Local clinical trial waiver for selected drugs is a double-edged sword says experts

India's new drug approval process waiver raises concerns about patient safety, research, and healthcare implications, experts warn.

A move to give patients in India faster access to medicines is a double-edged sword, experts have warned. This follows the Central Licensing Authority (CLA) recently allowing a local clinical trial waiver during the approval process for five categories of new drugs, sourced from six countries. This was notified under Rule 101 of the New Drugs and Clinical Trials Rules (NDCTR), 2019. A senior Health Ministry official said that the notification “will help faster decisions on waivers of requirements for local clinical trials, with consistency and predictability.’’ The countries and regions specified through the order include the US, United Kingdom, Japan, Australia, Canada, and the European Union. New drugs from these countries, including orphan drugs for rare diseases, gene and cellular therapy products, those used in pandemics, those used for special defence, and drugs that offer significant therapeutic advantages over current standard care, will be considered for clinical trial waivers, according to the Drugs Controller General (India) (DCGI). “India’s decision to waive local clinical trials for drugs approved in countries like the U.S., U.K., Japan, and the European Union represents a pivotal regulatory shift. While the move aims to expedite access to essential medications and enhance market availability, it raises significant concerns about patient safety, research and development (R&D), and broader healthcare implications,’’ noted Rajmohan Seetharaman in his paper titled The implications of waiving local clinical trials for drugs in India: a double-edged sword?’, published in The Lancet regional health (Southeast Asia) recently. He argues that waiving local clinical trials presents safety concerns and notes that trials are essential for assessing how drugs interact with diverse genetic profiles.

“India’s population diversity means bypassing trials could result in unanticipated adverse effects or reduced efficacy,’’ he said. He further noted that countries like Japan and China mandate local testing or foreign data analysis for ethnic sensitivity, emphasising the importance of safety through localised validation. Japan’s cautious approach to genetic diversity in drug metabolism and China’s regulatory framework highlight the need for India to consider its own population’s unique traits.

“Gene and cellular therapies, which manipulate genetic material, carry long-term risks that are not yet fully understood. Similarly, drugs with significant therapeutic advancements need careful scrutiny, as skipping local trials could compromise safety in a genetically diverse population. For example, CAR-T therapies, which modify immune cells, require thorough local testing to account for ethnic variability in genetic responses,’’ he noted warning that waiving these trials risks weakening India’s pharmaceutical innovation, as companies may lose incentives to conduct localised research. “Additionally, it could diminish India’s robust research infrastructure, including contract research organisations (CROs), and reduce investments in local drug development,’’ notes the paper adding that the waiver may disproportionately benefit multinational corporations (MNCs) by allowing faster market entry. Patient groups have also expressed their concerns with many stating that local trials are also a way of accessing costly medicines for several patients with rare diseases.

Patient advocacy groups (PAG) have highlighted that the Drugs Controller General of India (DCGI) directive to implement fast-track approvals for rare disease drugs represents a significant advancement in enhancing access to life-saving treatments for patients. “This initiative addresses several critical challenges, including accelerated drug availability and the reduction of long waiting periods for patients diagnosed with life-threatening conditions,” stated the mother of a 15-year-old patient with Acid sphingomyelinase deficiency (ASMD). She emphasised that adequate measures must now be taken to ensure that once regulatory approvals are granted, therapies are made available immediately.

Currently, the Central Technical Committee on Rare Diseases at the Ministry of Health and Family Welfare has yet to decide on including acid sphingomyelinase deficiency (ASMD) as a notified condition under the National Policy for Rare Diseases 2021, despite treatment being approved by the Subject Expert Committee of CDSCO as early as 2023.

Also voices from the industry, state that the move will expedite the approval process for new drugs and will help industry to respond faster in case of pandemic situations and bring in products for rare diseases to the market at the earliest. It added that this will also ease the regulatory pathway for new drug launches in the industry.

Meanwhile the regulator has clarified that the local clinical trial waiver for approval of a new drug already approved in other countries can be considered if the drug is approved and marketed in countries under specified rules and if no major unexpected serious adverse events have been reported.