Formulation

High-Yield Production of PASylated Human Growth Hormone Using Secretory E. coli Technology

Since the 1985 approval of the first recombinant human growth hormone (hGH, such as Protropin/somatrem human growth hormone from Genentech, now Roche), the number of clinical indications for therapy with hGH has steadily increased (1). That led to a highly successful drug with more than US$3 billion sales in 2011 (2). Even so, hGH shares a common problem with most other first-generation protein therapeutics: a very short plasma half-life of just about two hours in humans. Because such biologics are…

Drug Products for Biological Medicines

Traditionally, the CaSSS CMC Strategy Forum meetings have provided a scientific focus on the development of biotech drug substances and their manufacture and characterization, leaving the development of drug product formulation and filling, understanding primary containers, and considering novel delivery systems somewhat out of scope. Over recent years, however, the importance of investing more science and technology into drug product development has become evident as different product types, higher protein concentrations, and doses and requirements for improved delivery of biological…

The Influence of Polymer Processing on Extractables and Leachables

Polymers provide a unique set of material properties, including toughness, chemical resistance, versatility, and low cost for both multiple-use and single-use bioprocessing systems. Polymer materials are manufactured as fittings and tubing for research and development (R&D) laboratories, as containers for bulk chemical and biological storage, as filters and separation technologies for downstream processing, and as containers and bottles for drug substance storage. These components and systems are helping drug companies improve their manufacturing flexibility, reduce their operating costs and capital…

PEGylation of Biologics

In the 1970s, life-science researchers envisioned protein therapeutics as the ultimate targeted therapy. Companies could use them to address genetic deficiencies and cancer, among other disease classes, as well as to nudge the immune system for treating autoimmune disorders. The first therapeutic proteins were derived from animal or microbial cells, so patients launched immune responses to them that could curtail their activity and produce dangerous side effects. PEGylation was initially used to prevent immune responses with such drugs. PEG is…

Tunable Half-Life Technology

While a constantly developing market puts increasing pressure on pharmaceutical companies to provide advanced and personalized therapies, the industry is investing heavily in the development of targeted biologics. The aim is often to take new therapeutics through clinical trials and to market as quickly as possible and to develop more novel, tailored drugs. One common challenge for many biologics is their short plasma half-life. That often leads to reduced bioavailability, meaning that an administered drug will clear from a patient’s…

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…

Polysorbates, Immunogenicity, and the Totality of the Evidence

    Protein aggregation underlies many deleterious effects for biotherapeutics. Principal among those are loss of efficacy, induction of unwanted immunogenicity, altered pharmacokinetics, and reduced shelf life. Consequently, aggregation-preventing surfactants are essential components of many protein formulations. They facilitate the development, manufacture, and stability of dosage forms by helping formulators manage protein aggregation and reduce interactions with container and delivery device surfaces. Monoclonal antibodies (MAbs) present difficulties with respect to aggregation because they usually require relatively high doses for therapeutic…

A Decade of Formulation

    Although no biopharmaceutical pills are yet on the horizon, formulation and delivery have advanced over the past 10 years. Formulators have new biophysical technologies and new product types (such as protein–drug conjugates) to work with. The most important issues haven’t changed much, though — from aggregation to stability, freezing to freeze-drying — although the FDA’s quality by design (QbD) initiative changes the strategies used to address them. Fragile proteins and other biologically sourced macromolecules need protection to achieve…

Fight Cancer with Nanotechnology

    Imagine a diagnostic test that sifts through millions of molecules in one drop of a patient’s blood to detect the tell-tale protein signature of a cancer subtype. Envision a drug “ferry” that doesn’t release its cytotoxic contents until it slips inside cancer cells — or a molecule or small panel of proteins that can reveal within days whether a cancer treatment is working. Bioprocess Applications of Nanoparticles ()   Researchers have created nanosized particles and devices that are…