The regulatory framework for new drug development involves a lengthy multi-step process including drug discovery, pre-clinical research, and clinical trials on humans to test safety and efficacy. Key aspects of the framework include guidelines from the International Conference on Harmonisation (ICH) to harmonize technical requirements globally, oversight of clinical trials by institutional review boards, and Good Clinical Practice (GCP) standards to ensure trials are scientifically sound and respect participants. The overall goal is to develop new medications efficiently and ethically while protecting human subjects.

1. Regulatory Framework for
New Drug Development

2. Drug Development
• Drug discovery: is the process by which new
candidate medications are discovered.
• Historically: identifying the active ingredient from
traditional remedies or by serendipitous discovery.
• Modern drug discovery includes:
• Identification of screening hits,
• and optimization of those hits to increase the
affinity, selectivity (to reduce the potential of side
effect
• Efficacy/potency, metabolic stability (to increase
the half-life), and oral bioavailability.

3. • It is a lengthy, "expensive, difficult, and inefficient
process" with low rate of new therapeutic discovery
• Drug development:
• It includes:
• Pre-clinical research (microorganisms/animals)
• Clinical trials (on humans) and may include the
step of obtaining regulatory approval to market the
drug.

4. • Pre-clinical Phase:
• New chemical entities (NCE): compounds which
emerge from the process of drug discovery. These
have promising activity against a particular
biological target thought to be important in
disease; however, little is known about the safety,
toxicity, pharmacokinetics and metabolism of this
NCE in humans at that time.
• The information gathered from this pre-clinical
testing, and is submitted to regulatory authorities
as an Investigational new drug application or IND.
If the IND is approved, development moves to the
clinical phase.

5. • Clinical phase: three or four steps:
• Microdosing:
• Phase I trials: In healthy volunteers, for safety and
dosing.
• Phase II trials: Initial understanding of efficacy
and further explore safety in small numbers of sick
patients.
• Phase III trials: large, pivotal trials to determine
safety and efficacy in sufficiently large numbers of
patients.
• Phase IV: These are post-approval trials also called
post-market surveillance studies.

7. ICH
• The International Conference on Harmonisation of
Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) is a project
that brings together the regulatory authorities to
discuss scientific and technical aspects of
pharmaceutical product registration.
• The purpose of ICH is to:
• Reduce or obviate the need to duplicate the testing
carried out during the research and
• Development of new medicines by achieve greater
harmonisation in the interpretation and
application of technical guidelines

8. Benefits of ICH : It leads to more economical use of
• human,
• animal and
• material resources and
• elimination of unnecessary delay in new medicines
while maintaining safeguards on –
• quality,
• safety, and
• efficacy

9. Institutional Review Board/Independent Ethics
Committee (IRB/IEC)
ICH defines an Institutional review board (IRB) as
• a group to protect the rights,
• safety and
• well-being of humans involved in a clinical trial.
• IRBs can also be called independent ethics committees
(IECs).
• An IRB/IEC reviews the clinical trial protocol as well
as the risks and benefits to study participants.
• It ensures that clinical trial participants are exposed to
minimal risks.

10. • Reviews all study-related materials.
• Must operate in accordance with national and local
regulations, as well as with ICH-GCP guidelines
• An IRB/IEC should have:
• At least five members.
• Members with varying backgrounds.
• At least one member must represent a non-
scientific area (a lay member).
• an independent member who must not be affiliated
with the institution or the trial site.

11. • IRB/IEC Responsibilities Before, During and
After a Trial
• Before a site is allowed to start enrolling patients in
a clinical trial, the IRB/IEC must review all study-
related materials in an initial review.
• The IRB/IEC also performs periodic reviews
throughout the trial’s duration.
• The IRB/IEC may also ask for additional
information regarding payments and compensation
to study participants, and informed consent
process.

12. Good Clinical Practice guidelines
Good Clinical Practice (GCP) is an international
ethical and scientific quality standard for the-
• Design,
• Conduct,
• Performance,
• Monitoring,
• Auditing,
• Recording,
• Analyses and Reporting of clinical trials.

13. • GCP provides assurance that the -
• Data and reported results are credible and are
• Accurate and that the
• Rights, Integrity and Confidentiality of trial
subjects are respected and Protected.
• GCP is a legal obligation for all trials.

14. Historical Background
• The concept of the ‘good physician‘ dates back to the
Hippocratic Oath (460 BC).
• In the United States, the first landmark in the
regulation of drugs was the Food and Drugs Act of
1906.
• Manufacturers were required to test drugs for safety
and present the evidence of safety testing to the FDA
prior to marketing.
• In 1947, the Nuremberg Code was created as a result
of the unethical and horrific experiments carried out
during World War II at Nazi war camps by German
physicians, who were subsequently tried and charged
at the Nuremberg Military Tribunal.

