In general, Indian GCP guidelines are in line with ICH-GCP. However, there are significant
differences in some of the areas, which will make the task of compliance difficult for the
sponsors, investigators and ethics committees.
The Indian GCP (3.3.1) insists that the investigator should be qualified as per the requirement of
the Medical Council of India (MCI). This means that non-medical scientists e.g. pharmacists
who organise the bio-equivalence studies, cannot become investigators. Even in the medical
field, several eminent investigators have medical degrees from UK or US, which are not
prescribed by MCI.
The qualifications of some of the senior investigators were not recognised as the medical
institutions from where these investigators studied were not approved by MCI at that time.
Implementation of this provision will require the monitors and auditors to ask the investigators
for proof that their qualifications are in line with MCI. This provision can become a major hurdle
for sponsors in selecting investigators and needs to be modified in line with ICH-GCP.
Investigator and sponsor’s SOPs
The Indian guideline (3.1.3) mandates that the sponsor and the investigator should sign a copy of
the Standard Operating Procedures (SOPs). Besides, the investigator and his staff have to be
aware and comply with SOPs.
This provision is practically impossible, as the sponsor will have to obtain signatures of all
investigators in a trial on its large number of SOPs. Imagine the task of making multiple copies
of hundreds of SOPs, delivering them to investigators, and obtaining their signatures! Besides,
SOPs also get revised periodically and the whole cycle has to be repeated.
ICH-GCP expects the investigator to comply with the protocol and leaves the task of monitoring
compliance to SOPs to monitors and auditors.
Investigators responsibility for data analysis
As per ICH-GCP, when the trial is completed, the investigator has to provide the Independent
Ethics Committee (IEC) with a summary of the outcome of trial.
In contrast, Indian GCP demands that the investigator should sign and forward the data like Case
Report Forms (CRF), results and interpretations, analyses and reports of the study from his/her
centre to the sponsor and the ethics committee.
Usually data analysis is the function of the sponsor. However, this provision makes it a
responsibility of the investigator, increasing his burden. The CRFs are never sent to IEC unless
the IEC asks for them for some specific purpose e.g. suspected fraud. The IECs of major
institutes, which are involved in several international trials, are already struggling to cope with
large number of bulky documents submitted for their approval. This provision will increase
IECs’ troubles, as they will have to create space for bulky CRFs and the clinical trial reports.
Powers of IEC
According to Indian GCP (126.96.36.199), the IEC has power to order discontinuation of a trial if the
IEC finds that the goals of the trial have already been achieved mid-way or unequivocal results
As per ICH-GCP, this is the responsibility of independent data-monitoring committee (IDMC).
The sponsor may consider establishing an IDMC to assess the progress of a clinical trial,
including the safety data and the critical efficacy endpoints at intervals, and to recommend the
sponsor whether to continue, modify, or stop a trial. This is possible, as the sponsor has to
provide regular feedback and interim analysis of trial data on efficacy and safety to IDMC. For
most global trials, the sponsor establishes an IDMC in a western country.
As Indian centres are part of global trials, they are reviewed by IDMC. This means that Indian
IECs at different sites will not be involved in this process and cannot fulfill this requirement of
Indian GCP. IDMC is also recommended in Indian GCP (3.1.5). Hence, these two provisions are
likely to create a conflict of responsibilities between IEC and IDMC!
This provision also could become a nightmare for regulatory authorities, as there is scope for
misuse of this provision by sponsors of local Schedule Y open registration trial.
The goal of these local trials is to confirm whether the Indian safety and efficacy results are in
line with the international clinical trial data. If a sponsor finds that the results are comparable to
international data in initial 25-30 patients, he can submit this data to IEC to request them to stop
the trial and later present the IEC recommendation to the regulatory authorities for obtaining
Essential documents for IEC
In the appendix V, essential documents for IEC files are listed. This means the sponsor and the
investigator have to provide additional copies of most documents to IEC and also ensure that
they are filed. It will be difficult for the monitor and the auditor to check compliance to this
provision, as the sponsor does not have direct access to IEC documents.
Essential items for informed consent
Besides the essential items for informed consent listed in ICH-GCP, Indian guidelines (188.8.131.52)
also cover issues of biological samples.
The consent has to include:
Right to prevent use of his/her biological sample (DNA, cell-line, etc) at any time during the
conduct of the research
Foreseeable extent of information on possible current and future uses of the biological material
and of the data to be generated from the research and if the material is likely to be used for
secondary purposes or would be shared with others, clear mention of the same
Risk of discovery of biologically sensitive information
These items will make the consent form more complex to explain to the subject and may
discourage him from participating in the research.
In the essential items for consent, there are also mandatory clauses on compensation, which are
Free treatment for research related injury by the investigator/ institution
Compensation of subjects for disability or death resulting from such injury. In addition, there is a
whole section on compensation related issues (2.4.5 and 2.4.7).
Indian GCP mandates that when a subject is withdrawn from research for medical reasons related
to the study, the subject should get the benefit for full participation.
While this provision seems appropriate for studies in healthy volunteers e.g. bio-equivalence
study, it could lead to issues in a clinical trial of a chronic disease in patients. A cancer patient
taking part in a long trial of a new product is assured of regular follow up and costly
investigations. If he is withdrawn because of a medical reason e.g. adverse event, he receives
free medical treatment for the event but does not receive any other benefit.
However, such a patient can cite this provision and insist on regular follow up and free
investigations assured for the trial for the whole duration of trial!
The other provisions for compensation are prescriptive:
The sponsor (company, government, institution) should agree to provide compensation for any
serious physical or mental injury or to provide insurance coverage
Research subjects who suffer physical injury in a trial are entitled to financial/other assistance to
compensate them equitably for any temporary or permanent impairment or disability subject to
confirmation from IEC.
In cases of death, their dependents are entitled to material compensation. These provisions,
probably, are an attempt to protect Indian patients, who are often illiterate and from lower socio
economic class. Monitor’s Qualifications Indian GCP guidelines (3.2) suggest that the monitor
should have adequate medical, pharmaceutical and/or scientific experience. As most monitors
are pharmacists or science graduates, they would not have adequate medical experience and
hence will not qualify as monitors!
Monitor is supposed to inform the sponsor and IEC in case any unwarranted deviation from
protocol or any transgression from principles of GCP. The monitor is not in contact with IEC and
hence this requirement cannot be fulfilled. Monitor is also responsible for ensuring that CRFs are
legible. As per ICH-GCP monitor has to verify that the documents provided by the investigator
are legible. There is a glaring omission in the functions of the monitor. It does not include
verification of informed consent.
In the section on protocol (184.108.40.206), it is mentioned that drug label should include name and
contact numbers of investigator and name of institution. This is not a global practice. This will
lead to practical difficulties in global trials where the labels are uniform with minor changes
made if required by local laws and practice.
Indian GCP (3.1.5) mandates that the sponsor should make arrangements for safe and secure
custody of all study related documents and material for a period of three years after the
completion of the study or submission of the data to the regulatory authority (ies) whichever is
later. If the company does not get marketing approval within 3 years of completion of trial and if
there is a need for regulator inspection after marketing approval, the records will not be
available. It is desirable, as in the case of ICH-GCP, to link the records to marketing approval.
Time has to come to review some of the provisions of Indian GCP guidelines, as they are soon to
become a law. Some of the sections related to the investigator, IEC, monitor, drug label and
documentation have to be viewed pragmatically from compliance and practical considerations.
Some others - informed consent and compensation — need discussion on global practices vis-…-
vis Indian socioeconomic realities. Overall, there is an urgent need for another harmonisation
between Indian GCP and ICH-GCP!