I recently returned from the Fifth China Medicinal Biotech Forum held in Beijing, China from 07-09 November 2011. The purpose of this conference was to update graduate students in China on the latest trends in biotechnology. This forum also allowed scientists from Europe, Australia, Japan, US, and South America to collaborate with Chinese colleagues at the Chinese CDC and at universities and research institutions in Beijing, Shanghai and other areas in China. Some of the visiting scientists were also looking for funding for their research programs and some Chinese universities were looking to fill research professorships. Over lunches and dinners, scientific collaborations were being discussed and many scientists were staying after the conference to tour the laboratories of the universities, companies, and research institutes in Beijing.
At the Key Note event of this conference, senior Chinese government officials declared that China was focusing on biologics in a big way. The Chinese government has noted that half of the top 10 blockbuster drugs sold in the US last year were biologics – either recombinant proteins or monoclonal antibodies. For the next few years, these government officials declared that there will be a big push from the government in funding Chinese companies to bring biosimilars to market. Whether it is to market these biosimilars in China or around thew world is unclear.
I gave a talk on the topic of “Initiating a Gene Therapy Clinical Trial in the US.” This talk outlined the recent history of gene therapy and the extra regulatory requirements for gene therapy clinical trials as compared to small molecule or monoclonal antibody investigational drugs. These extra requirements are the submissions to the Recombinant DNA Advisory Committee of the NIH and the Institutional Biosafety Committee at the clinical site.
In addition to this talk, there were other gene therapy talks. In particular, there was one talk about a Phase IA clinical trial in the US sponsored by Marina Biotech for the treatment for Familial Adenomatous Polyposis (FAP). This gene therapy is first-in-class; it is the bacterial delivery of shRNA that is intended to reduce the amount of intracellular Beta-catenin; the Beta-catenin gene is known to be dysregulated in classical FAP. The bacteria in this gene therapy is live E. Coli and will be orally administered for 28 days. The primary objective of this study is to establish general safety and to determine the Maximum Tolerated Dose.
Of note in this conference, Dr. Fernandes of Ludger Ltd in the UK described how Genzyme ran into manufacturing problems when scaling up its Pompe Disease drug, alglucosidase alfa (Lumizyme) . FDA requested more information after its first review of the marketing application for Lumizyme because during the scale-up, the glycosylation pattern of the recombinant protein had changed. This change was the alteration of a key sugar residue. Therefore it pays to look closely at the glycosylation patterns of the recombinant protein or monoclonal antibody early in development and find the critical sugar residues and make sure it is maintained during scale-up. Putting careful thought up front before generating the Master Cell Bank for the cell line producing the recombinant protein will eventually increase both safety and efficacy – safety in terms of reduced immunogenicity and efficacy by generating the required pharmacological effect at a lower dose.
This is a post by Will Lee, Ph.D. Will is the Director, Regulatory Affairs at Cato Research.
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In the chaos of the holidays, you might have missed the release of an important new guidance from FDA. On 20 December 2011, FDA issued version 3 of “FDA Portable Document Format (PDF) Specifications,” fulfilling a promise made at the recent DIA Electronic Submission conference to release the document by year’s end. This new version is a welcome update to a guidance that was last revised in June 2008.
