Clinical trails unit for BTech and M.Sc. Chemistry students

1. by
Dr. B. Rama Devi,
Professor of Chemistry,
Dept. of Chemistry,
JNTUH-UCESTH.

2. l. Introduction to clinical trials:
Clinical trials are studies performed with human subjects to test new drugs or
combination of drugs, new approaches to surgery or radiotherapy or procedures to
improve the diagnosis of disease and quality of life of the patient.
2. History:
Clinical trials are sets of tests in medical, medical research and drug development that
generate safety and efficacy data (information about adverse drug reactions and adverse
effects of other treatments) for health interventions (e.g., drugs, diagnostics, devices,
therapy protocols).
Chapter-4: Fundamentals in clinical trials:

3. History of CT before 1750:
Persian physician and philosopher, Avicenna
In the canon medicine, he laid down rules for the experimental use and testing of drugs
and wrote a precise guide for practical experimentation in the process of discovering and
proving the effectiveness of medical drugs and substances. He laid out the following
rules and principles for testing the effectiveness of new drugs and medications.
1. The drug must be free from any extraneous accidental quality.
2. It must be used on a simple, not a composite, disease.
3. The drug must be tested with two contrary types of diseases, because sometimes a
drug cures one disease by its essential qualities and another by its accidental ones.
4. The quality of the drug must correspond to the strength of the disease.
5. The time of action must be observed, so that effect and accident are not confused.
6. The effect of the drug must be soon to occur constantly or in many cases, for if this did
not happen, it was an accidental effect.
7. The experimentation must be done with the human body, for testing a drug on a lion or
horse might not prove anything about its effect on man.

4. Adverse Drug Reaction:
In pre-approval clinical experience: All noxious and unintended responses to a medicinal
product related to any dose should be considered adverse drug reactions.
Regarding marketed medicinal product: A response to a drug which is noxious and
unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or
therapy of diseases or for modification of physiological function.
Adverse Event:
Any untoward medical occurrence in a patient or clinical investigation subject administered a
pharmaceutical product and which does not necessarily have a causal relationship this
treatment.
*Audit(of a clinical trial)
*Audit certificate, Audit Report and Audit Trial
*Blinding/Masking
*Case Report Form
*Clinical trial/study
*Clinical trial study report
*Comparator
*Compliance(in relation to trials)
*Confidentiality
*Contract
*CRO
*Direct Access *Documentation *Essential Documents *Good clinical practice
*IDMC (Independent Data-Monitoring Committee)
3.Terminologies:

5. 1. Treatment trials
2. Prevention trials
3. Diagnostic trials
4. Screening trials
5. Quality of life trials
4. Types of Clinical Research:

6. Clinical trials are conducted in phases. The trials at each phase have a different
purpose and help scientists answer different questions:
In Phase I trials, researchers test a new drug or treatment in a small group of healthy
people ( 20 -50) for the first time to evaluate its safety, determine a safe dosage range.
In Phase II trials, the study drug or treatment is given to aselected group of patients
(100 – 300) to see if it is effective and to further evaluate its safety.
In Phase III trials, the study drug or treatment is given to a large group of patients
(1000 – 3000) to confirm its effectiveness, monitor side effects, compare it
to commonly used treatments, and collect information that will allow the drug
or treatment to be used safely.
In Phase IV trials, post marketing studies delineate additional information including
the drug’s risks, benefits and optimal use.
5. Phases of Clinical Research:

7. * Each country has a drug regulatory body which governs approval process
* India- CDSCO (central drugs standards and control organization)
* US-FDA (food and drug administration)
* UK-MHRA ( medical and healthcare products regulatory agency)
* European Union-EMEA (European medicines agency)
* Drug must be proved to be safe and effective.
6. Role of clinical trial in new drug development:

8. Regulatory affairs play a pivotal role in ensuring the safety, efficacy, and quality of
pharmaceutical products and medical devices.
In the field of clinical research, regulatory affairs professionals are at the forefront of
ensuring compliance with the laws and regulations set forth by regulatory agencies such as
the FDA (Food and Drug Administration), EMA (European Medicines Agency), MHRA
(Medicines and Healthcare products Regulatory Agency), and PMDA (Pharmaceuticals and
Medical Devices Agency). Their expertise is essential in navigating the complex landscape of
clinical trials and ensuring that research studies meet the necessary regulatory requirements.
Introduction to Regulatory Affairs in
Clinical Research

9. Importance of regulatory affairs in clinical research
The importance of regulatory affairs in clinical research cannot be overstated. These
professionals are responsible for ensuring that clinical trials adhere to strict regulatory
guidelines, which are in place to protect the rights and welfare of study participants. Regulatory
affairs professionals work closely with researchers, sponsors, and regulatory agencies to ensure
that all necessary approvals and documentation are in place before a clinical trial can begin. They
are also responsible for monitoring ongoing trials to ensure compliance with regulatory
requirements and for reporting any adverse events or safety concerns to the appropriate
regulatory authorities.
Furthermore, regulatory affairs professionals play a crucial role in the post-approval phase of
clinical research. They are responsible for submitting regulatory filings and maintaining
compliance with regulatory requirements throughout the lifecycle of a product. This includes
ensuring that any changes to the product, such as formulation updates or manufacturing process
changes, are properly documented and approved by the regulatory authorities.
Without the expertise of regulatory affairs professionals, the entire process of bringing a new
drug or medical device to market would be fraught with risk and uncertainty.

