Gazing through the Crystal Ball – The Future of Clinical Trials in India

Nidhi Saxena

Chairman & CEO

Karmic Lifesciences

The Looking Glass: Current Market Scenario for Clinical Trial Services from India

The Indian CRO industry can be currently compared to agiganticEAGLE that is born to FLY and indeed SOAR but ironically has its wings tied down.

Globally, Clinical Research is a sizeable industry pegged at approximately US $ 26.0 Bn (2011) and growing at a CAGR of 25%+. Global Clinical Research Revenues are expected to touch US $ 32.7 Bn in 2015 and to exceed US $ 65.0 Bn in 2021, with the Top 10 CROs accounting for roughly 50% of the market.

The Indian Clinical Research industry valued at roughly $ 1.4 Bn (2011) and growing at roughly 20% CAGR is however still to show its mettle and was barely 5.38% of the global CRO industry. Also recent data suggests that the number of trials taking place in India (2171 studies) hasnot grown correspondingly in the last few years and even countries like Korea which hitherto had less trials than India seem to have surpassed India (3826 studies). From a trial numbers perspective India conducts just 1.7% of the total global clinical trials (132,526 studies).[1]

There are no two ways about it – the Indian CRO industry is going through turbulent times and while clinical trials from India still remains a huge potential opportunity, the business closures and materialization of large scale deals have been slow and the overall sentiment has been negative. However, it remains open to question wether the industry will show its trademark resilience and spring back to health.

My personal view is that while we are going through the standard process of chaos before order and our current challenges with respect to establishing a progressive regulatory framework incorporating patient care, subject compensation and clinical trial norms and uniformity with globally established standards is not very unlike the pain other developed countries have gone through, the industry has a silver lining and the fundamentals to make it bounce back sharply. Being an entrepreneur and the eternal optimist that I am, I am waiting like many others, for that one Inflection Point that will see the industry suddenly transform and start scaling enormously.

The Promise: Why India holdsUnbelievable Potential?

Given a substantial global industry size and growth rate, the next obvious question is which geographies will account for bulk of the Clinical Research revenues in the coming years.Also, the very nature of innovation is taking a quantum leap and moving from Mono-Centric, Western Focussed Models to Poly-Centric Global Models where the Emerging Markets including the BRICK countries (Brazil, Russia, India, China & Korea) and Eastern Europe clearly seem to show a promising trend towards increased overall Pharmaceutical, Biotech and Medtech Industry Sizes and Growth rates to the correspondent jump in pre-clinical and clinical research services.

The momentum clearly is accelerating when it comes to conducting clinical trials outside the boundaries of the United States or Western EMEA. 59% of respondents to the UBM TechWeb/Wipro Clinical Trial Research indicated they already have begun conducting clinical trials in emerging markets, and the remaining 41 percent had plans to begin doing so in the next 12 to 24 months. Asia is a main target for 46 percent of the UBM TechWeb survey respondents. Further, 26 percent of the respondents said that they are either acquiring local infrastructure, building it up using their own resources, or using a third-party contract research organization (CRO) to deliver services for site monitoring, data management and other clinical activities.

Looking closely at the opportunity that India presents, we as a collective need to question if are really meantto be at the periphery of the global drug development game or instead have the potential to be active players and indeed game changers here.

I do believe that there are several fundamental factors favouring India to emerge as the top-notch pharmaceutical, biotech, medtech and clinical research location and it is only a matter of exploring creative, indigenous clinical development and commercialization models. ClinicalTrials.gov, a registry and results database of federally and privately supported clinical trials conducted in the United States and around the world, currently reports close to 2171 studies being listed in India in 2011 i.e. 2.5% of the world’s clinical trials. This number is dispropotional to the world’s diseased population that India houses and can be easily quadrupled with a little regulatory reform and thrust from industry. Further, apart from traditional benefits of lower cost and faster patient recruitment, I am of the firm view that India offers an opportunity for highly strategic and innovative development models that can create a paradigm shift in the way the world does drug development today.

