In conventional fed batch process development approaches, batch operating parameters (such as pH, temperature, seeding density, dissolved oxygen concentration) are kept constant and only feeding parameters such as feeding time, post-feed concentration are manipulated. The batch and fed batch operating parameters are assumed to be independent of each other. This approach to process development ignores any interactions that might exist between the batch and fed-batch operating parameters are therefore not evaluated. However in a complex bioprocess, none of the factors affecting the process can be assumed to be independent of each other and mutually exclusive. Therefore in this study an attempt was made to study the interaction between fed-batch operating parameter-post feed glucose concentration (A) and batch operating parameters-seeding density (B), temperature (C), and dissolved oxygen concentration (D) by their simultaneous manipulation, as well as the effect of these interactions on cell growth and monoclonal antibody (mAb) production. NS0 cell line producing the mAb's against carcino-embryogenic antigen (Anti-CEA) was used. The final mAb concentration, viable cell density and integral of viable cell concentration (IVCC) were the responses evaluated. Statistical analysis experimental data showed that parameter (A) and its interaction with parameter (B) were the main factors affecting both the response variables. In comparison to the batch run which yielded 5.21 mg/L mAb, the developed fed batch process increased the mAb titer by 10 fold (59.40 mg/mL), and the IVCC was increased by 7 fold. The maximum VCD value (3.46×10 6 cells/mL) of the developed fed batch process was 1.25 over fold the value for batch.

Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the Western world. The answers to such life threatening diseases and cancers are monoclonal antibodies (MAb's) which are widely used as therapeutic agents. World demand for currently approved MAb's is on the order of a few kilograms per year. However, new therapeutic MAb's are under development and require doses of several hundred milligrams to a gram over the course of therapy. Very often to cater for the special requirements for the growth of mammalian cells, serum is added to the cell culture medium. However, removal of serum from the cell culture medium is often carried out, especially if the end product is to be used for human consumption, in order to eliminate various disadvantages such as high physiological variability, high batch to batch variability, risk of contamination and high cost, and challenges posed in the downstream processing of the product. In this paper, the adaptation of cholesterol requiring NS0 cells to commercially available serum free media is presented. ABSTRAK: Kanser kolorektum merupakan kanser ketiga paling umum dan kini berada di tempat kedua penyebab kematian berkaitan kanser di negara Barat. Jawapan kepada penyakit yang mengancam nyawa dan penyakit kanser adalah antibodi monoklon (monoclonal antibodies ((MAb's)) yang digunakan sebagai agen terapeutik. Permintaan dunia terhadap MAb's yang diluluskan adalah dalam bilangan beberapa kilogram setahun. Namun, terapeutik MAb's yang baru adalah di bawah penyelidikan dan memerlukan beberapa ratus dos milligram hingga satu gram dalam satu peringkat terapi. Sering kali untuk memenuhi permintaan terhadap tumbesaran sel mamalia, serum dicampurkan dengan sel kultur perantara. Walaupun begitu, pemindahan serum dari sel kultur perantara sering dilakukan, terutamanya jika produk akhir digunakan untuk kegunaan manusia; untuk mengurangkan pelbagai kelemahan seperti kebolehubahan psikologi yang tinggi, kebolehubahan yang tinggi daripada satu kumpulan ke satu kumpulan lain, risiko pencemaran, kos yang tinggi, dan cabaran mendatang dalam pemprosesan produk. Dalam perbentangan ini, kolestrol yang diubah memerlukan sel NS0 yang dikomersilkan dengan serum bebas perantara.