A country with large pool of patients, highly skilled Investigators and supportive regulations to promote clinical research is a desired destination for any organisation to conduct Clinical Trials. India has a lot more to offer besides these advantages, enabling you to enjoy timely completion of trials and cost benefits. (It is estimated that India offers 35 to 60 per cent cost advantage compared to the western markets.)
In spite of a good standing in clinical research, India is yet to utilize a significant part of its potential in conducting clinical trials.
- As per reports of clinicaltrials.gov, 1.4% of global clinical trials are done in India, while the country has 16% of the world’s population and carries 20% disease burden in the world.
- It’s not surprising to note that clinical trials in India may grow significantly 2018-19 onwards, primarily with Indian regulations for clinical trials becoming more stable and predictable.
There was a time, not far back, when Indian regulatory was bringing drastic changes causing a lot of concerns for those wishing to conduct clinical trials. Not any more. With rules clarified, processes smooth-lined, India has prepared itself for next phase of clinical research growth. (1)
Let’s have a look at current regulatory requirements for conducting clinical trials in India.
Some salient points..
- Clinical trial application language is English
- Regulatory and Ethical approval is parallel
- In country sponsor/representation is required
- Clinical trial registration is required
Which is the regulatory body in India?
The Central Drugs Standard Control Organization (CDSCO) is the National Regulatory Authority in India. Its equivalent counterparts elsewhere include
- United States Food and Drug Administration (US FDA),
- Health Canada (HC) and the
- European Medicines Agency (EMA).
The Drugs Controller General of India (DCGI), an official of the CDSCO, is the final regulatory authority for the approval of clinical trials in the country.
DCGI office is also responsible for inspections of trial sites, sponsors of clinical research and manufacturing facilities in the country. In case of noncompliance, study may be rejected or discontinued; suspend or cancel the clinical trial permission, or debar the investigator(s), sponsor including his representative to conduct any clinical trial in future by DCGI.
The DCGI review and approval process is conducted in parallel with the EC review, except in the case of clinical trials for academic/research purposes that are non-regulatory in nature. (2)
What is fee for DCGI approval?
Requisite fees as per the provisions of Drugs & Cosmetics Act and Rules are
- For Feasibility Study (i.e. Safety and efficacy study); which is equivalent to Phase I trials in case of drugs: INR 50, 000/- (approx 760 USD)
- For Pivotal Study (i.e. Confirmatory trials); which is equivalent to Phase II/III trials in case of drugs: INR 25, 000/- (approx 380 USD)
How to start, when conducting clinical trial in India?
Prerequisites of conducting a clinical trials in India
- Permission from the Drugs Controller General, India (DCGI).
- Approval from respective Ethics Committee where the study is planned.
- Mandatory registration on the Indian Council of Medical Research (ICMR) ICMR maintained CTRI website (2)
The sponsor must submit the clinical trial application to both the DCGI and the EC. The EC must grant a separate approval for each trial site to be used, and the DCGI must be informed of each approval.
The investigator must ensure that clinical trials are conducted as per the rules outlined below
- In compliance with an EC and a DCGI approved protocol
- In the case of IISs with ‘new drugs’, DCGI approval is no longer needed; only an EC approval is required
- In compliance with GCP guidelines
- All applicable regulations. (3)(4)
- India has a decentralized process for the ethical review of clinical trial applications, and requires ethics committee (EC) approval for each trial site. The majority of ECs are based at clinical or academic institutions and hospitals.
- Investigators and Administrators of Academic Institutes should ensure that their Institutional Ethics Committees (IECs) are registered with the central licensing authority and the registration renewed at the end of 3 years. This is mandatory for Regulatory Clinical Trials.
Approval from Institutional Ethics committee
- All clinical trials need to have approval from the IEC
- A recent regulatory change with respect to IISs is that academicians who carry out trials with ‘new drugs’ no longer need approval from the DCGI for the conduct of the trial and IEC approval would suffice.
- In the event that the IEC feels that there could be a potential overlap between the academic and regulatory purposes of the trial, they should notify the office of the DCGI. If the IEC does not hear from the DCGI within 30 days, it should be presumed that no permission is needed from the licensing authority.
