R&D Functional Areas

NPIL's R&D encompasses the entire gamut of drug discovery and development.

The different R&D Functions are:

The Natural Products group has collected microbes and plants from a wide variety of habitats and climatic zones in the far corners of India, ranging from tropical to alpine (Himalayas). These have been solvent- extracted and preserved to create a natural products library of over 32,000 microbial extracts including rare fungi, and 6,000 plant extracts. This is probably the only library of its kind in India in terms of size and diversity, and the secondary metabolites produced by these organisms will be a rich source of screening compounds.

The Herbal group focuses on obtaining potential leads from medicinal plants described in the ancient literature and texts of Ayurveda, Unani and Siddha. Medicinal extracts are standardized and the extraction procedures optimized to produce preparations that can be screened reproducibly for biological activity.

So far the Herbal group has developed Multi-ingredient formulations (Ploy-herbals) and Single-ingredient products (Mono-herbals) for treating lifestyle ailments.

Research activities, aimed at developing new herbal products, are in progress. The therapeutic areas are short listed for this purpose are:

• Oncology
• Arthritis
• Dermatology

The Medicinal and Synthetic Chemistry groups further supplement lead identification and lead optimization activities. The medicinal chemists build diverse collections of new molecules, based on understanding Structure-Activity-Relationships (SAR). The synthetic chemists devise methods to rapidly produce milligram- to gram-level quantities of these molecules with high purity for biological testing.

The Special Projects group is working on innovative ideas for creating novel molecular combinations called “pro-drugs,” which combine established drugs with other molecular entities that can significantly improve upon the pharmacological, efficacy and safety profiles of the original drug.

Cheminformatics is a relatively new field that utilizes advanced computational methods using the combined knowledge of mathematics, statistics, chemistry, biology and information technology. Its activities include developing compounds databases and software tools, modeling drug-receptor and drug-drug interactions in silico, optimizing drug structures and evaluating compounds.

The primary mission of the Process Development group is to develop cost-efficient methods of manufacturing drug compounds in kilogram- to ton-level scale under strict quality guidelines. Its activities include improvement of existing processes, analytical methods development and validation, impurity profiling, polymorph evaluation, and data generation and documentation for regulatory filings.

Pharmacology carries out in vitro and in vivo screening of compounds in the three therapeutic areas of Oncology, Inflammation and Diabetes. In vitro assays are set up using cell lines grown in tissue culture. Several animal models have been established for in vivo assays, including Severely Compromised Immuno-Deficient (SCID) mice for tumors, collagen-induced arthritic (CIA) rats, and genetically or chemically-induced diabetic mice and rats.

The Drug Metabolism & Pharmacokinetics (DMPK) group supports preclinical development by obtaining data on how lead molecules are absorbed, distributed, metabolized and excreted by animals, and the length of time spent by the molecules within the system.

Molecular Biology is engaged in gene cloning, expression and purification of therapeutic proteins, the development of cell-based assays to support discovery, and the development of gene expression profiling to study the mechanism of action of lead drug candidates. The group is also developing advanced screening techniques for protein-protein interactions using yeast models.

The Biomarker group is focusing on developing surrogate biological markers in patients that can be used in the design and monitoring of clinical trials. Biomarkers are physical signs (e.g., Blood Pressure) or laboratory measurements (e.g., blood glucose levels) that may be detected in association with a pathologic process and have putative diagnostic or prognostic utility.

The Clinical Research group has been recently established to take forward preclinical lead compounds into human clinical trials. The group is responsible for design of clinical trial protocols, monitoring of clinical trials, interaction with clinical investigators and regulatory authorities, and successful development and registration of a new drug.

The discovery R&D groups are further supported by five centralized departments:

• Analytical Sciences
• Pharmaceutical R&D
• Corporate Regulatory Affairs
• Patents
• Animal House

The Analytical Sciences department is well equiped with state-of-the-art, advanced instruments such as a MALDI TOF/TOF, 500 and 300 MHz NMR System, VG Quattro II Mass Spec, hyphenated systems such as LC-MS-MS and LC-MS-NMR. Using these advanced instruments our scientists have elucidated complex structures in relatively short spans. 

The MALDI TOF/TOF instrument has many advanced features and is being used to study protein-drug, protein-protein interactions and biomarker applications, viz. “biomarker-pattern” determination to distinguish normal and diseased serums. In addition to these, it is possible to carry out 2D MS/MS analysis and “MS imaging” to visualize the distribution of “actives” on the tissue surface.

The Pharmaceutical R&D group serves as the link between basic research and commercial operations. The primary goal of Pharma R&D is to take a safe and efficacious “lead” drug substance and formulate it into a safe and efficacious marketable “drug product.” In addition to NCE’s, this department is responsible for the development of all domestic and internationally marketed NPIL formulations and their manufacturing processes, and is currently working on over 60 projects encompassing conventional and novel drug delivery systems (e.g., oral disintegrating systems, controlled release, etc.).

The HTS

The Biomarker

The Regulatory Affairs group works pro-actively with all the groups at every stage of the drug discovery and development process to enable development for global markets. They ensure compliance, documentation and timely filings to deal with the most stringent global regulatory expectations. They provide training, interpret guidelines and support early intervention for GO/NO GO decisions. 

The Patents Department supports the drug discovery and development group for the identification and protection of inventions related to new molecules, processes, herbal compositions and drug delivery systems. The main functions carried out are novelty searches, patent searches, patentability and infringement analysis, drafting and filing of patent applications, and liaise with patent attorneys and patent offices during patent prosecution. Support is also provided to business development initiatives and export and regulatory clearance.

The Animal House at NPRC maintains and breeds laboratory animals to support drug discovery projects. It is one of the most modern facilities in the world, with stringent environmental and access controls. The animals are kept in individual cages under specifically controllable conditions. The facility has provisions for housing special animals such as SCID mice, which have no immunity and are used in cancer research.