In 2019, only 1.2 percent of global clinical studies included India, even though the country is estimated to bear 20 percent of the global disease burden. One reason for the slow growth of clinical research in India has been its stringent regulatory requirements. The Ministry of Health and Family Welfare, responsible for all health policy in India, took steps to clarify these requirements and address many sponsors’ concerns with the publication of its New Drugs and Clinical Trials Rules in 2019.

These regulations include provisions covering numerous topics, providing a comprehensive, well-balanced approach to improving ethics and quality standards for clinical trials while speeding up the process and giving patients earlier access to medications. With these changes, it is worthwhile for sponsors, especially biotech and specialty pharmaceutical companies, to consider the many opportunities that India and other Asia-Pacific countries offer. Some of the most significant changes are summarized below.

Clarification on the types of and approval processes for regulated studies

Previously, only bioavailability, bioequivalence, and clinical studies were regulated, providing no clarity on approval and compensation processes for other types of trials. The 2019 rules define research to include in vitro diagnostics, surgical intervention, assisted reproductive technology, public and epidemiological health surveys, and observational and noninterventional studies of old medications under Rules 16 and 17.

Additional considerations for academic clinical trials

The new rules include special considerations for academic trials, defined as clinical trials for an approved drug initiated by an investigator, academic, or research institution for a new indication, route of administration, dose, or dosage form. Importantly, the rules state that an academic trial cannot be used for seeking approval in any country.

Formalization of pre-submission meeting process

The document includes a provision to allow meetings with the central licensing authority or CLA-authorized officers to seek guidance on key requirements and laws, including processes for obtaining a license or manufacturing permission. This critically provides an opportunity to discuss available regulatory tracks for product registration and clarity before planning a regulatory submission.

Expanded definition of new drugs

New drugs now include phytopharmaceutical drugs, novel drug delivery systems, live modified organisms, monoclonal antibodies, stem-cell-derived treatments, and gene therapy products. New drugs are classified into two categories:

• Class (i): Converts to old drugs after four years of approval
• Classes (ii) and (iii): Considered new drugs at any time after approval; now includes sustained and modified release dosage

Considerations for Phase 4 studies

The new rules clarify ambiguity for Phase 4 and post-marketing study requirements, allowing studies covering drug-drug interactions, dose-response, and safety, as well as trials designed to support use under approved indications.

Post-marketing surveillance studies

These studies are conducted using new drugs under approved conditions of use, with scientific objectives approved by the CLA. Subjects may be chosen based on recommended use per the prescribing information or the package insert. Study drugs in the protocol are part of the patient’s treatment per the prescriber’s directions.

New provisions to support orphan drug research

Orphan drugs are defined as drugs treating conditions affecting not more than 500,000 people in India, differing from the U.S. definition. To promote research, new provisions include fast-track approval, special status, expedited review when safety and efficacy are established, and waiver of local clinical studies and Phase 4 upon CLA satisfaction.

Waivers of local clinical trial data in certain circumstances

Rule 75 provides options for local clinical trial requirements to be waived for new import or manufacture of drugs. These drugs must be under an ongoing global clinical trial in India while having already received approval in certain countries specified by the licensing authority in Rule 101, and there must be no major serious adverse events reported. Phase 4 study requirements may be relaxed if the drug is for serious conditions, diseases relevant to Indian health, rare diseases with no drugs available at reasonable expense, or orphan drugs.

New allowances for import and manufacture of unapproved new drugs:

In a revision of Rule 36 of the 1945 rules, a government hospital medical officer may now import unapproved drugs that are approved for marketing in the drug’s country of origin to treat patients with life-threatening or seriously disabling illnesses and unmet medical needs. Another provision allows manufacture of unapproved new drugs in limited quantity for drugs in clinical trials treating patients with life-threatening diseases.

Sponsors considering conducting clinical trials in India should consider working with a partner with global experience, mindset, local staff, and offices and experience in the country to ensure success.

Premier Consulting has been helping small to midsize pharmaceutical, biopharmaceutical, and medical device companies advance the development and registration of their products worldwide since 1995. Contact us today to see how we can assist you.

Author:

Kinjal Mehta
Senior Associate, Regulatory Affairs