Bio Equivalence Study

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					An Integrated Discussion
Indian GCP and ICH GCP

 “ICH is a joint initiative involving both
  regulators and industry as equal partners in the
  scientific and technical discussions of the testing
  procedures which are required to ensure and
  assess the safety, quality and efficacy of
  medicines.” [1]
 “ICH stands for International conference on
  Harmonization of technical requirements for
  registration of pharmaceuticals for human use.”

   European Commission (EU)
   European Federation of pharmaceutical Industries Association (EFPIA)
   Ministry of Health, Labour and Welfare, Japan (MHLW)
   Japan Pharmaceutical Manufacturer Association (JPMA)
   US Food & Drug Administration (FDA)
   Pharmaceutical Research & Manufacturers of America (PhRMA)
   Observers (Non-voting members):
   WHO
   EFTA (The European Free Trade area)
   Canada
   Associated Member:
   The International Federation of pharmaceutical Manufactures Association

   Indian GCP

   • Expert Committee set up by Central Drugs Standard Control
   Organisation (CDSCO) in consultation with clinical expert has
   formulated this GCP guideline
   • Drug Technical Advisory Board (DTAB), the highest technical body
   under D&C, Act, has endorsed adoption of this GCP guideline for
   streamlining the clinical studies in India
   • These guidelines have been evolved with consideration of WHO, ICH,
   USFDA and European GCP guidelines as well as the Ethical Guidelines
   for Biomedical research on Human Subjects issued by the Indian Council
   of Medical Research


  • ICH (International Conference on Harmonisation of technical
  requirements for registration of pharmaceuticals for human use)
  • This Guideline has been developed by the appropriate ICH Expert
  Working Group and has been subject to consultation by the regulatory
  parties, in accordance with the ICH Process. At Step 4 of the Process the
  final draft is recommended for adoption to the regulatory bodies of the
  European Union, Japan and USA.
  ICH GCP                                  Indian GCP

  A sponsor may transfer any or all of     Sponsor may transfer any or all of the
  the sponsor's trial-related duties and   Sponsor’s study related duties and functions
  functions to a CRO, but the ultimate     to a CRO but the ultimate responsibility for
  responsibility for the quality and       the quality and the integrity of the Study
  integrity of the trial data always       Data shall always reside with the Sponsor.
  resides with the sponsor.
                                           Any Study related duty, function or
  Any trial-related duty and function      responsibility transferred to and assumed by
  that is transferred to and assumed by    a local representative or a CRO should be
  a CRO should be specified in writing.    specified in writing.

  Any trial-related duties and functions   Any Study related duties, functions or
  not specifically transferred to and      responsibilities not specifically transferred to
  assumed by a CRO are retained by the     and assumed by a CRO or a local
  sponsor.                                 representative shall be deemed to have been
                                           retained by the Sponsor.

ICH GCP                                    Indian GCP

The sponsor is responsible for selecting   The Sponsor is responsible for selecting
the investigator(s)/ institution(s)        the Investigator(s) / Institutions taking
                                           into account the
                                           appropriateness and availability of the
                                           study site and facilities.

                                           The Sponsor must assure itself of the
                                           Investigator’s qualifications and
                                           availability for the entire duration of the

ICH GCP                                      Indian GCP
The investigator(s) should be qualified by   The investigator should be qualified by
education, training, and experience to       education, training and experience to
assume responsibility for the proper         assume responsibility for the proper conduct
conduct of the trial, should meet all the    of the study and should have qualifications
qualifications specified by the applicable   prescribed by the Medical Council of
regulatory requirement(s)                    India (MCI)

                                             The investigator should also
                                             ensure that other studies do not divert
                                             essential subjects or facilities away from the
                                             study at hand.

                                             He /
                                             she should clearly understand the time and
                                             other resource demands the study is likely
                                             to make and
                                             ensure they can be made available
                                             throughout the duration of the study
ICH GCP                                     Indian GCP
If required by the applicable regulatory    Subjects    may     be    paid for the
requirement(s), the sponsor should          inconvenience and time present, and
provide insurance or should indemnify       should be reimbursed for expenses
(legal and financial coverage) the          incurred, in connection with their
investigator/the institution against        participation in research
claims arising from the trial, except for
claims that arise from malpractice          However, payments should not be so large
and/or negligence                           or the medical services so extensive as to
                                            induce prospective subjects to consent to
The sponsor's policies and procedures       participate in research against their
should address the costs of treatment of    better judgment (inducement)
trial subjects in the event of trial-
related injuries in accordance with the     All payments, reimbursement and medical
applicable regulatory requirement(s)        services to be provided to research
                                            subjects should be
When       trial    subjects    receive     approved by the IEC
compensation, the method and manner
                                            - when a guardian is asked to give consent on behalf of an
of compensation should comply with          incompetent person, no remuneration should be offered
applicable regulatory requirement(s)        except a refund of out of pocket expenses
                                            - when a subject is withdrawn from research for medical
                                            reasons related to the study the subject
                                            should get the benefit for full participation
                                            - when a subject withdraws for any other reasons he/she
                                            should be paid in proportion to the amount
                                            of participation

