Early-Phase Drug Development in India: Regulatory and Quality

Hiren Mehta boasts over two decades of honed expertise in Clinical Pharmacology, Drug Development, and Regulatory Compliance. With a track record of orchestrating 16+ successful new drug submissions to FDA, EMEA, and CDSCO, he navigates the complete development spectrum. Proficiency in PK/PD, data analysis, and adherence to compliance standards underscores his capabilities. 

In an interaction with India pharma Outlook magazine, Hiren explores India's early-phase drug development, highlighting its regulation and stringent quality standards.

How do regulatory nuances in India influence the rigor of early-phase drug development, and what strategies ensure compliance without compromising quality? 

Over the years, India has established itself as one of the leading pharmaceutical hubs and a preferred destination for outsourcing research, leveraging our strong industry ecosystem that includes scientifically skilled human resources, global quality infrastructure and compliances, and cost competitiveness. 

Progressive regulatory changes streamlining the approval process and oversight for studies have benefitted the CRO market. The New Drugs and Clinical Trial Rules – NDCT-2019, provides clear guidelines for the application and approval for clinical trials besides strengthening the ethical oversight and the responsibilities and obligations of the sponsors thereby providing a predictable, transparent, and effective regulatory framework for clinical trials in India. These have supported the increase in clinical trials in India. The introduction of a three-tier review process is also expected to enhance regulatory standards while ensuring patient safety. 

There is further scope for developing the clinical research ecosystem, including regulatory pathways, to support more global clinical trials in India.

In the context of India, what regulatory hurdles stand out in early-phase drug development, and how does the industry navigate them effectively? 

In India, the regulatory environment significantly influences early-phase drug development.With the emergence of high-quality CROs that operate in compliance with global safety, ethical, and regulatory norms, stronger regulatory oversight of the industry and active industry forums bring together diverse stakeholders to enhance the operating ecosystem for the industry.

In India, the CRO industry has significantly matured and the perception has changed over the last several years, which is also reflected in the increasing volunteer participation in clinical research. We are seeing significantly more innovation development happening here in India both from large and emerging companies. The Indian government has placed a concerted effort on building capacity within the industry and supporting innovation. The government is also working on building industry capacity to support innovation, such as phase 1 clinical pharmacology, and analytical and bioanalytical facilities. There are discussions currently underway regarding how to build this infrastructure, in collaboration between the government, academia, and industry to create the right ecosystem.

The Council for International Organizations of Medical Sciences (CIOMS) has emphasized the need to create a research-friendly environment, infrastructure, and capacity. The establishment of product development centers under the National Virtual Centre for Clinical Pharmacology has increased the capacity to carry out phase I – IV studies, including studies on COVID-19 drugs. Additionally, a Technical Committee announced that companies would be required to include Indian patients in global clinical trials in order to market in India a new drug developed outside of the country, demonstrating the government’s focus on ensuring the safety and efficacy of drugs marketed in India.

What industry practices can be employed to ensure early-phase clinical trials in India mirror real-world conditions while maintaining high standards? 

In order to achieve desired results in real-world conditions, the contract research industry must emphasize three key management practices – implement robust Quality Systems, practice a culture of stringent compliance, and rigorous adherence to timelines. To support these practices, the industry has to play a proactive role in providing comprehensive training to investigators and site staff, ensuring protocol compliance along with a diverse participant pool, representing India's real-world patient population.

Clinical researchers can consider adaptive trial designs for flexibility based on accumulating data and encourage using more electronic health records along with implementing patient-centric approaches like remote monitoring can give an extra edge. The medical monitoring team can implement risk-based monitoring strategies for optimal data quality and operational efficiency. The clinical research investigators shall embrace transparency in reporting all the relevant data including patient-reported outcomes and consider sharing outcomes to contribute to the scientific community for external validity of the data.

Could you share key methods for upholding patient safety and ethical conduct during the early phase of drug development, particularly within the Indian context? 

To ensure ethical conduct and patient safety during the early phase of drug development in India, adherence to regulatory guidelines set by the Central Drugs Standard Control Organization (CDSCO) and the Drugs Controller General of India (DCGI) is crucial. Subject Expert Committees (SECs) and Ethics Review Committees (ERCs/ECs) play pivotal roles in reviewing clinical trial applications and ensuring adherence to ethical principles. Qualified investigators and staff, regular monitoring, independent audits, and a clear adverse event reporting mechanism are essential for maintaining compliance and data integrity. Data management systems must prioritize confidentiality, and community engagement is necessary to build awareness and address concerns. Transparency in reporting results, cultural sensitivity, and respect for traditional practices and beliefs are also important considerations. By incorporating these methods, researchers can enhance patient safety, uphold ethical standards, and contribute to the success of clinical trials in the Indian context, fostering trust within the community and ensuring the validity and integrity of the drug development process.

How does the pharmaceutical industry collaboratively engage with regulatory bodies to optimize and fortify early-phase drug development in India while addressing practical constraints? 

This can be achieved through a multifaceted approach that addresses practical constraints. The Indian regulator, DCGI has initiated discussions with the industry by recently started inviting representatives from associations of CROs, pharma companies, and researchers to understand the areas of improvement in global clinical trial approval and execution.

Additionally, open communication channels are established through regular meetings, workshops, and conferences, fostering a constructive and meaningful dialogue between the two. The proactive approach of Indian regulators is encouraging for drug developers, as early engagement allows companies to seek guidance on regulatory requirements, aligning trial designs and outcomes with regulatory expectations and minimizing delays.

Harmonization with global standards and best practices along with timely and constructive feedback mechanisms by the industry experts back to the regulators can foster continuous improvement, allowing the industry to learn from experiences, and adapt alternative strategies.

(Vote of thanks: For their deep insights into the topic, I would like to thank Mr. Ajay Tandon for his business perspective, Dr. Kiran Marthak for regulatory/medical perceptions, and Dr. Sailendra Goswami for scientific inputs while providing the responses.)