Quality considerations for the production of biopharmaceuticals

Seminar

Title: Quality considerations for the production of biopharmaceuticals

Speaker: Nigel Jenkins Ph.D.

Affiliation: National Institute for Cellular Biotechnology, Ireland

Host: Paula Alves, Animal Cell Technology Unit

Abstract
The production of therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry. However, most proteins used in drug therapy require complex post-translational modifications for efficient secretion, drug efficacy and stability. Common protein modifications include variable glycosylation, misfolding and aggregation, oxidation of methionine, deamidation of asparagine and glutamine, and proteolysis. These modifications not only pose challenges for accurate and consistent bioprocessing, but also may have consequences for the patient in that incorrect modifications or aggregation may lead to an immune response to the protein therapeutic.
Consequently, the two main drivers for innovation in upstream bioprocessing are the need to enhance product titer and quality. Media design can play and important part in bringing about improvements in both. Commercially available cell culture media can produce marked differences in terms of cell density, viability and protein yield. Therefore, there are material benefits to be gained for each biopharmaceutical manufacturer in optimizing media conditions for the product and cell line.
Quality considerations should not be considered secondary to obtaining high product titers. Many high-producing cell lines produce a large proportion of aggregated or misfolded protein. It is advantageous to select for cell lines that best marry high production with consistent product quality. Many established product quality assays are low-throughput and time-consuming, so there is a need establish assays to overcome these bottle-necks. Problems with product quality such as aggregation can occur at all stages of biopharmaceutical production, due to some of the stringent processed involved such as acidification and viral inactivation. This seminar will investigate the tools for monitoring protein modifications and the strategies (current and future) that can be used to minimize harmful modifications.

CV
Positions
Principal Investigator, National Institute for Bioprocessing Research & Teaching (NIBRT).
Adjunct Professor of Biotechnology, Dublin City University, Ireland.
Associate Research Scientist, National Institute for Cellular Biotechnology (NICB), Ireland.

Contact Details
NICB Office, Dublin City University, Glasnevin, Dublin 9, Ireland. Mobile: ++353 (0)87 266 8984. Assistant: Mags Beggan Tel: ++353 (0)1700 6262. Fax: 1700 5484. Email: Nigel.Jenkins@NIBRT.ie Website: www.nibrt.ie

Areas of Expertise
Recombinant protein expression and post-translational modifications (e.g. glycosylation, folding & aggregation); industrial bioprocesses; mammalian cell culture & media design; high-throughput cell & protein screening; therapeutic proteins & the biopharmaceutical business.
Prof. Jenkins has 9 years of industrial experience in biopharma PD & manufacturing at Lonza, Lilly & Serono and has been involved in the production of Xygris, Gonal-f, Ovidrel, Luveris, Saizen, Rebif and numerous cell lines and bioprocesses in clinical development. He is also trained in DOE, Lean Sigma & Six Sigma process improvement methodologies. NJ consults regularly for Glaxo-Smith Kline (GSK), Pfizer, Sigma Life Sciences (SAFC), Wyeth, Beckton Dickenson (BD), & the BBSRC.

Professional Affiliations
European Society for Animal Cell Technology (ESACT), and International Society for Protein Expression, American Chemical Society (ACS), & European Federation of Biotechnology (EFB), International Society for Pharmaceutical Engineering (ISPE), & Parenteral Drug Association (PDA).
Editor on the Journals “Current Pharmaceutical Biotechnology” and “Cell Engineering”.
Chairman of the Scientific Committee for the ESACT 2009 Conference in Dublin, Ireland.
Past Positions: Member of the UK Biotechnology & Bioengineering Research Council (BBSRC) Grants Committee (1994-1997). Member or EU Grants Committee for Biotechnology, Framework V, 1996. Session Chair, Cell Culture Engineering V (1996), VIII (2002) & X (2006).

Publications: 83 refereed scientific journal papers and book chapters & 2 worldwide patents, Also the textbook Jenkins, N. ed. (1999) “Animal Cell Biotechnology, Methods & Protocols”. Humana Press pp. 1-302.
1. Jenkins N, Murphy L & Tyther R (2008) Post-translational modifications of recombinant proteins: significance for biopharmaceuticals. Molecular Biotechnology 39, 113-118.
2. Patent Application: Jenkins et. al. of Merck-Serono (2007) Single IFN-beta fused to a mutated IgG Fc fragment. Filed in US Patent Office (61.007,142) and European Patent Office (07118980.7).
3. Jenkins, N. (2007) Modifications of Therapeutic Proteins: Challenges & Prospects. Cytotechnology 53, 121-125.
4. Patent Application: Jenkins et al of Eli Lilly & Co. (2004) Controlling glycoforms of the FLINT molecule. US Patent Application 20040176279.