ICH GCP                                        Indian GCP
IRB/IEC should include:                        The number of persons in an ethical
(a) At least five members.                     committee be kept fairly small (5-7
(b) At least one member whose primary          members)
area of interest is in a nonscientific area.
(c) At least one member who is                 It is generally accepted that a minimum of
independent of the institution/trial site.     five persons is required to compose a
Only those IRB/IEC members who are
independent of the investigator and the        12 to 15 is the maximum recommended
sponsor of the trial should vote/provide       number
opinion on a trial-related matter
                                               Chairperson of the Committee should
Only members who participate in the            preferably be from outside the Institution
IRB/IEC review and discussion should           and not head of the same Institution to
vote/provide their opinion and/or advise       maintain    the   independence   of    the

                                               Member Secretary who generally belongs to
                                               the same Institution should conduct the
                                               business of
                                               the Committee

ICH GCP                                         Indian GCP
trial protocol(s)/amendment(s), written         Protocol, Recent curriculum vitae of the
informed consent form(s) and consent            Investigators indicating qualification and
form updates that the investigator              experience, Subject recruitment procedures,
proposes for use in the trial, subject          Procedure for seeking and obtaining
recruitment            procedures       (e.g.   informed consent with sample of patient
advertisements), written information to be      information
provided to subjects, Investigator's            sheet and informed consent forms in English
Brochure        (IB),     available   safety    and vernacular languages, Proposed
information, information about payments         compensation and reimbursement of
and compensation available to subjects,         incidental expenses, Agreement to comply
the investigator’s current curriculum           with national and international GCP
vitae      and/or     other    documentation    protocols for clinical trials, Details of
evidencing qualifications, and any other        Funding agency / Sponsors and fund
documents that the IRB/IEC may need to          allocation for the proposed work
fulfil its responsibilities

ICH GCP               Indian GCP
-                     The Member Secretary should
                      communicate the decision in

                      An IEC may decide to reverse its
                      positive decision on a study in the
                      event of receiving information that
                      may      adversely     affect   the
                      benefit/risk ratio

                      The discontinuation of a trial
                      should be ordered if the IEC finds
                      that the goals of the trial have
                      already been achieved midway or
                      unequivocal results are obtained

                      The ethical review should be done
                      through formal meetings and
                      not resort to decisions through
                      circulation of proposals


ICH GCP                               Indian GCP
All serious adverse events (SAEs)     The Sponsor should provide ADR /
should be reported immediately        AE reporting forms to the
to the sponsor except for those       Investigator(s) / Institution(s). The
SAEs that the protocol or other       Sponsor
document (e.g., Investigator's        should expedite the reporting to all
Brochure) identifies as not           concerned (including the Ethics
needing immediate reporting           Committee and the regulatory
                                      authorities) of all serious and/or
The sponsor should expedite the       unexpected adverse drug reactions
reporting    to    all   concerned
investigator(s)/institutions(s), to   Any unusual, unexpected, or
the      IRB(s)/IEC(s),      where    serious adverse drug reaction
required, and to the regulatory       (ADR) detected during a trial
authority(ies) of all adverse drug    should be promptly communicated
reactions (ADRs) that are both        by the
serious and unexpected                sponsor to the Licensing Authority
                                      under Rule 21 and the other

Schedule Y quotes that trials to be conducted as per GCP.. thus GCP
indirectly becomes a regulation in India!!!

Guidelines : A guideline is any document that aims to streamline
particular processes according to a set routine. e.g. ICH GCP , it is kown
fact that if one follows GCP guidelines one is complying to the
international standards which will generate a quality data as well
protecting rights and well being of thetrial subjects.

Regulation :It is a law passed by the constitution of the country and one
has to abide with the law.e.g. Schedule Y.

Description: Bioequivalence study of fixed dose combination of Tenofovir disoproxil fumarate 300mg, Emtricitabine 200mg and Efavirenz 600mg with ATRIPLATM tablet in healthy, adult, human subjects under fasting Condition as well as to Monitor the safety of Subjects