All protocol amendments require CDSCO approval

In a multi-centric clinical trial, one site has asked for some changes in the ICD only and not in the protocol, then what is the procedure?

It is important to consider: (1) Why EC has asked for change in ICF? (2) What is the change in ICF? If the change is major e.g. impacting rights, safety and well being of the subjects, it would be desirable to make this change in ICF for all sites, and change the version. You will also have to notify the DCGI office.
If the change is not major, you can discuss with EC the need for such a change and make them understand the practical issues of changing ICF at one site. If they do not agree, you may consider three options (1) change the ICF for all sites, change the version and notify all ECS (2) change ICF at one site, no change in version, document the reason for change in the TMF and the fact that version was not changed (3) change ICF at one site, change in version, document the reason for change in the TMF and the fact that version was changed only for the site requesting ICF change.
It would be desirable to notify all ECs and regulatory agency about the change in ICF.

Do we require regulatory approval for protocol amendments?

All protocol amendments - minor or major – require CDSCO approval.
As per CDSCO pre-screening check list, major protocol amendments are:

• Amendment with respect to age limit of subject, dose, and treatment duration.
• Increase in number of subjects
• Amendment in study design
• Amendment in inclusion or exclusion criteria
• Amendment in safety or efficacy parameters
• Any other changes which has impact on safety of the subject

For approval of major protocol amendments the applicants should submit
Copy of CT permission letter
Copy of previous protocol amendment approval letter, if any
Copy of the amended protocol
Changes made in comparison with earlier protocol to be presented with rationale and major changes should be highlighted
Safety and efficacy data in support of proposed amendment
Regulatory approval from participating key country/countries (in case of language other than English, English Translated version along with Translation Certificate)

For approval of minor protocol amendments the applicants should submit

• Copy of CT permission letter
• Copy of previous protocol amendment approval letter, if any
• Copy of the amended protocol
• Changes made in comparison with earlier protocol to be presented with rationale

Do we require approval if there is any change in the site?

As per CDSCO checklist, any addition, deletion, closure of site or change of investigator or change of address requires approval.

What are recent regulatory expectations for EC?
Ethics Committee should be of same area where the site is located.

The proposed clinical trial study centres should be geographically distributed in the country and should also include clinical sites which have their own Institutional Ethics Committee.

For BE studies, additional information required for EC is:

• Authority under which ethics committee has been constituted.
• Composition of Ethics Committee
• Review and decision making process of the Ethics Committee.

Can an EC member fulfill two representations in the quorum e.g. social worker and lay person?

No. A person cannot represent two categories listed the quorum. The representation has to be decided when the EC is formed, should be documented in the composition and SOPs with clear representation. An EC member cannot change the representation during EC meeting.