Projects submitted essentially undergo two broad types of review-
- Full board or full committee review – for all projects that present more than minimal risk or
- Expedited review – for projects that pose no more than minimal risk; e.g., leftover clinical samples.
Projects like systematic reviews or meta-analysis may also be exempted from review. (2)(6)
Is there any Clinical Trials Registry?
Yes, The Clinical Trials Registry- India (CTRI) is a free and online public record system for registration of clinical trials being conducted in India (www.ctri.nic.in).
Trial registration in the CTRI has been made mandatory by the Drugs Controller General (DCGI).
Trial registration involves
- Public declaration and identification of trial investigators,
- Patient population etc, before the enrollment of the first patient.
- Submission of ethics committee and DCGI approval (if applicable) is essential for trial registration in the CTRI.
Trial already registered with another primary register, why need to register again with the CTRI?
A clinical trial being conducted in India, is also required to be registered in the CTRI as the CTRI captures data specific for the Indian arm of a trial, e.g. Site and PI details, name of Ethics Committee and approval status, target sample size in India, start date in India etc. However, Registrants must quote the Registration number of the other Primary Registry number in the Secondary ID section of the trial registration data set.
What about multi country trials?
Multi-country trials, where India is a participating country, which have been registered in an international registry, are also expected to be registered in the CTRI.
In the CTRI,
- Indian investigators,
- Trial sites,
- Indian target sample size and
- Date of enrollment
What is the Fee for registering clinical trials or accessing/viewing registered trials?
There is no charge for registering a trial. Registered trials are also freely accessible to the public.
When is a trial considered to be registered?
A trial is considered to be registered when internationally agreed set of information about the design, conduct and administration of clinical trials is publicly available in a Primary Registry, before the enrollment of the first patient
What is the UTN?
- The Universal Trial Number (UTN) (earlier known as the UTRN) is a unique number which aims to facilitate the unambiguous identification of clinical trials registered in WHO Primary Registries and displayed on the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal. It is not a registration number.
- A UTN should be obtained early of the trial and should become permanently attached to the trial. (5)
What are other expectations and requirements?
The sponsor is responsible for selecting the investigator and institution for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. (2)
Informed consent from participants
Investigators must ensure that
- Written, informed consent is obtained from all participants in a clinical trial; and
- Audio visual recording of the informed consent process, for trials that involve vulnerable participants (children or mentally challenged patients, for example) and a new chemical entity or a new molecular entity.
Submission and approval process
SEC: Subject Expert Committee, CTA: Clinical Trial Application
Approximately 4-5 months. (7)
Clinical trials of medical devices
- In India import, manufacturing, sale and distribution of Medical devices is regulated under Drugs and Cosmetics Act and Rules.
- The Indian Council of Medical Research (ICMR) is the apex body that is responsible for the formulation, coordination and promotion of biomedical research.
What are the requirements for conducting trials of medical devices?
Global Regulatory status of the device: (particularly in 5 GHTF countries- USA, Australia, Japan, Canada and European Union)
- Clinical trial in each participating country
- Regulatory status of device in other countries
Ethics committee approval letters (if available): Information for constitution of Ethics Committee and Format for approval of Ethics. (8)
Technical data to be submitted
- Design Analysis Data.
- Biocompatibility Data.
- Protocol for carrying out biocompatibility study
- Tests conducted for establishing biocompatibility (along with test reports) and rationale for selecting those tests
- Summary report of the biocompatibility study including the conclusion of the study.
After registration of trials
After a trial is registered, trial lists are expected to regularly update the trial status or other aspects as the case may be. All updates and changes will be recorded and available for public display.
Import/Export of biological samples
- Requirement of NOC for export of biological samples is no longer applicable.
- Customs authorities at the port of entry/exit shall permit export of biological samples without prior approvals from any government agency, provided the concerned firm submits an undertaking confirming adherence to rules for safe transfer, and disposal of biological samples.
- This is a positive step to facilitate ease of conducting clinical research in the country and has further simplified administrative process for study conduct.(9)