Pre-Clinical and Clinical Trials

T-Cell Suspension Culture in a 24-Well Microbioreactor

Cell therapy promises revolutionary new therapeutic treatments for cancer and other serious diseases and injuries. For example, T-cell therapy response rates of >50% and durable complete response rates of 20% have been reported in patients with metastatic melanoma who had failed other therapies (1). In another example, sustained remissions of up to a year were achieved among a small group of advanced chronic lymphocytic leukemia patients upon treatment with autologous T-cells expressing an anti-CD19 chimeric antigen receptor (2). Numerous other…

Preformulation Development of a Recombinant Targeted Secretion Inhibitor

Our company carried out a preformulation study on a recombinant targeted secretion inhibitor (TSI) with contract research organization (CRO) Avacta Analytical. In this protein, the binding domain of botulinum toxin is replaced to broaden the toxin’s therapeutic potential and allow drug development to be targeted towards a specific disease. In our study, we took advantage of the high-throughput, microvolume protein analysis of Avacta’s Optim 1000 fluorescence and light-scattering instrument (which is distributed in the United States by Pall Corporation). It…

Understanding the Patient Journey

    The biopharmaceutical industry is abuzz with talk regarding a 2011 US Food and Drug Administration (FDA) guidance on human factors and the mitigation of user-based risk in the development of medical devices (1). As expected, his talk is often accompanied by a sense of anxiety. Device developers and the growing number of biomanufacturers developing combination drug–device products now need answers to usability questions they are hardly familiar with. Wrong answers may have direct (and troubling) implications from a…

The Global Cold Chain

In biopharmaceutical development, ancillary business operations such as logistics and supply chain management are frequently perceived as secondary objectives to the ultimate goal of discovering treatments and cures for devastating diseases. However, in the hypercompetitive world of drug development, forward-thinking companies have found that optimizing their clinical-trial supply chain can provide a strategic advantage to accelerating drug development. The globalization of clinical research has made the safe, punctual, and compliant transport of study drugs and other temperature-sensitive materials increasingly complex.…

A New Path in the Fight Against Melanoma

    Increased activation of cell survival signaling cascades helps tumor cells grow and makes cancer cells difficult to kill. Inhibiting proteins involved in those survival pathways is a useful strategy for selectively destroying such cells. The mitogen-activated protein kinase (MAPK) pathway is one such signaling cascade. Preclinical research finds that it is activated in most melanomas. One key kinase involved has become the focus of some targeted melanoma therapies. MAPK/ERK kinase (MEK), also known as MAPKK, has several known…

Listening to Patients’ Voices

    The role of patients in changing the pharmaceutical industry’s research agenda is evolving. Patients are greatly affected by drug R&D, with its potential to provide cures or treatments for a wide range of different medical conditions. But new product development does not always meet all patients’ needs. For example, drugs for Parkinson’s disease most often aim to treat movement disorders, whereas patients are also concerned about pain, sleep problems, lack of bowel and bladder control, and sexual dysfunction…

Advancements in Processing That Optimize Samples for Future Research

    Many factors contribute to the quality of biospecimen collections, and most are not mutually exclusive. How we assess the value of a biosample at the time of collection may be very different from at the time of analysis, which can be (and often is) an event in the distant future. To help ensure quality and create a sample resource that is not easily depleted, both novice and experienced “biobankers” can follow some general sample life-cycle management principles to…

Addressing Image-Based Compliance and Validation Issues

    Review times for 510(k) submissions have increased by >55% since 2005 because of poor-quality submissions by medical device manufacturers, according to a US FDA July 2011 report (1). Such setbacks can debilitate research and development (R&D) budgets of medical device and pharmaceutical companies and significantly affect their return on investment. As the FDA increases scrutiny of submissions, organizations must ensure adequate controls in assessing drug and device efficacy for preclinical animal studies and clinical trials. Doing so lends…

Clinical Development of Biosimilars

    Biosimilars require comparative studies that are different from the typical placebo-control clinical trials for first-generation proteins. A typical clinical trial programs must show equivalence of a biosimilar to the originator protein. Hans-Peter Guler, senior vice president of clinical development at INC Research, recently discussed with me the primary objectives and approaches to conducting an equivalence design.   By contrast with trials for originator proteins, equivalence trials require a different statistical approach. The biosimilars company needs agreement from the…

Disposable Downstream Processing for Clinical Manufacturing

Although disposable parts and modules have been used in the biopharmaceutical industry since the 1970s, as detailed in the “History” box, total disposable manufacturing has become a viable option only very recently. Whereas liquid storage became disposable in the 1990s, processing operations such as depth filtration, tangential-flow filtration (TFF), and chromatography have still required skids with reusable flow paths that needed cleaning and sanitization. Important recent milestones in total disposable technology included introduction of stirred bioreactors by HyClone (Thermo Scientific)…