Illiterate healthy volunteer can not be included in BE study

Is it acceptable to include healthy illiterate subjects of adult age group 18-45 in bioequivalence studies?
Dr Muneesh Garg

BE study in volunteer is a non-therapeutic trial. BE is a non-therapeutic trial. There is no benefit to the volunteer. A non-therapeutic trial (i.e. a trial in which there is no anticipated direct clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the written informed consent form.

In view of this , an illiterate healthy volunteer can not be included in a BE study.
ICH GCP for non-therapeutic trial recommends as follows:

4.8.13        Except as described in 4.8.14, a non-therapeutic trial (i.e. a trial in which there is no anticipated direct clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the written informed consent form.

4.8.14        Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative provided the following conditions are fulfilled:
(a)    The objectives of the trial can not be met by means of a trial in subjects  who can give informed consent personally.
(b)    The foreseeable risks to the subjects are low.
(c)    The negative impact on the subject’s well-being is minimized and low.
(d)    The trial is not prohibited by law.
(e)    The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/ favourable opinion covers this aspect.

Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended. Subjects in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.

For one of the study we got the EC approval with recruitment strategies. Now we want to start pre-screening to minimize the screen fail ratio. In pre-screening we are going to perform some study inclusion/exclusion criteria related procedures (i.e. few fasting lab test and physical exam).
In above scenario do we need to take EC approval or notification is sufficient before start these pre-trial activity?  In which guideline we will get the clear idea?
Vishal Barge

If you plan to conduct some protocol lab tests for inclusion-exclusion, this will require a subject to give consent. The consent form has to be approved by EC before you can plan pre-screening.

After Initial EC approval, we receive the Clinical Trial Agreement from the sites. Do we have to submit these CTA and get their approval from their respective EC? or Notification is sufficient?
If approval is mandatory then EC Quorum is required for this approval or it will come under expedited review?
Vishal Barge

As per Schedule Y, the document has to be part of EC review. If you have a submitted a draft agreement for review, then final agreement will go as a notification. If not, you will need EC to review the document in a full meeting.

Can you clarify what is verbal consent in PMS study and how to ascertain that it is duly obtained from subjects? Also can PMS study be run by Institution without EC approval?
Rohit Prasad

There is no provision for verbal consent in PMS study.

All PMS studies require EC and / or regulatory approval. See ICMR guideline below:

Phase IV - The Phase IV studies should have valid scientific objectives. After approval of the drug for marketing, phase IV studies or post marketing surveillance is undertaken to obtain additional information about the risks and benefits resulting from long term usage of drug. It is an important aspect of drug trial on the long term effects of the drugs and the adverse reactions induced by drugs, if any, should be brought to the notice of the Ethics Committee. There is a need to correlate the adverse events reported during Phase IV trials with the toxicity data generated in animals, to draw markers for future warnings of potential adverse events likely to occur with other drugs. These trials may not be necessary for approval of new drug for marketing but may be required by the Licensing Authority for optimizing its use. These studies also include those on specific pharmacologic effect, drug-drug interaction(s), dose-response studies, trials designed to support use under approved indication(s) e.g. mortality/morbidity studies, clinical trials in a patient population not adequately studied in the pre-marketing phase, e.g., children; and epidemiological studies etc. Bioequivalence and bioavailability study also falls under this category.
In addition there are Phase IV studies that are designed to evaluate the marketed drug in specifically designed studies, which have inclusion/exclusion criteria, objectives and end points. The drug is used for the labelled indication in these studies. Therefore Licensing Authority permission is not needed. However, EC permission is needed.

A third type of post-marketing study involves evaluation of the drug for a new indication of a marketed drug, e.g. studies with letrazole. Here, DCGI permission and EC approval are needed which really makes the trial a Phase III study.

What should be the minimum qualification of a lay person as a member of EC.
Dr. Muneesh Garg

There is no minimum qualification for lay person.
The definition of lay person is
a person who does not have specialized or professional knowledge of a subject
a person who is a non expert in a given field of knowledge

Hence, this is a person who does not have qualifications of an expert e.g. lawyer, doctor, scientist, chartered accountant etc.