REGULATORY REQUIREMENTS FOR CLINICAL TRIALS IN INDIA

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THIS ARTICLE WAS WRITTEN BY NITHIKA ELIZABETH REBELLO, A STUDENT OF SCHOOL OF LAW, CHRIST UNIVERSITY.

INTRODUCTION

The development of new drugs has the capability of increasing the life-span of a patient. As clinical trials play an important role in development of new drugs, the government is trying to ensure that the safety as well as rights of the human subjects are secure and the quality of the trials completed in India expand to international standards[1]. The economic, social and cultural circumstances of global pharmaceutical operations are undergoing a change of pace, especially in India, which happens to be one of the countries spearheading pharmaceutical development. The facilitation of quality research in consonance with guidelines laid down contributes to the progress of patient care, leading to better outcomes with relation to protecting human health, although research is a time-consuming, labour-intensive process capable of taking eons to lead to fruition.

From initial testing processes until human trials, drug development research is fully funded by the pharmaceutical industry. The industry also ensures that the research studies are in compliance with the country’s regulatory requirements. The main objective of this research is to provide a comparative overview of the regulatory requirements as well as the process involved in conducting clinical trials in India and to study challenges involved in it.

REGULATIONS AND FUNDAMENTALS FOR CONDUCTING A CLINICAL TRIAL IN INDIA

In India, a set of regulations are set to assure safety, protection and welfare of subjects in conducting clinical trials. These regulations are based on the Drugs and Cosmetics Act 1940 and Rules 1945, schedule Y for clinical research by Central Drugs Standard Control Organisation or CDSCO and the ICMR and GCP guidelines. The National Regulatory Authority in India is the Central Drugs Standard Control Organisation or CDSCO. Being a department under the Ministry of Health and Family Welfare, Government of India, it is responsible for public health through ensuring safety assurance, efficacy control and quality check with regard to cosmetics, drugs and medical devices.[2] The responsibility of formulation, promotion and coordination of biomedical research is headed by the Indian Council of Medical Research (IMCR), funded by the Ministry of Health and Family Welfare and the Department of Health Research, Government of India[3].

The Drugs and Cosmetics Act 1940 and Rules 1945 sets out rules regarding approval to perform clinical trials, compensation in case of trial-related injury or death and ethics committee registration. Schedule Y mandates the guidelines regarding the approval required for the import and manufacture of new drugs for sale and for clinical trials. The ICH-GCP guidelines are with regard to the responsibilities of the ethics committee, safety assessment, inspection and quality assurance. These include the GCP and ICMR requirements.

The fundamentals of conducting a clinical trial consists of three steps:-

(1) Approval from the Drugs Controller General, India.

(2) Permission from the particular Ethics Committee where the clinical study is designed.

(3) Compulsory registration on the ICMR website.

ETHICAL ASPECT OF CLINICAL TRIALS

The main ethical issues in conducting clinical trials in India are with regard to the informed consent process and documentation, empowerment of ethical committees to be independent and competent and patient awareness about safety and compensation rights.

The ethics committee acts as the bridge between the researcher and the ethical guidelines of the country. Concepts of vulnerable populations, therapeutic misconception and post-trial access hold special importance in ethical conduct of research, especially in developing countries like India, where most of the research participants are uneducated and economically backward[4]. They are responsible to ensure independent and timely review of all the ethical aspects involved in conducting ethical trials, be it in order to safeguard the rights of the participants or looking into the consent process. Regular evaluation of research also needs to be maintained and therefore, ethical committees serve as an important part of ethical research in the country.

NEW DRUGS AND CLINICAL TRIAL RULES, 2019

In the new rules, new drug definition has been broadened, covers newer therapeutic options like SR/MR, NDDS, Living modified organisms, monoclonal antibodies, stem cells derived products, gene therapeutic products, xenografts etc. The NDCT Rules are applicable to, and regulate, all new drugs, investigational new drugs for human use, clinical trials, bioequivalence studies, bioavailability studies and Ethics Committees[5]. The ethics committee has to be set up by whoever intends to conduct the clinical trials. The application in order to conduct clinical trials need to be submitted to the Central Licensing Authority. Provisions related to compensation have been included in the new rules of 2019. The rules mandate that in case of manufacturing or the import of a new drug, permission must be obtained from the central licensing authority.

