Ramakrishnan M S

Worked with both established organisations and start ups. Provided advice on the pipeline programs for process & analytical development and for preparation of documentation for global regulatory submissions.

Lead a team of 160 employees focusing on the following key analytical functions that are used for characterising monoclonal antibodies (mAbs) and recombinant insulins. A. With our successful approvals of 3 biosimilars in both Europe and USA – Pegylated GCSF, Trastuzumab and Insulin Glargine, the company’s management infused additional funding of more than USD 5 Million to upgrade our analytical capabilities. My team focussed on the following functional modules- B. Physicochemical characterisation – Established a laboratory with high end Mass Spectrometers (Orbitrap XL and Elite, MALDI TOF, Triple Quad and HDX-MS – Orbitrap Lumos). Analytical tools for determination of Higher Order Structure (HOS). C. Mechanism of action studies for biosimilars and novel biologics D. Development and validation of in vitro functional assays. E. Characterisation of Host Cell Protein (HCP) and analytical method qualification for assessment of clearance of process specific impurities including HCP, host cell DNA (HCDNA) and Leached Protein A (LPA). F. Bio-analytical methods for pre-clinical and clinical studies Pharmacokinetic (PK) measurements of biologics. Immunogenicity assessment including assay validation for binding and neutralizing antibodies for both monoclonal antibodies (meso scale discovery platforms for binding ADA assays, cell based and competitive ligand binding assays for neutralizing antibodies) and recombinant insulins (radio immunoprecipitation assays).

Led a team of 65 scientists who have expertise in mechanism of action studies, in vivo pharmacology studies and process and analytical development of bi-specifics. Our first novel bispecific entered the Phase 1 clinical trials in USA under an FDA approved IND.

Led a team of 7 experienced technical leads involved in providing integrated product development expertise for maturing biosimilar programs for global regulatory approvals.

 Spearheaded the development and regulatory approval of Itolizumab, a humanized anti-CD6 monoclonal antibody. Focussed on key differentiators for global development of Itolizumab, after its 2013 approval in India a) Reducing Cost of Goods (COGS) Changing expression cell line from NS0 to CHO – the NS0 derived Itolizumab was approved in India. Changing cell culture process from Perfusion to Fed Batch. b) Developing a lyophilized formulation for s.c. route of administration (ROA) instead of I.V. Completed a comparability exercise and implemented recommendations from the pre-IND advice of FDA to support our assessment that the change in the cell line and culture process would not impact patient safety and efficacy. Oversaw a Phase 1 single ascending dose study in Normal subjects (NHVs) in Australia to evaluate the pharmacokinetics and immunogenicity through the s.c. ROA of the CHO derived itolizumab. Secured the FDA approval (out-licensed to a start up and we supported them with data submissions) for the IND package to initiate Phase 1 clinical trials in USA for itolizumab using the CHO cell line product.

 Spearheaded the development and regulatory approval of Itolizumab, a humanized anti-CD6 monoclonal antibody in India. A. Technical assessment to enable in-licensing of the asset. B. Technology transfer of the perfusion manufacturing process that used NS0 cell line for expression of the drug. C. Built a team of 20 employees to focus on development and optimization of mAbs downstream purification processes and in process analytics for manufacturing scale up to 650L & 2000L. D. Product development for Phase 2 and Phase 3 clinical trials in India. E. Successfully completed the Phase 3 clinical trials which demonstrated therapeutic efficacy in moderate to severe plaque psoriasis. F. Completed the process validation at manufacturing scale of 650L to enable product commercialisation. G. Secured the approval for Itolizumab in 2013 in India for treatment of moderate to severe plaque psoriasis.

Built the team that focusses on in vitro functional assays for bio-therapeutics. The team delivered on numerous cell based assays for different bio-therapeutics.

Development and scale up of multiple fermentation processes for a. anti-hypercholesteremic drugs (lovastatin, pravastatin), b. anti-obesity precursor drug (lipstatin), and c. immunosuppressant drugs (mycophenolate mofetil and rapamycin). Successfully scaled up a bio-transformation process at 30,000L for manufacture of pravastatin which involved control of an epimer impurity and 4x increase in productivity. Developed a lab process (fermentation and purification and crystallization of the active pharmaceutical ingredient) ready for scale up of rapamycin using Streptomyces hygroscopicus.

Understanding Structure Function Relationship of Hsp104 in Saccharomyces cerevisiae

Studies on Asparaginases produced by Rhodosporidium toruloides CBS14.