Drug Development Life Cycle (DDLC)

1. Overview of Drug Development
and Clinical Trials
Rajendra.Sadare
Senior Software Engineer-Testing and Validation
Arisglobal Software Pvt.Ltd

2. The Drug Development Process
 Each country has a regulatory body which
governs the approval process
 Drug must be proved to be safe and effective
 Pre-clinical testing (laboratory and animals)
 Clinical testing (clinical trials in humans)

3. Clinical Trial
 Give (new drug to a number of subjects and assess outcome
(uncontrolled)
 Give new drug to one group and control to another group and assess
outcome (controlled clinical trial)

4. Clinical Trials: Major Questions
 What happens to the drug in the body?
 What happens to the body when given the drug?
 Is the drug clinically effective?
 Is the drug clinically safe / tolerable?
 How should the drug be taken?

5. Concepts In Clinical Development
 Pharmacokinetics (PK): Evaluation or quantification of
(absorption, distribution, what the body does to a drug
metabolism, elimination - substance over time.
A.D.M.E.)
 Pharmacodynamics (PD): Evaluation or quantification of
(effects on organs or systems) what a drug substance does to
the body over time, and over
drug concentrations.

6. Concepts In Clinical Development
 Efficacy
- A treatment is considered ineffective unless scientifically /
clinically proven efficacious.
 Safety
- A treatment is considered unsafe unless scientifically /
clinically proven safe / tolerated.
Key is risk / benefit ratio!

7. Standards Of Clinical Development
Key concepts in clinical trial design
• Control: active (positive)
placebo (negative)
others
• Randomization: treatment assignment left to chance
• Blinding: double-blind, single blind, open
• Parallel groups vs. cross-over vs. Others
(simultaneous) (sequential in time)
• Dose titration vs. fixed dose
• Stratification: balancing relevant subset of patients

8. Patient Control Groups: Why?
• To provide a standard for comparison of new therapy
• To eliminate positive bias toward new therapy, including “placebo”
effect.
• To protect new therapy against negative bias concerning adverse
experiences.
• To increase scientific and regulatory acceptance of study results

9. The History of Clinical Trials
 First controlled clinical trial
 1753 – Lind’s study comparing the use of different treatments
for scurvy
 Treatment - lime & oranges, seawater etc.
 2 patients in one group
 Two patients on limes & oranges were cured

10. The History of Clinical Trials
 First randomised controlled clinical trial
 1948- First use of a randomised control group: streptomycin
treatment of pulmonary tuberculosis
 Treatments: streptomycin (antibiotic) versus bed rest
 Patients received streptomycin OR just bed rest at random
(randomised clinical trial)
 Outcome: streptomycin was effective

11. Development of New Drug -
A High-Risk Undertaking
 Time: 8 -12 years from discovery to market.
 Cost: average of $800-900 million.
 Success: 1 in 4000 compounds synthesized or 1 in 5 tested in humans
reaches the market.
 Return: 1 in 3 drugs reaching the market recaptures development costs.

12. Major Stages of Drug
Development
Preclinical Testing
IND Application
Clinical Testing – Phase I
Clinical Testing – Phase II
Clinical Testing – Phase III
New Drug Application
Clinical Testing–Phase IV

13. Drug Development Process
Preclinical I
Clinical NDA Review Post-Marketing
N Phase I
D
Adverse
Initial Reaction
Synthesis Phase II Reporting
A
P
Phase IV
P
Animal L Phase III Surveys/
Testing I Sampling
C Testing
A
T Treatment Use
I
O
N Inspections
Range 1-3 Range 2-10 Yrs.
FDA Time
Yrs. Avg: 5 Yrs. Range 2 Mon – 7
30 Day Yrs.
Avg:18 Mos. Safety Review NDA NDA
Avg:24 Mos.
Submitted Approved
Average of Approximately 100 Months From Initial Synthesis to Approval of NDA

14. Preclinical Testing
 Laboratory and Animal Testing is Done
 Is compound safe in living organisms ?
 Is compound biologically active?
 If YES, file an IND Application

15. IND Application (Investigational New Drug)
 Report the results of preclinical testing
 Describes how the drug is made
 If the FDA does not disapprove of the IND application within
30 days, then testing in humans can begin

16. Clinical Testing – Phase I
 Involves giving the drug to a small number of healthy volunteers
 Determines the safety of the drug as well as the safe dosage range
 Takes a year or less to complete

17. Clinical Testing – Phase II
 Involves giving the drug to a large group (100-300) of patients who
have the disease that the drug is expected to treat
 Purpose is twofold….
- Does the drug work in the disease population?
- At what dosage does the drug demonstrate efficacy?
 Takes about 2 years to complete

18. Clinical Testing – Phase III
 Involves administering the drug to a large number of patients
(1000-3000)
 Purpose is to….
- Confirm earlier efficacy results
- Identify adverse events which occurs when the drug is given to a
larger population over a longer period of time
 Takes about 3 years to complete

19. NDA – New Drug Application
 If the results of all the previous testing is positive, then the
pharmaceutical company files an NDA
 NDA contains all of the information gathered during
preclinical to phase III
 NDA can be thousands of pages long
 Can take 2-3 years for FDA to review

20. Clinical Testing – Phase IV
 Once the NDA is approved and the drug is available, post-marketing
studies are conducted to further confirm safety and efficacy during
long-term use
 Can include mail-in questionnaires and personal interviews

21. Standards of Clinical Development
US law requests “substantial evidence” to support claim of
effectiveness for new drugs.
Basis for determining the claim is to evaluate if a clinical
investigation is “adequate” and “well controlled”.

22. Good Science + Good Study Logistics
=
Good Clinical Development
 Regulatory authority satisfaction
 Public health protection
 Marketable product

23. Thank U