Challenges for biosimilar drug development, scale up & higher scale manufacturing: Developed and developing country landscape

<p>Sumant Chaubey</p>

Challenges for biosimilar drug development, scale up & higher scale manufacturing: Developed and developing country landscape

Sumant Chaubey

3B Biotech, India

: J Nephrol Ren Dis

Abstract

The global biosimilars market estimated worth of $2.3 billion in 2015, and is expected to grow at a CAGR of 22.1% by 2020. Various factors contributed for the rise in demand for biopharmaceutical products e.g. drop in healthcare expenditure, growing demand for cost-effective generics, growing occurrence of chronic diseases, and growing aging population. Biosimilars industry is divided into recombinant nonglycosylated proteins, recombinant glycosylated proteins, and recombinant peptides. The recombinant nonglycosylated proteins includes insulin, granulocyte colony-stimulating factor (G-CSF), interferons, and human growth hormones and the recombinant glycosylated proteins includes erythropoietin and monoclonal antibodies. Biologics and biosimilar market is dominated by products from mammalian cell cultures (>75%).There is great opportunities in biopharmaceuticals, novel biologics & biosimilar r-proteins, Vaccines development and process parameter set up. Different scale-up criteria have been practiced depending on the type of fermentation and bioreactors. Growing mammalian cells in fermenters/bioreactors and to produce the protein of interest is a very cautious and tricky process. Process parameters e.g. pH or dissolved oxygen concentration, toxic byproduct concentration need to be controlled very strictly to corroborate the consistency of a product. Minor deviations of the predefined process parameters causes abrupt changes of product critical quality attributes(CQA) like glycosylation, aggregation, c-terminal clipping or acidic variation, which can affect the pharmacokinetics of the protein e.g. case study for eryhtropoetin,Darbepoetin,Mabs etc. Concept of QbD and PAT was introduced as per international guidelines(ICH,USFDA,Global Guidelines) to control the quality of biologics / biosimilars by strict IPQC methods.In reality scale-up of laboratory and pilotplant data to commercial size industrial bioreactors is complicated. Problem of dead zone, improper distribution of air/oxygen, uneven distribution of media,growth pattern causes the great impact on product formation and quality at higher scale o operation. No actual data or correlation or existing formula is fixed for scale-up. Different Biopharma giants e.g. Amgen, Dr Reddy Lab, Biocon, Biogen, Merck Sereno, uses different scale-up criteria to design commercial size bioreactor systems. In fermentation or cell culture based biopharma industry there are a lot of trade secrets on scale-up of bioreactors and fermenters and very few published results.