Hello, friends. Welcome back to the course
that is Current Regulatory Requirement for
Conducting Clinical Trial for New Drug and
Investigational New Drug in India. Up to this
we have seen many of the lectures up to lecture
8, and in the lecture 7 and 8 we have seen
that the Ethics Committee which is registered
with the Central Licensing Authority required
to oversee the BA/BE study conduct and the
clinical trial study conduct.
So, in the lecture that is lecture 9, it is
related to the Ethics Committee Registration
and Re-registration we are going to see what
is means by this exactly Ethics Committee
we have referred in our lecture 7 and lecture
8.
So, after completion of this lecture the learners
will come to know the requirement for Ethics
Committee registration; what is Ethics Committee;
which Rule s as per New Drug and Clinical
Trial are applicable; once it has been registered
what is the validity period; then how to apply
for Ethics Committee registration at CDSCO
that in Central Licensing Authority and whether
it is the in the hard copy that is offline
or online that will also see. Further, how
to apply for the registration and re-registration
these things will cover.
So, let us start first with what is ethics
committee. So, if you recall in our first
course, we have given all the schedule wise
related Rule s and the 1945 D & C Rule s wherein
the definition in the RRule 122 has been given
which is related to the ethics committee.
As per these definition an Ethics Committee
is a committee comprising of medical, scientific,
non-medical, non-scientific members whose
responsibility is to ensure the protection
of the right safety and well being of human
subject involved in clinical trial and it
shall be responsible for reviewing and approving
the protocol, the suitability of the investigators
facilities method and adequacy of information
to be used for obtaining and documenting informed
consent of the study subject and adequacy
of confidentiality safeguard.
So, this is little bit and the definition
of the ethics committee. Now, let us see why
it is required to have the Ethics Committee
and why its registration is mandatory.
So, as per the RRule 6 of New Drug and Clinical
Trial Rule , whoever intend to conduct clinical
trial or bioavailability study or the bioequivalence
study what we have seen in our previous lecture.
It shall be required to have approval of an
Ethics Committee for clinical trial register
under RRule 8. So, in this Rule it has been
stipulated that the registered Ethics Committee
approval is acceptable.
So, the Ethics Committee shall apply for registration
with the Central Licensing Authority it is
mentioned under Rule 8.
Let us see what should be the composition
or the constitution of the Ethics Committee
for clinical trial Rule . So, dear friends
I would like to mention here in this New Drug
and Clinical Trial Rule , we have mentioned
about two Ethics Committee that is one for
the Ethics Committee which is for clinical
trial, as per the definition we have seen
what is clinical trial. So, if it is fit in
that definition then Ethics Committee has
to be registered with the CDSCO and one more
Ethics Committee that is committee related
to the Biomedical and Health Research that
will see in our subsequent slides. So, there
are two types of ethics committee.
Let us have a look for the constitution of
Ethics Committee for clinical trial. So, it
is given under Rule 7. The Ethics Committee
for clinical trial shall have minimum of seven
members and these members from medical, non-medical,
scientific, and non-scientific areas with
at least one lay person should be there, then
one woman representative should be there,
then to handle the legal matters one legal
experts, one independent member from any other
related field such as social scientists or
representative of the non-government organization
or philosopher this should be there so, one
member from this.
And, the important things to know that the
Ethics Committee they shall consist of at
least 50 percent of its members who are not
affiliated with the institute or organization
in which such committee is constituted.
The one member of Ethics Committee who is
not affiliated with the institute or organization
shall be the chairperson. The chairperson
should not be affiliated to the institution.
The one member who is affiliated with the
institution shall be appointed as a member
secretary. Then the committee shall con include
at least one member whose primary area of
interest or the specialisation is non-scientific.
So, that he can think it properly and without
involving the science and at least one member
who is independent of the institution.
The members of Ethics Committee shall follow
the provision of the Rule s. So, the whosoever
the member they should be conversant with
the Rule s regulation of related to the ethics
committee. They should be aware about the
Rule s regulation and good clinical practices
guideline so that they can safeguard the right
safety and well being of a trial subject.
The every member of Ethics Committee shall
require to undergo such training. So, not
only the when the certificate of root that
they have undergone such training that should
be there.