10. Roles and responsibilities of regulatory affairs professionals
Regulatory affairs professionals have a wide range of roles and responsibilities in
clinical research. They are responsible for interpreting and implementing regulations,
guidelines, and policies related to clinical trials. This includes staying up to date with
the latest developments in regulatory requirements and ensuring that all stakeholders are
aware of their obligations. They are also responsible for preparing and submitting
regulatory submissions, including investigational new drug applications (INDs) and
marketing authorization applications (MAAs), and for coordinating with regulatory
agencies throughout the review and approval process.
In addition, regulatory affairs professionals are responsible for maintaining compliance
with regulatory requirements throughout the lifecycle of a product. This includes
ensuring that all documentation, such as clinical trial protocols, informed consent forms,
and case report forms, are complete and accurate. They are also responsible for
monitoring ongoing trials to ensure that they are conducted in accordance with the
approved protocols and that any deviations or safety concerns are properly addressed.

11. Regulatory agencies play a crucial role in overseeing and regulating clinical research
activities. These agencies are responsible for ensuring the safety and efficacy of drugs
and medical interventions before they are approved for use in the general population.
Some of the major regulatory agencies involved in clinical research include the Food
and Drug Administration (FDA) in the United States, the European Medicines Agency
(EMA) in Europe, the Medicines and Healthcare products Regulatory Agency (MHRA)
in the United Kingdom, and the Pharmaceuticals and Medical Devices Agency
(PMDA) in Japan.
Regulatory agencies in clinical research
- FDA, EMA, MHRA, PMDA

12. •The FDA is perhaps the most well-known regulatory agency in the world. It is responsible for
regulating drugs, biologics, medical devices, and food products in the United States. The FDA
sets rigorous standards for clinical trial design, data collection, and analysis, and reviews all
applications for new drug approvals. The agency also conducts inspections and audits to
ensure compliance with regulatory requirements.
•In Europe, the EMA is the regulatory agency responsible for the evaluation and supervision
of medicinal products. It plays a key role in the approval process for new drugs and provides
scientific advice to pharmaceutical companies. The EMA collaborates closely with national
regulatory agencies in European Union member states to ensure consistent standards and
regulatory oversight across the region.
•The MHRA is the regulatory agency responsible for ensuring the safety, quality, and efficacy
of medicines in the United Kingdom. It assesses the safety and regulatory compliance of
clinical trials conducted in the UK and provides guidance and support to researchers and
sponsors.
•In Japan, the PMDA is the regulatory agency responsible for the evaluation and approval of
pharmaceuticals and medical devices. It works closely with the Ministry of Health, Labour,
and Welfare to ensure the safety and efficacy of drugs and medical interventions.
These regulatory agencies play a critical role in safeguarding the interests of study participants
and the general public by ensuring that clinical trials are conducted in compliance with
applicable regulations and guidelines. Their oversight and review processes are essential for
the approval and commercialization of new drugs and medical interventions.

13. Regulatory requirements for clinical trials
Clinical trials are subject to a wide range of regulatory requirements to ensure the safety
and well-being of study participants. These requirements vary depending on the country
or region in which the trial is being conducted. In general, regulatory requirements for
clinical trials include obtaining ethical approval from an institutional review board
(IRB) or ethics committee, obtaining regulatory approval from the appropriate regulatory
agency, and adhering to Good Clinical Practice (GCP) guidelines.
Ethical approval is obtained by submitting a detailed study protocol and informed consent
form to an IRB or ethics committee. The IRB or ethics committee reviews the protocol to
ensure that the study is scientifically valid and that the rights and welfare of study
participants are protected. Regulatory approval is obtained by submitting a regulatory
submission, such as an IND or MAA, to the appropriate regulatory agency. The regulatory
agency reviews the submission to ensure that the study meets the necessary regulatory
requirements.
Good Clinical Practice guidelines provide a set of internationally recognized standards for
the design, conduct, recording, and reporting of clinical trials. These guidelines ensure
that the data collected from clinical trials is reliable and can be used to support regulatory
decisions. Compliance with GCP guidelines is essential for regulatory approval and for
ensuring the integrity of the clinical trial data.

