International pharmaceuticals companies are now increasingly looking at India as the destination for conducting clinical trials, as the country offers certain advantages, including:
● It has large pool of patients in various therapy areas. So time factor for generating data is much lower
● There are some international class institutions, where trials can be conducted
● Costs are of 1/3 compared to USA or Europe
● Large number of investigators are trained in modern good clinical practices (GCP)
● There are international standard clinical pharmacology training centers
Earlier, India was lagging behind in the clinical trial arena, largely due to delay in implementing good clinical practices in India's clinical trial regulation - Schedule Y. This regulation was enacted way back in 1998 and amended in 2005. This amendment has given the necessary boost to clinical trial scene in India.
In India, drug regulatory process comes under the purview of Drugs Controller General of India (DCGI) who is also the head of Central Drugs Standard Control Organization (CDSCO), based in Delhi.
The amended Schedule Y has brought in the much needed changes like:
1. Clarity in approval for clinical trials.
2. Spelt out the responsibilities of:
● Sponsors
● Responsibilities of the investigators
● Need and details of informed consent
● Responsibilities of ethics committee
Application for permission for clinical trials is made on Form 44 of the Drugs and Cosmetic Act 1940.
Import license application is made by completing Form 12 of the Drugs and Cosmetic Act 1940.
Certain information/documents need to be submitted with the application for permission for clinical trials and import license. They are:
● Regulatory status of the drug in other countries
● Latest version of the protocol
● Investigator's brochure
● Case record sheet form
● Patient information sheet
● Informed consent form with translation in local language
● Chemical and pharmacological information on the drug
● Animal pharmacology data
● Human pharmacology data as available
● List and address of investigators
● CV and undertakings of the investigators
● Ethical committee's approval if available
● Laboratory details
Clinical trial approval
Clinical trial on new drug can be initiated only after due approval from the licensing authorities.
All trial investigators should possess appropriate qualification, training and experience. They also should have access to such investigational and treatment facilities that are relevant to the proposed protocol. Laboratories used for generating data for clinical trails should be compliant with good laboratory practices (GLP).
Protocol amendments, if become necessary before initiation or during the course of clinical trails, all such amendments, should be notified to the licensing authorities in writing along with the approval of the ethics committee.
Responsibilities of sponsors
Clinical trail sponsors are responsible for implementing and maintaining quality assurance system to ensure that the clinical trail is conducted and data generated, documented and reported in compliance with the protocol and good clinical practices (GCP) guidelines issued by the Central Drugs Standard Control Organisation, Directorate General Health Services, Government of India as well as all applicable statutory provisions.
Any unexpected serious adverse event (SAE) as defined in the GCP should be communicated within 14 calendar days by the sponsor to the licensing authority.
Investigators' responsibilities
The investigator is responsible for the conduct of the trail according to the protocol and GCP guidelines and also for compliance as per the undertaking given. Investigator has to ensure that adequate medical care is provided to the subject in the instance of adverse event. He also needs to report the event both to the sponsors and the ethics committee.
Informed consent
In all trials, a freely given, informed, written consent is required to be obtained from each subject, in the language the subject can understand.
Ethics committee
Responsibility of the ethics committee is also clearly defined in the Schedule and need to be followed.
Human pharmacology/ Phase 1
The objective of studies in this phase is the estimation of safety and tolerability with initial administration of an investigational new drug (IND) into human(s).Studies in this phase of development usually have non-therapeutic objectives and may be conducted in healthy volunteer subjects or certain type of patients. Drugs with significant potential toxicity - e.g. cytotoxic drugs - are usually studied in patients. Phase I trials should preferably be carried out by investigators trained in clinical pharmacology with access to the necessary facilities to closely observe and monitor the subjects.
Studies conducted in Phase I usually involve one or combination of the following:
● Maximum tolerated dose. These studies include both single and multiple dose administration
● Pharmacokinetics, i.e., characterisation of a drug's absorption and excretion
● Pharmacodynamics: Depending on the drug and the endpoints, pharmacodynamics studies blood levels related to drugs in healthy volunteer subjects or in patients with targeted disease
Phase I approval
For a new drug discovered in India, DCGI grants approval for phase I clinical trial. But for new drug discovered outside India, phase I data from the other country is to be submitted along with the application. DCGI can grant permission for phase II or ask them to repeat phase I in India.
The amendment of Schedule Y in 2005 has removed the earlier hurdles and concurrent clinical trials are now permitted in the country. By offering cost and time advantage, apart from quality services, clinical trial is poised to attain new horizons in India.
(The author is chairman of Cliphamed Pvt. Ltd., Mumbai)