March 2011

Opportunities in Regenerative Medicine

Capitol Hill fly-in days (see the last page of this issue) … A focus of Google Ventures (www.google.com/ventures) … A favored new investment arena for GE’s CEO Jeffrey Immelt, the recently named head of President Obama’s economic recovery advisory panel, and Life Technologies’ Greg Lucier … Hardly a day skipped without a major news publication covering some exciting aspect of the science … The provocative cover of Wired magazine’s (www.wired.com/magazine) November 2010 issue … It all sounds like the stuff…

Distinctions Between Analytical and Bioanalytical Test Methods

Analytical methods used for characterization, release, and stability testing of biotechnological/biological products are often automatically referred to as “bioanalytical” methods by some in the field. Many times the term is used to distinguish between test methods applied to small-molecule chemical products and those for macromolecular, biologically based products. It seems sensible enough: We use analytical methods to test chemical pharmaceutical products, so aren’t test methods used for biopharmaceutical products therefore bioanalytical methods? Any way, who cares whether the term is…

Stem-Cell–Based Therapies

A recent review of therapeutics in clinical development revealed 68 stem cell-based approaches (1). The majority of those leverage a patient’s own hematopoietic stem cells; others are exploring use of mesenchymal, neural, or embryonic stem cells. Here I highlight new therapeutic applications of stem cells and explore advances in the areas of induced pluripotent stem cells (iPS cells) and process-scale production of stem cells. Both should create new opportunities for stem cell-based therapies. Types of Stem Cells Hematopoietic stem cell…

A 483 Primer

The words of George Santayana — “Those who do not remember the past are condemned to repeat it” — ring especially true for companies regulated under good manufacturing practices (GMPs). Learning from and reacting to lessons from past inspections (both your own and those of other companies) is one of the best ways to prepare for future inspections. Regular review and close study of 483 notices issued during inspections can be an efficient and accessible means of identifying and absorbing…

Technologies on the Cutting Edge

    On the brink of bringing exciting new therapies to commercialization, cell therapy developers are taking notice of how other companies are addressing processing and technical challenges. Here, leaders from Dendreon, Advanced BioHealing, and Pluristem describe their current cell therapy programs. And two organizations —the Alliance for Regenerative Medicine (ARM) and McLaughlin–Rotman Center for Global Health —provide details on the promises of regenerative medicine.   Cellular Immunotherapy   Dendreon’s Provenge (sipuleucel-T) cell therapy induces an immune response to aid…

Think Strategically for Design of Experiments Success

Global competition fueled by the power of information technology has forced the pharmaceutical and biotechnology industries to seek new ways to compete. The US Food and Drug Administration (FDA) has promoted quality by design (QbD) as an effective approach to speed up product and process development and create manufacturing processes that produce high-quality products that are safe and effective (1,2,3). Statistical design of experiments (DoE) is a tool that is central to QbD and the development of product and process…

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…