Rajgopal Srinivasan, Ph.D.
Principal Scientist & Head Bio IT R&D, TCS Innovation Labs, India
Interpretation of Genomic Variation – Identifying Rare Variations Leading to Disease
Genome sequencing technologies are generating an abundance of data on human genetic variations. A big challenge lies in interpreting the functional relevance of such variations, especially in clinical settings. A first step in understanding the clinical relevance of genetic variations is to annotate the variants for region of occurrence, degree of conservation both within and across species, pattern of variation across related individuals, novelty of the variation and know effects of related variations. Several tools already exist for this purpose. However, these tools have their strengths and weaknesses. A second issue is the development of algorithms, which, given a rich annotation of variants are able to prioritize the variants as being relevant to the phenotype under investigation.
In my talk I will detail work that has been done in our labs to address both of the above problems. I will also illustrate the application of these tools that helped identify a rare mutation in the ATM gene leading to a diagnosis of AT in two infants.
Lalitha Subramanian, Ph.D.
Chief Scientific Officer & VP, Services at Scienomics, USA
Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery
Lalitha Subramanian, Dora Spyriouni, Andreas Bick, Sabine Schweizer, and Xenophon Krokidis Scienomics
The discovery of a compound which is potent in activity against a target is a major milestone in Pharmaceutical and Biotech industry. However, a potent compound is only effective as a therapeutic agent when it can be administered such that the optimal quantity is transported to the site of action at an optimal rate. The active pharmaceutical ingredient (API) has to be tested for its physicochemical properties before the appropriate dosage form and formulation can be designed. Some of the commonly evaluated parameters are crystal forms and polymorphs, solubility, dissolution behavior, stability, partition coefficient, water sorption behavior, surface properties, particle size and shape, etc. Pharmaceutical development teams face the challenge of quickly and efficiently determining a number of properties with small quantities of the expensive candidate compounds. Recently the trend has been to screen these properties as early as possible and often the candidate compounds are not available in sufficient quantities. Increasingly, these teams are leveraging nanoscale simulations similar to those employed by drug discovery teams for several decades. Nanoscale simulations are used to predict the behavior using very little experimental data and only if this is promising further experiments are done. Another aspect where nanoscale simulations are being used in drug development and drug delivery is to get insights into the behavior of the system so that process failures can be remediated and formulation performance can be improved. Thus, the predictive screening and the in-depth understanding leads to experimental efficiency resulting in far-reaching business impacts.
With specific examples, this talk will focus on the different types of nanoscale simulations used to predict properties of the API in excipients and also provide insight into system behavior as a function of shelf life, temperature, mechanical stress, etc.
Syed Salman Lateef and Vinayak A K
Development of Supercritical Fluid Chromatography methods for the replacement of existing USP Normal phase liquid chromatography methods
Normal phase liquid chromatography methods often have long run times and involve environmentally toxic/costly solvents. Supercritical chromatography methods on the other hand are faster, inexpensive, and eco-friendly. The low viscous supercritical carbon dioxide operates at high flow rates compared to LC without losing separation efficiency. In this work, SFC methods are developed to replace three United States Pharmacopeial (USP) normal phase achiral methods – prednisolone, tolazamide and cholecalciferol. System suitability parameters of the normal phase method are compared against the SFC method. Precision, linearity and robustness of the new SFC methods are demonstrated. SFC methods were found to be cost effective in terms of analysis time and solvent savings. The SFC method does not require purchase and disposal of expensive environmentally hazardous chemicals. Hence, the newly developed SFC method provides a faster and safer solution.