The global pharmaceutical industry is faced with increasing pressure to introduce innovative new treatments and remain profitable in an ever competitive environment. Companies invest in clinical trials to experiment with new and modified formulations hoping to produce the next blockbuster drug. At the same time, numerous products go off patent and are being replaced by generic drugs, requiring further clinical research. India’s contract research organizations (CROs) are rapidly becoming the suppliers of choice for huge cost-savings, world-class production skills and a highly skilled workforce. India’s CRO industry is currently one of the highest ranked in the world and is projected to grow by 20% compounded annual growth by 2012. Regulatory compliance, speed-to-market, cost-efficiency and return on investment (ROI) are key challenges for CROs operating in the highly competitive generic drugs market. State-of-the-art instrumentation and software infrastructure help CROs address these challenges, gain a competitive advantage, and secure more contracts from Western pharmaceutical and biotechnology sponsors.

CRO Challenges
Indian CROs must comply with strict US regulations. They must perform efficient bioequivalence studies to demonstrate pharmaceutical equivalence between a generic drug and the corresponding brand-named drug in order to meet the US Food and Drug Administration (FDA) Abbreviated New Drug Application (ANDA) guidelines. Bioequivalence studies must also be completed within short timeframes to take advantage of the US Hatch-Waxman Amendment, which stipulates the first generic manufacturer to submit an ANDA that successfully challenges the validity of the brand manufacturer’s patent is granted 180 days of marketing exclusivity.

It is also crucial for Indian CROs to maximize the return-on-investment for their sponsors by simplifying and speeding up sample preparation procedures that can otherwise be particularly time-consuming and costly. In addition, Indian CROs are responsible for producing data reports on the results of its clinical trials which are subsequently submitted by the sponsor company to the US FDA for approval of new drug entities. Reports must be produced in a format compatible to that implemented by the sponsor in-house and also in full compliance with the US FDA requirements.

To remain competitive, Indian CROs must meet the standards established by Western pharmaceutical and biotechnology sponsors. This can be achieved by adopting the same technology used by these companies.

Addressing the Challenges
In an attempt to accelerate the drug development process and push new products through regulatory review, Indian CROs have shifted from using liquid chromatographic ultraviolet (LC-UV) methodology to adopting electrospray-based liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS reduces chromatographic and sample preparation, and has proven to be 10 times faster and 100 times more sensitive, enabling researchers to easily limit the impact of chemical noise.

Triple stage quadrupole (TSQ) mass spectrometers offer a fast and sensitive solution, especially for pharmacokinetics studies for drug discovery and development. Contemporary TSQ instruments are equipped with intelligent ion optics systems and electrostatic field technology to capture virtually every ion and efficiently transfer them to mass analyzers. In addition, the inherent selective reaction monitoring technology eliminates chemical noise, lowers detection limits and reduces the likelihood of generating false positives while new collision cells accelerate selected reaction monitoring scans and minimize cross-talk. The Thermo Scientific TSQ Vantage mass spectrometer, for example, provides sensitive simultaneous analysis of up to 3,000 compounds at ultra-low quantitation levels.

Coupled with a TSQ instrument, the Thermo Scientific Transcend system with TurboFlow(TM) methods accelerates sample preparation, reduces matrix effects and requires minimal equipment, consumables and human resources. Overall, the configuration delivers fast and efficient quantitative results, minimizes analysis failures and considerably reduces cost-per-sample.