The members representing the medical scientists
and clinicians shall possess at least post
graduate qualification in their respective
area of specialization. They should have further
adequate experience in the respective field
and requisite knowledge about the GCPguideline
and Rule s and regulations.
As far as possible, based on the requirement
of research areas such as HIV or genetic disorder
specific patient group may also be represented
in the ethics committee. If it is the trial
is related to the aids drug or the HIV drug
in the; for that the Ethics Committee they
can have if possible the patient from such
community.
Then, regarding the conflict of interest of
these members so, as per the Rule s no member
of the Ethics Committee having conflict of
interest shall be involved in the oversight
of the clinical trial or BA/BE study protocol
and in this regard they have to sign a declaration
that there is no conflict of interest.
While considering an application which involves
a conflict of in interest of any member of
Ethics Committee such member may voluntarily
withdraw from the Ethics Committee review
meeting. If any member for example, if PI
is involve in such a study then he may withdraw
from that study and, the details in respect
of such conflict of interest shall be recorded
in the minutes of the meeting, why he has
not attended the minutes of meeting that should
be mentioned in the minutes of the meeting.
Let us have a look about registration of Ethics
Committee related to the clinical trial BA/BE
studies.
So, this is given in the RRule 8 of New Drug
and Clinical Trial Rule . So, as per this
Rule s every Ethics Committee constituted
under Rule 7, as we have seen, shall make
an application for a grant of registration
to central licensing authority in form CT-01.
So, those who are willing to register the
Ethics Committee required to apply in CT-01
form and the document information required
that is given in the Table 1 of the third
schedule. We will see that in the later.
Also, we have covered in our another lecture
which is exclusively for the tables given
in the NDCT Rule s.
The Central Licensing Authority after scrutinizing
such submitted information, document which
are furnished by the application if require
they can make an entry and if considered and
after being satisfied that the requirement
of these Rule s have been complied with may
grant registration to the Ethics Committee
in form CT-02.
And, in case if the Central Licensing Authority
is not satisfied with the compliance of these
Rule s by the applicant Ethics Committee it
may reject the application, but in that case
the licensing authority has to be given the
reason why they have rejected it. And, they
have to give the communication in this regard
within a period of forty-five working days
to the applicant from the date of receipt
of the application.
If in case the applicant is not satisfied
with the decision taken by the licensing authority
he can appeal and he may file an appeal before
the Central Government in the Ministry of
Health and Family Welfare. That appeal should
be within a sixty working days from the date
of receipt of order of rejection.
And, Central Government after scrutinizing
his appeal they have to dispose this appeal
within a sixty working days. If they have
found that the applicant who is registration
has been cancel was not proper, then they
can revoke that order and if they found that
it is consistent with the Rule s and regulation
and it has not followed the stipulated condition
they can continue this registration.
The validity period was the registration has
been granted, it is valid for five years unless
it is suspended or cancel and it is from the
date of issue. Then for the renewal of registration
of Ethics Committee on expiry of validity
period, the applicant can make an application
for renewal of registration in the same form
that is CT-01 and the document which are mention
in the table-1. And, this has to be applied
within the 90 days prior to the date of the
expiration of the registration certificate.
Let us have the look for the functions of
the Ethics Committee which are given in Rule
11 of New Drug and Clinical Trial. So, the
function of Ethics Committee is to review
and accord approval to clinical trial bioavailability,
bioequivalence, study protocol.
The first is that they have to review the
protocol submitted by the sponsor to them.
Then after approval from the Ethics Committee
and approval after approval from the Central
Licensing Authority, it is the responsibility
of Ethics Committee to monitor and have internal
audit report furnished by the sponsor or by
visiting the study style. They can have the
internal audit also or they can they can verify
the report of the internal audit or they can
directly go and inspect the study also.
They have to indicate the reason that weighted
with the while rejecting or asking for a change
or notification the protocol in writing and
copy of such reason shall also be made available
to the Central Licensing Authority. So, in
case of the serious adverse events which occurs
to a trial subject or study subject during
this trial, the Ethics Committee shall analyse
the relevant documents pertaining to such
an event and forward its report to the Central
Licensing Authority and comply with the provision
of the Chapter VI. So, if any SAE is there
then it is the duty of the Ethics Committee
to analyse all this document in documentations
and results and whatever the outcome or whatever
the opinion they are having they are forwarding
to the Central Licensing Authority.