14. Regulatory submissions and approvals
Regulatory submissions and approvals are a critical part of the clinical research process. These
submissions and approvals are necessary for initiating a clinical trial, obtaining regulatory
clearance to market a new product, and maintaining compliance throughout the product lifecycle.
In the pre-approval phase, regulatory affairs professionals are responsible for preparing and
submitting regulatory submissions to the appropriate regulatory agency. These submissions
include detailed information about the study protocol, the investigational product, and the safety
and efficacy data obtained from preclinical and clinical studies. The regulatory agency reviews the
submission and may request additional information or clarification before granting approval to
proceed with the clinical trial.
In the post-approval phase, regulatory affairs professionals are responsible for maintaining
compliance with regulatory requirements and for submitting post-marketing reports and updates to
the regulatory agency. These reports and updates may include information about adverse events,
changes to the product labeling, and updates to the manufacturing process. Regulatory affairs
professionals must ensure that all changes are properly documented and approved by the
regulatory agency to maintain compliance and ensure patient safety.

15. Challenges in regulatory affairs in clinical research
Regulatory affairs professionals in clinical research face numerous challenges in their
work. These challenges arise from the constantly evolving regulatory landscape, the
complexity of the drug development process, and the need to balance regulatory
requirements with efficient and timely completion of clinical trials.
Some of the key challenges faced by regulatory affairs professionals include the
following:
1. Evolving regulations and guidelines: Regulatory requirements are constantly
evolving as new scientific discoveries are made and as regulators strive to ensure the
safety and efficacy of drugs and medical interventions. Regulatory affairs professionals
must stay up-to-date with these changes and ensure that clinical trials and studies are
conducted in compliance with the latest regulations and guidelines.
2. Global harmonization: Clinical trials are increasingly conducted on a global scale,
with multiple sites in different countries participating in a single trial. This presents
challenges in terms of harmonizing regulatory requirements across different jurisdictions
and ensuring consistent standards of ethical conduct and data integrity.
3. Time and resource constraints: Clinical trials are often time-sensitive, with strict
deadlines for recruitment, data collection, and reporting. Regulatory affairs professionals
must work within these tight timelines while ensuring compliance with regulatory
requirements. This can be particularly challenging when dealing with complex or large-
scale trials.

16. 4. Communication and collaboration: Regulatory affairs professionals play a crucial
role in facilitating communication and collaboration between researchers, sponsors, and
regulatory agencies. Effective communication is essential for the successful completion
of clinical trials and the timely approval of new drugs. However, communication
breakdowns or delays can result in regulatory delays or non-compliance issues.
5. Regulatory inspections and audits: Regulatory agencies conduct inspections and
audits to assess compliance with regulatory requirements and to ensure the integrity and
reliability of trial data. These inspections can be stressful and time-consuming for both
researchers and regulatory affairs professionals, requiring meticulous preparation and
attention to detail.
6. Adapting to technological advancements: The use of technology in clinical
research is rapidly evolving, with new tools and platforms being developed to streamline
data collection, analysis, and reporting. Regulatory affairs professionals must stay
abreast of these technological advancements and ensure that they are implemented in
compliance with regulatory requirements.
Despite these challenges, regulatory affairs professionals play a crucial role in ensuring
the successful completion of clinical trials and the approval of new drugs. Their
expertise and attention to detail contribute to the integrity and reliability of the data
generated and the safety and well-being of study participants.

17. Career opportunities in regulatory affairs
The field of regulatory affairs offers a wide range of career opportunities for professionals
with a passion for healthcare and a strong attention to detail. Regulatory affairs professionals
can work in a variety of settings, including pharmaceutical companies, medical device
manufacturers, contract research organizations (CROs), and regulatory consulting firms.
Entry-level positions in regulatory affairs typically require a bachelor's degree in a scientific or
healthcare-related field, along with a strong understanding of regulatory requirements and
guidelines. As professionals gain experience and expertise, they can advance to more senior
positions, such as regulatory affairs manager or director. These positions typically require a
master's degree or higher, along with extensive experience in regulatory affairs and a deep
understanding of the regulatory landscape.
Regulatory affairs professionals can also specialize in specific areas, such as clinical trials,
postmarketing surveillance, or regulatory strategy. Specialization can enhance career prospects
and provide opportunities for advancement and leadership within the field.
To pursue a career in regulatory affairs, individuals typically need a strong background in life
sciences or a related field. A bachelor's or master's degree in pharmacy, medicine,
biochemistry, or a similar discipline is often required. In addition, obtaining certifications from
professional organizations such as the Regulatory Affairs Professionals Society (RAPS) or
the Association of Clinical Research Professionals (ACRP) can enhance career prospects
and demonstrate expertise in regulatory affairs.

18. Conclusion
In conclusion, regulatory affairs play a crucial role in ensuring the safety, efficacy, and
quality of pharmaceutical products and medical devices in clinical research. Regulatory
affairs professionals are responsible for navigating the complex regulatory landscape,
ensuring compliance with regulatory requirements, and maintaining patient safety
throughout the product lifecycle.
The field of regulatory affairs offers numerous career opportunities for professionals
with a passion for healthcare and a strong attention to detail. By working closely with
regulatory agencies, researchers, and sponsors, regulatory affairs professionals
contribute to the advancement of medical knowledge and the improvement of patient
outcomes.