Contents

• Good clinical practice

• Objectives
• Historical Background
• Sections
• Principles
• Ethics Committee
• Sponsor responsibilities
• Investigators responsibilities
• Clinical trial protocol
• Informed consent process
• Conclusion
• References

ICH GUIDELINE FOR PHARMACOVIGILANCE Good clinical practice

in pharmacovigilance Studies

Good clinical practices is a set of internationally recognized ethical and

scientifically quality requirements which must be observed for designing,
conducting, recording and reporting clinical trials that involves the participation
of human subjects. Compliance with this good practice provides assurance and
the rights, safety and well-being of trial subjects are protected and that results of
clinical trial are credible.

• A standard for the design, conduct, monitoring, auditing, recording,

analyses and reporting of clinical trials that provides assurance that the data and
reported results are credible and accurate and that the rights, integrity, and
confidentially of trial subjects are protected.

• ICH-GCP is an International Conference on Harmonization Good

Clinical Practices the guidelines was developed with consideration of the
current good clinical practices of the European Union, japan, and the United
States as well as those of Australia, Canada, the Nordic countries and the world
health organization.
OBJECTIVES
 To harmonize the regulations and the guidelines for the drug
development.

 To ensure the scientific validity and credibility of the data collected

inhuman clinical studies.

 To protect the rights of human subjects participating in the clinical trials.

 More economical use of human, animal and material resources.

 Minimizing the risks and maximizing benefits associated with

investigational drugs.

 Providing reliable information of regulatory authorities, healthcare

providers and patients.

 Promoting transparency and accountability in the conduct of clinical

trials.
  Enhancing public trust in the pharmaceutical industry and healthcare
research.

Historical Background
•Nuremberg Code, 1946

•German Physician conducted medical experiments on prisoners of war without

their consent. Most participants died or permanently crippled.
•Set of principles established in 1946 in response to the unethical medical
experiments conducted during World War II particularly by Nazi doctors. It
Emphasizes voluntary consent, absence of coercion, and the necessity for
experiments to yield fruitful respect for society among other guidelines.

• Kefauver Amendments, 1960

• 6000-12000 children had congenital anomalies d/t maternal use of
thalidomide.

• 1962 US Senate hearing Kefauver Amendment passed into law for the
manufacturers were required to prove FDA The effectiveness of their product
before marketing them.

•Declaration of Helsinki

•A statement of ethical principles to provide guidance to physicians and other

participants in medical research involving human subjects.

•The declaration specifically addressed clinical research, reflecting changes in

medical practice from the term Human Experimentation used in the Nuremberg
Code.

•Tuskegee Syphilis study-1932 to 1972

•The US Public health services conducted a syphilis study on 600 low income
African American individuals.
Stopped in 1972
•Led to the 1979 Belmont report and the establishment of OHRP.
• 1996 ICH-GCP Guideline issued

• 1997 ICH-GCP Guidelines become law in some countries.

Sections of ICH-GCP Guidelines

1) GLOSSARY
2) PRINCIPLES OF GCP
3) REQUIREMENTS FOR IRB/IEC
4) RESPONSIBILITIES OF THE SPONSOR
5) RESPONSIBILITIES OF THE INVIGILATOR
6) CLINICAL TRIAL PROTOCOL
7) INVESTIGATOR’S BROCHURE
8) ESSENTIAL DOCUMENT

PRINCIPLES
1. Clinical trials should be conducted in accordance with the ethical
principles that have their origin in the Declaration of Helsinki, and that are
consistent with GCP and the applicable regulatory requirement(s).
2. Before a trial is initiated, foreseeable risks and inconveniences should be
weighed against the anticipated benefit for the individual trial subject and
society. A trial should be initiated and continued only if the anticipated benefits
justify the risks.

3. The rights, safety, and well-being of the trial subjects are the most important
considerations and should prevail over interests of science and society.

4. The available nonclinical and clinical information on an investigational

product should be adequate to support the proposed clinical trial.

5. Clinical trials should be scientifically sound, and described in a clear, detailed

protocol.

6. A trial should be conducted in compliance with the protocol that has received
prior institutional review board (IRB)/independent ethics committee (IEC)
approval/favourable opinion.

7. The medical care given to, and medical decisions made on behalf of, subjects
should always be the responsibility of a qualified physician or, when
appropriate, of a qualified dentist.

8. Each individual involved in conducting a trial should be qualified by

education, training and experience to perform his or her respective task(s)

9. Freely given informed consent should be obtained from every subject prior to
clinical trial participation.

10. All clinical trial information should be recorded, handled, and stored in a
way that allows its accurate reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects should be
protected, respecting the privacy and confidentiality rules in accordance with
the applicable regulatory requirement(s).

12. Investigational products should be manufactured, handled, and stored in

accordance with applicable good manufacturing practice (GMP). They should
be used in accordance with the approved protocol.

13. System with procedures that assure the quality of every aspect of the trial
should be implemented.

ETHICS COMMITTEE RESPONSIBILITIES

1. The responsibilities of ethics committees in good clinical practices (GCP)

are crucial for ensuring the ethical conduct of clinical trials and protecting the
rights, safety, and well-being of research participants.
2. The GCP guidelines emphasize ethical conduct, informed consent, study
design and protocol development, investigator responsibilities, and monitoring
and quality assurance.

3. Ethics committees play a significant role in ensuring compliance with

these principles. They are responsible for reviewing and approving clinical trial
protocols, ensuring that the risks and benefits are adequately weighed, and that
the rights, safety, and well-being of trial participants are protected.

