Drug discovery and development of yester years Drug discovery and development now Preclinical Drug Organization Clinical IT & Data management Approval Postapproval

1. Pharmaceutical Industry – Change in
Discovery and Development Approaches
Dr. Bhaswat S. Chakraborty
Senior Vice President,
Research and Development
Cadila Pharmaceuticals Ltd.

2. Contents
1. Drug discovery and development of yester years
2. Drug discovery and development now
3. Preclinical
1. Drug
2. Organization
4. Clinical
1. IT & Data management
5. Approval
6. Postapproval
7. …

3. Drug discovery and development until
1980’s
• Discovery was restricted to rich pharma companies and
academic institutions of excellence
• Trial and error and serendipity
• Very few players knew the game and its rules
• Simple evaluations of “drug efficay” and “safety” (along
with CMC)
• Randomized control trials were not as developed as
today
• Development of generics, NDDS and pharmacovigilance
were in their nascence

4. Atenolol (Tenormin), for example
• Atenolol is a cardio-selective β-blocker discovered and developed by
ICI
• Possesses the advantages both of propanolol and practolol
▫ Practolol, first cardio-selective β-blocker, also discovered and
developed by ICI in 1960s, but withdrawn because of toxicity
(worst – blindness)
▫ Practolol was also less potent than prpraonolol
• Atenolol is as potent as propanolol, as cardio-selective as practolol,
but without the side effect of the either
• It was launched in 1976s and became the best selling β-blocker.
• Developed, tested and launched in 3 years (1973-1976); 2 CTs for
efficacy
Takuji Hara in Pharmaceutical Innovation

6. Takuji Hara in Pharmaceutical Innovation

7. Pitavastatin (Livalo) for Dyslipidemia
• Similar situation like atenolol (related structure to
atorvastatin)
• Similar safety and efficacy profile
• Discovered by a different and small company
• 7 clinical trials
• 2 additional postmarket trials in special population
committed
• Took 7 years
• Lawsuit with Novartis
• Much higher CMC requirements
• PV requirements
• ….

8. What do we have now?
• Significant changes from now though 2033
• Big molecule (biotech) medicine
• Small molecule – drug and diagnostics
• Government regulations
▫ Tougher safety and efficacy regulations
▫ Clearer Biotech regulations
▫ More international harmonization on regulations
• Frequently changing market conditions & technology
• New emerging markets
▫ India ~USD 25 Billion by 2018
• Country-relevant research
• More NDDS & branded generics
• Personalized medicine

9. Systematic and complex nature of drug
discovery and development today
Pritchard et al. Nature review

10. The market for pharmaceutical innovations

11. Source: Centrewatch

13. Research is also changing healthcare
decisions

17. Clinical research – diverse goals
• Disease mechanisms
• Translational research
• Clinical knowledge
▫ detection, diagnosis, and natural history of disease
• Therapeutic interventions including clinical trials
• Prevention and health promotion
• Behavioral research
• Heath services research
• Epidemiology and post marketing research
• Community-based and managed care-based research

18. “The present ain’t what it used to be”
paraphrasing Yogi Berra

19. Data flow in an EDC system

21. Pharmacovigilance: Waller & Evans Model
1. Known problems
i. Known problem but unknown rate &
possibly risk factors are unknown
ii. Potential but not actually known to
occur
Risk Management
2. Unknown –any possible AE
i. “Data mining” in medical record/clinical
databases
ii. Spontaneous reporting
Data mining for
Signal Detection
Waller & Evans. Pharmacoepidemiol Drug Saf. 2003;12:17-29

22. Preparedness and changes
• Preparedness in the area of small molecule discovery as well as biotechnology–based
new entities and biosimilar products.
• Training and discovery capabilities in chemistry and biotechnology
• Requires multidisciplinary expertise and information exchange
• Pre-clinical research adequacy and lead molecule selection
• Formulation development with proper design of experiment
• A variety of safety and tolerance study design in humans
• Shallow dose-response needs special care in design
• Strategic planning for clinical research in order to define site infrastructure,
investigators’ required expertise, site and investigator training
• Efficient design and conduct of proof of concept and higher phase studies
• Efficient, and responsive program for research compliance and the protection of
human subjects
• Regulatory strategy and time management
• Sales and marketing preparedness
• Fulfilling the post-marketing commitments
• Future studies, collaboration, pharmacovigilance
• …..

23. Thank You Very Much