Where at any stage of clinical trial it comes
to conclusion that the trial is likely to
compromise the right safety or well being
of trial subject the committee may order discontinuation.
So, the Ethics Committee is also having the
power to order such a sponsor to discontinue
or suspend or suspend this clinical trial
and whatever the order given that same shall
be intimated to the head of the institution
conducting the clinical trial and the BA/BE
study and also to the centralization of authority.
The committee as we have seen in the BA/BE
study centre, the centre should allow the
auditor, in the same manner the Ethics Committee
also should allow an officer authorized by
the Central Licensing Authority to inspect
any record or premises any document related
to the clinical trials or furnish information
to any query raised. They comply with the
requirement or condition in addition to the
requirements specify. The Ethics Committee
also has been stipulated with certain condition
that they are required to comply with.
Let us see the proceeding of Ethics Committee
and members requirement.
So, no clinical trial or BA/BE protocol and
deleted document shall be reviewed by Ethics
Committee unless at least five of its member
are available. So, we have seen at least seven
members should be there, but for the quorum
or to review this protocol at least five members
should be there and fromthis five member one
should be the medical scientist, preferably
it should be a pharmacologist, then clinician,
one legal experts, social scientists or representative
of any NGO or ethicist and one lay person
who is not related to all this and we can
think it critically the lay person should
be there.
The Ethics Committee if require they can constitute
a sub-committee to assist its function assigned
to it and it may associate such expert who
are not its member in its deliberation. So,
they can take a help of you in case of for
example, there is a case or there is a protocol
for the HIV drugs so, they can take a assistance
from those who are expert in that field. But,
in this case, the expert shall not have voting
rights if any. So, they cannot work in case
of an agreement or disagreement.
Further any change in the membership or constitution
of the registered Ethics Committee that shall
be intimated in writing to the Central Licensing
Authority within thirty days.
The Ethics Committee shall maintain a record
like data of all the protocol reviewed, then
registered another document and they have
to keep it for five years after completion
of such clinical trial.
In particular and without prejudice to the
generate of sub Rule the Ethics Committee
shall maintain the record for period of five
years and these records what are the record
to be maintained it is given here the constitution
and composition of the ethics committee. So,
the record of the constitution who were the
members and what were their qualification,
their that has to be maintained.
Then the SOPs which are followed for the proceeding
SOPs which are followed for other things that
has to be maintained.
Then national and international guideline
followed by the Ethics Committee which are
the guidelines they are followed whether it
is ICH guidelines, CDSCO guideline, WHO guidelines,
the record of that also required to be follow.
Then copies of the protocol, data collection
format, case report form, investigator brochure
whatever submitted by the sponsor for the
review and whatever they have accorded the
approval that everything they are to maintain
the record.
Then all correspondence with the committee
members investigator regarding application
decision and follow up whether it is through
the mail or by hard copy all the records whatever
the correspondence they have made in case
of if they are having any doubt and if they
require to ask it to the sponsor or to the
investigator that should that communication
should be through either mail or document
and whatever these communication whatever
the reply obtained that has to be maintained.
Agenda of all Ethics Committee meetings: so,
whenever there is a conduct of meeting the
agenda and the minutes of the meeting that
should be signed with the chairperson has
to be maintained.
Copies of decision communicated to the applicant
whatever the copies of decision communicated
applicant that is required to be maintained.
Records relating to any order issued for premature
termination; in case if Ethics Committee is
found that the conduct is not as per the rule
and there is a major deviations they can order
we have seen to the suspension or premature
of the conduct of the study and in this case
they have to maintain the record of such orders.
Recommendation given by the Ethics Committee
for determination of the compensation, in
case of any SAE is there then Ethics Committee
we have seen has to evaluate the report and
the final outcome has to be given to the Central
Licensing Authority and head of the institution
within 14 days. So, record of these required
to be maintained. Then after giving the compensation
what compensation the sponsor has given the;
they have to inform it to the Ethics Committee
and Ethics Committee also required to maintain
the record related to the compensation paid.
