Thursday, December 1, 2011 Daily Archives

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…

Differential Cell Culture Media for Single-Cell Cloning

    Recombinant therapeutic protein production using cell culture systems is a US$70 billion market. Most biotherapeutic proteins, including monoclonal antibodies (MAbs), are produced in Chinese hamster ovary (CHO) cells, which can generate the posttranslational modifications required for full biological function. Single-cell cloning is an important step in generating homogenous recombinant protein-producing mammalian cell lines. Recent advances in media development technologies have enabled limiting dilution cloning (LDC) and protein production in a serum-free environment to meet regulatory requirements.   LDC…

Analysis and Immunogenic Potential of Aggregates and Particles

    The conclusion of this CMC Forum continued to focus on the latest developments in detection and characterization of protein aggregates (1). Afternoon sessions detailed the most recent experiments probing the role of protein aggregates in immunogenicity, with discussions on the best models to use and initial results. Topics included potential thresholds for immunogenicity, linking laboratory and clinical data, and predicting and testing potential immunogenicity of products throughout a development lifecycle.     Afternoon Sessions   Amy Rosenberg (Division…

Production and Purification of a PER.C6-Expressed IgM Antibody Therapeutic

    Immunoglobulin G (IgG) antibodies have been used to treat cancer for many years (1). Another class of antibodies—immunoglobulin M (IgM)—has been overlooked in spite of offering unique advantages that make them highly desirable as cancer therapeutics. Serving a valuable function in our innate immune system, IgM antibodies are the first to be secreted when an abnormal cell is present (2). These antibodies play a critical role in recognition and elimination of infectious particles (3,4), in removal of intracellular…

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…

How QbD and the FDA Process Validation Guidance Affect Product Development and Operations, Part 2

    Earlier this year, the FDA issued its long-awaited process validation guidance document, which had been several years in development. It is well written and effectively articulates what many progressive companies have been thinking and doing for years. But many people in the industry are asking questions.   Part 1 of this article described the history of process validation before the FDA’s quality by design (QbD) initiative and discussed QbD in general. It also described the new process validation…

Shifting the Bioprocess Paradigm

    The need for transformation is a powerful driving force in the biopharmaceutical industry. Opinions and predictions about the best way forward are plentiful. As drug developers seek to enhance productivity, reduce costs, and improve their return on investment in research and development, new ways of doing business are explored, evaluated, and acted upon — with varying degrees of success. Faced with intense pressure to evolve, the biopharmaceutical industry is smart to leverage approaches that have driven success in…

Americans Say Yes to Stem Cell Research

    University of Nevada, Reno, researchers reported in Nature Biotechnology this past summer on their survey of >2,000 Americans about stem cells and other controversial research topics. Supporters of using embryonic stem cells in disease research outnumbered opponents five to one. Most respondents (>66%) also approved of induced pluripotent stem cell treatments. But opponents of stem-cell–based cosmetic treatments outnumbered supporters by almost two to one.

Innovation Is One Key to Economic Future Success

    Following up on its 28 June 2011 innovation forum, the Hamilton Project (an economic policy initiative of the Brookings Institution, www.hamiltonproject.org) created a new document detailing A Dozen Economic Facts About Innovation for the United States. Drawing from insightful comments by panelists during the event, authors Michael Greenstone and Adam Looney focused on three specific points: Innovation has historically improved the US standard of living through higher wages, lower prices, and health advancements. The pace of innovation has…

From the Editor

      Kudos once again to our IBC colleagues for another excellent BioProcess International Conference and Exposition. Throughout the week of 31 October– 4 November more than 1,400 attendees and 125 exhibitors engaged in lively discussions on critical issues affecting our industry. The Long Beach, CA, convention center proved to be a comfortable and accessible venue for multiple session tracks, technical workshops, and seminars. Among the trends and topics that made frequent appearances in presentations were the ongoing challenges…