March 2011

Cell Therapy Bioprocessing

          The past 15 years have seen approval and commercialization of the first cell-based therapeutics, including cartilage repair products; tissue-engineered skin; and the first personalized, cellular immunotherapy for cancer. Those successes are outnumbered, however, by all too common product failures. Notable failures can be attributed to commercial concerns such as high cost of goods (CoGs) and technical hurdles such as inadequate characterization, high process variability, and loss of product efficacy when manufacturing is scaled up (1).…

Predicting Virus Filtration Performance with Virus Spike Characterization

Evaluating a virus filter should, in theory, be a straightforward exercise. Membrane-based filtration is a robust virus reduction technology that plays an important role in virus safety for most drug production processes. An appropriate virus filter for a given process is generally selected through preliminary testing with relevant drug feed material. Data acquired during such tests are used to determine hydraulic performance targets such as expected flow rates and total throughputs. A virus clearance evaluation study is then performed in…

Meeting the Challenges in Manufacturing Autologous Cellular Therapies

Personalized medicine is a promising new approach to disease treatment. The ultimate in personalized medicine is a cellular therapy manufactured specifically for an individual patient using his or her own cells. But this autologous approach to generating immunotherapies has unique manufacturing challenges. Each patient receives an individual product batch, which needs to be manufactured, tested, and released. So thousands to tens of thousands of batches could be made for each indication every year. Given the personalized nature of these therapies,…

Development of an In-House, Process-Specific ELISA for Detecting HCP in a Therapeutic Antibody, Part 1

    After production and purification of biopharmaceuticals generated by cell culture expression systems, endogenous cell line proteins — commonly referred to as host-cell proteins (HCPs) — sometimes contaminate finished products. HCPs can elicit an immune response following administration of those drugs to patients (1), and cause potentially deleterious side effects. It is therefore imperative to minimize HCP contamination in finished biologics. Regulatory health authorities require monitoring of HCP contamination. They expect validation of each purification process to demonstrate its…

Industry Roundtable

    With one eye on commercialization and the other on monitoring every-day challenges, cell therapy manufacturers are asking critical questions about process efficiency, ensuring quality, and satisfying regulatory demands. In this “virtual” roundtable discussion (participants were asked questions separately), cell therapy industry representatives answer key questions in hopes of broadening understanding about this new class of biopharmaceuticals. Participants in this roundtable are Timothy Fong, PhD (director cell therapy, Becton Dickinson Biosciences), Annemarie Moseley, PhD, MD (CEO, Repair Technologies), Firman…

Minimizing Variation of Volume Withdrawn from a Vial Drug Package

Concerns for safety in administration of injectable drug products have escalated in recent years. As a result, scrutiny of administration practices has increased. Pharmaceutical manufacturers are placing greater emphasis on providing the best patient and caregiver experience as well as improving the convenience of drug administration. In fact, many drugs that are regularly administered for chronic conditions are now being offered for at-home preparation and administration. These trends highlight the importance of providing therapies that are not only effective, but…

Addressing Business Models, Reimbursement, and Cost of Goods

The early ISCT organization provided a powerful forum for sharing solutions, developing standards, and moving the emerging concepts in cell therapy forward as the field grew up and out of academia. Currently, the ISCT organization is uniquely positioned to facilitate sharing of best practices, standards, and strategies across the for- profit cell therapy industry through its Commercialization committee. The Business Models, Reimbursement and CoGS (cost of goods sold) subcommittee of the ISCT Commercialization committee was formed to address several key…

From The Editor

          Early on in the life of BPI we offered a few “closer” pages that we called “Defining Moments.” It was to be a forum for distinguishing between terms that are misused and for proposing new definitions for new approaches. In fact, because one particular topic came up again in a conference I attended this past January regarding the terms analytical and bioanalytical, we decided to revisit one of these entries from 2005 (with a few…

Model-Assisted Process Development for Preparative Chromatography Applications

Process modeling is a core technology in biopharmaceutical production that ensures faster, safer processing and process development. Developing a model involves quite some work, so it is important to use the model efficiently. We describe an industry example of how a mechanistic model is best used under process development and how it increases process understanding and performance.   Present State of Process Development   Biopharmaceutical process development relies heavily on experimentation and previous experience expressed as “rules of thumb” and…

Building a Bridge to Commercial Success

The history of the biopharmaceutical industry is one of continual invention and reinvention, of business models that have adapted to weather uncertain product futures and shifting economic fortunes. Some of us followed the up-and-down (and often financially painful) progress of monoclonal antibodies toward their eventual commercial success — a wealth of experience to draw from as other classes of products make their way from laboratories and onto the market. The vast majority of regenerative medicines are still produced at laboratory…