The United States Pharmacopeia (USP) is a not-for-profit nongovernmental organization founded in 1820 that develops public standards for drug substances and products; these standards are enforceable by FDA and have been adopted by many nations around the world. USP General Chapters provide industrial and academic researchers alike with crucial guidance, particularly in areas where there is a regulatory void. A good recent example is the proposed USP general information chapter…
BioProcessing Journal Posts
Poliovirus is a small (28-30 nm diameter) non-enveloped RNA virus belonging to the family Picornaviridae. The ability of poliovirus to cross the blood-brain barrier and its natural infectivity of central nervous system (CNS) tissue via the CD155 receptor, found exclusively in primates, has promoted the investigation of an attenuated poliovirus for the treatment of malignant gliomas. However, use of the virus in clinical testing is limited due to low yields obtained from conventional purification methodologies…
Today concentrated efforts are underway to improve the bioactivity of therapeutic proteins with the aim of reducing: (i) the number and concentration of the applied doses of the therapeutic protein, (ii) undesired side effects, and (iii) the cost of a therapy. A very promising strategy is to optimise the glycosylation of these biotherapeutics. A novel expression platform, GlycoExpress™, has been developed to produce proteins with fully human glycosylation, optimised sialylation, and improved bioactivity…
The Dale and Betty Bumpers Vaccine Research Center (VRC) at the National Institutes of Health (NIH) was established to facilitate research in vaccine development. The VRC is dedicated to improving global human health through the rigorous pursuit of effective vaccines for human diseases. It was established by former president Bill Clinton as part of an initiative to help develop an AIDS vaccine and is part of the NIAID organization. Since the inception of the VRC, its mission has expanded to include the development of vaccines against bioterrorism and emerging infectious diseases…
The approval of a new biological drug for therapeutic use requires supporting data from a variety of studies, including those that demonstrate the suitability of the manufacturing process. The regulatory guidance advocates that one of these studies address the issue of cell substrate stability by testing for consistent production of the product of interest by a characterised cell bank, generally the working cell bank (WCB). The study should evaluate stability during cultivation for production by examining a minimum of two time points — at a minimal number of population doublings and at or beyond the limit of in vitro cell age for production. The guidelines state that, “Evaluation of the cell substrate with respect to the consistent production of the intended product of interest should be the primary subject of concern”…
Total market share of biopharmaceuticals is estimated to increase from $33 billion now to more than $45 billion in 2007. These numbers are accounted for by the 64 products approved by European and US regulators and some of the 500 products currently under clinical evaluation. More than 2,000 products are in discovery and preclinical development. Monoclonal antibodies (MAbs) and recombinant glycoproteins constitute a major part of these new biotech leads. The estimated demands for MAbs alone are more than 6,000 kg per year in 2006. Currently, 16 MAbs are licensed by the U.S. Food and Drug Administration (FDA) for pharmaceutical use and more than 130 are in clinical trials. This fast-growing class of biotherapeutics is expected to reach worldwide sales of more than $15 billion per year in 2008. In the coming years, mammalian cell culture technology will remain the production system of choice for MAbs and other recombinant glycoproteins. Therefore, efficient, cost-effective production systems need to be in place to meet the demands…
Short Monolithic Columns — An Enabling Technology for the Purification of Proteins, DNA, and Viruses
The last 30 years have seen rapid and dramatic developments in recombinant DNA technology and the related biological sciences. In 1972, Paul Berg’s group used restriction enzymes to cut DNA in half and then used ligases to stick the pieces of the DNA back together. By doing this, they produced the first recombinant DNA. Within a year, the first genetically engineered bacterium existed. A little more than ten years later, recombinant human insulin was approved for diabetic patients and became the first recombinant healthcare product. Before the end of the 1980s, the first gene therapy trial had occurred. Today, a large number of recombinant proteins are used as marketed drugs and even more are in clinical trials targeting a wide range of diseases…
New regulatory initiatives often produce paranoid responses. These over-reactions are often a result of initial rumors fueled by less-than scrupulous consultants or by misinterpreted statements reported out of context from unscripted regulators. The “remote monitoring capability” incorporated into the emerging Process Analytical Technology (www.fda.gov/cder/OPS/PAT.htm) initiative is a prime example. Put the fear back in the closet: remote monitoring will not lead to unannounced or secret FDA electronic visits, unscheduled remote audits, or regulatory spying on industry processing activities…