15. The Nuremburg Trial

16. Historical background of GCP
• 460BC Oath of Hippocrates
• 1930 U.S. Food, Drugs and Cosmetic Act
• 1947 Nuremberg Code
• 1948 Declaration of Human Rights
• 1962 Kefauver-Harris Amendment
• 1964 Declaration of Helsinki
• 1979 The Belmont Report
• 1982 International Guidelines for Biomedical
Research Involving Human Subjects
• 1996 ICH-GCP guidelines issued
• 1997 ICH-GCP guidelines becomes law in some
countries

17. • In 1964, the Declaration of Helsinki was
developed by the World Medical Association,
forming the basis for the ethical principles that
underlie the ICH-GCP guidelines we have today.It
is widely regarded as the cornerstone document of
human research ethics
• In 1962 Kefauver-Harris Amendments was passed
in response to the reports of severe foetal limb
deformities linked to the use of maternal
Thalidomide use, which required the FDA to
evaluate all new drugs for safety and efficacy.
• In 1979 Belmont report was issued by the National
Commission for Protection of Human Subjects of
Biomedical and Behavioural Research.The
principles of this report are as follows:

18. Respect for Persons:
• Dignity and freedom of every person.
• It requires obtaining informed consent
Beneficence:
• Researchers maximise benefits and minimise harms
associated with research.
Justice:
• Equitable selection and recruitment and fair treatment
of research subjects.

19. • The Indian GCP Guidelines:
• Central Drugs Standard Control Organisation
(CDSCO), has formulated the Indian GCP guideline in
2002.
• The Drug Technical Advisory Board (DTAB), has
endorsed adoption of this GCP guideline to streamline
clinical studies in India.
• CDSCO’s Head quarter is located at New Delhi and the
present the current DCGI is Dr. G.N. Singh.

20. The 13 Core principles of ICH-GCP are:
• Clinical trials should be conducted in accordance
with the Declaration of Helsinki.
• foreseeable risks and inconveniences should be
weighed against anticipated benefit. A trial should
be initiated and continued only if the anticipated
benefits justify the risks.
• The rights, safety and well-being of the trial subjects
should prevail over interest of science and society.

21. • The available non-clinical and clinical information
on an investigational product should support the
proposed clinical trial.
• Clinical trials should be scientifically sound, and
described in clear, detailed protocol.
• A trial should be conducted in compliance with the
protocol of institutional review board (IRB)/
independent ethics committee (IEC)
• The medical care given to, subjects should always be
the responsibility of a qualified physician.

22. • Each individual involved in conducting a trial should
be qualified and experience.
• Freely given informed consent should be obtained from
the subject.
• All trial information should be recorded, handled, and
stored to allows its accurate reporting, interpretation
and verification.
• The confidentiality of records that could identify
subjects should be protected.

23. • Investigational products should be manufactured,
handled and stored in accordance with applicable
Good Manufacturing Practice (GMP).
• Systems with procedures that assure the quality of
every aspect of the trial should be implemented.

24. Participants of GCP in clinical trials and
their respective responsibilities
• Regulatory Authorities - Review submitted clinical
data and conduct inspections
• The sponsor - Company or institution/organization
which takes responsibility for initiation, management
and financing of clinical trial
• The project monitor - Usually appointed by sponsor
• The investigator - Team leader. Responsible for
conduct of clinical trial at the trial site.

25. • The pharmacist at trial location - Responsible for
maintenance, storage and dispensing of
investigational products.
• Patients - Human subjects
• Ethical review board or Committee for protection of
subjects - Appointed by Institution or if not
available then the Authoritative Health Body in
that Country will be responsible.
• Committee to monitor large trials - Overseas
Sponsors eg. Drug Companies

26. • Summary of GCP Guidelines:
• All clinical trials should be conducted in accordance
with the
• Ethical principles,
• Sound scientific evidence and
• Clear detailed protocols.
• The benefits of conducting trials should outweigh the
risks.
• The rights, safety and wellbeing of trial participants are
of paramount importance and these should be preserved
by obtaining informed consent and maintaining
confidentiality.
• The care must be given by appropriately qualified
personnel with adequate experience.
• Records should be easily accessible and retrievable for
accurate reporting, verification and interpretation
• Investigational products should be manufactured
according to Good Manufacturing Practice.

27. • The events that led up to the culmination of the
ICH-GCP guidelines
• brought forth public awareness that there was a
need to control and regulate clinical trials dealing
with drugs and human subjects.
• The ICH-GCP guidelines are therefore considered
the ‘bible’ of clinical trials, and have become a
global law which safeguards humanity as we know
it today.

28. GUIDELINES FOR GOOD CLINICAL
LABORATORY PRACTICES (GCLP)
• In biomedical research , achieving a set standard of
quality produces credible results and allows
comparison between studies carried out at different
institutes nationally and internationally.
• GLP embodies a set of principles that provides a
framework within which laboratory studies are
• planned
• performed,
• monitored,
• reported and
• archived.

29. • The Organization for Economic Cooperation and
Development (OECD) evolved Good Laboratory
Practice (GLP) guidelines. India is a signatory to
OECD.
• Government of India, provides GLP compliance
certification to the test facilities involved in
conducting safety studies on chemicals.
• These guidelines should be adopted by all ICMR
laboratories engaged in research as well as patient
care.

