2017

Platform Solutions for Cell Therapy Manufacturing

by , and

Advances in cell therapy have resulted in significant progress toward treating some widespread and difficult diseases, many of which represent unmet medical needs. For example, phase 3 clinical trials are already under way for therapies based on mesenchymal stem cells (MSCs), including therapies for graft-versus-host disease, acute myocardial ischemia, and chronic obstructive pulmonary disease (COPD) (1–3). Successful cell therapy treatments for such afflictions will be not only significant medical breakthroughs, but also in very high demand. However, their commercialization is…

February 13, 2017

Scalable Purification of Viral Vectors for Gene Therapy: An Appraisal of Downstream Processing Approaches

by , , , , and

Gene therapy is the transfer of genetic material to a patient’s cells to achieve a therapeutic effect. Therapeutic DNA is largely delivered using viral vector systems based on adenoviruses (Ad), adenoassociated viruses (AAV), and lentiviruses (LV). With the application of such viral vectors as clinical therapeutics growing, scalable commercial processes (particularly for purification) are being investigated and optimized to best ensure that critical quality attributes (CQAs) are retained. Herein we review viral vector purification techniques and the effect of different…

February 13, 2017

3D Bioprinting Possibilities and Challenges

by

Three-dimensional (3D) bioprinting is the newest addition to the regenerative medicine family. Now within the industry dedicated to providing more personalized drug products, this new additive-manufacturing technology has the potential to truly focus on individual tissue repair and replacement. In a short period of time, 3D bioprinting has been applied in studies using bones, blood vessels, composite tissues, vascular grafts, tracheal splints, cartilaginous structures, heart tissue (e.g., two-valve heart), and vaginal organs (1). View the full article below – Login…

February 13, 2017

February From the Editor

by

The real word twitterpated (meaning infatuated or obsessed, in a state of nervous excitement) apparently was coined in Disney’s Bambi movie. Use of the word has increased over the past five or six years, achieving a new relevance. Now it can mean Twitter-headed, and I am finally beginning to catch on to the role that tweeting plays, for good and ill. As expected from a Hollywood word, it focuses our attention on the ephemeral, the superficial glitz of a person…

February 13, 2017

Spotlight for February 2017

by

Introducing New Editorial Advisor Jason Condon is a senior CMC project manager at Vaccinex, Inc., in Rochester, NY as well as an assistant adjunct professor in biomedical engineering at the University of Rochester. He has held roles in biopharmaceutical manufacturing and process development at Bristol Myers Squibb and Janssen R&D. His expertise in cell culture and current good manufacturing practice (CGMP) manufacturing has contributed to developing manufacturing processes for monoclonal antibody (MAb), cell therapy, and vaccine production throughout his 13-year…

February 13, 2017

BioPhorum Operations Group Technology Roadmapping, Part 2: Efficiency, Modularity, and Flexibility As Hallmarks for Future Key Technologies

by

For a complex biopharmaceutical industry, setting out to forecast future technologies must involve considering how such technologies will be used. In the first article (1), I discussed why there was a need to develop a technology roadmap for the biopharmaceutical industry and the trends shaping its future: namely, the introduction of new product classes, the continued growth of the biopharmaceutical market, pressure to reduce costs, and uncertainty in approval and sales of new products. Herein I discuss the technology roadmap’s…

February 13, 2017

Buffers in Biologics Manufacturing

by , , and

Biotechnology has enabled commercialization of protein-based drugs including insulin, growth factors, blood factors, and antibodies. Production and purification of such biologic products require different buffers for pH control and stabilization of reactions in different steps during biomanufacture. These processes include cell culture production (the “upstream” phase), purification (the “downstream” phase), and a final phase in which excipients are introduced to the drug substance to create a drug product (“formulation and storage”). In upstream processes, buffers are primarily used for their…

February 13, 2017

Residual Host-Cell DNA in Biopharmaceutical Products: 96-Well Plate-Based Extraction and Real-Time PCR Assay for Quantitative Measurement

by , , , , and

Regulatory guidelines that cover the development of biopharmaceutical products require testing of host-cell deoxyribonucleic acid (DNA) impurities. Real-time polymerase chain reaction (PCR) has become a popular technology for DNA quantitation and monitoring of process impurities associated with biomanufacturing. One critical challenge associated with host-cell DNA impurity testing is that recombinant proteins (e.g., monoclonal antibodies, MAbs) and their corresponding buffer components often interfere with DNA quantitation in real-time PCR reactions (1, 2). Some sample types do not require a full extraction…

February 13, 2017

A Statistical Approach to Assess and Justify Potential Product Specifications

by and

As stated in ICH Q6B, specifications are critical quality standards that are both proposed and justified by drug product manufacturers. Xiaoyu et al. provide information on several statistically based strategies to establish specification acceptance criteria (SAC) (1). Here we address an alternative approach to relate proposed SAC for quantitative data to relevant lot history. In particular, proposed SAC can be derived in part by using calculated limits for which the lower bound of an approximate 95% confidence interval for the…

February 13, 2017

Examining Single-Use Harvest Clarification Options: A Case Study Comparing Depth-Filter Turbidities and Recoveries

by , , and

Steadily increasing demand for biopharmaceutical drugs has led the industry to examine its manufacturing scales while pressuring research and development groups to produce high-yielding clones and processes. Improved media, feed supplements, bioreactor designs, and control of process parameters have helped biomanufacturers achieve multifold increases in volumetric productivity from production bioreactors. However, cell culture processes are significantly affected by their bioreactor’s ability to support cells at higher densities and sustain cultures at lower viabilities. With the implementation of a number of…

February 13, 2017