Now, Ethics Committee shall furnish the information
maintained as and when required by the central
licensing authority. So, this is one of the
condition that the whenever the Central Licensing
Authority requires such information whether
they have conducted meeting or not, what the
compensation they are paid - so, everything
they require to produce to the Licensing Authority
as and when it is required.
Now, let us see what is the procedure for
suspension or cancellation of ethics committee.
So, this right is with the central licensing
authority where the central licensing authority
is of the opinion that any Ethics Committee
if it fails to comply with any provision of
the act or this Rule or the condition stipulated
while giving the registration to this ethics
committee, then the Ethics Committee for the
Ethics Committee the central licensing authority
may issue shape show cause notice to such
ethics committee. And, the reason should be
mentioned there and whatever the base for
giving the show cause notice that is non-compliances
observed or the violation observed that that
should be mentioned in to the show cause notice.
While giving such show cause notice the licensing
authority may stipulate some period within
which the Ethics Committee required to reply.
On receipt of such reply for the show cause
notice within a period specified in the show
cause notice, the Central Licensing Authority
can also give an opportunity of being heard,
in person to such ethics committee. And, after
consideration of the fact and reply given
by the Ethics Committee the Central Licensing
Authority, may take one or more of the actions
and, this action are like they can withdraw
the show cause notice if the Ethics Committee
has replied properly to the show cause notice.
If it is not replied properly they can issue
a warning to the Ethics Committee and in that
warning they have to describe the deficiency
or defect observed during the inspection or
otherwise which may adversely affect the right
or well being of the trial subject or validity
of the clinical trial BA/BE study conducted.
The licensing authority can reject the result
of clinical trial or BA BE study. So, for
those which I have been accorded by the Ethics
Committee and if it is not proper then that
also can be suspended. It can suspend for
such a period as consider appropriate by the
licensing authority. The licensing authority
can debar its member to oversee any clinical
trial in future for period as maybe consider
appropriate.
Then after cancellation, rejection or suspension,
debar whatever the action if the licensing
authority has taken and if the applicant is
not satisfied with the decision taken by the
licensing authority, then there is a provision
for appeal where the Ethics Committee or any
member of the committee is aggrieved by such
an order, they may within period of 60 working
days of the receipt of the order they can
appeal to the central government that is the
Ministry of Health and Family Welfare.
And, after filing such approval or after making
such inquiry as it things necessary and after
giving the opportunity of being heard to the
applicant the Central Government may pass
such an order in relation there to as it thinks
appropriate. If they found that rejection
is inappropriate they can revoke that rejection
and if they find the rejection is inconsistent
with the provision of D & C act and Rule s
where under they can continue this. So, this
decision is communicated to the applicant
within sixty working days from the filing
and appeal.
Now, as I have mention there are two ethics
committees, one is for the clinical trial
of new drug and IND, and the Ethics Committee
to be constituted for those research which
is not comes under the clinical trial and
this is for the biomedical and health research.
So, in the Chapter IV it is given the Ethics
Committee for biomedical and health research
let us see what are the rule position.
So, Ethics Committee for biomedical and health
research - any institution or organization
intend to conduct such type of results shall
require to have an Ethics Committee approval
as per the detail in National Ethical Guideline
for Biomedical and Health Research involving
participants. So, any research which is going
to be happen on the human subject which is
not a part of the clinical trial or new drugs
or IND, they also required to take a approval
from the Ethics Committee which is exclusively
prepared for the such type of biomedical and
health research.
The constitution and composition we have seen
for the Ethics Committee in this regard the
constitution and function of the Ethics Committee
it should be as per the national ethical guideline
for biomedical and health research involving
human participant which is a prepared by the
ICMR in 2017.
So, the registration of such type of Biomedical
and Health Research ethics committee, they
shall be required to register with the authority
designated by the Ministry of Health and Family
Welfare, Department of Health and Research.
So, earlier it was not designated, now it
has been designated that the Department of
Health and Research will register such type
of Ethics Committee and the applicant has
to apply in form CT-01.
Information and document these are same as
what we require for the Ethics Committee for
the clinical trial and a new drug which is
stipulated in the Table 1. In this case the
validity period for such type of Ethics Committee
is for the two years provisionally and after
having the inquiry about the documentation
and the whether the Ethics Committee has followed
the rule s regulation that can be continue
for a 5 years.