Let us step back for a moment and analyze the traditional clinical research models wherein majority of the research has been taking place in developed ICH countries including US, Germany, UK, Switzerland, Japan, Australia etc. Here the Regulatory Bodies have a complex and elaborate drug approval process and the costs and timelines are stupendous. As an example, it costs between US $ 70-100 Mn at a minimum and upto a $ 1 Bn and between 8-10 years to take a molecule from concept to clinic using the standard US-FDA/EMA IND pathway. Many of these studies are multi-country and multi-centric in nature and are co-located in the emerging markets given the need for multiple ethnicities to participate as well as generating data from emerging markets that could have huge future revenue potential. Hence currently multinational big pharma companies, who conduct over 90 percent of the industry-sponsored studies, use Indian sites mostly as a part of their global studies which means that India is peripheral and not core to their development strategy. Further Indian pharma companies primarily conduct studies in India for local registration only and they too look out for and locate complex, early phase work in US or Europe

Indian CROs can leverage an alternate clinical development and regulatory pathway in terms of in-licensing global molecules post Phase I (and in some cases, right from the pre-clinical stage) and conducting the Phase II and Phase III programs in India, gaining local marketing approval and then going back to the IND pathway and exploring opportunities for a US FDA approval leveraging a single/smaller Phase IIIb study or try to get a waiver and approval based on data generated from India. This model can accomplish the same concept to clinic cycle albeit with US $ 10-15 Mn i.e. 1/10th of the standard IND investment and a 4-5 year timeline. These ideas can be further extended to development in specific areas such as Diabetes, Oncology, Bio-similars etc.

Not only that, India offers a huge opportunity for Chemistry, Biology and Pre-Clinical Services outsourcing as well as some excellent GMP certified manufacturing units and bio-Informatics companies.  Over the last 15 years, Indian pharma companies together with Indian CROs specializing in BA/BE studies have grown steadily to make India a dominant player in the generic business and India today accounts for the second largest number of ANDA filings in the world. In fact, CROs who conduct both healthy volunteer studies (for generic research) and clinical or patient studies (for ethical research) have a significantly larger portion of their business coming from offering services to the generic industry.

Primary opportunities for Indian CRO are:

a) Phase I Studies for NCEs/NBEs (this should be allowed in India)

b) Indian Arm of Global Phase II and Phase III pivotal programs

b) Large India / APAC specific Phase IV and PMS programs

c) Generic B2-505 and Bio-Similars programs

d) BA / BE Studies for Generics in regulated and un-regulated markets

e) Clinical Data Management, Bio-Statistics and Pharmacovigilance Services

f). In-Licensing, Out-Licensing and Co-Development programs with Indian CRO as a strategic stakeholder in the IP

Ten-Step Program: What needs to be done to revive the India CRO Shining Story

The real challenges impeding the Indian CRO industry are only a handful and easily resolvable. Main issues pertain to regulatory ambiguity, patient care and compensation guidelines and clinical practices / data integrity and these further create a big question mark on scaling.

Below is a Ten-Step suggested program to resolve the current issues and bolster the industry for scalability:

ü  Single Regulatory Body and Single Window Approvals for each and every type of pre-clinical and clinical trial, merge pre-clinical and clinical trial related functions of CDSCO, ICMR, Ayush, RCGM/DBT, CPSCEA etc. to form a single window clearance body for all research and development studies in the country.

ü  Complete Parity of Indian Regulatory Norms with the US-FDA, EMA and Global Guidelines with respect to Pre-Clinical and Clinical Submission requirements. Follow the IND and IMPD structure for dossiers with no additional India specific requirements.

ü  Allowing of Phase I and First-in-Man studies to provide equal contribution from India for Global Drug Development R&D.

ü  IND level approval as opposed to Protocol level approval for each new IND, the individual Protocols to be approved by IRBs/IECs.

