Pharmaceutical industry – change in discovery and development

Pharmaceutical Industry – Change in Discovery and Development Approaches

Dr. Bhaswat S. ChakrabortySenior Vice President,

Research and DevelopmentCadila Pharmaceuticals Ltd.

Contents1. Drug discovery and development of yester

years2. Drug discovery and development now3. Preclinical

1. Drug2. Organization

4. Clinical1. IT & Data management

5. Approval6. Postapproval7. …

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

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▫ Practolol, first cardio-selective β-blocker, also discovered and developed by ICI in 1960s, but withdrawn because of toxicity (worst – blindness)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

Takuji Hara in Pharmaceutical Innovation

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• ….

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

Systematic and complex nature of drug discovery and development today

Pritchard et al. Nature review

The market for pharmaceutical innovations

Source: Centrewatch

Research is also changing healthcare decisions

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

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

Berra

Data flow in an EDC system

Pharmacovigilance: Waller & Evans Model

1. Known problems i. Known problem but unknown rate &

possibly risk factors are unknownii. Potential but not actually known to

occur

2. Unknown –any possible AEi. “Data mining” in medical record/clinical

databasesii. Spontaneous reporting

Risk Management

Data mining for Signal Detection

Waller & Evans. Pharmacoepidemiol Drug Saf. 2003;12:17-29

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 • …..

Thank You Very Much