IMPACT OF NEW REGULATORY AMENDMENTS

The New drugs and Clinical trials rules 2019 are aimed at improving the speed at which clinical trials are conducted and to hasten the approval of new drugs. The changes also have an impact on the ethics committee associated with the clinical trials. Ethics committees have been reconstituted with an increased period of validity. This increase in period not only promotes greater compliance as the process of registration renewal is reduced but it also allows them to function for a longer duration.

The new regulatory amendments specify a more structured procedure for appeals and consideration of rejected applications. A more streamlined timeline for review is also provided. The new rules provide a more practical procedure for compensation in case of injury or death during a clinical trial by changing the wording from “the day of occurrence of a serious adverse event” to “knowledge of the occurrence of a serious adverse event”[6].

Now the way forward should be by maintaining the highest standards without compromising the participation in clinical trials as this could affect the availability of safe and effective products. The monopoly in the CRO segment should be broken down by promoting healthy competition as this could result in bringing down the cost of conducting trials in India. A intertwined understanding of both the disease burden with the administrative prerequisites will be beneficial in alleviating disease associated burden in the country.

CHALLENGES FOR PERFORMING CLINICAL TRIALS IN INDIA

The prospect of ensuring a hassle-free, safe clinical trial all while offering quality assurance is a distant dream for India. There are several ethical, regulatory, quality, media, training and cultural considerations which may pose to be difficult to overcome in the future. India is a country with a plethora of resources for clinical research, including manpower and regulations, however, multinational companies lose faith due to a long-standing history of unethical practices. There is no assurance of confidentiality of results and protection of the human subject. There also seems to be no compliance with safety protocols, which leads to the development of a casual attitude when it concerns the health and safety of the test subjects. It is observed that there is a long-standing delay for clinical trial approval due to absence of trained researchers. Informed consent is not understood by the trial participants, which is the moral obligation of the conductors of the trial. It must be ensured that the subject understands their rights and all terms of consent. These are some concerns that have been under scrutiny regarding the procedural aspect of clinical trials.

CONCLUSION

India has worked towards developing a regulatory framework that is more streamlined with the main focus of protecting Indian clinical trial participants. India mandates compensation in case of research related injury and steps have been taken to ensure that ECs are properly trained. The empowering of IECs by the regulator towards approving studies with ‘new’ drugs without the need for regulatory approval means that researchers, IECs and institutional administrators should have mechanisms in place for greater participant protection, assessment and analysis of SAEs and budgetary provisions in place for insurance and compensation of participants in these trials[7]. Indian regulatory bodies work with international agencies to maintain an updated clinical trial process and system. However, India still has to do a lot to match the international standards. Implementation of regulations need to be done speedily with necessary investment and infrastructure support. Without a proper administrative

[1] Kalpana Kamnoore, M P Venkatesh, Balamuralidhara V, T M Pramod Kumar, Regulatory requirements for conducting clinical trials in India, RESEARCH JOURNAL OF PHARMACY AND TECHNOLOGY, (April 20, 2021, 8:45 AM), https://rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2020-13-3-81.

[2] CENTRAL DRUGS STANDARD CONTROL ORGANISATION, https://www.cdscoonline.gov.in/CDSCO/homepage, (last visited April 20, 2021).

[3] INDIAN COUNCIL OF MEDICAL RESEARCH, https://www.icmr.gov.in/, (last visited April 20, 2021).

[4]J Sanmukhani and C. B. Tripathi, Ethics in Clinical Research: The Indian Perspective, NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267294/, (last visited April 18, 2021, 6:45 PM).

[5] Ashwin Sapra, New Drugs and Clinical trial rules 2019- A regulatory overview, MONDAQ, https://www.mondaq.com/india/healthcare/832924/new-drugs-and-clinical-trials-rules-2019-a-regulatory-overview, (last visited April 18, 2021, 12:50 PM).

[6] V. Vennu and P. P. Saini, India’s Clinical Trial Regulatory Changes, Indian Researcher Awareness of Recently Changed Regulations, and the Impact of the New Drugs and Clinical Trial Rules: A Review, INDIAN JORNAL OF PHARMACEUTICAL SCIENCES, (April 19, 2021, 2:45 PM), https://www.ijpsonline.com/articles/indias-clinical-trial-regulatory-changes-indian-researchers-awareness-of-recently-changed-regulations-and-the-impact-of-the-new-dr-4023.html.

[7] Nithya J Gogtay, Renju Ravi, and Urmila M Thatte, Regulatory requirements for clinical trials in India: What academicians need to know, NCBI, (April 19, 2021, 3:12 PM), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372399/.