Pre-Clinical and Clinical Trials- Its design and Conduct, Risk Analysis, Quality assurance and Quality Control in a Drug Development

1. Pre-Clinical and Clinical Trials- Its design
and Conduct, Risk Analysis, Quality
assurance and Quality Control in a Drug
Development

2. • In drug development, pre-clinical development, also
named preclinical studies and nonclinical studies, is a
stage of research that begins before clinical trials (testing in
humans) can begin, and during which important feasibility,
iterative testing and drug safety data is collected.
• The main goals of pre-clinical studies are to determine the
safe dose and start to assess product’s safety profile.
Products may include new or iterated or like-kind medical
devices, drugs, gene therapy solutions, etc.

3. • Pre-Clinical Trials and Clinical Trials are the processes by which
scientists test drugs and devices to see if they are SAFE and
EFFECTIVE.

4. What is a Preclinical Trial?
• Preclinical trial - a laboratory test of a new drug or a
new medical device, usually done on animal subjects,
to see if the hoped-for treatment really works and if it is
safe to test on humans.

5. There are several steps involved with doing a Pre-
Clinical Trial:
File for approval as an Investigational New Drug
(IND)5
4
3
2
1
Establish Effective and Toxic Doses
Screen the Drug in the Assay
Develop a Bioassay
Indentify a Drug Target

7. • Clinical trials are experiments done in clinical research.
• Clinical trials are experiments done in clinical research. A critical
part in the process of bringing new therapies to patients is clinical
development, the study of potential new therapies in humans.
• It typically takes 12 years from the moment of discovery in the lab
for a potential new therapy to gain approval for use and reach
patients. Clinical development is the most time intensive and
expensive part of this research and development
• There are 3 phases of clinical trials: Phase I, Phase II, and Phase III

8. Phase I Clinical Development (Safety and Exposure)
• After the drug pass its Pre-Clinical Trial Tests, it begins a Phase I
clinical trial.
• Phase I studies are used to evaluate exposure and tolerance,
typically in healthy volunteers.
• These studies may include initial single-dose studies, single dose
escalation studies, and short-term repeated-dose studies.
• An attempt is made to establish the dose range tolerated by
volunteers for single and for multiple doses
• Phase 1 trials usually focus on ensuring the therapy is safe to use
in people, rather than how effective it may be as a treatment for a
given disease.

9. Phase II Clinical Development (Safety and
Efficacy)
• Phase II clinical studies are small-scale trials to
evaluate a drug’s efficacy and side-effect profile.
• These studies are usually conducted in patients –
typically selected because they could benefit from
the new drug.
• They may vary in size, but are often from 100 to 250
patients.
• Additional safety and clinical pharmacology studies
are also included in this category

10. Phase III Clinical Development (Safety and confirmation of Efficacy)
• Phase III studies are larger scale clinical trials for safety and efficacy in a significant
number of patients.
• Phase III studies are in progress, preparations are made for submitting the Biologics
License Application (BLA) or a New Drug Application (NDA) for registration.
• BLAs are currently reviewed by the FDA’s Centre for Biologics Evaluation and
Research (CBER); NDAs are reviewed by the Centre for Drug Evaluation and
Research (CDER).
• Nonclinical activities to define safety continue throughout the Clinical Development
phase of drug development.

11. • These nonclinical activities may include ongoing ADME studies to define
metabolic pathways, potential drug-drug interactions and distribution, and
long-term safety studies designed to define the reproductive and carcinogenic
risk to human subjects.
• These studies are timed to coincide with the various phases of Clinical
Development and to provide safety information to support those trials.
• Nonclinical activities during the Clinical Development phase may also include
in vivo exposure studies in animal models to evaluate the pharmacokinetic
behaviour or determine the relative bioavailability of various drug
formulations.
• Drug formulations are often refined continuously throughout the Clinical
Development phase, culminating in a final dosage form that can be used in
definitive clinical trials and allow registration of the NCE as new drug.

13. • Each project is unique, some degree of uncertainty always exists. As
uncertainty is a characteristic of projects is a risk.
• Risks always will be an essential part of project-oriented working.
• In effect, no one can avoid project risks.
• There are two categories under the heading impact of the risk: business
risks and insurable risks. Business risks are uncertain values having both
opportunity and risk sides while insurable risks only have a negative side.
• Risk management is the systematic process of identifying, analysing, and
responding to project risk.
• The purpose of risk management is to improve project performance by
systematically identifying and assessing risks, developing strategies to
reduce or avoid them and maximising opportunities. In effect, risk
management is a creative and constructive process

16. Pharmaceutical quality assurance—Pharmaceutical quality assurance may be defined
as the sum of all activities and responsibilities required to ensure that the medicine that
reaches the patient is safe, effective, and acceptable to the patient.
Pharmaceutical quality control—As defined by WHO, quality control is the part of the
firm’s process concerned with medicine sampling, specifications, testing, and the
organization’s release procedures that ensure that the necessary tests are carried out and
that the materials are not released for use, nor products released for sale or supply, until
their quality has been judged satisfactory.
QC functions to test and measure material and product while QA establishes system for
ensuring the quality of the product.

17. QA & QC* Systems Evolve During Drug Development
• Quality assurance and quality control systems begin being established during early
clinical trials and involve:
• equipment validation (IQ, OQ, PQ)
• manufacturing controls and limits
• product specifications
• Process optimization continues through the development process, leading to
• identification of critical in-process control parameters
• final product specifications for QC purposes
• final process validation
• Stability
• Batches produced by the defined manufacturing process are studied at different
storage conditions to verify consistent quality and performance of the product
throughout shelf-life
• QC generally means product testing, and QA an independent review of the
results