Clinical Trials-Biopharmaceuticals.

1. Clinical Trials

2. What is a clinical trial?
• Systematic investigation into the safety and efficacy of any new drug
in human subjects

3. Why do we need clinical trials?
• Does the new treatment work in people?
• If it works, how well it works?
• Is it better than treatment now being used?
• If it’s not better, is it as good and cause fewer side effects?
• Does it work in some people who aren’t helped by current treatments?
• Is the new treatment safe? No treatment or procedure – even one
already in common use – is without risk. But do the benefits of the new
treatment outweigh the risks?

4. Before initiating any testing of drugs in human beings, they are
extensively tested on animals or human cell lines.
It involves years of experiments

5. • Investigational New Drug (IND) application: If the drug
studies are found safe in animals, the sponsor then files
an IND application to FDA (Food and Drug
Administation)
After approval by FDA, human testing begins……….
In India Central Drugs Standard Control Organisation(CDSCO)
is responsible for approval of clinical studies
• Requires pre-clinical data
• Composition of drug
• Source of drug
• Manufacturing information
• Proposed clinical plans
• Ethical committee clearance…….

6. Phases of clinical trials
Phase-0
• Phase 0 trials are also known as human micro-dosing studies
• This may help save time and money that would have been spent on later phase trials.
• Phase 0 studies use only a few small doses of a new drug in a few people.
• Unlike other phases of clinical trials, there’s almost no chance the people in phase 0 trials will
benefit.
• The benefit will be for other people in the future. And because drug doses are low, there’s also
less risk to those in the trial.
• Phase 0 studies aren’t widely used, and there are some drugs for which they wouldn’t be helpful
• Phase 0 studies are very small, often with fewer than 15 people, and the drug is given only for a
short time. They’re not a required part of testing a new drug.

7. Phase-I
Is the treatment safe?
• Are usually the first that involve people.
• Find the highest dose of the new treatment that can be given safely
without causing severe side effects.

8. • The first few people in the study get a very low dose of the treatment
and are watched very closely.
• If there are only minor side effects, the next few participants get a
higher dose.
• This process continues until doctors find a dose that’s most likely to
work while having an acceptable level of side effects.
• Phase I trials are also looking at what the drug does to the body and
what the body does with the drug.

9. • Because of the small numbers of people in phase I studies, rare side
effects may not be seen until later phases of trials when more people
receive the treatment.
• Phase I trials carry the most potential risk.
• Sometimes people choose to join phase I trials when all other
treatment options have already been tried.

10. Phase-II trials
Does the treatment work?
• Larger numbers of patients get the treatment in phase II trials, so less
common side effects may be seen.
• If enough patients benefit from the treatment, and the side effects
aren’t too bad, phase III clinical trials are begun.

11. Phase-III
Is it better than what’s already available?
• Therapeutic confirmational trials
• Target: 100-3000 people
• Time: upto 4 years
• Establishing the efficacy of a drug in a larger population, longer period.
• Comparing the safety and efficacy of the drug with respect to the
available treatments.
• These studies are often done in many places across the country (or even
around the world) at the same time.

12. • Phase III clinical trials are more likely to be offered in local community
hospitals and doctor's offices.
• These studies tend to last longer than phase I and II studies.

14. New Drug Application (NDA)
• Formal proposal to FDA to approve a new
drug for sale.
• It can be 1000’s of pages long.
• Can take 2-3 years for FDA to review the
application.
• Based on the review, the FDA decides
whether to approve the treatment for use in
patients with the illness the drug was tested
on.
• If the FDA feels that more evidence is needed
to show that the new treatment's benefits
outweigh its risks, it may ask for more
information or even require that more studies
be done

15. Phase-IV
What else do we need to know?
• No fixed duration
• Drugs approved by the FDA are often watched over a long period of time
in phase IV studies.
• Studies continue to collect data: effects and side effects in various
populations
• Long term effects of drugs: Are there rare side effects that haven’t been
seen yet, or side effects that only show up after a person has taken the
drug for a long time?
• Primarily they are observational and non-experimental in nature

16. The Central Drugs Standard Control
Organisation (CDSCO)
• CDSCO is responsible for approval of Drugs, Conduct of Clinical Trials, laying down the standards for Drugs, control over
the quality of imported Drugs in India. It is equivalent of the FDA in the US
• Further CDSCO along with state regulators, is jointly responsible for grant of licenses of certain specialized categories
of critical Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.

17. RULES GOVERNING CLINICAL TRIALS
• Rule 122-A -Application for permission to import new drug
• Rule 122-B -Application for approval to manufacture new drug
• Rule 122-DA-Mandatory requirement of permission from DCG (I) for conduct of clinical trial of new drug;
• Rule 122 DAB -Provision for examination of serious adverse event (SAE) of injury and death and payment of
compensation in clinical trial related cases. Provision for debarment of the applicant in case of failure to pay
compensation;
• Rule 122 DAC -Conditions of permission for conduct of clinical trial which includes mandatory requirement to
follow Good Clinical Practice (GCP) guidelines, guidelines and requirements specified in Schedule Y of Drugs and
Cosmetics Rules and other applicable regulations. Provision for debarment of applicant and investigator in case of
non- compliance

18. • Each phase is designed to answer certain questions while keeping the
people taking part as safe as possible.
• Results from these phases show if the new drug or treatment is
reasonably safe and effective.

19. Efficacy data demonstrates 65.2% protection against the SARS-
CoV-2, B.1.617.2 Delta variant.
Pre-clinical studies: Demonstrated strong immunogenicity and
protective efficacy in animal challenge studies conducted in
hamsters & non-human primates.
The vaccine received DCGI (Drugs Controller General of India)
approval for Phase I & II Human Clinical Trials in July, 2020.