Manufacturing

Progress Toward Commercial Scale and Efficiency in Cell Therapy Bioprocessing

Regenerative medicine includes both cell and gene therapies. Currently 672 regenerative medicine companies operate around the world, and 20 products have been approved by the US Food and Drug Administration (FDA). Of 631 ongoing clinical trials by the end of 2015 (1), over 40% are in oncology, followed in prominence by cardiovascular and infectious diseases. Here I focus on gene and cell therapy bioprocessing in which the final products delivered to patients are cells. Cell therapies are either autologous (derived…

Manufacturing Plasmid DNA: Ensuring Adequate Supplies for Gene and Cell Therapies

The concept of gene therapy is far from new, with initial studies performed over 20 years ago (1). However, in the past few years an explosion of interest in this area has gone beyond initial regenerative approaches using viral vectors. Interest is now moving increasingly into potential use of T cells modified using recombinant viral vectors for immunotherapy applications. Such therapies are based on using either adenoassociated virus (AAV) or lentivirus (1), both vectors being frequently generated through transient expression…

Designing the Optimal Manufacturing Strategy for an Adherent Allogeneic Cell Therapy

Cell therapies (CTs) offer potential treatments for a wide range of medical conditions (1–6) by replacing cells, repairing tissues affected by either disease or damage (7), or delivering genetic or molecular agents that promote self-healing (8). CT research and development is continuously growing (9), with increasing numbers of CT candidates reaching phase 3 clinical trials (9–11). Developers aim to make products that can survive in a competitive landscape while complying with stringent regulatory requirements to control the quality and safety…

Biosimilar Therapeutic Monoclonal Antibodies: Gaps in Science Limit Development of an Industry Standard for Their Regulatory Approval, Part 1

Biosimilars are biologically derived pharmaceuticals intended to have clinical similarity to a legally marketed innovator product when that product’s patent or market exclusivity has expired. By contrast with generic small-molecule drugs, clinical performance of a biologic pharmaceutical is a function of its structural complexity and higher-order structure (HOS). Biomanufacturing controls of such complex products cannot fully ensure chemical similarity between an innovator product and putative biosimilar because minor differences in chemical modifications and HOS can significantly alter a product’s safety…

Emerging Technology Trends in Biologics Development: A Contract Development and Manufacturing Perspective

For a contract development and manufacturing organization (CDMO), process development and manufacturing of recombinant proteins must be linked because of tight timelines driven by client expectations. Those are in turn driven by a need for rapid progression to clinical testing. Early in process development, the choice of raw materials needs to reflect existing supply chain and manufacturing infrastructure, but remain suitable for scaling up to meet future needs. One approach is to establish platform processes for a class of molecules…

Validation of Controlled Freezing and Thawing: A 9-L Bottle Study

Freeze–thaw processes affect the quality of biopharmaceutical proteins (1–13) and human cells (14). It has been reported that no method consistently controls freezing and thawing rates for biological formulations (1). My recent study refutes that claim with validated rate-controlled freezing and thawing of such formulations in 16-L single-use bags (15). The study reported herein presents a consistent method for controlled-rate freezing and thawing of bottled formulations. It also highlights the effect of load and container position on freeze rates. The…

Biopharmaceutical Contract Manufacturing Technology and Capacity Investments

The market for biopharmaceutical contract manufacturing has shown robust growth over the past few years. The continuing growth of biopharmaceuticals and the increase in new and novel drug projects entering clinical pipelines are fueling the market’s double-digit growth rate. Responding to these new demands, contract manufacturing organizations (CMOs) are expanding both their capabilities and capacities. Background Information presented here draws from recent interviews with six executives at biopharmaceutical contract manufacturing organizations, and from HighTech Business Decisions’ latest report, Biopharmaceutical Contract…

The Virtual Pharmaceutical Company: A New Pathway to Market?

In our modern biopharmaceutical industry, the maxim “bigger is always better” no longer applies. The industry’s modest virtual model persists in its popularity, emerging as a contemporary method of workplace efficiency. With an absence of manufacturing, virtual biopharmaceutical companies have found themselves unburdened by the multiple layers of bureaucracy that often plague large companies. With such freedom, they have operated much more efficiently in terms of time, resources, product specialization, and finances. As a result, virtual biopharmaceutical companies are growing…

Outsourcing and Biomanufacturing Challenges for Emerging Therapies: A Roundtable Discussion at BIO 2016’s BPI Theater

The biopharmaceutical industry is increasingly interested in a range of emerging therapies. “We’re really starting to get beyond the monoclonal antibody,” said Patricia Seymour (senior consultant with BioProcess Technology Consultants) in her introduction to a lunchtime BPI Theater roundtable at the 2016 Biotechnology Industry Organization annual convention in San Francisco, CA, this past June. The discussion brought together three industry insiders for strategic outsourcing to talk about emerging biotherapies and their manufacturing challenges: Mark Angelino (senior vice president of pharmaceutical…

Managing Customer and Regulatory Expectations

Partnering with a contract development and manufacturing organization (CDMO) allows drug-product sponsors to turn fixed costs into variable costs. Market forecasting by pharmaceutical companies drives numerous decisions in development programs: sales-force resources, geographic resource distribution, and (of course) manufacturing planning. It is a widely accepted fact in the pharmaceutical industry that accurate forecasting is a challenge, especially for new drug launches. A number of models can be used to develop drug forecasts, but none of these models is perfect. No…