30. Mission of GLP
• Test systems
• Archiving of records and materials
• Apparatus, material and reagent facilities.
• Quality assurance programs.
• Performance of the study.
• Reporting of study results.
• Standard operating procedures (SOP)

31. • Scope:
Good Clinical Laboratory Practices should be used by
all laboratories where tests are done on:
• Microbiology & Serology
• Hematology & Blood Banking
• Molecular Biology and Molecular Pathology
• Clinical Pathology
• Clinical Biochemistry
• Immunology (Immunohematology and Immunobiochemistry)
• Histopathology/Pathology and Cytology
• Levels of laboratories:
• Primary Level: PHC and urban health centres.
• Hb and routine urine analysis

32. • Secondary Level: District hospitals,
• Pathology, clinical pathology, biochemistry, serology,
microbiological investigations.
• Tertiary Level: Medical colleges hospitals and non-
teaching large hospitals, receive referrals from
primary as well as secondary levels
• Reference Laboratories, Research Laboratories
and Specific Disease Reference Laboratories:
Provide services in a specialized field or area of
importance.

33. • Guidelines of GCLP:
• Infrastructure
• Personal training and development
• Equipment
• Reagents and Materials
• Specimen Collection
• Reporting test results
• Specimen rejection record
• Data Management

34. • Standard operating procedure (SOP):
• It is a document, which contains detailed, written
instructions describing the stepwise process and
technique of performing a test or procedure in the
laboratory.
• SOP helps to ensure
• uniformity,
• consistency and
• control over the processes
• It ensures that the procedures are done in exactly the
same way each time irrespective of the operator.

35. • Safety in laboratories
• Biosafety Precautions:
• Four levels of biosafety laboratories (BSL) - 1, 2, 3 and
4, have been designed for handling biohazardous
material.
• Ethical Considerations
• Quality Assurance
• Quality Assurance Programme (QAP)
• Internal Quality Control (IQC)
• External Quality Assessment (EQA)
• Internal Audit

36. Good Manufacturing Practices
Purpose and Principles of GMP
• The first WHO draft text on good manufacturing
practices (GMP) was prepared in 1967 by a group
of consultants at the request of the Twentieth
World Health Assembly.
• Provides a high level assurance that medicines are
manufactured in a way that ensures their safety,
efficacy and quality.
• GMP applies to both Active Pharmaceutical
Ingredients (APIs) and Finished Pharmaceutical
Products (FPPs)

37. GMP Guidelines:
• Quality assurance: ensuring that pharmaceutical
products are of the quality required for their
intended use.
• Good manufacturing practices for
pharmaceutical products (GMP): aimed primarily
at diminishing the risks inherent in any
pharmaceutical production like cross-
contamination and mix-ups.
• Sanitation and hygiene: A high level of sanitation
and hygiene should be practised in every aspect of
the manufacture of drug products.

38. • Qualification and validation: what qualification
and validation work is required to prove that the
critical aspects of their particular operation are
controlled.
• Complaints: All complaints and other information
concerning potentially defective products should be
carefully reviewed.
• Product recalls: There should be a system to recall
from the market, products known or suspected to
be defective.
• Self-inspection and quality audits: to evaluate
the manufacturer’s compliance with GMP in all
aspects of production and quality control.

39. • Personnel: there must be sufficient qualified
personnel to carry out all the tasks
• Training: manufacturer should provide training for
all personnel whose duties take them into
manufacturing areas or into control laboratories
• Personal hygiene: A high level of personal hygiene
should be observed by all those concerned with
manufacturing processes
• Premises: Premises must be located, designed,
constructed, adapted, and maintained to suit the
operations to be carried out.

40. • Equipment: Equipment must be located, designed,
constructed, adapted, and maintained to suit the
operations to be carried out.
• Documentation: Good documentation is an
essential part of the quality assurance system and,
as such, should exist for all aspects of GMP.
• Good practices in production
• Good practices in quality control

41. Committee for the Purpose of Control and
Supervision of Experiments on Animals
-CPCSEA
• A number of animals are used for conducting a
variety of experiments.
• There has been a long felt need to prescribe
guidelines and procedures for animal
experimentation covering all aspects.
• The goal of these Guidelines is to:
• promote the humane care of animals used in
research.
• provide specifications that will enhance animals
well being and quality of research

42. The Guiding Principal of Three "R“
1. Replace - replace animals with non animal
methods.
2. Reduce - reduce the number animals used.
3. Refine - refine experimental techniques to make
them less painful.
4. Rehabilitation - of laboratory animals.

43. • CPCSEA guidelines include:
• Adequate veterinary care.
• Quarantine, Stabilization and Separation.
• Surveillance, Diagnosis, Treatment and Control
of disease.
• Location of animal facilities to laboratories .
• Anaesthesia
• Euthanasia
• Animal ethics.