In case the rejection of the registration
of such Ethics Committee there is also provision
for the appeal. Within 60 working days the
applicant has to appeal to the central government
and after receiving the appeal the Ministry
of Health form Family Welfare that is central
government has to dispose of the application
within period of sixty working days.
In case, after the expiration of the registration
of such as ethics committee, there is provision
for renewal and that renewal for the renewal
the applicant has to apply to the concern
authority at least ninety days prior to the
expiration. So, if there is a; if there is
no action or the file is spending with the
designated of a authority then if it has been
applied prior to the 90 days, the existing
RC would continue to be work and this would
not be null and void.
For renewal of fresh set of document, the
information and the documents for you have
to seen for the registration, all this document
may not be required to be furnished if there
is a no change. And, if there is no change
the certificate in to that effect has to be
given by the applicant that there is no change
in the ethics committee.
So, in case of non-compliance of rule s and
regulation as life for the other Ethics Committee
which we have seen for clinical trial new
drug, here also there is provision for suspension
and cancellation.
So, the level the authority who has given
the registration to the biomedical and health
research Ethics Committee can cancel or suspend
the registration. After cancellation there
is a provision we have seen within 45 working
days, he has to appeal for that.
Now, let us see what are the documents required
to be submitted for registration of the Ethics
Committee as given in the Table 1 of the third
schedule.
So, the information to be submitted by the
applicant for grant of registration of ethics
committee, in the first, he has to submit
name of the ethics committee. Then authority
under which it has been constituted, who are
the members, the requirement for the membership,
then the what are the TOR the term of references,
conditions of appointment, the quorum required.
Then the procedure for resignation; if any
member would like to resign from the Ethics
Committee what the procedure has to follow.
Then address of the office of the ethics committee,
then detail real like name address qualification
mail address brief profile of the chairperson.
Then name qualification organizational title
and further other detail like telephone number
tax etcetera of the members of the ethics
committee.
Then detail of the supporting staff also has
to be given. Then the SOPs to be followed,
the list of the SOPs and the copy of SOP is
required to be given. Then policy regarding
training of new and existing committee members;
we have seen the Ethics Committee member required
to undergo training, then the what policy
they have made to train the educate the members
that is required to be given.
Then, policy to monitor or prevent the conflict
of interest along with the SOP; we have seen
there should be no conflict of interest of
the any members while living in the protocol.
So, what is the policy they have adhered to
be that required to be submitted.
Now, let us see what are the format for according
approved to clinical trial protocol by the
ethics committee. So, the format has been
given the New Drug and Clinical Trial Rule
. You can see this is the format for recording
approval to clinical trial protocol by the
ethics committee.
So, in this format they have to accord the
approval and they have to accord the approval
and communicated communicate in this format
to the sponsor. So, this is the format.
So, this is about the Ethics Committee and
now, let us see what we have learned from
this lecture. So, in this lecture we have
learned briefly about what is Ethics Committee
as per Rule 122 DD.
And, what is the procedure to register this
ethics committee? There are two types of Ethics
Committee we have seen. One is for the clinical
trial new drug and IND and another is for
the biomedical and health research. Then,
we have seen what is the procedure for registration,
re-registration; then procedure for inspection
and what in case of the cancellation, what
is the time period for renewal; then again
we have seen its appeal and the composition
of these committees.
Now, it is your time to recall your memory.
So, the question for you, for this lecture;
the first question - the information and documents
required for the registration of Ethics Committee
are given in the which table of schedule?
So, you have to mention the table also and
schedule also in which it is given. So, it
is a table 1 of Schedule 3.
The next question which is very easy, Ethics
Committee shall have minimum of dash members.
How many members should be there at least
? So, we have seen there are there should
be minimum of seven members. Good.
Then what is the validity period of Ethics
Committee register for the CDSCO? We have
seen there are two Ethics Committee registered
under DHR and registered under the CDSCO.
So, you have to tell validity period for the
Ethics Committee registered with CDSCO that
is central licensing authority. So, it is
a 5 years.
So, this is about the Ethics Committee registration,
re-registration. We will see in our next lecture.
Till then you take care, all the best and
thank you for paying the attention.
Bye.