ü  Time-bound approvals.rejection of application within a finite 60 day period including query resolutions.

ü  Finalize Bio-Similar and Medical Device guidelines which are still in draft stage and make them effective in line with global standards.

ü  Finalize Subject Care and Compensation guidelines for all clinical trials. Rather than have complex compensation formula with multiple variables, have a fixed compensation value for each specific SAE category and/or Death and push for mandatory locally admissible insurance.

ü  Registration and Inspection of IRBs/IECs on an annual/bi-annual basis firmly applied clearance criteria and parameters.

ü  Registration and Inspection of CROs on an annual/bi-annual basis with firmly applied clearance criteria and parameters.

ü  Training and ICH-GCP certification of all Medical Doctors and special licensing prior to them being allowed to conduct clinical trials in order to control trial and data integrity.

Gazing through the Crystal Ball: India CRO Industry 2020

ü  World’s Top 3 Clinical Research Outsourcing & Pharmaceutical Destinations

ü  A > 25% Market Share of Global Clinical Trials Market and ~ 10,000 clinical trials

ü  World’s Capital for Scientific Writing, Clinical Data Management and Pharmacovigliance Services with > 50% Market Share

ü  An aggressiveInnovation Climate with several NCE / NBE / New Medical Devices indigenous discovery and development programs to solve disease problems including Oncology, Cardio-Diabeto, Immunology and Infectious Diseases. 

ü  An emergence of novel clinical development and commercialization models including In-Licensing, Co-Development and Out-licensing

ü  50%+ Lifesciences and Healthcare Funding to IP, Innovation & Research based Business Models as opposed to generics and services based models.

Conclusion: The Karmic Cycle

They say in India, everything is governed by a Karmic Cycle – What goes down, comes back up and things always happen for the best in the end.

The Indian CRO Industry has every chance of getting right back to the top and actualizing the vision of being the Sunrise Industry that it always held the promise of being – we only need to turn the Karmic wheels a little faster to get to the destination!

Author Profile

 Nidhi is a first generation woman entrepreneur and Founder, Chairman& CEO of Karmic Lifesciences, one of India’s leading Contract Research Organization (CRO). Nidhi comes with over 15 years of industry experience and combines strong entrepreneurial flair and cross-functional skills with an in-depth understanding and passion for the lifesciences industry. Adept at envisioning and establishing new businesses from ground-up, Nidhi founded Karmic in 2005 and has built a robust customer base comprising of several global Pharmaceutical and Biotechnology companies as well as a scalable Clinical Operations and Data Management group in India within a very short time. She has further driven successful forays into key verticals including Oncology, Cardiovascular, Diabetes, Neurology & Medical Devices and is currently working on novel bio-markers for Oncology and other indications. Nidhi has further consulted several global pharmaceutical corporations on their product development and commercialization strategy.

Nidhi further brings robust IT and Clinical Data Management expertise and has conceived and developed kTrials^TM eClinical Suite, A 21 CFR Part 11 and CDASH/CDISC Compliant, Integrated Clinical Trial Management System (CTMS) with Operational Analytics, Electronic Data Capture (EDC), Electronic Trial Master File (eTMF), SDTM Mapping, and Unified Clinical Data Repository Platform, planned to make the clinical operations automated at Karmic. kTrials^TM eClinical Suite is currently under a provisional patent application.

Nidhi holds an MBA from SP Jain, Mumbai and is a certified Six Sigma Black Belt from KPMG. She has presented at several clinical/business conferences and forums, authored industry whitepapers and featured several times in leading pharma/business media including Pharma Bio, Express Pharma, ET Now Business TV Channel etc. Nidhi earlier held key positions with global service providers including GE, Wipro Technologies, WNS North America and Hexaware Technologies.

As President of an organization called Women In Bio – India chapter, which is the first chapter outside of the United States, Nidhi is excited about creating widespread awareness about WIB as well as promoting the vast scientific talent of women in biotechnology and other areas from India.