The cell therapy industry continues to make progress, as measured by increasing numbers of clinical trials and patients treated (1). Although discussions of the differences between “off-the-shelf” (allogeneic) and “patient-specific” (autologous and matched allogeneic) therapies continue, we are confident that both will find success. The best way to approach development for a cell therapy product is to consider these three fundamental drivers that guide development: Speed to market (Which pathway will allow for fastest access to the commercial market?) Operational…

According to the late Norman Cousins, “Wisdom consists of the anticipation of consequences.” When it comes to regulatory inspections, those consequences can be severe. However, the consequences of a problem anticipated can be prevented — given effective action to remediate the issue. In two previous articles (1, 2), I discussed the whys and hows of using the US Food and Drug Administration's (FDA's) notices of deficiency, FDA warning letters, and other information about inspection results to create an effective system…

Calorimetry (from the Latin calor for heat and the Greek metry for measuring) measures thermodynamics in chemistry. If energy enters or leaves a system, its temperature changes, and most chemical reactions involve changes in energy. Exothermic processes generate heat; endothermic processes consume it. So calorimeters measure the heat of chemical reactions or physical changes to a system. Since calorimetry's advent in the late 18th century, a number of different techniques have been developed. Early techniques were based on simple measurement…

Antibody-purity analysis is critical to successful development of monoclonal antibody (MAb) biopharmaceuticals. Their manufacture involves processes of protein purification, formulation, and stability evaluation. All those processes need highly accurate and reproducible analytical results to support decisions made by product developers and manufacturers. A common technology for antibody-purity analysis is sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In this technique, a polypeptide chain binds SDS proportionally to its relative molecular mass. The detergent nature of SDS denatures proteins by disrupting their noncovalent…

Purification process development of monoclonal antibodies (MAbs) has traditionally relied on a strategic trial-and-error approach using small-scale preparative chromatography for determining the operational parameters that would be optimal for clinical manufacturing. Doing so is demanding of both time and resources, and it thus restricts the number of early phase therapeutic drug molecules that can be evaluated in a company's development pipeline toward clinical trials. With high-throughput (HT) technologies incorporated at key points in development and laboratory operations, an operating space…

The only method of stable and long-term — practically infinite — preservation and storage of perishable biological materials (biostabilization) is to keep them in a glassy (vitreous) state. This was understood by Father Luyet when he titled his pioneering works in the 1930s, “The Vitrification of Organic Colloids and of Protoplasm” and “Revival of Frog's Spermatozoa Vitrified in Liquid Air” (1,2). He and other pioneers of the cryobiological frontiers clearly understood that only a glassy state would ensure stable and…

At the core of every drug development program is the challenge to successfully express active and high-quality proteins. Drug developers often are faced with protein-expression issues, struggling to express a specific protein for months (and sometimes years) with varying degrees of success. Low or no expression, insoluble expression, and proteolytic clipping of an expressed protein or a combination thereof are examples of the hurdles encountered in product development efforts. With protein expression being vital to the success of every stage…