# Presentation: 153142

## Smoking Cessation Pharmacotherapy: Accelerating Discovery to DevelopmentMedications Development Overview

- SRNT
- February 19, 2003
- Frank Vocci, Ph.D.
- DTR&D / NIDA / NIH /DHHS

## What is Drug Discovery, Development & Review?

- Drug Discovery & Development is the integration of the many disciplines, including:

***basic research***
***non-clinical development***
***clinical development***
***biostatistics***

***data management***
***pharmacometrics***
***regulatory***
***marketing***

## identify
evaluate
develop
achieve regulatory approval
successful launch ...
      of new chemical entities (NCEs/NMEs) and 
      new biological entities (NBEs).

- evaluate
- develop
- achieve regulatory approval
- successful launch ...
-       of new chemical entities (NCEs/NMEs) and
-       new biological entities (NBEs).

- What is Drug Discovery, Development & Review?

## Regulatory Review is the integration of many disciplines, including 
pharmacology/toxicology
non-clinical
clinical/biostat
pharmacometrics
regulatory & DDMAC
risk management

- pharmacology/toxicology
- non-clinical
- clinical/biostat
- pharmacometrics
- regulatory & DDMAC
- risk management

- What is Drug Discovery, Development & Review?

## ...to determine whether there is:
adequate knowledge about the new NME/NBE 
to make an informed evaluation about the benefit-risk ratio...
to decide whether the product should be: 
approved for marketing, and 
for which segments of that nation’s population

- adequate knowledge about the new NME/NBE
- to make an informed evaluation about the benefit-risk ratio...
- to decide whether the product should be:
- approved for marketing, and
- for which segments of that nation’s population

- What is Drug Discovery, Development & Review?

## Drug Discovery, Development & Review Stages

- The stages of drug development & review include:
- Identification 	(Drug discovery)
- Optimization  	(Lead selection)
- Evaluation(s)     	(Proof of mechanism)
- 					(Proof of principle/concept)
- Development  	(Evidence) _Effectiveness/Safety_
- Review           	(Regulatory review)
- Launch	   		(Product introduction)
- Post-Marketing 	(Market expansion)

## Decisions--Fail Early & Fail Cheaply

- The intent here is to conduct the crucial experiments early in order to identify as soon as possible projects that normally would be failing later in the clinical development process.

## Drug Discovery & Development Decisions

- First we see the key decision points represented by a
- Lead identification
- Enter development
- First in humans (FIH) (What dose?)
- Proof of mechanism/concept/principle (PoM/PoC/PoP)
- Phase 2/3 transition (Differentiation)
- Submission
- Approval , Risk management program and Launch
- Post-market program
- Post-market surveillance
- Next generation products

## Drug Discovery, Development & Review

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

*Drug Discovery, Development & Review*

**~$ 500-800 Million / ****4-10 Years**

**Decisions:**

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug Discovery, Development & Review* Adapted from* Pharmaceutical Executive*, January 2000, page 80

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Eval-**
**uate**

**Lead**
**Optimi-**
**zation**

**Lead**
**identifi-**
**cation**

**Scale**
**up **
**&**
**Launch**

**Post**
**Market**

**~$ 500-800 Million / ****4-10 Years**

**Drug**
**Develop-**
**ment**

**Regula-**
**tory**
**Review**

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug Discovery, Development & Review* Adapted from* Pharmaceutical Executive*, January 2000, page 80

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Eval-**
**uate**

**Lead**
**Optimi-**
**zation**

**Lead**
**identifi-**
**cation**

**Scale**
**up **
**&**
**Launch**

**Biotech**

**Drug**
**Discovery**

**Genomics &**
**proteomics**

**Post**
**Market**

**High**
**Throughput**
**Screening**

**Drug**
**Develop-**
**ment**

**Regula-**
**tory**
**Review**

**~$500-800 Million / ****4-10 Years**

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug *Discovery*, Development & Review* Adapted from* Pharmaceutical Executive*, January 2000, page 80

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Eval-**
**uate**

**Lead**
**Optimi-**
**zation**

**Lead**
**identifi-**
**cation**

**Scale**
**up **
**&**
**Launch**

**Toxicity Testing**

**Post**
**Market**

**Clinical  Trials**

**Regulatory Interactions**

**Chemistry & ADME**

**Drug**
**Develop-**
**ment**

**Regula-**
**tory**
**Review**

**~$ 500-800 Million / ****4-10 Years**

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug Discovery, *Development* & Review* Adapted from* Pharmaceutical Executive*, January 2000, page 80

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Eval-**
**uate**

**Lead**
**Optimi-**
**zation**

**Lead**
**identifi-**
**cation**

**Scale**
**up **
**&**
**Launch**

**Post**
**Market**

**Document Preparation**

**Bulk & Finished Prod. Manufacturing**

**Regulatory Interactions**

**Drug**
**Develop-**
**ment**

**Regula-**
**tory**
**Review**

**~$ 500-800 Million / ****4-10 Years**

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug Discovery, Development & *Review Adapted from* Pharmaceutical Executive*, January 2000, page 80

## Drug Discovery, Development & Review Adapted from Pharmaceutical Executive, January 2000, page 80

**Eval-**
**uate**

**Lead**
**Optimi-**
**zation**

**Lead**
**identifi-**
**cation**

**Scale**
**up **
**&**
**Launch**

**Biotech**

**Drug**
**Discovery**

**Genomics**

**Toxicity Testing**

**Post**
**Market**

**Clinical  Trials**

**High**
**Throughput**
**Screening**

**Document Preparation**

**Bulk & Finished Prod. Manufacturing**

**Regulatory Interactions**

**Chemistry & ADME**

**Drug**
**Develop-**
**ment**

**Regula-**
**tory**
**Review**

**~$ 500-800 Million / ****4-10 Years**

**Lead**
**ID**

**Enter**
**Develop-**
**ment**

**FIH**

**Proof**
**of**
**Concept**

**Ph 2/3**
**Trans.**

** ****Submission**

**Approval**

**Decisions:**

*Drug Discovery, Development & Review* Adapted from* Pharmaceutical Executive*, January 2000, page 80

## The Outcome of R&D 

**INDs**
**FILED**

**I**

**II**

**III**

**NDAs**
**BLAs**
**Files**

**NDA**
**BLA**
**Appr’d**

**5**

**4.5-5**

**3.5**

**1.6**

**1.3**

**1**

- The Outcome of R&D

***Impact of “Unprecedented Targets?”***

## Drug Development Process:Reasons for Research AbandonmentINDs filed 1985-1989

- Efficacy					41%
- Safety (Human & Animal)		26%
- Economics					29%
- Other						  4%

**J. DiMasi, *****Clinical Pharmacology and Therapeutics*****, July 1995, pages 1-14 **