4. They also ensure that the investigators are qualified and that the trial is
conducted in accordance with the protocol and GCP guidelines.
5. Addition, ethics committees are responsible for ensuring that informed
consent is obtained from every trial participant, and that the clinical trial data
are recorded, handled, and stored in a way that allows accurate reporting,
interpretation, and verification.
6. They also ensure that the confidentiality of records that could identify
subjects is protected, and that the investigational products are manufactured,
handled, and stored in accordance with applicable good manufacturing practice
(GMP)

7. Furthermore, ethics committees are responsible for ensuring that there are
systems in place to assure the quality of every aspect of the trial, and that
regular monitoring is conducted to ensure that clinical trials adhere to the GCP
guidelines

8. They also ensure that quality assurance measures, such as site visits, data
verification, and audits, are implemented. In summary, ethics committees play a
critical role in ensuring that clinical trials are conducted ethically and in
compliance with GCP guidelines. They are responsible for reviewing and
approving clinical trial protocols, ensuring that the rights, safety, and well-being
of trial participants are protected, and that the trial is conducted in accordance
with the protocol and GCP guidelines. They also ensure that informed consent
is obtained from every trial participant, and that the clinical trial data are
recorded, handled, and stored in a way that allows accurate reporting,
interpretation, and verification. Additionally, ethics committees ensure that the
confidentiality of records that could identify subjects is protected, and that the
investigational products are manufactured, handled, and stored in accordance
with applicable good manufacturing practice (GMP).

9. Finally, ethics committees ensure that there are systems in place to

assure the quality of every aspect of the trial, and that regular monitoring is
conducted to ensure that clinical trials adhere to the GCP guidelines.

SPONSER RESPONSIBILITIES
The sponsor is responsible for ensuring that clinical trials are conducted
ethically and in compliance with GCP guidelines, including implementing and
maintaining quality assurance and quality control systems, securing direct
access to all source data/documents and reports, selecting qualified
investigators, providing medical expertise, designing the trial, managing the
trial, handling data, keeping records, validating computerized systems, ensuring
subject safety and data reliability, and ensuring that all trial-related activities are
conducted in accordance with relevant GCP requirements. The sponsor should
also ensure oversight of any trial-related duties and functions carried out on its
behalf and ensure that any incidents that might have an impact on the safety of
trial participants or/and trial results are reported by the service provider.

INVESTIGATORS RESPONSIBILITIES
Investigators play a critical role in ensuring that clinical trials are conducted
ethically and in compliance with GCP guidelines.
• They are responsible for ensuring that the study is conducted in
accordance with the protocol and GCP guidelines, that the investigational
product is used appropriately, and that the rights, safety, and well-being of
research participants are protected.
• They should also ensure that informed consent is obtained from every
trial participant, and that the clinical trial data are recorded, handled, and stored
in a way that allows accurate reporting, interpretation, and verification.
• Additionally, investigators should ensure that there are systems in place
to assure the quality of every aspect of the trial, and that regular monitoring is
conducted to ensure that clinical trials adhere to the GCP guidelines.

CLINICAL TRIAL PROTOCOL

A GCP-compliant protocol should include the following elements:

1. Introduction: The protocol should include a clear statement of the study's

objectives and a brief description of the background and rationale for the study.

2. Study design: The protocol should describe the study design, including
the type of study (e.g., randomized controlled trial, observational study), the
study population, the inclusion and exclusion criteria, and the sample size
calculation.

3. Interventions: The protocol should describe the interventions to be tested,

including the dosage, frequency, and duration of the intervention, as well as any
comparators or control groups.
4. Outcome measures: The protocol should specify the primary and
secondary outcome measures, including the methods for assessing these
outcomes.

5. Data collection and management: The protocol should describe the

methods for collecting, handling, and storing data, including the use of
electronic data capture systems and data management plans.
6. Statistical analysis: The protocol should describe the statistical analysis
plan, including the methods for analysing the data and the level of significance.

7. Ethics and regulatory considerations: The protocol should include

information on the ethical and regulatory considerations, including the informed
consent process, the role of the ethics committee, and the reporting of adverse
events.

8. Quality control and assurance: The protocol should describe the systems
and procedures for ensuring the quality of the trial, including monitoring and
auditing procedures.

INVESTIGATORS BROCHURE

The Investigator's Brochure (IB) is a compilation of clinical and nonclinical

data on the investigational product(s) that are relevant to the study of the
product(s) in human subjects
The IB should include information on the sponsor's name and the identity of the
product, a confidentiality statement, a compilation of results gathered from non-
clinical and clinical studies of the medicine, background information on the
properties and history of the investigational medicinal product, and a summary
of data and guidance for investigators.
INFORMED CONSENT PROCESS
The informed consent process is a critical component of GCP, involving
ongoing communication and mutual understanding between a patient and
investigator. It is designed to protect the rights and welfare of research
participants, ensuring that they are fully informed and able to voluntarily decide
whether to participate in a study.

Conclusion
Good clinical practices ensures the ethical and scientific quality of clinical trials
and for protecting the rights, safety, and well-being of trial subjects. It includes
historical background. There are eight sections of ICH-GCP Guidelines. GPC
includes thirteen principles. There are various responsibilities of Ethics
committee, Investigator, and Sponsor. GPC includes investigators brochure and
informed consent process.
References
https://gcp.nidatraining.org/
Textbook of Pharmacovigilance SK Gupta, Jaypee Brothers, medical publishers
https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice-scientific-
guideline

https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf

https://www.slideshare.net/abelmathew5/ichgcp-guidelines