Gene Therapy Use

The SAMPLE program — a Standard Approach to ATMP Tissue collection — is intended to help build capacity for the UK National Health System (NHS) to expand the use of next-generation cell and gene therapies for both cancer and noncancer illnesses. Now it has been given the green light by Innovate UK (IUK), the United Kingdom’s technology strategy agency. An award through the Industrial Strategy Challenge Fund is supporting the program for standardizing how cell and gene samples are collected…

Immunotherapy: Taking Aim at Solid Cancers

As cell and gene therapies arrive on the market, all eyes have focused on autologous chimeric antigen receptor (CAR) T – cell therapies. At the 2019 Phacilitate Leaders World and Stem Cell Summit in Miami, FL, delegates looked at where the biopharmaceutical industry is going in the cellular immunotherapy space. Whether for off-the-shelf CAR T-cell products, personalized cancer vaccines, or modified natural killer (NK) cells derived from human induced pluripotent stem cells (iPSCs) — cell and gene therapy development is…

Supply Chain Solutions for Cell and Gene Therapy Companies

Stakeholders across the supply chain stress that quality of starting material will be key to the success of cell and gene therapies. This is a topic that has created issues in the past, is puzzling the industry presently, and is likely to cause more problems going forward. This topic was front and center at the 2019 Phacilitate Leaders World and World Stem Cell Summit in Miami FL, with presentations focusing on supply chain solutions to address these complex challenges; cell…

Automation in Cell and Gene Therapy Development

The US approvals of chimeric antigen receptor (CAR) T-Cell therapies Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) and gene therapy Luxturna (voretigene neparvovec) in 2017 heralded a “new frontier of medicine.” But with great innovation comes great costs and criticism (such as the Kymriah’s US$475,000 price tag). Many companies argue that these one-off therapies represent good value for patients and payers compared with traditional treatments, however, no matter your perspective, the COGs picture for cell and gene therapies isn’t good and…

Manufacturing of Cell and Gene Therapies

The peak of demand for curative cell and gene therapies will be unlike that of traditional drugs and thus could cause forecasting and overcapacity issues going forward. Predicting the future is always difficult, and poor decisions can be costly and highly damaging for a company. At the 2019 Phacilitate Leaders World and Stem Cell Summit in Miami, FL, several presentations and conversations focused on the forecasting dilemma and how manufacturing needs innovation, just to name two. This eBook details these…

eBook: Allogeneic Cell Therapies Commercialization Strategies

Manufacturers of allogeneic cell therapies face development and commercialization challenges unlike those of traditional cell therapies. In a discussion with Phil Vanek of GE Healthcare, we outline several of the key challenges of processing these products and bringing them to market. Approaches for reducing development costs and lowering pricing are highlighted, and a separate analysis presents three pricing models specific for allogeneic “off the shelf” cell products.

Large-Scale Capacity Strategies: Single Use, Multiuse, or Both?

Early manufacturing facilities for large-scale production of biopharmaceuticals were, by necessity, very large. Low expression titers and blockbuster-market products such as monoclonal antibodies (MAbs) combined to require massive bioreactors — with capacities of 10,000– 20,000 L or more — and supporting infrastructure. In my early days covering the industry, I visited a few such facilities and was always awed by the huge tanks and what seemed like miles of piping. A 2010 Pharmaceutical Engineering article described a process modeling approach…

Continuous Biomanufacturing: A New Approach to Process Scale

The BioPhorum first-edition Technology Roadmap outlined a 10-year vision for therapeutic protein production in the biopharmaceutical industry (1). The roadmap describes multiple manufacturing scenarios ranging from large-scale (~20,000-L production) to small and agile, portable production facilities. It includes detailed analyses of the needs for the future in each of the following areas: Process technologies (2) Inline monitoring and real-time release (3) Automated facilities (4) Modular and mobile (5) Knowledge management (6) Supply partnership management (7). Since the 2017 publication of…